Neuro&General&Localization–Approach&

HxOTaking:!
Cerebral!Cortex:! Higher!Mental!Function!Deficit,!↓Memory,!↓Orientation,!Dysphasia,!
! ! ! ! Apraxia!(Button/Unbutton,!Mimick!Clock,!Draw!Intersecting!Pentagon),!↓Consciousness,!
! ! ! ! Hallucination,!Seizure!
Extrapyramidal:!! Coordination!of!movement,!Stiffness,!Tremor,!Abnormal!movement,!Falls,!Dysphagia!
Cerebellum:! ! Coordination!&!Rhythm!of!movement,!Falls;! Cerebellar!Vermis!–!Truncal!Ataxia!
Peripheral!N:! ! Motor!&!Sensory!function,!LMN!signs!&!Numbness!&!Pins/Needles!
NMJ:!! ! ! Muscle!Weakness!(Diurnal!Variation,!Fatigability),!Diplopia,!Dysphagia,!Ptosis!
Muscle:! ! ! Proximal!Muscle!Weakness!(Climbing!Stairs,!Standing!up!from!low!chair,!Combing!hair),!
! ! ! ! May!have!Muscle!Tenderness/Pain,!May!Not!have!Muscle!Wasting,!No!Sensory!disturbance!
Temporal!Hx:! ! Toxic/Metabolic!can!be!any!time!course!
! Acute:! ! Minutes!to!1h:! Vascular,!Convulsive!
! ! ! ! ! ! ! Hemiplegic!Migraine:!Sudden!Onset!then!Resolution!with!Severe!Headache!
! ! ! ! ! ! ! TIA:! ! ! ! Sudden!Onset!then!Resolution!without!Headache!
! Subacute:! ! Hours!to!Days:! Inflammatory!(eg.!Meningitis,!Cerebral!Abscess,!GBS)!
! Chronic:! ! Myopathy,!Tumor,!Degenerative!
PE!Approach:! ! Bilateral?!Symmetrical?!
! ! ! ! UL!or!LL?!Cranial?!
! ! ! ! Motor!or!Sensory?!Autonomic?!
! ! ! ! Proximal!or!Distal?!
! ! ! ! Myotomal/Dermatomal!or!NerveOspecific?!Glove!&!Stocking?!
! ! ! ! Flexor!or!Extensor?!
Hard!Physical!Signs:! Wasting,!Fasciculation,!CogOwheel!Rigidity,!Limb!Reflex,!Babinski,!
! ! ! ! Nystagmus,!Dysconjugate!Gaze,!Gag!Reflex,!Corneal!&!Pupillary!Reflex,!
Soft!Physical!Signs:! Sensory!Deficit!(Unreliable!on!its!own),!Unsteadiness!
Approach!to!LL!Weakness:!
! Hx!Taking:!! Affect!UL?!Affect!Face?!
! ! ! ! Dysphagia/Dysarthria?!
! ! ! ! Urinary/Bowel!Sx?!
! ! ! ! Bilateral?!Symmetrical?!
! ! ! ! ProximalODistal:!
! ! ! ! ! UL:! Comb!Hair?!Writing?!Holding!Chopsticks?!
! ! ! ! ! LL:! Can!climb!up!stairs?!Can!stand!up!from!squatting/sitting!position?!
! ! ! ! Sensory!problems?!
! ! Other!Q:! Previous!Episode?!DM?!
! PE:! ! ! If!identify!UMNL!in!LL!only!
! ! ! ! >!Check!Sensory!Dermatome!in!Trunk!(Thoracic)!to!locate!level!of!lesion!
! ! ! ! ! (Always!check!from!No!sensation!to!sensation>!More!Sensitive)!
!

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 Neuro&Lesion&Location&
Cerebral!Cortex:!
! Lobes:! Frontal:! Disinhibition!(like!Alcohol),!! Emotionally!Lability,!
! ! ! ! ! ↓Planning!ability,! ! ! Expressive!Dysphasia!(BrocaOInferior!Frontal!Gyrus)!
! ! ! Temporal:!Amnesia,! ! Aggression,! Receptive!Dysphasia!(WernickeOSuperior!Temporal!Gyrus)!
! ! ! ! ! TLE!(Temporal!Lobe!Epilepsy),! Upper!Quadrant!VF!defect!‘STIP’!
! ! ! Parietal:! Agnosia!(Tactile,!Visual),! ! Lower!Quadrant!VF!defect!‘STIP’,!
! ! ! ! ! Apraxia!(difficulty!with!familiar!&!purposeful!task!despite!normal!strength),!
! ! ! ! ! Acalculia!(can’t!Calculate),!! Hemispatial!Neglect!(NonODominant!lobe)!
! ! ! Occipital:! Visual!Hallucination,! ! ! Contralateral!Hemianopia!with!Macula!Sparing!
! Consider:! Lesion!of!Dominant!vs!NonODominant!hemisphere!
! ! ! ! Dominant:!! Apraxia,!Agnosia,!Dysphasia!most!easily!observed!
! ! ! ! ! ! ! ROhanded:!100%!(95%)!L!lobe!dominance!
! ! ! ! ! ! ! LOhanded:!50%!L!lobe!dominance!
! ! ! ! (Tally!–!Dominant!Parietal!–!Gerstmann's!syndrome:!
! ! ! ! ! ! AALF:! Acalculia,!Agraphia,!LeftORight!Disorientation,!Finger!Agnosia)!
! ! ! Diffuse!Cortical!lesion!(eg.!Encephalopathy)!
! Higher!Mental!Function:! Take!Consciousness!into!account!
! ! Orientation:! ! ! ! Time,!Place,!Person!
! ! Concentration!&!Calculation:! Serial!7’s!
! ! Memory:! Immediate!Recall:! Name!3!objects!and!Pt!repeat!them!
! ! ! ! Short!term!Recall:! Rmb!the!3!objects!for!3!minutes!
! ! ! ! Short!term!Memory:! What!did!you!eat!this!morning?,!Recent!news!
! ! ! ! Long!term!Memory:! Address,!Telephone!number,!Names!of!famous!ppl!
! ! Language:!Confrontation!Naming:! What!is!this?!A!watch,!a!pen!
! ! ! ! Repetition:! ! !
! ! ! ! Comprehension:! Verbal:! Pick!up!the!paper!with!R!hand,!fold!in!half!&!put!on!table!
! ! ! ! ! ! ! ! Visual:! Read!the!instructions!on!the!paper!“Clap!your!hands”!
! ! Judgement!(Concrete!thinking):!Similarity!between!Apple!&!Banana:!
! ! ! ! ! ! ! ! ! Fruits:!Abstract;!! Have!Skin:!Concrete!
! ! VisualOSpatial!Orientation!(Apraxia):! Draw!intersecting!Pentagons!
! ! Others:! Knowledge,!Mood!(Anxious,!Depressed),!Content!of!Thought!(Delusion)!
Thalamus:!! ! Input!for!Sensory!Afferents!
! ! ! ! Cerebellar!+!Basal!Ganglia!output!to!Cerebral!Cortex!
! ! ! ! Contralateral!Sensory!loss/Impairment!
Pyramidal!(Somatic!Motor)!System:!
! ! ! ! Corticospinal!&!Corticobulbar!tract!
! ! ! ! Motor!function:!! Weakness,!Dysphagia,!Abnormal!Gait!
! Corticospinal:! H&N!spared!
! ! ! ! Above!C5:!UMN!signs!Below!level!of!lesion!(eg.!Quadriplegia)!if!affecting!Both!sides!
! ! ! ! C5OT1:! LMN!signs!in!UL,!UMN!signs!in!LL!

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Neuro! Lesion! Location!
! ! ! ! T2O12:! Sensory!level!Trunk,!UL!spared,!UMN!signs!in!LL!
! ! ! ! L1OS5:! UL!spared,!LMN!signs!in!LL,!Sphincter!disturbance!
! Corticobulbar:! Same!as!Brainstem!lesions!
Basal!Ganglia!(Extrapyramidal!System):!
! Anatomy:! ! Caudate,!Putamen,!Globus!Pallidus,!Substantia!Nigra!
! Clinical:! ! Parkinsonian!features:!
! ! ! ! ! Tremor!(Resting)!
! ! ! ! ! Rigidity!(CogOwheel,!LeadOpipe)!
! ! ! ! ! Bradykinesia!(Arm!swing,!Speech,!Dysdiadochokinesia)!
! ! ! ! ! Unstable!Gait!(Stooped!Posture,!Shuffling,!Turning!Difficulty,!Retropulsion)!
! ! ! ! ! Mask!face,!Glabellar!tap,!Small!Handwriting!(Micrographia)!
! ! ! ! Dystonia!
! ! ! ! Other!Movement!disorders,!eg.!Choreoathetosis!
Cerebellar!System:!
! Vermis:! ! Truncal!Ataxia!(eg.!Difficulty!Sitting!up),!Dysarthria!
! Cerebellar!Hemispheres!(Ipsilateral!side!affected):!
! ! ! ! Horizontal!Nystagmus!
! ! ! ! Dysarthria!(Cerebellar!Dysarthria)!
! ! ! ! Rebound!phenomenon!–!No!quick!Damping!from!Antagonistic!muscle!
! ! ! ! Finger!Nose!&!Heel!Shin!test!for!Dysmetria:!
! ! ! ! ! PastOpointing,!Intention!Tremor!(End!of!movement)!
! ! ! ! Dysdiadochokinesia!(Rapid!Repetitive!movement)!–!Palm,!Feet,!Thumb!Opposition!
! ! ! ! BroadObased!Gait!
Brainstem:! ! Specific!syndrome:! Lateral/Medial!Medullary!syndrome!
! ! ! ! May!develop:!
! ! ! ! ! Vertical!Nystagmus,!problem!with!Conjugate!Gaze!
! ! ! ! ! Specific!CN!deficit!(Pons:!CN7!Nucleus>!LMNL):!
! ! ! ! ! ! Diplopia,!Dysphagia,!Facial!numbness,!Deafness,!Difficulty!Talking/Chewing!
! ! ! ! ! Internuclear!Ophthalmoplegia!(Medial!Longitudinal!Fasciculus)!
! ! ! ! ! UMN!signs!in!UL!&!LL!(eg.!Spastic!Quadriplegia)!
! ! ! ! ! ! Corticobulbar!+!Corticospinal!tracts!meet!in!Midbrain!at!Cerebellar!Peduncles!
! ! ! ! ! ! Lesion!in!Midbrain!Downwards!usually!affects!Both!sides!
! ! ! ! ! Coma!(Reticular!Activating!System)!
! ! ! ! ! Constricted!Pupils!(PinOpoint!Pupils)!
! ! ! ! ! Dysarthria,!Dysphagia!(esp!if!Medulla!affected)!
! Ddx:! ! ! Midbrain!from!Dorsal!aspect:!
! ! ! ! ! Mesencephalic!N!of!CN5!very!Long!(Sensory)!from!Midbrain!to!Upper!Cervical!cord!
! ! ! ! ! Lesion!at!C1O2!may!involve!this!tract!(innervates!Nose)!
! ! ! ! Midbrain!(CN!3O4),! Pons!(CN!5O7),! ! Medulla!(CN!9O12)!

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! !!
! Midbrain:!
! ! Weber’s!Syndrome:! ! Ipsilateral!CN3!Palsy,!Contralateral!UMN!Signs!
! ! Benedikt’s!Syndrome:! Ipsilateral!CN3!Palsy,!Contralateral!Rubral!Tremor!

!
! Pons:!
! ! CerebelloPontine!Angle!Syndrome:!
! ! ! Ipsilateral:!! Cerebellar!Signs,!CN7!LMN!Palsy,!CN8!SNHL,!
! ! ! ! ! ! CN5!Facial!Numbness!(CPA!Mass!may!only!affect!Corneal!Reflex)!
! ! Alternating!Abducent!Hemiplegia:!
! ! ! Ipsilateral:!! CN6!Palsy!
! ! ! Contralateral:! UMN!Signs!
! Medulla:!
! ! Wallenberg’s!Syndrome!(Lateral!Medullary!Syndrome):!
! ! ! Ipsilateral:!! Cerebellar!Signs,!Horner!Syndrome,!CN5!Facial!Numbness,!Bulbar!Palsy!(Dysarthria)!
! ! ! Contralateral:! Pain/Temp!Loss!
! ! Alternating!Hypoglossal!Hemiplegia:!
! ! ! Ipsilateral:!! CN12!Tongue!Paralysis!
! ! ! Contralateral:! UMN!Signs,!Vibration/Proprioception!Loss!
Spinal!Cord:! ! Cervical!C1O8,! Thoracic!T1O12,!! Lumbar!L1O5,! Sacral!S1O5!

! Page!681!
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! ! ! ! Brachial!plexus!C5OT1,! Lumbosacral!plexus!L4OS5!
! ! ! ! Ventral!Root!–!Motor,! Dorsal!Root!–!Sensory!(Cell!body!outside!SC)!
! ! ! ! ! (Together!they!form!a!Spinal!Root;!If!affected>!Radiculopathy)!
! ! ! ! Cauda!equina:! Nerve!Root!of!Lower!SC!
! ! ! ! Glove!&!Stocking!Sensory!Loss:! All!nerves!(rather!than!Specific!nerve!or!Nerve!roots)!
! SC!Level:! ! Motor:! LMN!signs!At!level!of!lesion,!UMN!signs!Below!lesion,!Unaffected!Above!lesion!
! ! ! ! Sensory:! Dermatomal!Sensory!level!At!level!of!lesion!
! ! ! ! ANS:!! T1!Lateral!Horn>!Sympathetic!affected>!Horner’s!Syndrome!
! ! ! ! ! ! ! >!Partial!Ptosis,!Miosis,!Sunken!Eyeballs,!Loss!of!Sweat!
! Spinal!Root:! LMN!Signs!
! ! ! ! Dermatomal!Sensory!level!
! ! ! ! Cauda!equina!(Multiple!Nerve!Roots,!Sphincter!in!Bladder)!
! Plexus:! ! Plexopathy!(Usually!Unilateral;!Multiple!nerves!affected)!
! Type!of!SC!Lesion:! Complete!Transverse!lesion,!BrownOSequard!syndrome!(Unilateral!Transverse!lesion),!
! ! ! ! ! Central!Cord!syndrome,!Anterior!Spinal!A!syndrome,!Posterior!Column!disease!
Peripheral!Nerves!(LMN):!
! ! ! ! Both!Motor!&!Sensory!functions:!Usually!All!Sensory!modalities,!but!some!More!than!others!
! ! ! ! Weakness,!Numbness,!Pin/Needles,!LMN!signs!
! Generalized!Neuropathy:! ! ! *DM!
! ! ! ! Longer!nerves!affected!more!!
! ! ! ! LMN!signs!in!LL!>!UL!(Distal!>!Proximal!Weakness)!
! ! ! ! Glove!&!Stocking!Sensory!Loss!
! ! ! ! Respiratory!muscles!may!be!affected!
! Isolated!Compressive!Neuropathy:! Carpal!Tunnel!Syndrome,!Radial/Ulnar!Compression!
! ! ! ! LMN!signs!of!affected!nerve!
! ! ! ! Dermatomal!deficit!of!affected!nerve!
! ! ! ! Eg.!Ulnar!N>!Intrinsic!Hand!Muscles!(Hypothenar,!Dorsal!Interossei)!+!Sensory!Loss!in!C8OT1!
NMJ:!! ! ! Muscle!Weakness:! Eyelid,!External!Ocular!M,!Pharyngeal!M,!Neck,!Jaw,!Limbs,!Respiratory!M!
! ! ! ! ! ! ! ! >!Ptosis,!Diplopia,!Dysphagia!
! ! ! ! No!Sensory!deficit!
! ! ! ! Diurnal!Rhythm!&!Fatigability!(Worse!towards!End!of!day)!
! NB:! ! ! MG!100%!involve!Eyes!!
! ! ! ! In!PE,!check:! Central!Line!(Plasmapheresis!for!Acute!MG),!Midsternotomy!(Thymomectomy),!
! ! ! ! ! ! ! Sunburn!on!Chest!(RT!for!Invasive!Thymoma)!
Muscle:! ! ! Eg.!Polymyositis,!DMD,!Secondary!to!HypoK!
! ! ! ! Power:! Proximal!Weakness!Greater!than!Distal!(eg.!Holding!Chopsticks)!
! ! ! ! ! ! Proximal!Weakness:! Climbing!stairs,!Standing!from!sitting,!or!Combing!hair!
! ! ! ! Possible!Signs:! Winging!of!Scapula,!Difficulty!standing!up!from!Squatting!position,!
! ! ! ! ! ! ! Swinging!Gait!(Pelvic!Girdle!Weakness)!
! ! ! ! May!have!Wasting,!Muscle!Tenderness/Pain!(Polymyositis:!Pain!but!not!much!Wasting)!
! ! ! ! No!Sensory!disturbance!

! Page!682!
Neuro! Lesion! Location!
! ! ! ! EMG!–!Distinguish!between!Myopathy!&!Neuropathy!(Pyramidal!system)!
Sensory!System:! Numbness,!Pin/Needles!
! ! ! ! Different!Sensory!modalities!(Dorsal!column/Spinothalamic)!
! ! ! ! Distribution!of!Dermatomes!
! ! ! ! Dermatomal!Sensory!vs!Glove!&!Stocking!Distribution!
Ddx!of!Acute!Flaccid!Paralysis:!
! ! ! ! Brainstem!Stroke!
! ! ! ! Brainstem!Encephalitis!
! ! ! ! Acute!Anterior!Poliomyelitis:! Caused!by!Poliovirus!or!other!Neurotropic!viruses!
! ! ! ! Acute!Myelopathy:! ! ! SOL,!Acute!Transverse!Myelitis!
! ! ! ! Peripheral!Neuropathy:! ! GBS,!PostORabies!vaccine!Neuropathy,!Diphtheritic!
Neuropathy,!
! ! ! ! ! ! ! ! ! ! Heavy!Metals/Biological!Toxins/Drug!Intoxication,!
! ! ! ! ! ! ! ! ! ! Acute!Intermittent!Porphyria,!Vasculitic!Neuropathy,!
! ! ! ! ! ! ! ! ! ! Critical!illness!Neuropathy,!Lymphomatous!Neuropathy!
! ! ! ! NMJ!disorders:! ! ! ! MG,!Biological/Industrial!Toxins!
! ! ! ! Muscle!disorders:! ! ! HypoK,!HypoPO4,!Inflammatory!Myopathy,!
! ! ! ! ! ! ! ! ! ! Acute!Rhabdomyolysis,!Trichinosis,!Periodic!Paralysis!
Ddx!of!Mixed!UMNL!&!LMNL!signs:!
! ! ! ! May!manifest!as!Absent!Knee!&!Ankle!Jerk,!with!Extensor!Plantar!response!
! Ddx:! ! ! MND:! Early:! Both!UMNL!&!LMNL!
! ! ! ! ! ! Late:!! Only!LMNL!manifested!
! ! ! ! Subacute!Combined!Degeneration!of!Cord,!Pellagra!
! ! ! ! Tabes!dorsalis!
! ! ! ! Friedreich's!Ataxia!
! ! ! ! Cervical!MyeloRadiculopathy,!Conus!medullaris/Cauda!equina!lesion!
! ! ! ! ! Spinal!roots!&!Pyramidal!tracts!are!in!Close!proximity!
! ! ! ! MS!(If!Severe!Sensory!involvement,!may!break!Reflex!arc!despite!Corticospinal!involvement)!
!

! Page!683!
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 Neuro&Lesion&Nature&
Lesion!Type:! ! Vascular!&!Trauma!are!common!
! Type:!
! ! Congenital/Developmental:! ↓Age,!+ve!FHx,!Consanguineous!Birth!(eg.!Pakistani,!Jews)!
! ! Vascular:! !! ! ! ! Sudden!Onset,!Transient,!RF!of!Vascular!disease!
! ! Degenerative:! ! ! ! Age,!Gradual!Onset,!Progressive!course!
! ! (Para)Neoplastic:! ! ! Insidious!Onset,!Progressive,!General!features!(eg.!↓Weight/Appetite)!
! ! Demyelinating:! ! ! ! Exacerbating/Remitting!course!(Episodic)!
! ! Inflammatory:! ! ! ! Infective/AI,!Fever!(Acute/Chronic),!General!Malaise,!
! ! ! ! ! ! ! ! Signs!of!Infection/Inflammation!(eg.!LN,!Skin!Rash,!Pain)!
! ! Metabolic/Toxic:! ! ! Precipitating!cause!(eg.!Drugs),!
! ! ! ! ! ! ! ! Exacerbation!of!Previous!system!disorder!(eg.!Encephalopathy)!
! ! Trauma:! ! ! ! ! Cause!&!Effect!usually!seen/from!Hx!
! Clues:! ! Lesion!Location,!Spectrum,!Pattern!of!Clinical!features!
! ! ! ! Demyelinating!lesion:! Usually!Paraventricular!region!
! ! ! ! Hemangioblastoma:! ! Usually!Posterior!Fossa!
! ! ! ! *cause!of!CN7!Palsy:! ! Bell’s!Palsy!(Don’t!say!surgeons!cut!it!)!
! Note:! ! Lymphadenopathy:! Infection,!Neoplasm!(eg.!Lymphoma),!AI!(eg.!Vasculitis)!
Herpes!Zoster:!

! ! ! ! !
Cervical!Spondylosis:!Tend!to!get!LL!affected!more!(because!in!Corticospinal!Tract,!fibres!fo!LL!are!more!Outside)!
! ! ! ! Cf!Central!Cord!Syndrome:!! UL!more!affected!(Tend!to!have!Sacral!sparing)!

! ! ! ! !
Lateral!Medullary!Syndrome!(Wallenberg!Syndrome):!
! ! ! ! Most!common!syndrome!in!Brainstem;! Eg.!from!Stroke!
! Spinal!Nucleus!&!Descending!tract:!
! ! ! ! Ipsilateral!Loss!of!Trigeminal!(PinOprick,!Temp,!Proprioception!&!Vibration!in!Face)!At!level!
! Descending!Sympathetic!pathway:!
! ! ! ! Ipsilateral!Horner's!syndrome!(Partial!Ptosis,!Miosis,!Anhidrosis,!Enophthalmos)!
! Spinothalamic!tract:!
! ! ! ! Contralateral!Loss!of!Pain!&!Temp!sensation!in!Trunk!&!Limb,!occasionally!Face!
! Involve!some/all!structures!in!OpenOMedulla!on!Dorsolateral!side:!
! ! ! ! Inferior!Cerebellar!Peduncle:! Ipsilateral!Cerebellar!Ataxia!
! ! ! ! Vestibular!Nuclei:! ! ! Nystagmus,!Vertigo,!Nausea/Vomiting!
! ! ! ! Fibres/Nucleus!of!CN9+10:!! Ipsilateral!Pharyngeal,!Laryngeal,!Palatal!Paralysis:!
! ! ! ! ! (Nucleus!Ambiguus)! ! Dysphagia,!↓Gag!reflex,!Hoarseness!(Vocal!cord!Paralysis)!

! Page!684!
Neuro! Lesion! Nature!
! ! ! ! ! ! ! ! ! ! (This!is!a!Localizing!lesion!
! ! ! ! ! ! ! ! ! ! ! All!others!can!occur!in!Lateral!Pontine!syndrome)!
Cauda!Equina!Syndrome:!
! ! ! ! Compression!of!Cauda!Equina!Roots!(Beyond!Termination!at!L1/L2)!
! ! ! ! LBP!with:! Unilateral/Bilateral!Sciatica/LMN!Weakness!(Think!of!Plexopathy!too!if!Unilateral)!
! ! ! ! ! ! Saddle!(Perineal)!Anesthesia!
! ! ! ! ! ! Urinary!dysfunction:! Urinary!Retention,!Overflow!Incontinence!
! ! ! ! ! ! ! ↓Sphincter!Tone,!Detrussor!Weakness!
! ! ! ! ! ! Bowel!dysfunction:! Fecal!Incontinence,!Constipation!(esp!if!Rectal!Prolapse)!
! ! ! ! ! ! Sexual!dysfunction:! ED!
! Cause:! ! *Lumbar!disc!herniation!
! ! ! ! Others:! Tumor,!Trauma,!Infection,!Degeneration,!Inflammation,!etc!
!

! Page!685!
Neuro! Lesion! Nature!
 Neuro&Headache&
The!HIS!(International!Headache!Society)!Classification:!
! Primary:! ! Migraine,!*TensionOtype!Headache,!Cluster!Headache!&!Chronic!Paroxysmal!Hemicrania,!
! ! ! ! Misc!Headache!unassociated!with!Structural!lesion!
! Secondary:! Headache!asso!with:! Head!Trauma,!Vascular!disorder,!NonOVascular!Intracranial!disorder,!
! ! ! ! ! ! ! ! Substance!or!their!Withdrawal,!NonOCephalic!Infection,!
! ! ! ! ! ! ! ! Metabolic!disorder,!Disorder!of!various!Cranial/Facial!Structures,!
! ! ! ! Cranial!Neuralgia!&!Nerve!Trunk!Pain!&!Deafferentiation!Pain!
! ! ! ! Headache!Not!Classifiable!
Hx!for!Headache:! Onset!(SAH!is!Acute),!Location,!Duration,!Attack!Frequency!&!Timing,!Severity,!Nature,!
! ! ! ! Aggravating/Precipitating/Relieving!factors!(↑ICP!may!be!aggravated!by!Cough,!Straining…),!
! ! ! ! Drug!Hx,!Social!Hx!(Alcohol),!FHx!(Familial!Hemiplegic!Migraine),!
! ! ! ! Past!Headache!Hx,!Impact!of!Headache!
International!Classification!of!Headache!Disorder!(ICHD)OII:!
! Primary!Headache:!
! ! ! ! Migraine!
! ! ! ! TensionOtype!Headache!(TTH)!
! ! ! ! Cluster!Headache!&!other!Trigeminal!Autonomic!Cephalalgias!(TACs)!
! ! ! ! Other!Primary!Headaches!
Headache!of!Sudden!Onset:!
! Primary:! ! Crash!Migraine,!Cluster!Headache,!Benign!Exertional!Headache,!Benign!Orgasmic!Cephalalgia!
! Secondary:!
! ! Vascular!disorder:!
! ! ! ! Unruptured!Saccular!Aneurysm,!SAH,!ICA!Dissection,!Cerebral!Venous!Thrombosis,!
! ! ! ! Acute!HT!(Pressor!Response,!Pheochromocytoma)!
! ! NonOVascular!Intracranial!disorder:!
! ! ! ! Intermittent!Hydrocephalus,!Benign!Intracranial!HT,!Pituitary!Apoplexy,!
! ! ! ! Infection!(MeningoEncephalitis,!Acute!Sinusitis),!Acute!Mountain!Sickness,!
! ! ! ! Disorders!of!Eyes!(Acute!Optic!Neuritis,!Acute!Glaucoma)!
Primary!Chronic!Daily!Headache:!
Disorder! M:F!Ratio! Prevalence! Clinical!Features!
Transformed!Migraine! 1:3! 2%! Migraine!±!Aura!>15!days!per!month!for!>3!month!
Chronic!TTH! 1:1! 2%! MidOModerate!Severity,!No!Migrainous!Sx,!Bilateral!
New!Daily!Persistent! *F! Rare! Bilateral,!Persistent,!Moderate;!
Headache! May!be!preceded!by!Viral!Infection;!May!resemble!Migraine/TTH!
Hemicrania!Continua! *F! Rare! Unilateral,!Constant!Exacerbation!of!Severe!Headache;!
Cranial!Autonomic!Sx,!IceOpick!Pain;!
Responsive!to!Indomethacin!by!definition!
Cluster!Headache! 3:1! 0.4%! Cluster!period!last!4O8!weeks!1O3!times!per!year;!
Daily,!often!Nocturnal,!Occur!1O8!times/day,!Lasting!1h!Average;!

! Page!686!
Neuro! Headache! &! Neuralgia!
 Extremely!Severe,!Mostly!Periorbital/Temporal;!
Asso.!Motor!Restlessness!&!Autonomic!Sx!(Tearing,!Rhinorrhea)!
Hypnic!Headache! 1:2!Among! 0.07%! Occur!Daily!but!only!during!Sleep;!Moderate,!often!Bilateral,!
Elderly!(>60)! Lasting!1h;!Not!associated!with!Autonomic!Sx!
Paroxysmal! 1:2! Rare! Headache!identical!to!CH,!
Hemicrania! except!more!Often!(>5,!up!to!24/day)!&!Briefer!(8O25!min);!
Responsive!to!Indomethacin!by!definition!
SUNCT! 3:1! Rare! Headache!resembling!Cluster!&!Paroxysmal!Hemicrania,!
except!more!Often!(30O100/day)!&!Briefer!(20O120s);!
May!be!mistaken!for!TN,!
except!Pain!is!Strictly!Periorbital!(V1)!with!Cranial!Autonomic!Sx!
NeuroImaging:!
! Plain!CT!Brain:! Convenient,!Fast,!Superior!to!MRI!Brain!in!detection!of!Acute!Blood!(SAH,!Acute!SDH,!ICH)!
! ! ! ! Need!transfer!to!CT!room!
! ! ! ! ! Assess!Sick!Pt!focussing!on!Vital!signs!(ABC,!BP,!PR,!SaO2,!Mental!state)!before!transfer!
! ! ! ! ! May!need!Medical/Paramedical!staff!to!escort!
! ! Cons:! Normal!Plain!CT!brain!canNot!exclude!↑ICP,!SAH,!SDH!
! Contrast!CT!Brain:! Considered!for!Pt!Contraindicated!for!MRI!
! ! ! ! Useful!to!detect!Brain!Tumor,!Metastases,!Abscess!
! ! Cons:! Contrast:! Potential!Nephrotoxicity,!Allergy!
! ! ! ! Inferior!to!MRI!with!Gadolinium!for!Brain!Parenchymal!lesion!esp!Small!lesion!
! MRI!Brain:!! Preferred!for:! Brain!Tumor!(Primary/Metastases,!esp!Small),!Small!Abscess,!Encephalitis,!
! ! ! ! ! ! ! MeningoEncephalitis,!Small!Infarct,!Early!Infarct!(DWI),!Demyelination,!AVM!
! ! ! ! Gadolinium!useful!in!Inflammation,!Tumors,!Abscess,!Encephalitis,!Leptomeningeal!Infiltration!
! ! Cons:! Time!consuming!
! ! ! ! Some!Pt!Phobic!to!MRI!
! ! ! ! Cardiac!Pacemaker,!Prosthetic!Cardiac!Valves,!Metallic!Implants/Prosthesis!contraindicated!
!

! Page!687!
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TTH!
TensionOtype!Headache!(TTH):!
Dx!Criteria:! ! A.!≥10!Attacks!for!≥3!months!fulfilling!BOD!
! ! ! ! B.!Attack!lasting!from!30!min!–!7!days!
! ! ! ! C.!≥2!of!following!features:! !
! ! ! ! ! Bilateral!Localization,!! Press/Tightening!(NonOPulsating!Quality),!
! ! ! ! ! Mild/Moderate!Intensity,! Not!Aggravated!by!Routine!PA!(Walking,!Climbing!Stairs…)!
! ! ! ! D.!No!Nausea/Vomiting!+!No!more!than!1!of!Photophobia!or!Phonophobia!
! ! ! ! ! (Stricter!Criteria:! No!Photophobia!&!Phonophobia!at!all;!Prefered!by!Lecturer)!
! ! ! ! E.!Not!attributed!to!another!disorder!
Pathophysiology:! PMT=Pericranial!Myofascial!Tissue! ! ! BI=Brainstem!Interneurons!
! ! ! ! MN=Motor!Nuclei! ! SH/TNC=Spinal!Horn/Trigeminal!Nucleus!Caudalis!
! ! ! ! ↑Muscle!tone!in!PMT!causing!Pain!
! ! ! ! Abnormal!Pain!Modulation!from!BI!and!SH/TNC!(Trigeminal!Cervical!Complex)!

! ! ! ! !
Tx:! ! ! ! Aim:!Prevent!TTH!from!becoming!Chronic!!
! ST!Abortive!Tx!of!Attacks!(mainly!Pharmacological):!
! ! ! ! NSAID:! ! ! Ibuprofen!800!mg,!Naproxen!825!mg,!Aspirin!500!mg/1000!mg!
! ! ! ! COXO2!Inhibitor:!! Lumiracoxib!
! ! ! ! Paracetamol!(500!mg/1000!mg)!
! ! ! ! Combination:! ! NSAID,!Sedative,!Caffeine,!Tranquillisers!
! ! ! ! Topical!Tiger!Balm!( )!or!Peppermint!Oil!
! LT!Prophylactic!Tx:!
! ! NonOpharmacological:!
! ! ! ! Stress!Mx,!Relaxation!therapy!
! ! Pharmacological:!
! ! ! ! AntiDepressant:!! ! Amitriptyline,!Maprotiline,!Mirtazapine,!Slow!release!Venlafaxine!
! ! ! ! α2OAgonist!(Muscle!Relaxant):! Tizanidine!(+!Amitriptyline)!
! ! ! ! AntiEpileptic!Drug:! ! Topiramate!
Putative!Pathophysiological!Targets!of!Preventive!Therapy!for!TTH:!

! Page!688!
Neuro! Headache! &! Neuralgia!
! ! ! ! !
! ! ! ! ! (Acupuncture:! Not!proven!useful!in!multiple!RCT)!
!

! Page!689!
Neuro! Headache! &! Neuralgia!
Migraine!
! ! ! ! Neurovascular!disorder!of!Brain!(NOT!Psychiatric);!Common,!Chronic,!Incapacitating!
! ! ! ! Attacks!of:!! Severe!Headache!(Never!Mild)!
! ! ! ! ! ! ! ANS!Dysfunction!
! ! ! ! ! ! ! Aura!involving!Neurologic!Sx!(in!some)!
! ! ! ! Migraine!Pt!defined!as!Individuals!having:! ≥2!Attacks!with!Aura,!or!
! ! ! ! ! ! ! ! ! ! ! ! ≥5!Attacks!without!Aura!
ICHD\II!for!Migraine!without!Aura:! Probable!when!Episodes!fulfill!All!Except!1!of!Criteria!AOD!
! ! ! ! A.!≥5!Attacks!fulfilling!BOD!
! ! ! ! B.!Attack!lasting!4O72h!(In!Children!<15!yo,!may!last!2O48h)!
! ! ! ! C.!≥2!of!following!features:!
! ! ! ! ! Unilateral!Location,! ! ! Pulsating!Quality,!
! ! ! ! ! Moderate/Severe!Intensity,! Aggravation!by/Causing!Avoidance!of!Routine!PA!
! ! ! ! D.!At!least!1!of!following:! Nausea/Vomiting!
! ! ! ! ! ! ! ! ! Photophobia!+!Phonophobia!
! ! ! ! E.!Not!attributed!to!another!disorder!
Prevalence:! ! 10%!General!population!(6%!M,!15%!F)!Active!Migraineurs!
! ! ! ! Between!Age!10O19:! Sharp!but!Transient!↑!in!1Oyear!Prevalence!
! ! ! ! ! In!Women,!this!is!followed!by!a!Less!Abrupt!2nd!↑!until!Age!40!
! ! ! ! From!Age!16,!2O3x!more!frequent!in!F!than!M!
! ! ! ! Female!Age!40:!Highest!Prevalence!(24%)!
! ! ! ! Lifetime!Prevalence!at!least!18%!(figures!Inflated!by!Recall!Bias!at!Older!age)!
! ! ! ! Onset!nearly!always!(90%)!before!Age!50!
! ! ! ! Peak!Incidence:!Age!10O12!for!M,!14O16!for!F!
Types:! ! ! Pt!may!have!>1!type!of!Primary!Headache!(eg.!Migraine!+!TTH)!
! ! ! ! 2!Main!types:! Migraine!Without!Aura!(75%)!vs!Migraine!With!Aura!(1/3)!
! ! ! ! ! ! ! Up!to!33%!experience!Both!Types!of!Attacks!
! With!Aura:! ≥1!Transient!Focal!Neurological!Aura!Sx!
! ! ! ! Gradual!development!of!Aura!Sx!over!>4!min,!or!Several!Sx!in!Succession!
! ! ! ! Aura!Sx!last!4O60!min!
! ! ! ! Headache!follows/accompanies!Aura!within!60!min!
! ! Aura!Sx:! Visual!(99%)!(eg.!Fortification!Spectra,!Lashley’s!Aura),!together!with!
! ! ! ! ! Sensory!(31%),!Aphasic!(18%),!and!Rarely!Motor!(6%)!
! ! ! ! Typically!Progress!over!min!or!Different!Sx!Succeed!one!another!
! ! ! ! Usually!in!Alternating!body!sites!in!different!attacks!
! ! ! ! Nearly!Always!Precede!Headache;! Usually!last!5O60!min!(Motor!Sx!Longer)!
! ! ! ! Up!to!42%!may!have!Migraine!Aura!without!Headache!
MigraineOLike!Sx!may!be!caused!by:!
! ! ! ! AVM,!ICA!Dissection,!Epilepsy,!
! ! ! ! Mitochondrial!DNA!disorders:!
! ! ! ! ! Mitochondrial!EncephaloMyopathy!with!Lactic!Acidosis!&!StrokeOlike!Episodes!(MELAS)!

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Neuro! Headache! &! Neuralgia!
! ! ! ! Cerebral!AD!Arteriopathy!with!Subcortical!Infarction!&!Leucoencephalopathy!(CADASIL)!
Proposed!Mechanism:!
! ! ! ! Vasodilation!
! ! ! ! Dysfunction!of!Brainstem!&!Diencephalic!Nuclei!that!Normally!Modulate!Sensory!Input!
! ! ! ! ! (Central!Sensitization/Dysfunctional!Central!Control!of!Pain)!
! ! ! ! ! ! Trigeminovascular!input!from!Meningeal!vessels!
! ! ! ! ! ! TrigeminoOAutonomic!Reflex!(Exaggerated!in!TrigeminalOAutonomic!Cephalalgias)!
! ! ! ! ! ! Modulation!of!Trigeminovascular!Nociceptive!input,!
! ! ! ! ! ! ! from!Dorsal!Raphe!Nucleus,!Locus!Ceruleus,!Magnus!Raphe!Nucleus!
! ! ! ! Neurogenic!Inflammation!(NI):! ! Neuropeptide!such!as!CGRP,!Substance!P!
! ! ! ! Cortical!Spreading!Depression!(CSD):! Migraine!Aura!

! ! ! ! !
! Afferent!&!Efferent!Pathway!involved!in!Pain!Perception!&!Modulation!in!Migraine:!

! ! ! ! !
! Neuropeptide:!

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! ! ! ! !
! Cortical!Spreading!Depression:!
! ! ! ! Cortical!Spreading!Depression!with!Suppressed!Activation!of!Cerebral!cortex,!
! ! ! ! ! associated!with!↓Cerebral!Blood!flow!(Oligemia),!underlies!Migraine!Aura,!
! ! ! ! ! preceded!by!a!phase!of!Focal!Hyperemia!(unknown!reason)!
! ! ! ! ! (Spreading!Suppression!of!Cortical!Activation!during!Migraine!Aura!
! ! ! ! ! ! Consistent!with!Progression!of!Aura,!
! ! ! ! ! ! ! from!Central!to!Peripheral!Eccentricities!in!corresponding!Visual!Field)!
! Familial!Hemiplegic!Migraine:! (M>F,!instead!of!F>M!in!usual!Migraine)!
! ! ! ! FHM1!caused!by!Mutations!in!different!sites!of!VoltageOgated!Ca!channel!(VGCC)!α1!subunit!
! ! ! ! FHM2!caused!by!Mutations!of!Na/KOATPase!α2!subunit!

! ! ! ! !
! ! ! ! SCN!=!Sodium!channel,!Glu!=!Glutamate!(Excitatory),!CSD!=!Cortical!Spreading!Depression!
! ! ! ! FHM!genes!mutations!cause!↑Neuronal!Excitability!&!Susceptibility!to!CSD!
! ! ! ! All!3!genes!are!implicated!in!Ion!Transport!!
Triggers:! ! ! Sleep!deprivation,!Fatigue,!Stress!
! ! ! ! Hormonal:!! Menstruation,!OCP!
! ! ! ! Certain!Food!(Alcohol,!Chocolate,!Cheese)!
! ! ! ! Vasodilators!
Migraine!Tx:!

! Page!692!
Neuro! Headache! &! Neuralgia!
1.!Acute!Attack!Tx!(Abortive!Tx):!
! ! ! ! Limited!to!2O3!days!per!week!(Avoid!Analgesic!Overuse!!)!
! ! ! ! Keep!Headache!Diary!–!Monitor!for!↑!in!drug!use!
! ! ! ! Avoid!Opioids:! Mask!Pain!without!Suppressing!Pathophysiologic!mechanism!of!attack!
! ! ! ! ! ! ! Can!cause!Cognitive!Impairment/Addiction!
! Agents:!
! ! Simple!Analgesic:!
! ! ! ! Paracetamol!(1000!mg;!Usually!Not!so!useful)!
! ! ! ! Aspirin!(900!mg)!(Aspirin/NSAID!can!target!Neurogenic!Inflammation)!
! ! ! ! NSAID!(eg.!Naproxen!400O800!mg,!Ibuprofen,!Mefenamic!Acid)!
! ! ! ! Combination!
! ! AntiOEmetic/ProOKinetic!(eg.!Metoclopramide)!
! ! Ergot!Derivative:!
! ! ! ! Ergotamine/Dihydroergotamine!Ergot!derivatives!(Target!Vasodilation)!
! ! ! ! Sustained!Generalized!Vasoconstrictor!effects>!Adverse!Vascular!events!
! ! ! ! High!risk!of!Overuse!syndromes!&!Rebound!Headache!
! ! ! ! (Vasoconstrictor!is!Not!so!preferred!due!to!↑MI,!CVA…)!
! ! Triptans:! Eg.!Sumatriptan!
! ! ! ! Selective!pharmacology;!Simple,!Consistent!Pharmacokinetics!
! ! ! ! Moderate!S/E,!Well!established!Safety!record!
! ! ! ! Serotonin!5OHT1B/1D!Receptor!Agonists!–!3!potential!mechanisms!of!action:!
! ! ! ! ! Cranial!Vasoconstriction!
! ! ! ! ! Peripheral!Neuronal!Inhibition!
! ! ! ! ! Inhibition!of!Transmission!via!2ndOorder!neurons!of!TrigeminoCervical!Complex!(TCC)!
! ! ! ! ! >!These!Inhibit!effects!of!Activated!Nociceptive!Trigeminal!Afferents!
! ! ! Possible!Site!of!Action!in!Trigeminovascular!system:!

! ! ! ! !
! Analgesic!Headache/Medication!Overuse!Headache:!
! ! ! ! Misuse!of!AntiMigraine/Analgesic!(esp!with!Caffeine),!frequently!complicates!Migraine!

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! ! ! ! Characterized!by:! Gradual!↑Headache!Frequency!&!Drug!Consumption!
! ! ! ! ! ! ! ! Change!in!Headache!Characteristics!
! ! ! ! Ultimately,!take!Painkillers!(&!Large!quantities!of!CaffeineOcontaining!Beverages)!
! ! ! ! ! to!treat!Daily!Atypical!Headaches,!Alternating!with!MigraineOlike!Aggravations!
! ! ! ! Frequent!Headaches:!! Ask!about!Use!of!Caffeine!&!Painkillers!(esp!without!a!Prescription)!
! ! ! ! No.!of!doses!used!Important:!
! ! ! ! ! Daily!use!of!Low!dose!much!Riskier!than!very!Large!amount!on!1!day!a!week!
! ! ! ! Frequent!Headache!Sufferers!using!Painkillers/AntiMigraine!drugs!>1O2!days/week!
! ! ! ! ! Should!Withdraw!Abruptly!from!All!Analgesics!(&!Caffeine)!
! ! ! ! After!a!few!weeks!of!Withdrawal!Sx,!
! ! ! ! ! Headache!Severity!&!Frequency!usually!↓!&!Original!Headache!Characteristics!Return!
! ! ! ! ! ! >!Permitting!Correct!Dx!&!Tx!
2.!Prophylactic!Tx:!
! Indication:!! Attacks!Weekly!or!Several!times!a!Month!
! ! ! ! Attacks!Less!often!but!very!Prolonged!&!Debilitating!
! Mechanism:! Methysergide:! ! ! 5HT2!antagonism!
! ! ! ! CCB:!! ! ! ! Regulation!of!VoltageOgated!ion!channels!
! ! ! ! BB,!TCA:! ! ! ! Modulation!of!Central!Neurotransmitters!
! ! ! ! Valproate,!Gabapentin:! Enhancing!GABAergic!inhibition!
! Agents:! ! Most!effective!agent:!! Typically!↓Headache!Frequency!by!at!least!50%!in!50%!Pt!
! ! BB:! ! Propranolol!
! ! ! S/E:! Lethargy,!Tiredness,!Depression,!Postural!Sx;!Contraindicated!in!Asthma!
! ! CCB:!! Flunarizine,!(Verapamil:!Less!effective,!but!widely!more!available)!
! ! ! S/E:! Tiredness,!Weight!Gain,!Depression,!Parkinsonism!
! ! TCA:!! Amitriptyline!(Good!choice!for!Combined!Migraine!+!TTH)!
! ! ! S/E:! Drowsiness,!AntiCholinergic!S/E,!Weight!Gain!
! ! 5HT2!Antagonists:!
! ! ! ! Pizotifen,!Methysergide!
! ! ! S/E:! Pizotifen:! ! Drowsiness,!Weight!Gain!
! ! ! ! Methysergide:! Drowsiness,!Leg!Cramps,!Alopecia,!
! ! ! ! ! ! ! Retroperitoneal!Fibrosis,!Mediastinal!Fibrosis,!Cardiac!Valve!Fibrosis!
! ! AntiConvulsants:!
! ! ! ! Valproate,!Topiramate!
! ! ! S/E:! Valproate:!! Drowsiness,!Weight!Gain,!Tremor,!Alopecia,!Fetal!abnormalities,!
! ! ! ! ! ! ! Thrombocytopenia,!Hepatotoxicity!
! ! ! ! Topiramate:! Sedation,!Cognitive!Impairment!(Slow,!Gradual!Titration),!Paresthesia,!
! ! ! ! ! ! ! Weight!Loss!(Attractive!to!some!Pt),!↑Risk!of!Renal!Stones!
! ! GABA!analog:!
! ! ! ! Gabapentin!(Used!for!Neuropathic!Pain!too)!
! ! ! S/E:! Dizziness!(common!S/E),!Sedation!
Status!Migrainosus:! Severe!Migraine!Headache!without!Aura,!lasting!>72h!

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! ! ! ! May!require!InPt!Tx!
!

! Page!695!
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Cluster!Headache!
Cluster!Headache!&!other!TACs:!
! ! ! ! Cluster!Headache,! ! ! ! Paroxysmal!Hemicrania,!
! ! ! ! ShortOlasting!Unilateral!Neuralgiform!Headaches!with!Conjunctival!Injection!&!Tearing!(SUNCT),!
! ! ! ! Probable!TAC,! ! ! ! ! Refractory!TAC!
Cluster!Headache:!
! ICHDOII:! ! A.!≥5!Attacks!fulfilling!BOD!
! ! ! ! B.!Severe/Very!Severe!Unilateral!Orbital/Supraorbital/Temporal!Pain!lasting!15O180!min!
! ! ! ! C.!Headache!accompanied!by!at!least!1!of!following:!
! ! ! ! ! Ipsilateral!Conjunctival!Injection/Lacrimation!
! ! ! ! ! Ipsilateral!Nasal!Congestion/Rhinorrhea!
! ! ! ! ! Ipsilateral!Eyelid!Edema!
! ! ! ! ! Ipsilateral!Forehead!&!Facial!Sweating!
! ! ! ! ! Ipsilateral!Miosis/Ptosis!(May!look!like!Horner!)!
! ! ! ! ! Sense!of!Restlessness/Agitation!
! ! ! ! D.!Attacks!Frequency!from!1!every!other!day!to!8!per!day!
! ! ! ! E.!Not!attributed!to!another!disorder!
! Types:! ! Episodic!Cluster!Headache:! At!least!2!Cluster!periods!lasting!from!7O365!days,!
! ! ! ! ! ! ! ! ! ! Separated!by!Pain!Free!Remissions!of!>1!month!
! ! ! ! Chronic!Cluster!Headache:!! Attacks!Recur!for!>1!year,!No!Remission!period!or!<1!month!
! Epidemiology:! Sex:! ! ! M:F!=!3:1!
! ! ! ! Prevalence:! 0.9%!
! ! ! ! Age!of!Onset:! 28O30!
! Pain:!! ! Quality:! ! Piercing,!Throbbing;! ! ! Autonomic!Sx:! ! ! ++!
! ! ! ! Intensity:! ! Extremely!High;!! ! ! Circadian!Rhythmicity:! +!
! ! ! ! Localization:! Periorbital;! ! ! ! Alcohol!Trigger:!! ! ++!
! ! ! ! Duration:! ! 15O120!min!
! ! ! ! Frequency:! 1O8/day!
! Pathogenesis:! fMRI!during!attack!reveal!Activation!of!Hypothalamus!

! ! ! ! !
! Tx:! ! ! Acute!Tx:! ! 100%!O2!15!L/min,!Intranasal!Lidocaine,!Sumatriptan!
! ! ! ! Preventive!Tx:! Verapamil,!Lithium,!Corticosteroid,!Topiramate,!Methysergide!

! Page!696!
Neuro! Headache! &! Neuralgia!
! ! ! ! 2nd!line!Tx:!! Valproic!Acid,!Ergotamine,!Melatonin,!Pizotifen,!Indomethacin!
Compare!Migraine!&!Cluster!Headache:!
Migraine! Cluster!Headache!(CH)! Common!Characteristics!
No!Periodicity!(except!with! Periodicity!(Annual!&!Daily)! Incapacitating!
Menses)!
Attack!>4h! Attacks!<3h! Alcohol!is!a!Trigger!
F>M! M>F! Triptan!Effective!(Spray,!SC)!
Prostration,!Quietness! Restless,!Agitation! Dysautonomic!Sx!
(Typical!in!CH,!but!may!occur!in!Migraine)!
Moderate!to!Severe! Severe! !
*Unilateral!but!can!be!Bilateral! Unilateral! !
Nausea!&!Photophobia!typical! Nausea!&!Photophobia!can!occur! !
but!Not!Typical!
Dietary!&!Hormonal!Triggers! No!Dietary!Trigger!except!Alcohol! N.B.#the#2#headache#disorders#may#Coexist!
Trigeminal!Autonomic!Cephalalgia!TAC:!
! Clinical!Features:!

! ! ! ! !
!

! Page!697!
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Temporal!Arteritis!
Secondary!Headache:! Dx!of!Primary!Headache!need!careful!Exclusion!of!Secondary!Cause!
Temporal!Arteritis!(Giant!Cell!Arteritis):! Typically!Elderly!
! Sx:! ! ! Headache!(72%),!typically!Bitemporal!
! ! ! ! Polymyalgia!Rheumatica!(58%),!over!Shoulders!&!Pelvis!
! ! ! ! Malaise,!Fatigue!(56%)!
! ! ! ! Jaw!Pain!during!Chewing!(Jaw!Claudication)!(40%)!
! ! ! ! Fever!(35%),! ! ! ! ! ! Cough!(17%),!
! ! ! ! Neuropathy!(14%),! ! ! ! ! Sore!Throat,!Dysphagia!(11%),!
! ! ! ! Amaurosis!Fugax!(10%):! Ophthalmological!Cx,!mostly!Optic!Neuropathy,!in!20%!
! ! ! ! ! ! ! ! ! Tx!with!Systemic!Steroid!promptly!to!prevent!Blindness!!
! ! ! ! Permanent!Visual!Loss!(8%),! ! ! Limb!Claudication!(8%),!
! ! ! ! TIA/Stroke!(7%),! ! ! ! ! NeuroOOtological!disorder!(7%),!
! ! ! ! Scintillating!Scotoma!(5%),!! ! ! Tongue!Claudication!(4%),!
! ! ! ! Depression!(3%),! ! ! ! ! Double!vision,!Diplopia!(2%),!
! ! ! ! Myelopathy!(0.6%)!
! Dx!Criteria:! Hx:! Age!of!Onset!≥50!
! ! ! ! ! New!Headaches!
! ! ! ! PE:! Abnormalities!of!Temporal!A!at!clinical!examination!
! ! ! ! Ix:! ↑ESR!(≥50!mm/h)!(Or!↑CRP!>5!mg/L)!
! ! ! ! ! Abnormal!findings!on!Biopsy!of!Temporal!Artery!
! ! NB:! ! ≥3!Criteria:!Dx!of!TA!with!91.2%!Specificity!&!93.5%!Sensitivity!
!

! Page!698!
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Trigeminal!Neuralgia!
Neuralgia:!! ! Sudden,!Intense,!Sharp,!Aching,!Lancinating!( ),!Burning,!Stabbing!Pain,!
! ! ! ! ! Lasting!Seconds!to!<2!min!
! ! ! ! Recurring!Repeatedly!within!Short!Periods!
! ! ! ! Triggered!by!Sensory/Mechanical!stimuli!
Trigeminal!Neuralgia:!Most!Frequent!Facial!Neuralgia!
! ! ! ! Prevalence:!3O6!per!100,000;! Incidence!↑with!Age;! 70%!Onset!>60yo!
Clinical!Hallmark:! Paroxysms!of!Pain,!Very!Intensive,!
! ! ! ! Almost!Exclusively!Unilateral!in!Trigeminal!Distribution!
! Distribution:! Typical:! Mostly!in!V2/V3;!V1!division!in!5%!Pt!only!
! ! ! ! Both!V2!&!V3!division!in!1/3!Pt!
! ! ! ! 3%!Bilateral>!Suggesting!a!Secondary!origin!(Must!do!Imaging!to!rule!out)!
! ! ! ! ! Secondary!causes:! MS,!Pontine!Structural!lesions,!etc!
Trigger:! ! ! Spontaneous!or!Precipitated!by!Sensory!Stimulation!of!certain!areas!in!Face!
! ! ! ! Cheek,!Chin,!Lip,!Tongue;!Trigger!spots!
! ! ! ! Touching/Washing!face,!Shaving,!Brushing!teeth,!Chewing:!Typical!Triggers!
Disease!course:!! Stereotypic!Pain!Attacks!usually!Many!times!per!day,!for!weeks/months!
! ! ! ! ! Then!Suddenly!Stop,!Subsequent!PainOfree!periods!for!months/years!
! ! ! ! Pain!attacks!tend!to!become!more!Frequent!over!years,!&!Remission!Shorter!
! ! ! ! Rarely,!attacks!become!Longer!Lasting!&!sometimes!a!Dull!Background!Pain!become!
Permanent!
! PreTrigeminal!Neuralgia:!
! ! ! ! Atypical,!Longer!Lasting!(Several!hours)!Facial!Pain,!Triggered!by!Jaw!movements/Drinking!
! ! ! ! Followed,!after!a!Latency!of!days!to!years,!by!Typical!Neuralgia!
Cause:! ! ! Idiopathic!TN!(Primary!TN):! Normal!Neurological!&!MRI!examination>!No!cause!detectable!
! ! ! ! *Identifiable!cause:! Compression!of!CN5!Nerve!Root!by!an!Aberrant!Loop!of!BV!(60O90%),!
! ! ! ! ! ! ! ! ! In!Neurosurgical!&!Neuroradiological!series!
! ! ! ! MRI!for!detection!of!Neurovascular!Contact:!
! ! ! ! ! Sensitivity!(50–95%),!Specificity!(65–100%),!False!+ve!(7–15%),!False!–ve!(10%)!
! ! ! ! In!up!to!15%!Pt,!an!Underlying!cause!can!be!identified:!
! ! ! ! ! MS!esp!Young!Pt!&!when!Bilateral!(Prevalence!2%)!
! ! ! ! ! Other!Structural!lesions!mainly!in!Pontine!region:!
! ! ! ! ! ! Vestibular/Trigeminal!Schwannoma,!Meningioma!
! ! ! ! ! ! Epidermoid!or!other!Cysts!
! ! ! ! ! ! Vascular!Brainstem!lesions!esp!Pontine!Infarction,!Angioma,!AVM!
! ! ! ! Symptomatic!TN:! Often!associated!with!other!Motor/Sensory!deficits!
! ! ! ! ! ↑in:!! Bilateral!involvement,!Abnormal!Trigeminal!Reflex,!Trigeminal!Sensory!Deficits!
Tx:! ! ! ! TN!due!to!Focal!lesion!Compressing!Sensory!Root!of!CN5!–!Surgical!Decompression!
! ! ! ! Primary!TN!–!Medical/Surgical!
! Medical:!
! ! Carbamazepine:! Most!Effective!Drug!(75%!Responsive;!1st!Line)!

! Page!699!
Neuro! Headache! &! Neuralgia!
! ! ! ! Initiated!with!Small!dose!(50O100!mg),!↑Slowly!as!Tolerated!
! ! ! ! Once!Pain!controlled!completely,!Dose!can!be!Tapered!every!few!weeks!to!determine!
Remission!
! ! ! ! Regular!CBC!in!first!few!months,!then!yearly!for!Agranulocytosis!
! ! ! S/E:! Common!in!Elderly;!Affect!Cerebellar!Function!(Vertigo,!Drowsiness,!Ataxia)!
nd
! ! 2 !line:! Considered!for!Trial,!Alone!or!in!Combination,!when!CBZ!Not!Helpful/Not!Tolerated!
! ! ! Eg.! Gabapentin!(Benign!S/E,!Beneficial!in!Neuropathic!Pain)!
! ! ! ! Phenytoin,!Valproate,!Lamotrigine,!Topiramate,!Oxcarbazepine!(Prodrug!of!CBZ;!Less!S/E)!
! ! ! ! Baclofen!
! ! ! ! Clonazapam!
! NonMedical:! Alcohol!Block!of!Peripheral!branch!of!CN5!(Relapse!Common)!
! ! ! ! Microvascular!Decompression!(Separation!of!CN5OCompressing!Vessel):! For!Young!!
! ! ! ! ! 70%!Excellent!Pain!Relief!10!years!later;!No!Anesthesia!after!surgery!
! ! ! ! ! But!Mortality!1O2%!&!Risk!of!damage!to!other!CN!
! ! ! ! Percutaneous!Radiofrequency!Thermocoagulation!of!CN5!Sensory!Root:! For!Elderly!!
! ! ! ! ! Corneal!Sensory!Loss!can!lead!to!Serious!Eye!Cx!
! ! ! ! ! Anesthesia!Dolorosa,!a!distressing!Pain!in!the!Numb!area,!occurs!occasionally!
! ! ! ! Section!of!Sensory!Root!of!CN5!(Surgical)!used!Less!often!now!
!

! Page!700!
Neuro! Headache! &! Neuralgia!
 Neuro&Consciousness&Disorder&
Consciousness:! ! State!of!Awareness!of!Self!&!Surrounding!
! Alteration:!! 1st!Type:! Affect!Arousal!(Awake)!
! ! ! ! 2nd!Type:! Cognitive!&!Affective!Mental!Function!(Aware)!
! ! ! ! ! ! ! (eg.!Dementia,!Delusion,!Confusion,!Inattention)!
! Maintenance:! Reticular!formation!in!Upper!Brainstem!(Midbrain!&!Pons)!
! ! ! ! Bilateral!Cerebral!Cortex!
RAS:! ! ! ! Loosely!grouped!aggregation!of!neurons!located!in!Upper!Brainstem!&!Medial!Thalamus!
! ! ! ! ! (Brainstem!Stroke/PCA!territory!Stroke!may!affect!RAS,!but!this!is!Uncommon)!
! ! ! ! Maintain!Cerebral!cortex!in!a!state!of!Wakeful!Consciousness!
! ! ! ! Circuitry!between!Thalamus!&!Cerebral!cortex,!
! ! ! ! ! where!Thalamic!Relay!neurons!activate!Cortical!Pyramidal!neurons,!either!in:!
! ! ! ! ! ! Tonic!mode!(Wakefulness!or!REM!sleep),!or!
! ! ! ! ! ! Burst!mode!(NREM!sleep),!possible!mediated!by!TOtype!Ca!channels!
! Normal!NREM!Sleep:!Thalamic!Relay!neurons!in!Burst!mode!
! ! ! ! ! Activate!Cortex!in!Rhythmic,!Bilaterally!Synchronous!way!(Sleep!Spindles!on!EEG)!
! Normal!Awake!state:!Thalamic!Relay!neurons!fire!in!Tonic!mode!
! ! ! ! ! Activate!Cortex!(Sensory!info)!in!NonRhythmic!(Desynchronized)!manner!
! ! ! ! ! ! (It’s!Normal!to!be!Desynchronized;!If!Synchornized,!can!be!Seizure)!

! EEG:!! !
Coma!&!related!disorders!of!Consciousness:!
! ! ! ! Alert:! Perfectly!Normal!state!of!Arousal!
! ! ! ! Sleep:! The!Only!Normal!form!of!Altered!Consciousness!
! ! ! ! Coma:! Deep!Sleeplike!state,!Pt!Can’t!be!Aroused,!Complete!Unresponsiveness!to!Arousal!
! ! ! ! Stupor:! State!of!Baseline!Unresponsiveness,!Pt!can!only!be!Aroused!by!Vigorous!Stimuli!
! ! ! ! Lethargy:! Between!Alertness!&!Stupor!
Disorder!of!Consciousness:!
! Persistent!Vegetative!State:!
! ! ! ! Awake!but!Unresponsive!state!
! ! ! ! Lost!Cognitive!Neurological!function,!but!retain!Vegetative/NonOCognitive!Neuro!function,!
! ! ! ! ! such!as!Cardiac!action,!Respiration!&!BP!maintenance!
! ! ! ! ! (Yawning,!Coughing,!Swallowing,!Limb!&!Head!movements!Persist,!
! ! ! ! ! but!few,!if!any,!Meaningful!responses!to!External/Internal!Environment)!
! ! ! ! Extensive!Cortical!Gray!or!Subcortical!White!Matter!lesion,!
! ! ! ! ! with!relative!Preservation!of!Brainstem!function!
! ! Cause:! Cardiac!Arrest!&!Head!Injury:! Most!common!causes!of!Vegetative!states!
! ! Prognosis:!Once!Vegetative!state!has!supervened!for!several!months!(PVS),!

! Page!701!
Neuro! Consciousness! Disorder!
! ! ! ! ! Prognosis!for!Regaining!Mental!function!is!almost!NIL!
! Akinetic!Mutism:!Partially/Fully!Awake,!Able!to!form!Impressions!&!Think!but!remain!Immobile!&!Mute!
! ! ! ! Damage!in!Medial!Thalamic!Nuclei,!Frontal!lobe!or!Hydrocephalus!
! Abulia:! ! Mental!&!Physical!Slowness!&!↓Ability!to!Initiate!activity!(Mild!form!of!Akinetic!Mutism)!
! Inattention:! Inability!to!sustain!Uninterrupted!Thought!&!Action!
! ! ! ! Disorientation!is!Earliest!Outward!Sign!
GCS:!! ! ! 3O15!
! ! ! ! To!elicit!Pain:! Press!on!Sternum!with!Fist,!or!Ear!lobe,!or!Supraorbital!ridge!
! E:! Eye!Opening:! ! ! 4! Spontaneous!
! ! ! ! ! ! ! 3! To!Speech!
! ! ! ! ! ! ! 2! To!Pain!
! ! ! ! ! ! ! 1! Nil!
! M:! Best!Motor!Response:! 6! Obey!! ! ! ! ! ‘Plz!Raise!your!Hand’!
! ! ! ! ! ! ! 5! Localize!
! ! ! ! ! ! ! 4! Withdraw!
! ! ! ! ! ! ! 3! Abnormal!Flexion!
! ! ! ! ! ! ! 2! Extensor!Response!
! ! ! ! ! ! ! 1! Nil!
! V:! Verbal!Response:! ! 5! Oriented! ! ! ! ! ‘Where!are!you,!Who!am!I…’!
! ! ! ! ! ! ! 4! Confused!Conversation!
! ! ! ! ! ! ! 3! Inappropriate!Words!
! ! ! ! ! ! ! 2! Incomprehensible!Sounds!
! ! ! ! ! ! ! 1! Nil!
Coma:!
Ddx:! PVS!
! (Minimally!Conscious!State:!
! ! ! ! ! Unlike!PVS,!Minimal!but!Definite!Behavioral!evidence!of!Awareness!(May!be!
Intermittent))!
! LockedOin!Syndrome:!Alert!&!Aware;!Quadriplegic!with!Lower!CN!Palsy!(Can!move!eyes,!don’t!misDx!as!PVS)!
! ! ! ! ! Due!to!Bilateral!Ventral!Pontine!lesion!(eg.!In!Basilar!A!Thrombosis)!
! Akinetic!Mutism!&!Abulia!
! Catatonia:!! ! Hypomobile!&!Mute!syndrome!associated!with!a!major!Psychosis!
! ! ! ! ! Appear!Awake!with!Eyes!Open!but!make!No!Voluntary/Responsive!movement!
! ! ! ! ! Blink!Spontaneously,!Swallow!and!may!Not!appear!Distressed!
! ! ! ! ! NO!clinical!evidence!of!Cerebral!damage!
! PseudoComa!
Principle:! ! ! 1.!Lesions!that!damage!RAS!or!its!Projections!
! ! ! ! 2.!Destruction!of!Large!portions!of!Both!Cerebral!hemispheres!
! ! ! ! 3.!Suppression!of!ReticuloOCerebral!function!by!Drugs,!Toxins,!
! ! ! ! ! or!Metabolic!derangements!such!as!Hypoglycemia,!Anoxia,!Azotemia,!or!Hepatic!Failure!
Cause:!

! Page!702!
Neuro! Consciousness! Disorder!
! Symmetrical:!
! ! NonStructural:! Toxin:! Pb,!Thallium,!Mushrooms,!Cyanide,!Methanol,!Ethylene!glycol,!CO!
! ! ! ! ! Drug:! Sedative,!Barbiturate,!Tranquillizer,!Bromide,!Alcohol,!Opiate,!Paraldehyde,!
! ! ! ! ! ! ! Salicylate,!AntiCholinergic,!Amphetamine,!Li,!MAOI!
! ! ! ! ! Metabolic:! ! Hypoxia,!HyperCapnia,!Hyper/HypoOThermia,!
! ! ! ! ! ! ! ! Hyper/HypoONa,!Hyper/HypoOCa,!HyperMg,!
! ! ! ! ! ! ! ! WE!(Wernicke),!HE,!Uremia,!HypoGlycemia,!DKA,!DNKC,!Lactic!Acidosis,!
! ! ! ! ! ! ! ! Porphyria,!Addisonian!Crisis,!AminoAciduria,!Dialysis!Encephalopathy!
! ! ! ! ! Infection:! Bacterial!Meningitis,!Viral!Encephalitis,!PostInfectious!Encephalomyelitis,!
! ! ! ! ! ! ! Syphilis,!Sepsis,!Typhoid!Fever,!Malaria,!WaterhouseOFriderichsen!syndrome!
! ! ! ! ! Others:! PostIctal,!Diffuse!Ischemia!(CHF,!MI,!Arrhythmia),!Fat!Embolism,!
! ! ! ! ! ! ! Hypotension,!Hypertensive!Encephalopathy,!HypoT!
! ! Structural:!! Bilateral!ICA!Occlusion,!Bilateral!ACA!Occlusion,!Basilar!Occlusion,!
! ! ! ! ! SAH,!Thalamic!Hemorrhage,!Pontine!hemorrhage,!
! ! ! ! ! Trauma!(Contusion,!Concussion),!Hydrocephalus,!Midline!Brainstem!Tumor!
! Asymmetrical:!
! ! Structural:!! TTP,!DIC,!Thrombophlebitis,!NonBacterial!Thrombotic!Endocarditis,!SBE,!Fat!Emboli,!
! ! ! ! ! Unilateral!Hemispheric!Mass!(Tumor,!Bleed)!with!Herniation,!Bilateral!SDH,!ICH,!
! ! ! ! ! Brainstem!Hemorrhage,!Brainstem!Infarction,!Pituitary!Apoplexy,!
! ! ! ! ! Massive/Bilateral!Supratentorial!Infarction,!Multifocal!LeukoEncephalopathy,!CJD,!
! ! ! ! ! LeukoEncephalopathy!asso.!with!Chemo,!Adrenal!Leukodystrophy,!ADEM,!MS,!
! ! ! ! ! Cerebral!Vasculitis,!Cerebral!Abscess,!Subdural!Empyema!
Approach!to!Pt!with!Altered!Consciousness:!
! ! ! ! ABC,!Assess!GCS!level,!Consider!Intubation!if!GCS!≤8!
! ! ! ! Vital!Signs:! BP!&!Pulse,!ECG!monitoring,!H’stix,!Temp!
! ! ! ! Hx!&!PE:! ! Clues!from!Witness!
! ! ! ! ! ! ! GE:! ! ! Complexion!(eg.!Jaundice!–!HE;!Cherry!Red!–!CO!poisoning),!
! ! ! ! ! ! ! ! ! ! Wounds,!Alcohol!Smell,!etc;!Note!Pt’s!Posture!
! ! ! ! ! ! ! CNS!Exam:!! Focal!Neurological!deficits!
! ! ! ! ! ! ! ! ! ! Features!of!Convulsion!
! ! ! ! ! ! ! ! ! ! Features!of!CNS!Infection!
! ! ! ! ! ! ! Other!Systems!
Mx!for!Coma!Pt:!
! Targeted!Ix:! Neuroimaging,!Blood!test,!Toxicology!Screening,!LP,!EEG!(Good!for!NCSE)!
! Specific!therapy!where!appropriate:!
! ! ! ! Thiamine!200!mg!iv!for!Alcoholic/Malnourished!Pt!
! ! ! ! ! D50!40!ml!iv!for!Hypoglycemia,!after!iv!Thiamine!(if!give!before!Thiamine>!Neuro!damage)!
! ! ! ! Naloxone!(Narcan)!0.4!mg!to!2!mg!iv!stat,!
! ! ! ! ! then!every!2!min!prn!up!to!10!mg!for!suspected!Narcotic!overdose!
! ! ! ! Flumazenil!(Anexate)!0.2!mg!followed!by!0.3!mg!at!1!min,!
! ! ! ! ! then!0.5!mg!every!1!min!to!a!total!of!3!mg!for!suspected!Benzodiazepine!overdose!

! Page!703!
Neuro! Consciousness! Disorder!
! ! ! ! Antidote/Specific!therapy!(if!available)!for!other!Drug!overdose!
! ! ! ! Hyperventilation,!Mannitol!0.5O1.0!g/kg!if!clinical!evidence!of!↑ICP/Herniation!
! ! ! ! Definitive!Tx!for!Cause!of!Coma!
!

! Page!704!
Neuro! Consciousness! Disorder!
 Neuro&Delirium&
Confusion:!! ! Mental!&!Behavioral!state!of!↓Comprehension,!Coherence!&!Capacity!to!Reason!
! ! ! ! As!Confusion!Worsen,!More!Global!Mental!Impairment!occur,!including!Impairment!of:!
! ! ! ! ! Memory,!Perception,!Comprehension,!Problem!solving,!Language,!Praxis,!
! ! ! ! ! Visuospatial!function,!Emotional!behavior!
Delirium:! ! ! Acute!Confusional!State!characterized!by!Acute!Decline!in!Attention!&!Cognition!
! ! ! ! ! (In!contrast,!Dementia!is!a!Chronic!Confusional!State)!
! ! ! ! Common,!LifeOthreatening!&!Potentially!Preventable!clinical!syndrome!among!Elderly!>65!
! ! ! ! Rate!Highest!among!Hospitalized!Older!Pt;!Prevalence!at!Hospital!Admission!14O24%!
! ! ! ! Incidence!↑during!Hospitalization:! 5O53%!of!Older!Pt!in!PostOop!period!
! ! ! ! ! ! ! ! ! ! ! 70O87%!of!Older!Pt!in!ICU!
! ! ! ! Overall!Prevalence!only!1O2%!in!Community,!↑with!Age!(14%!among!population!>85!yo)!
! ! ! ! Delirium!is!a!Sx!that!often!herald!presence!of!LifeOthreatening!conditions,!
! ! ! ! ! in!10O30%!of!Older!Pt!presenting!to!A&E!
! ! ! ! Mortality!Rate!among!Hospitalized!Pt!22O76%;! OneOyear!MR!associated!with!Delirium!35O40%!
Dx:! ! ! ! Primarily!Clinical:! Bedside!Observation!of!Key!features!
! ! ! ! Often!Unrecognized!by!Medical!&!Paramedical!staff!due!to:!
! ! ! ! ! Fluctuating!Nature,! ! ! ! ! Overlap!with!Dementia,!
! ! ! ! ! Lack!of!Formal!Cognitive!Assessment,!! Under!Appreciation!of!Clinical!Consequences,!
! ! ! ! ! Failure!to!consider!the!Dx!of!Delirium!as!Important!
! Diagnostic!criteria:!
! ! ! ! (DSMOIVOR)!include!≥2!of!the!following:!
! ! ! ! ! Perceptual!Disturbance!(Misinterpretation,!Illusions,!Hallucination)!
! ! ! ! ! Incoherent!Speech!at!times!
! ! ! ! ! Disturbance!of!SleepOWake!Cycle!
! ! ! ! ! ↑/↓Psychomotor!Activity!
! Clinical!Features:!
! ! Acute!Onset:! ! ! Occur!Abruptly,!usually!over!hours/days!
! ! ! ! ! ! ! Reliable!informant!often!needed!to!ascertain!the!time!of!Onset!
! ! Flucuating!Course:! ! Sx!tend!to!come!&!go,!or!↑!&!↓!in!Severity,!over!24h!period!
! ! ! ! ! ! ! Characteristic!Lucid!Intervals!
! ! Inattention:! ! ! Difficulty!Focusing,!Sustaining!&!Shifting!Attention!
! ! ! ! ! ! ! Difficulty!Maintaining!Conversation!or!Following!Commands!
! ! Disorganized!Thinking:! Manifested!by!Disorganized/Incoherent!Speech!
! ! ! ! ! ! ! Rambling/Irrelevant!Conversation!or!Unclear/Illogical!Flow!of!Ideas!
! ! Altered!Consciousness:! Clouding!of!Consciousness,!with!↓Clarity!of!Awareness!of!Environment!
! ! Cognitive!Deficit:! ! Typically!Global/Multiple!deficits!in!Cognition,!
! ! ! ! ! ! ! ! inc.!Disorientation,!Memory!deficit,!Language!Impairment!
! ! Perceptual!Disturbance:! Illusion/Hallucination!in!30%!Pt!
! ! Psychomotor!Disturbance:!Psychomtor!Variant!of!Delirium:!
! ! ! ! ! ! ! ! Hyperactive:! Marked!by!Agitation!&!Vigilance!

! Page!705!
Neuro! Delirium!
! ! ! ! ! ! ! ! Hypoactive:! Marked!by!Lethargy,!with!marked↓level!of!Motor!
activity!
! ! ! ! ! ! ! ! Mixed!
! ! Altered!SleepOWake!Cycle:!Characteristics!SleepOCycle!Disturbances!
! ! ! ! ! ! ! Typically!Daytime!Drowsiness,!Nighttime!Insomnia,!Fragmented!Sleep,!
! ! ! ! ! ! ! ! Or!Complete!SleepOCycle!Reversal!
! ! Emotional!Disturbance:! Common;! Manifested!by!Intermittent!&!Labile!Sx!of:!
! ! ! ! ! ! ! ! ! ! Fear,!Paranoia,!Depression,!Irritability,!Apathy,!Anger,!Euphoria!
Pathogenesis:! ! Pathophysiology!remains!Poorly!understood!
! ! ! ! EEG:!Diffuse!Slowing!of!Cortical!Background!Activity!(NOT!correlate!with!underlying!causes)!
! ! ! ! Neuroimaging!&!Neuropsychological!studies:!
! ! ! ! ! Generalized!Disruption!of!Higher!Cortical!functions!with!dysfunction!in:!
! ! ! ! ! ! Prefrontal!cortex,!Subcortical!structures,!Thalamus,!Basal!ganglia,!
! ! ! ! ! ! Frontal!&!TemporoParietal!cortex,!Fusiform!cortex,!Lingual!gyri!
! ! ! ! Evidence!support!Role!of:!
! ! ! ! ! Cholinergic!Deficiency!
! ! ! ! ! Dopaminergic!Excess!
! ! ! ! ! Cytokines:!! Breakdown!BBB!+!Altered!Neurotransmission!
! ! ! ! ! Chronic!HyperCortisolism!
Evaluation:! ! Determine!Acuity!of!change!in!Mental!status>!Essential!1st!step!
! ! ! ! Every!Older!Hospitalized!Pt!should!undergo!Brief!but!Formal!Cognitive!testing,!
! ! ! ! ! with!use!of!instruments!such!as!MMSE!
! ! ! ! Subtle!Delirium!is!often!Missed!
! ! ! ! Older!Pt!should!be!Aroused!during!Ward!rounds,!
! ! ! ! ! And!Evaluated!daily!for!Hypoactive!form!of!Delirium!(often!Overlooked!!)!
! ! ! ! Search!for!Underlying!Cause!&!Precipitating!factors!of!Delirium!
! ! ! ! Delirium!is!often!the!Sole!manifestations!of!Serious!underlying!disease!
Precipitating!Factors:!! Leading!RF:!Dementia;! 2/3!Delirium!occur!in!Dementia!Pt!
! ! ! ! ! NB:!Delirium!can!last!for!months!or!years!(Persistent!Delirium)!
! ! ! ! Demographic:! ! ! Age!≥65,!Male!
! ! ! ! Cognitive!Status:! ! Dementia,!Cognitive!Impairment,!Hx!of!Delirium,!Depression!
! ! ! ! Functional!Status:! ! Functional!Dependence,!Immobility,!Low!level!of!Activity,!Hx!of!Fall!
! ! ! ! Sensory!Impairment:!! Visual!Impairment,!Hearing!Impairment!
! ! ! ! ↓Oral!Intake:! ! ! Dehydration,!Malnutrition!
! ! ! ! Drugs:! ! ! ! Multiple!Psychoactive!Drugs!Tx,!Many!Drugs!Tx,!Alcohol!Abuse!
! ! ! ! Coexisting!Condition:!! Severe!Illness,! ! ! ! Multiple!Coexisting!condition,!
! ! ! ! ! ! ! ! ! Chronic!Renal/Hepatic!disease,! Hx!of!Stroke,!
! ! ! ! ! ! ! ! ! Neurologic!disease,! ! ! Metabolic!Derangement,!
! ! ! ! ! ! ! ! ! Fracture/Trauma,! ! ! Terminal!Illness,!
! ! ! ! ! ! ! ! ! HIV!Infection!
! ! ! ! Drugs:! ! ! ! Sedative!Hypnotics,!Narcotics,!AntiCholinergics,!

! Page!706!
Neuro! Delirium!
! ! ! ! ! ! ! ! ! Tx!with!Multiple!Drugs,!Alcohol/Drug!Withdrawal!
! ! ! ! Primary!Neurologic!disease:! Stroke!(esp!NonODominant!Hemisphere),!ICH,!
! ! ! ! ! ! ! ! ! ! Meningitis/Encephalitis!
! ! ! ! Intercurrent!Illness:! ! Infection,!Iatrogenic!Cx,!Severe!Acute!Illness!(eg.!AMI,!DKA),!
! ! ! ! ! ! ! ! ! Hypoxia,!Shock,!Fever/Hypothermia,!Anemia,!Dehydration,!
! ! ! ! ! ! ! ! ! Poor!Nutritional!Status,!Low!Serum!Albumin,!
! ! ! ! ! ! ! ! ! Metabolic!Derangement!(eg.!Electrolyte,!Glucose,!AcidOBase)!
! ! ! ! Surgery:! ! ! ! Orthopedic,!Cardiac,!Prolonged!Cardiopulmonary!Bypass,!etc!
! ! ! ! Environmental:!! ! Admission!to!ICU,!
! ! ! ! ! ! ! ! ! Use!of!Physical!Restraints/Bladder!Catheter/Multiple!Procedures,!
! ! ! ! ! ! ! ! ! Pain,!Emotional!Stress!
! ! ! ! Prolonged!Sleep!Deprivation!
Evaluation:! ! Review!Medications!(Past!&!Current)!&!Alcohol!Intake!
! EEG:!! ! Limited!Role;!False!–ve!17%,!False!+ve!22%!
! ! ! ! Most!useful!for!detecting!Occult!Seizures!&!Differentiate!Delirium!from!Psychiatric!disorders!
! Neuroimaging:! Low!clinical!yield,!performed!when:!
! ! ! ! ! New!Focal!Neurological!signs,! ! Hx/Signs!of!Head!Trauma,!
! ! ! ! ! Fever!(?Encephalitis/Meningitis),! No!other!identifiable!cause,!
! ! ! ! ! Nil/Incomplete!Hx,! ! ! ! Neurological!Examination!can’t!be!Completed!
Ix:! ! ! ! Basic:! CBC,!LRFT,!Electrolyte!
! ! ! ! Neuroimaging!(for!ICH)!
! ! ! ! LP!(for!Meningitis/Encephalitis)!
! ! ! ! Septic!Workup!including!Blood!Culture!
! ! ! ! ECG!(for!AMI)!
! ! ! ! Blood!Glucose!&!Ketone!(for!DKA)!
! ! ! ! ABG!(for!Resp!Failure)!
Prevention:! ! Yale!Delirium!Prevention!Trial:! Effectiveness!of!Intervention!toward!6!RF:!
! ! ! ! ! Orientation!&!Therapeutic!activities!for!Cognitive!Impairment!
! ! ! ! ! Early!Mobilization!
! ! ! ! ! NonPharmacological!Approaches!(Minimize!Psychoactive!drugs!use)!
! ! ! ! ! Interventions!to!Prevent!Sleep!Deprivation!
! ! ! ! ! Communication!Methods!&!Adaptative!Equipment!for!Vision!&!Hearing!Impairment!
! ! ! ! ! Early!intervention!for!Volume!Depletion!
Tx:! ! ! ! Search!&!Treat!Underlying!causes!
! ! ! ! Supportive!Care:!
! ! ! ! ! ABC,!Maintain!Hydration!&!Nutrition!
! ! ! ! ! Positioning!&!Mobilization!to!prevent!Pressure!Sores!&!DVT!
! ! ! ! ! Avoid!Physical!Restraints!
! ! ! ! ! NonPharmacological!means!for!Sx!of!Delirium!
! ! ! ! ! Calm!Comfortable!Environment!
! ! ! ! ! Orienting!Influences!(calenders,!clock,!familiar!objects!from!home)!

! Page!707!
Neuro! Delirium!
! ! ! ! ! Regular!Orienting!Communication!with!Staff!
! ! ! ! ! Limiting!Room!&!Staff!changes!
! ! ! ! ! Coordinate!Schedules!for!Drugs,!Vital!signs!Assessment!&!Procedures!
! ! ! ! ! Uninterrupted!Sleep!(Low!level!of!Noise!&!Lighting)!
! ! ! ! ! Encourage!Normal!SleepOWake!Cycle!
! ! ! ! Prevent!Cx!
! ! ! ! Treat!Behavioural!Sx!
Pharmacological!Tx:! Reserved!for!Delirium!Sx!threatening!Self/Others’!Safety,!
! ! ! ! ! or!Interruption!of!Essential!Therapy!(eg.!Mechanical!Ventilation)!
! AntiPsychotic:! Haloperidol!(started!with!Low!dose!0.25!mg!or!0.5!mg!nocte)!
! ! S/E:! ! Extrapyramidal!Sx,!esp!if!Dose!>3!mg!per!day!
! ! ! ! Prolonged!Corrected!QT!Interval!
! ! ! ! Avoid!in!Withdrawal!Syndrome,!Hepatic!Insufficiency,!Neuroleptic!Malignant!Syndrome!
! ! Comment:!Usually!Agent!of!Choice;!Effectiveness!demonstrated!in!RCT!
! ! ! ! Avoid!IV!use!due!to!Short!duration!of!action!
! Atypical!AntiPsychotic:! Risperidone,!Olanzapine,!Quetiapine!
! ! S/E:! ! Extrapyramidal!effects!Equivalent!or!Slightly!Less!than!Haloperidol!
! ! ! ! Prolonged!Corrected!QT!Interval!
! ! Comment:!Tested!only!in!Small!Uncontrolled!trials!
! ! ! ! Associated!with!↑Mortality!among!Older!Pt!with!Dementia!
! Benzodiazepine:! Lorazepam!
! ! S/E:! ! Paradoxical!Excitation,!Resp!Depression,!OverSedation!
! ! Comment:!2nd!line!agent;!Associated!with!Prolongation!&!Worsening!of!Delirium!Sx!
! ! ! ! Reserve!for!Undergoing!Sedative,!Alcohol!Withdrawal,!PD,!Neuroleptic!Malignant!Syndrome!
! AntiDepressant:!! Trazodone!
! ! S/E:! ! OverSedation!
! ! Comment:!Tested!only!in!Uncontrolled!studies!
!

! Page!708!
Neuro! Delirium!
 Neuro&Seizure&
Richard!Chang:! ! Convulsion:! A!kind!of!Seizure!with!Motor!manifestation!
! ! ! ! Seizure:! ! Apart!from!Convulsion,!there!are!other!types,!eg.!Absence!Seizure!
! ! ! ! Epilepsy:! ! A!tendency/disease!to!have!repeated!Seizures!
! ! ! ! ! ! ! It’s!an!Electroclinical!Dx:! EEG!+!Clinical!(Convulsive/NonOConvulsive)!
Epileptic!Seizure:! Transient!occurrence!of!S/S!due!to!Abnormal!Excessive/Synchronous!Activity!in!the!Brain!
Dx:! ! ! ! Clinical!features:! ! Careful!Hx!=!Single!Most!Important!element!
! ! ! ! Transient!occurrence!of:! Altered!Awareness,!Abnormal!Behavior,!Involuntary!Movement!
! ! ! ! Dx!based!on!Hx!+!Selected!Test!
Ddx:! HyperVentilation:!
! ! ! ! Anxiety!&!Overbreathing!evident!(esp!Young!Female!with!Thyrotoxicosis)!
! ! ! ! Often!Perioral!Cyanosis,!Hand!Paresthesia,!Carpopedal!Spasm!
! ! ! ! Environmental!Trigger!may!be!evident!
! ! ! ! (Dx:!Ask!Pt!to!breath!in!a!bag>!breathe!back!the!air!expired>!Sx!improve)!
! Migraine:! ! Slow!Progression!of!Neurologic!Sx;!Visual!Sx!prominent!
! ! ! ! Basilar!Migraine!has!Unusual!features:! Confusion,!Stupor,!Bilateral!Blindness!
! ! ! ! Headache!may!be!Minimal/Absent!
! Panic!Attack:! Abrupt!Onset!with!Intense!feeling!of!Dread/Fear!
! ! ! ! Often!sense!of!Impeding!Death!or!Inability!to!Breathe!
! ! ! ! Prominent!Autonomic!features!(eg.!Tachycardia,!Sweating,!Nausea)!
! ! ! ! Last!Longer!(5O30!min)!than!typical!Seizure;!No!LOC!
! Psychogenic!Seizure:!
! ! ! ! Psychiatric!Hx;!Pt!usually!Motionless!with!Eyes!Closed!at!Onset!
! ! ! ! Fluttering!Eye!movement!&!Forceful!Eye!closure!common!
! ! ! ! OutOofOphase,!Thrashing!Limb!movement!&!Pelvic!Thrusting!common!
! ! ! ! Urinary!Incontinence!Unusual;!Refractory!to!Tx!
! Syncope:! ! Precipitating!circumstances!usually!Identifiable!
! ! ! ! Prodrome!of!Wooziness!but!No!Aura!or!Unilateral!Sx!
! ! ! ! LOC!Brief!(<20s),!with!Rapid!Return!to!Normal!
! ! ! ! Few!Muscle!Jerks!(Convulsive!Syncope)!can!occur!at!end!due!to!Hypoxia!
! Transient!Global!Amnesia:!
! ! ! ! Isolated!Amnesic!syndrome;!Prolonged!Duration!(Several!Hours)!
! ! ! ! No!Alteration!of!Consciousness,!Confusion,!Weakness,!Aphasia!
! ! ! ! Persistent!Memory!Gap!during!period!of!Attack;!Recurrence!Unusual!
! TIA:! ! ! Sudden!Onset!without!Progression!of!Sx!
! ! ! ! Variable!Sx!related!to!Brain!&!Vascular!Anatomy!
! ! ! ! –ve!features!(Eg.!Weakness,!Sensation!Loss,!Aphasia)!predominant!
Provoked!Seizure:! Seizure!Common!in:! Metabolic:! ! Uremia,!Hyper/HypoOGlycemia,!Hepatic!Failure!
! ! ! ! ! ! ! ! Toxic:! ! Drug!Overdose/Withdrawal!
! ! ! ! ! ! ! ! Infection:! ! Meningitis,!Encephalitis!
! ! ! ! Seizure!in!such!conditions!(Provoked!Seizure)!do!NOT!necessarily!confer!a!Dx!of!Epilepsy!
! Page!709!
Neuro! Seizure!
Epilepsy:! ! ! ≥2!Seizures!NOT!Provoked!by!other!illnesses!or!circumstances!(≥2!Unprovoked!Seizures)!
Epidemiology:! ! Affect!45!million!people!worldwide;! Prevalence!6O8!per!1,000!population!
! ! ! ! Incidence!26O40!per!100,000!personOyears,!Higher!among!Infant!&!Ppl>60yo!
! ! ! ! 70%!adults!with!NewOonset!Epilepsy!have!Partial!(Focal)!Seizures!
Cause:! ! ! Unknown!(62%)!–!Majority!! ! ! Neurodegenerative!disease!(4%)!
! ! ! ! Stroke!(9%)! ! ! ! ! ! Static!Encephalopathy!(3.5%)!
! ! ! ! Alcohol!(6%)! ! ! ! ! ! Brain!tumors!(3%)!
! ! ! ! Head!trauma!(9%)! ! ! ! ! Infection!(2%)!
! ! ! ! AI!(recently!recognized,!eg.!NMDA!receptor!AutoAb!associated!Encephalitis)!
Seizure!Classification:! According!to!Clinical!features!
! Generalized:! Absence!Seizure,!Myoclonic!Seizure,!Clonic!Seizure,!*TonicOClonic!Seizure,!
! ! ! ! Tonic!Seizure,!Atonic!Seizure!(Astatic!Seizure)!
! Partial!(Focal/Local):!
! ! ! ! Simple!Partial!Seizure!(SPS):! Unimpaired!Consciousness!
! ! ! ! Complex!Partial!Seizure!(CPS):! Impaired!Consciousness!
! ! ! ! Secondarily!Generalized!TonicOClonic!Seizure!
! Unclassifiable!
Epilepsy!Classification:!
! ! ! ! Epilepsy!Syndormes!can!be!classified!by:!
! ! ! ! ! Types!of!Seizures!
! ! ! ! ! Presence/Absence!of!Neurological!&!Developmental!abnormalities!
! ! ! ! ! EEG!findings!
! ! ! ! Eg.!Juvenile!Myoclonic!Epilepsy!(JME)!is!characterized!by:!
! ! ! ! ! Myoclonic!Seizures,!GTCS!&!Less!Frequently!Absence!Seizures!in!Adolescents!
! ! ! ! ! Normal!Intellectual!function!
! ! ! ! ! EEG:!Rapid,!Generalized!SpikeOwave!&!PolyspikeOwave!discharges!
! Generalized:! Predominant!type!of!Seizures!begin!Simultaneously!in!Both!Cerebral!hemispheres!
! ! ! ! Many!forms!have!a!Strong!Genetic!component!
! Partial!(LocalizationOrelated):!
! ! ! ! Seizures!originate!in!1!or!more!Localized!Foci!
! ! ! ! Most!believed!to!be!due!to!≥1!CNS!insults!(But!Not!identified!in!many!Pt)!
! International!Classification!of!Epilepsy!&!Epileptic!Syndrome:!

! Page!710!
Neuro! Seizure!
! ! !
Seizure!Mechanism:! Function!of!brain!depend!on!Cooperation!between!disparate!Networks,!
! ! ! ! ! Probably!mediated!through!Oscillations!within!these!networks!
! ! ! ! Cortical!neurons!generate!Oscillations!which!depend!crucially!on:!
! ! ! ! ! Inhibitory!neurons!
! ! ! ! ! Neuronal!Communication!(eg.!Synaptic!Transmission)!
! ! ! ! ! Intrinsic!Neuronal!properties!(eg.!Ability!to!Maintain!Burst!Firing)!
! ! ! ! Occurrence!of!Epileptic!activity!might!be!an!Emergent!property!of!such!Oscillatory!networks!
! Epileptic!Seizure:!
! ! ! ! Due!to!Abnormal!Excessive/Synchronous!activity!in!brain!
! ! Interictal!EEG:!
! ! ! ! Brief!Synchronous!activity!of!a!group!of!neurons!lead!to!Interictal!Spike!(Duration!<70!ms)!
! ! ! ! Interictal!Spike!is!distinct!from!a!Seizure!
! ! ! ! ! (Site!of!Interictal!Spike!can!be!Separate!from!the!Zone!of!Seizure!Onset)!
! ! ! Epileptic!Discharge!on!EEG:!

! Page!711!
Neuro! Seizure!
! ! ! ! !
Epilepsy!Mechanism:!Transition!from!Normal!to!Epileptiform!behavior!probably!caused!by!
! ! ! ! ! Greater!Spread!&!Neuronal!Recruitment!Secondary!to!Combination!of:!
! ! ! ! ! ! ↑Connectivity,! ! ! ! ! ↑Excitatory!Transmission,!
! ! ! ! ! ! Failure!of!Inhibitory!Mechanism,! Change!in!Intrinsic!Neuronal!Properties!
Generalized!Epilepsy:!Absence!Epilepsy!
! ! ! ! Onset!4O8!years!with!Absence!Seizures,!more!rarely!GTCS!
! ! ! ! Absence!Seizure:!
! ! ! ! ! Stare!&!Cease!Normal!activity!for!a!few!seconds,!then!return!Immediately!to!Normal!
! ! ! ! ! No!Memory!of!event;! ! Tens!to!Hundreds!times/day!
! ! ! ! ! Mimic!AttentionODeficit!disorder!or!Daydreaming!
! ! ! ! Classic!EEG!–!3!Hz!Generalized!SpikeOwave!discharges!in!Childhood!Absence!Epilepsy!
! Absence!Epilepsy:!
! ! ! ! Abnormal!Neuronal!circuit!
! ! ! ! ! >!Rhythmic!Activation!of!Cortex!(typical!of!NREM!sleep)!during!Wakefulness!
! ! ! ! ! >!Abnormal!Paroxysmal!episodes!of!Rhythmic!Cortical!Activation!(Absence!Seizures)!
! ! ! ! Abnormalities!of!circuit!Uncertain,!may!involve:!
! ! ! ! ! TOtype!Ca!channel!
! ! ! ! ! Altered!GABA!receptor!function!
! ! ! ! ! Changes!in!Modulatory!Input!from!Brainstem!
! ! Possible!Mechanism:!
! ! ! ! Burst!Firing!of!Cortical!Neurons!
! ! ! ! ! >!Recruitment!of!Reticular!Thalamic!(RT)!Neuronal!Network!
! ! ! ! ! >!Release!GABA!onto!Thalamocortical!(TC)!neurons!
! ! ! ! ! >!Hyperpolarization!through!Activation!of!GABAA!&!GABAB!Recepors!
! ! ! ! ! >!Deinactivation!of!TOtype!Ca!channel!
! ! ! ! On!Repolarization,!these!Ca!channel!Open!
! ! ! ! ! >!Burst!of!AP!from!TC!neurons!drives!Cortical!neuron!
! General!Epilepsy!Associated!with!IonOchannel!mutations:!
! ! ! ! Most!Generalized!Epilepsies!have!Complex!Inheritance!patterns,!
! ! ! ! ! Few!have!Mendelian!Inheritance!pattern!associated!with!Single!Gene!mutations!

! Page!712!
Neuro! Seizure!
! ! Generalized!Epilepsy!with!Febrile!Seizures!Plus:!
! ! ! ! Febrile!Seizures!+!at!least!1!of!other!types:!Absence,!Myoclonic,!Atonic,!Afebrile!GTCS!
! ! ! ! AD,!Incomplete!Penetrance;! Linkage!to!Ch19q!
! ! ! ! Mutation!in!gene!for!VoltageOgated!Na!channel!β1!subunit!(SCN1B)!
! ! ! ! ! >!Modify!Gating!&!Inactivation!properties!of!Na!channel!
! ! ! ! In!neuron,!promotes!Depolarization!&!Hyperexcitability!

! ! ! ! !
! ! ! ! B:! ↑Na!current>!Greater!Depolarization!during!AP!&!↑Tendency!to!fire!Repetitive!Burst!
! Epilepsy!Syndrome!associated!with!SingleOGene!Mutations:!

! ! ! ! !
Partial!Epilepsy:!! Complex!Partial!Seizure!(CPS)!
! ! ! ! CPS!common!in!Temporal!Lobe!Epilepsy!(TLE)!
! ! ! ! Can!Begin!with:!! Olfactory/Gustatory!Hallucination,!Epigastric!Sensation,!
! ! ! ! ! ! ! ! Psychiatric!Sx!(Déjà!vu/Jamais!vu/Depersonalization),!

! Page!713!
Neuro! Seizure!
! ! ! ! ! ! ! ! Stare!Blankly!
! ! ! ! Once!Progress!to!Loss!of!Awareness,!Pt!may:!
! ! ! ! ! Speak!Unintelligibly,!Lip!Smacking,!Picking!at!Clothing,!
! ! ! ! ! Other!Automatisms!(eg.!Screaming,!Crying,!Laughing)!
! ! ! ! ! ! Automatisms!are!Coordinated!Involuntary!Motor!activity!
! ! ! ! ! ! Occurring!during!Clouding!of!Consciousness!either!in!or!after!a!Seizure!
! ! ! ! ! ! Usually!Without!Recollection!
! Mechanism:! Partial!Seizures!–!Most!Common!Seizure!disorder!in!Adults!
! ! ! ! Often!stem!from!Local!lesions!such!as:! Head!Trauma,!Stroke,!Tumor!
! ! ! ! Most!Common!lesion!(Surgically!Resected!tissue)!in!Medial!TLE!(MTLE)!is!Hippocampal!Sclerosis!
! ! Mesial!TLE!(mTLE):! Most!Prevalent!Partial!Epilepsy,!features!CPS!arising!from!Mesial!Temporal!lobe!
! ! ! ! ! ! Ictal!Onset!in!Mesial!Temporal!lobe!structures!such!as:!
! ! ! ! ! ! ! Hippocampus,!Amygdala,!Parahippocampal!cortex!
! ! ! ! ! ! Resection!of!these!areas!may!Abolish!Seizures!

! ! ! ! !
! ! ! ! Hippocampal!Sclerosis!is!the!Most!common!identified!Pathological!feature!in!mTLE!
! ! ! ! Normally:!
! ! ! ! ! Input!to!Hippocampus!from!Entorhinal!Cortex!to!Dentate!Granule!cells!via!Perforant!path!
! ! ! ! ! Dentate!Granule!cells!project!to!CA3!sector!as!First!step!in!Hippocampal!Output!pathway!
! ! ! ! Hippocampal!Sclerosis:!
! ! ! ! ! Morphologic!changes!in!Dentate!Granuel!cell!layer:!
! ! ! ! ! ! Newly!Sprouted!Mossy!fibres!from!Dentate!Granule!cells!
! ! ! ! ! ! ! Can!Synapse!on!Dendrites!of!Neighboring!Dentate!Granule!cells!
! ! ! ! ! ! ! ! >!Recurrent!Excitatory!Circuit!
! ! ! ! ! ! ! Can!also!Sprout!onto!Inhibitory!Interneurons!
! ! ! ! ! Excitation!Interneurons,!which!Normally!Activate!Inhibitory!Interneurons,!
! ! ! ! ! ! May!be!Selectively!Vulnerable!to!Brain!insult!
! ! ! ! ! Neurogenesis!of!New!Dentate!Granuel!cells!Continue!into!Adult!Life!
! ! ! ! ! ! New!neurons!may!integrate!themselves!into!Abnormal!Circuits!
Epilepsy!Evaluation:! Neurological!Exam:! Mostly!Normal!

! Page!714!
Neuro! Seizure!
! ! ! ! Skin!Abnormalities!in!Neurocutaneous!Syndrome!(eg.!NF,!Tuberous!Sclerosis)!
! ! ! ! If!Unprovoked!First!Seizure:! EEG,!Neuroimaging!(CT/MRI!Brain),!Selected!Blood!Test!
! EEG:!! ! Epileptiform!EEG!patterns!such!as!Spikes!&!Sharp!waves:!
! ! ! ! ! Assist!in!Dx!&!Classification!of!Seizures!as!Focal!or!Generalized!
! ! ! ! A!Normal!EEG!can!Not!Exclude!a!Dx!of!Epilepsy!
! ! ! ! Interictal!EEG!abnormalities!can!Not!confirm!a!Dx!of!Epilepsy!
! ! ! ! EEG!Abnormal!(Epileptiform!Discharges)!in!only!50%!of!Pt!presenting!with!a!First!Seizure!
! ! ! ! Incidence!of!Abnormalities!↑when!EEG!Repeated!or!performed!After!Sleep!Deprivation!
! ! ! ! Video!EEG!Monitoring:! Necessary!if!NonEpileptic!events!are!concerned!
! Neuroimaging:! CT!appropriate!for!Emergent!situations!
! ! ! ! MRI!more!Sensitive!in!detecting!Structural!lesions!casually!related!to!Epilepsy!
! Blood!Test:! CBC,!(H’stix!&!Glucose),!Electrolyte!(Na,!Ca,!±!Mg),!LFT,!Albumin,!(Toxicology),!(AED!level)!
! ! NB:! ! (HypoCa!can!cause!Seizure)!
! ! ! ! Albumin!level!is!checked!Before!admin!of!High!ProteinObound!Drugs,!eg.!Phenytoin!&!
Valproate,!
! ! ! ! ! Fraction!of!Unbound!(Active)!Drugs!is!Higher!with!HypoAlbuminemia!
! ! ! ! Adolescents/Adults!with!Unexplained!Generalized!Seizures:!Screen!for!Substance!Abuse!
Bidirectional!Association!between!Epilepsy!&!Psychiatric!disorder:!
! ! ! ! ↑Risk!of!Epilepsy!in!Psychiatric!disorder,!↑Risk!of!Psychiatric!disorder!in!Epilepsy!
Epilepsy!Mx:!
NonPharmacological:!
! Dx!of!Epilepsy!has!considerable!effect!on:!
! ! ! ! Mood,!Interpersonal!Relationship,!Employability,!Social!Functioning,!QOL,!Ability!to!Drive!
! ! ! ! Early!&!Repeated!discussions!of!these!issues!suggested!
! Discouraged!from!Activities!for!which!Seizure!↑Risk!of!Injury/Mortality:!
! ! ! ! Driving:! Prohibited!from!driving!(Need!to!inform!Transport!Department)!
! ! ! ! ! ! Can!consider!driving!if!SeizureOfree!period!reaches!certain!duration!(varies!by!places)!
! ! ! ! ! ! ! US:! ! 3!months!to!1!year!(Depending!on!states;!Mostly!6!months)!
! ! ! ! ! ! ! UK:! ! 1!year!
! ! ! ! ! ! ! Others:! Usually!1O2!years!(China!is!prohibited!forever?)!
! ! ! ! Operating!HighOrisk!Power!equipment!
! ! ! ! Working!at!Heights,!Hiking!Alone!
! ! ! ! Swimming/Bathing!Alone!(Low!bath!tub!Water!level)!
! ! ! ! Cooking!over!fire!Alone!(Use!NonOfire!heat!source)!
Pharmacological:! Pt!with!a!Single!Seizure!–!Controversial!
! ! ! ! ! 25%!Pt!have!Recurrent!Seizures!within!2!years,!
! ! ! ! ! ! in!the!Absence!of!Factors!that!predict!a!High!Probability!of!Recurrence:!
! ! ! ! ! ! ! 1.!Epileptiform!Activity!on!EEG!
! ! ! ! ! ! ! 2.!Known!Cause!such!as!a!remote!major!Head!Trauma!
! ! ! ! ! ! With!≥1!RF,!Risk!of!Recurrent!Seizures!≤40%!
AntiOEpileptic!Drugs!(AED):!

! Page!715!
Neuro! Seizure!
! ! ! ! Almost!Always!Justified!when!a!Dx!of!Epilepsy!has!been!made!
! BroadOSpectrum:! Initial!choices!in!most!adult!Pt!regardless!of!type!of!Seizures/Epilepsy!Syndromes!
! ! ! ! ! Eg.!Valproate,!Lamotrigine,!Topiramate,!Levetiracetam,!Zonisamide!
! NarrowOSpectrum:! Restricted!to!Focal!Epilepsy!having!Partial!&!Secondarily!Generalized!Seizures!
! ! ! ! ! Eg.!Carbamazepine,!Oxcarbazepine,!Phenytoin,!Tiagabin,!Pregabalin!
! ! Cons:! ! Less!Effective!than!BroadOSpectrum!in!Idiopathic!Generalized!Epilepsy!Syndromes,!
! ! ! ! ! ! Eg.!Juvenile!Myoclonic!Epilepsy!(JME),!Childhood!Absence!Epilepsy!
! ! ! ! ! May!even!Exacerbate!some!Seizure!types!in!these!Pt!
! ! ! ! ! ! Eg.!Phenytoin,!Carbamazepine,!Gabapentine!&!Pregabalin,!
! ! ! ! ! ! ! May!Worsen!Absence!Epilepsy!&!Myoclonic!Seizures!
Valproate:!! ! Effective!in!Primary!GTCS,!Absence!&!Myoclonic!Seizures!
! ! ! ! 2nd!line!agent!for!Partial!Seizures!
! ! ! ! Limit!Sustained!Repetitive!Neuronal!Firing!through!VoltageOdependent!Blockade!of!Na!channels!
! ! ! ! ! (Other!Mechanisms:! Eg.!↑GABA!Inhibition)!
! PK/PD:! ! Highly!ProteinObound,!HalfOlife!7O17h,!Metabolized!in!Liver!
! ! ! ! Does!Not!induce!Hepatic!enzymes;!Inhibit!several!Hepatic!Metabolic!function!
! SE:! ! ! Tremor,!Weight!Gain,!Thinning!of!Hair,!Ankle!Swelling,!Sedation,!
! ! ! ! Pancreatitis,!BM!Suppression,!Thrombocytopenia,!Impair!Platelet!function,!
! ! ! ! Hepatotoxicity!(Rare!in!Adults),!Interfere!Urea!cycle!(Mild!↑Ammonia),!
! ! ! ! Teratogenicity:! Children!exposed!to!Valproate!in!utero!have!Lower!IQ!score!at!age!4.5!
! ! ! ! ! Contraindicated!in!Female!of!Reproductive!Age!!
Phenytoin!(PHT):! Established!>50!years!ago;!Effective!in!Partial!Seizures!&!GTCS!
! ! ! ! Induce!VoltageOdependent!Blockade!of!Na!channels!
! PK/PD:! ! Metabolism!through!Hepatic!P450!mixed!oxidase!system!
! ! ! ! ! Catabolic!enzymes!Saturable>!ZeroOorder!Kinetics!
! ! ! ! At!point!of!Saturation,!Small!dose↑!lead!to!Large↑!in!Serum!Concentration!
! ! ! ! ! (Narrow!Therapeutic!Index!–!Not!a!good!drug)!
! ! ! ! Highly!Protein!bound;!Systemic!disease!&!Drug!Interaction!change!Conc!of!Unbound!fraction!
! SE:! ! ! DoseOrelated!Neurotoxicity!(Nystagmus,!Dizziness,!Unsteady!Gait,!Lethargy),!
! ! ! ! Hypersensitivity!Skin!reactions,!Gingival!Hyperplasia,!Hirsutism,!Coarsening!of!Facial!features,!
! ! ! ! HypoCa!in!NonAmbulatory!Pt!(Impair!Vit!D!Absorption),!
! ! ! ! Megaloblastic!Anemia!(Interfere!Folate!Metabolism)!
! Alternative:! Fosphenytoin:! Prodrug,!Less!Irritative,!for!Parenteral!use!
Carbamazepine!(CBZ):! For!Partial!Seizure!&!GTCS!
! ! ! ! ! NOT!Effective!(may!even!Exacerbate)!in!Absence!&!Myoclonic!Seizures!
! ! ! ! Prevent!Repetitive!Firing!in!Depolarized!neurons!through!Blockade!of!Na!channels!
! PK/PD:! ! Hepatic!Metabolism:!Produce!Epoxide!Metabolism!which!also!has!AntiConvulsant!activity!
! ! ! ! Induce!own!Metabolism>!↑dose!after!1st!month!necessary!
! ! ! ! Significant!Complex!Unpredictable!Interaction!with!other!AED!and!other!drugs,!
! ! ! ! ! Eg.!Corticosteroid,!Theophylline,!Haloperidol,!Warfarin,!EstrogenOcontaining!OCP!
! ! ! ! EnzymeOinducing,!may!render!OCP!Ineffective!

! Page!716!
Neuro! Seizure!
! SE:! ! ! DoseOrelated!Neurotoxicity!(Diplopia,!Dizziness,!Headache,!Nausea,!Somnolence),!
! ! ! ! Allergic!Morbilliform!Rash!(can!progress!to!SJS),!
! ! ! ! HypoNa,!Toxic!Hepatitis,!Orofacial!Dyskinesia,!Cardiac!Arrhythmia,!
! ! ! ! Reversible!Mild!Leukopenia,!Severe!Idiosyncratic!Blood!Dyscrasias!(Rare)!
Lamotrigine!(LG):! Effective!for!Partial!Seizures!&!GTCS;! Preferred!as!1st!line!AED!for!Elderly!
! ! ! ! AntiFolate!activity!(Inhibit!Dihydrofolate!Reductase),!Inhibit!VoltageOdependent!Na!currents!
! ! ! ! Broader!Spectrum!of!activity!than!CBZ!&!PHT!
! PK/PD:! ! 55%!Protein!bound;!Hepatic!Metabolism,!Excreted!in!Urine;!HalfOlife!30h!(Monotherapy)!
! ! ! ! NOT!affect!Metabolism!&!Plasma!levels!of!CBZ,!PHT,!Phenobarbital!or!Valproate!
! ! ! ! ! (Minimal!Drug!Interaction!–!Good!for!Elderly!taking!multiple!drugs)!
! SE:! ! ! Rash!that!can!progress!to!StevenOJohnson!syndrome,!
! ! ! ! Drowsiness,!Dizziness,!Unsteady!Gait,!Headache,!Tremor,!Nausea!
Levetiracetam!(LV):! Mechanism!Uncertain:! Bind!to!Synaptic!Vesicle!Protein!SV2A!
! ! ! ! ! ! ! ! ! Appear!to!act!Presynaptically!to!modulate!its!Exocytoic!function!
! ! ! ! ! ! ! ! ! Possibly!↑Release!of!Inhibitory!NT!
! ! ! ! Efficacious!as!Adjunct!for!Partial!Seizures!±!Secondary!Generalization!
! PK/PD:! ! Minimal!Protein!binding!
! ! ! ! Partially!Metabolized!by!Enzymatic!Hydrolysis,!NOT!dependent!on!P450!system!
! ! ! ! Drug!&!Metabolite!Excreted!in!Urine!(↓dose!in!Renal!Impairment!Pt)!
! ! ! ! Half!life!6O8h!Unaffected!by!other!AED!
! ! ! ! NOT!alter!level!of!other!AED,!&!NOT!affect!Kinetics!of!other!drugs!like!OCP,!Warfarin,!Digoxin!
! SE:! ! ! HyperActivity,!Somnolence,!Asthenia,!Dizziness,!Infection!
Different!Drug!Mechanisms!&!Targets:!

! ! ! !
AED!Selection:! ! HeadOtoOhead!trials!suggest!Similar!Efficacy!of!various!AED!against!Partial!Seizures!
! ! ! ! Although!a!RCT!of!Generalized!Epilepsy!suggest!Valproate!more!Effective!than!Lamotrigine,!
! ! ! ! ! Differences!in!Efficacy!may!be!Absent/Minimal!

! Page!717!
Neuro! Seizure!
! ! ! ! AED!should!be!selected!according!to!Pt!Characteristics:!
! ! ! ! ! Type!of!Seizure/Epilepsy!Syndromes,!Age,!Sex,!
! ! ! ! ! Coexisting!conditions/drugs!that!affect!frequency!of!Adverse!Effects/Drug!Interactions!
! Seizure!type:!
! ! GTC:!! 1st!line:! Carbamazepine,!Lamotrigine,!Valproate,!Topiramate!
nd
! ! ! ! 2 !line:! Clobazam,!Levetiracetam,!Oxcarbazepine,!Zonisamide!
! ! ! ! Others:! Acetazolamide,!Clonazepam,!Phenobarbital,!Phenytoin!
! ! ! ! Avoid:! Tiagabine,!Vigabatrin!
! ! Absence:! 1st!line:! Ethosuximide,!Lamotrigine,!Valproate!
nd
! ! ! ! 2 !line:! Clobazam,!Clonazepam,!Topiramate!
! ! ! ! Avoid:! Carbamazepine,!Gabapentin,!Oxcarbazepine,!Tiagabine,!Vigabatrin!
st
! ! Myoclonic:!1 !line:! Valproate,!Topiramate!
! ! ! ! 2nd!line:! Clobazam,!Lamotrigine,!Levetiracetam,!Piracetam,!Zonisamide!
! ! ! ! Avoid:! Carbamazepine,!Gabapentin,!Oxcarbazepine,!Pregabalin,!Tiagabine,!Vigabatrin!
! ! Tonic:! 1st!line:! Lamotrigine,!Valproate!
nd
! ! ! ! 2 !line:! Clobazam,!Clonazepam,!Topiramate,!Zonisamide!
! ! ! ! Others:! Acetazolamide,!Felbamate,!Levetiracetam,!Phenobarbital,!Phenytoin!
! ! ! ! Avoid:! Carbamazepine,!Oxcarbazepine!
! ! Atonic:! 1st!line:! Lamotrigine,!Valproate!
nd
! ! ! ! 2 !line:! Clobazam,!Clonazepam,!Topiramate,!Zonisamide!
! ! ! ! Others:! Zonisamide,!Felbamate,!Levetiracetam,!Phenobarbital!
! ! ! ! Avoid:! Carbamazepine,!Oxcarbazepine,!Phenytoin!
! ! Focal!±!Secondary!Generalization:!
! ! ! ! 1st!line:! Carbamazepine,!Lamotrigine,!Oxcarbazepine,!Valproate,!Topiramate!
! ! ! ! 2nd!line:! Clobazam,!Gabapentin,!Levetiracetam,!Pregabalin,!Tiagabine,!Zonisamide!
! ! ! ! Others:! Acetazolamide,!Clonazepam,!Phenobarbital,!Phenytoin!
! ! Epilepsy!Syndrome:!
! ! Juvenile!Absence!Epilepsy:!
! ! ! ! 1st!line:! Lamotrigine,!Valproate!
nd
! ! ! ! 2 !line:! Levetiracetam,!Topiramate!
! ! ! ! Avoid:! Carbamazepine,!Gabapentin,!Oxcarbazepine,!Phenytoin,!Pregabalin,!Tiagabine,!
! ! ! ! ! ! Vigabatrin!
! ! Juvenile!Myoclonic!Epilepsy:!
! ! ! ! 1st!line:! Lamotrigine,!Valproate,!Topiramate!
! ! ! ! 2nd!line:! Clobazam,!Clonazepam,!Levetiracetam,!Zonisamide!
! ! ! ! Others:! Acetazolamide!
! ! ! ! Avoid:! Carbamazepine,!Gabapentin,!Oxcarbazepine,!Phenytoin,!Pregabalin,!Tiagabine,!
! ! ! ! ! ! Vigabatrin!
! ! GTCS!only:!1st!line:! Carbamazepine,!Lamotrigine,!Valproate,!Topiramate!
nd
! ! ! ! 2 !line:! Levetiracetam,!Zonisamide!
! ! ! ! Others:! Acetazolamide,!Clobazam,!Clonazepam,!Oxcarbazepine,!Phenobarbital,!Phenytoin!

! Page!718!
Neuro! Seizure!
! ! ! ! Avoid:! Tiagabine,!Vigabatrin!
! Focal!Epilepsies:!
! ! Cryptogenic,!Symptomatic:!
! ! ! ! 1st!line:! Carbamazepine,!Lamotrigine,!Oxcarbazepine,!Valproate,!Topiramate!
! ! ! ! 2nd!line:! Clobazam,!Gabapentin,!Levetiracetam,!Phenytoin,!Pregabalin,!Tiagabine,!Zonisamide!
! ! ! ! Others:! Acetazolamide,!Clonazepam,!Phenobarbital!
! ! Benign!Epilepsy!with!CentroTemporal!spikes:!
! ! ! ! 1st!line:! Carbamazepine,!Lamotrigine,!Oxcarbazepine,!Valproate!
! ! ! ! 2nd!line:! Levetiracetam,!Topiramate!
! ! ! ! Others:! Sulthiame!
! ! Benign!Epilepsy!with!Occipital!Paroxysms:!
! ! ! ! 1st!line:! Carbamazepine,!Lamotrigine,!Oxcarbazepine,!Valproate!
! ! ! ! 2nd!line:! Levetiracetam,!Topiramate!
Caution!in!Women:! Valproate!associated!with!Polycystic!Ovaries,!Anovulatory!Cycles!&!HyperAndrogenism!
! ! ! ! Hepatic!enzymeOinducing!AED!(PHT,!CBZ,!Phenobarbital,!Topiramate)!↑Clearance!of!OCP!
! ! ! ! Lamotrigine!dose!need!Adjustment!with!OCP!intake:! OCP!↑Clearance!of!LG!
! ! ! ! Pregnancy!↑Clearance!of!many!AEDs,!particularly!LG!
! Baby:! ! Babies!born!to!Women!with!Epilepsy:!↑Rate!of!Malformations!(attributable!to!AED)!
! ! ! ! No!AED!can!be!considered!Absolutely!Safe:!
! ! ! ! ! Risk!Highest!with!Valproate,!Lowest!with!Carbamazepine!
! ! ! ! Monotherapy!&!Minimal!Effective!dose!encouraged!to!Minimize!risk!of!Birth!defects!
! ! ! ! Valproate!associated!with!↑risks!of!Birth!defects!(Most!convincing):!
! ! ! ! ! Avoid!in!Women!of!Childbearing!Age!unless!No!Alternative!
! ! NB:! ! Valproate!&!Carbamazepine!are!both!Category!D;!Lamotrigine!is!Category!C!(2012!MCQ!20)!
! Effect!on!Cognition!of!Offspring:!
! ! ! ! Valproate!poses!an!↑risk!of!Poor!Cognitive!outcomes!(Lower!IQ)!
! ! ! ! Also!reported!for!Phenytoin!
! ! ! ! 5!recent!studies!showed!Carbamazepine!does!NOT!↑such!risk!
! ! ! ! Children!exposed!to!Valproate!in!utero!have!Lower!IQ!score!(10!points!Lower)!at!age!4.5!
! ! ! ! ! Compared!to!PHT,!CBZ,!LG!
AED!Initial!Toxicity:! Common!during!Initiation!of!AED!therapy:! Sedation,!Dizziness,!Ataxia,!Headache,!Nausea!
! ! ! ! ↓Dose!by!25O50%!&!Wait!for!2!weeks!for!Tolerance!to!develop,!
! ! ! ! ! Then!Tx!with!Initial!dose!or!Gradually!↑ing!doses!can!be!resumed!
! ! ! ! Most!AED!can!cause!Rash!Rapidly!Tapered!if!No!danger!Signs!
! ! ! ! Danger!Signs!for!Risk!of!Severe!Reaction:! Stop!Drug!with!these!Signs!
! ! ! ! ! Temp!>40°C,!Exfoliation/Mucosal!Lesion,!Facial!Edema/Confluent!Erythema,!
! ! ! ! ! Skin!Pain,!Palpable!Purpura/Skin!Necrosis,!LN!Enlargement,!Asthmatic!Sx!
Inadequate!Seizure!Control:!
! ! ! ! Check!Compliance,!Monitor!Drug!level!may!help!
! ! ! ! With!Maximal!Tolerated!dose!of!a!1st!line!AED!and!Seizures!Not!controlled,!
! ! ! ! ! Another!1st!line!AED!or!2nd!line!AED!should!be!added!

! Page!719!
Neuro! Seizure!
! ! ! ! Once!2nd!Drug!given!at!Full!dose,!
! ! ! ! ! There!are!Strong!Arguments!for!Gradually!Withdrawing!First!drug!
! ! ! ! ! (↓Risks!of!Idiosyncratic!Reaction,!Drug!Interaction,!Teratogenicity!&!other!adverse!
effects)!
! ! ! ! But,!if!2!AEDs!control!Seizures!well,!Withdrawal!of!1st!AED!bears!risks!of!Recurrent!Seizures!
Response!to!AED:! 1/2!Pt!with!Newly!diagnosed!Epilepsy!become!SeizureOfree!while!taking!First!AED!
! ! ! ! 2/3!Pt!become!SeizureOfree!after!receiving!2nd/3rd!AED!
! Flowchart:!! 1st!Seizure:! ! 40%!Seizure!freedom:! Tx,!Pt!preference!
! ! ! ! ! ! ! ! 60%!become!Early!Epilepsy!
! ! ! ! Early!Epilepsy:! ! 65%!Single!Drug!Tx!
! ! ! ! ! ! ! ! 35%!become!Chronic!Epilepsy!
! ! ! ! Chronic!Epilepsy:! 20%!Combination!of!AED!
! ! ! ! ! ! ! ! 80%!become!Drug!Resistant!
! ! ! ! Drug!Resistant:! ! 5%!Modern!AED!
! ! ! ! ! ! ! ! 20%!Persistently!Drug!Resistant!
! ! ! ! ! ! ! ! ! 60%!Epilepsy!Surgery!
Discontinuation:! Once!AED!initiated,!Maintained!for!≥2!years!even!if!Free!of!Seizures!
! ! ! ! After!2!years,!if!remain!SeizureOfree,!Withdrawal!should!be!considered!
! ! ! ! Disadvantage!of!Continuing!AED!therapy!indefinitely:!
! ! ! ! ! Risks!of!S/E,!Drug!Interaction,!Teratogenicity,!Cost!
! Risk!of!Recurrence:!
Factors! Etiology! Onset! EEG! Neurological! Severity!
High!Risk! Known!Structural!lesion! Adolescence!Abnormal! Abnormalities!Severe!Epilepsy!
(Frequent!Seizures/Require!>1!
AED)!
Low!Risk! Idiopathic!Epilepsy! Childhood! Normal! Normal! Easy!control!with!1!AED!
!

! Page!720!
Neuro! Seizure!
 Neuro&Status&Epilepticus&
SE:! ! ! ! 2!in!10!Pt!with!Epilepsy!have!SE!
! ! ! ! 1!in!1!Pt!with!Epilepsy!present!as!SE!
Definition:!! ! Prolonged!(5O30!min,!varied!between!references)!or!Repeated!Seizures,!
! ! ! ! ! without!Full!Recovery!of!Consciousness!between!Attacks!
! Cutoff!Definition!by!Epilepsy!Foundation:!
! ! ! ! SE:! ! ! Single!unremitting!seizure!>30!min,!or!≥2!sequential!seizures!
! ! ! ! Impending!SE:! >5!min!(Self!termination!of!many!seizures!less!likely!after!5!min)!
Importance:! ! Medical!Emergency!!(Risk!of!Resp!Failure)!
! ! ! ! ! (In!practice,!do!Not!wait!to!count!how!long!the!Seizure!has!lasted)!
! ! ! ! ! (May!initiate!Tx!if!detect!Impending!SE)!
! ! ! ! The!Later!a!Seizure!is!stopped,!the!More!Difficult!is!it!to!be!stopped!(More!neurons!recruited)!
Type:!
! Convulsive!SE:! Most!commonly!recognized!SE!with!clinically!evident!Convulsions!
! ! ! ! Eg.!Generalized!TonicOClonic!Status!
! NonOConvulsive!SE:!
! ! ! ! Often!Unsuspected,!occur!in!up!to!10%!Critically!ill!Pt!with!Abnormal!Mental!status;!Difficult!Dx!
! ! ! ! Eg.! Absence!SE:! ! Confusion,!Clouding!of!Consciousness!
! ! ! ! ! Complex!Partial!SE:! Partial!Responsiveness,!Semipurposeful!Automatism,!
! ! ! ! ! ! ! ! ! Total!Unresponsiveness,!Speech!Arrest,!Stereotypical!Automatisms!
Causes:! ! ! Breakthrough!Seizure!of!poorly!controlled!Epilepsy!
! ! ! ! AED!rapid!Withdrawal,!AED!overdose!
! ! ! ! Acute!Cerebral!Insult:!
! ! ! ! ! CNS!Infection!(classically!Encephalitis)!
! ! ! ! ! Neurotoxins!(including!Drugs,!eg.!Lignocaine,!Amphetamine,!Ectasy,!Alcohol)!
! ! ! ! ! Also!Cerebral!Anoxia/Ischemia,!Electrolyte!disturbances!
! NB:! ! ! In!Adults,!most!SE!derives!Not!from!Exacerbation!of!Earlier!Epilepsy!syndromes,!
! ! ! ! ! but!due!to!Acute!illness!leading!to!Seizures!&!SE!in!Pt!who!did!Not!have!them!before!
Cx:! Hypoxemia:! Related!to!Cause:! Sepsis!
! ! ! ! Related!to!SE:! ! Airway!obstruction!by:!
! ! ! ! ! ! ! ! ! Salivary!secretion,!Bronchial!secretion,!Trismus,!Tongue!swelling!
! ! ! ! Related!to!Tx:! ! Resp!depression!caused!by!prolonged!AED!use!
! Metabolic!Acidosis:!
! ! ! ! Lactic!Acidosis!from!↑Neuronal!&!Muscle!catabolism!
! Hyperglycemia/Hypoglycemia:!
! ! ! ! Cause!of!SE:! May!be!HHS/DKA!causing!Seizure!
! ! ! ! Due!to!SE:!! Sympathetic!activity!
! ! ! ! Subsequently!Hypoglycemic!because!Glucose!Not!sufficient!to!sustain!High!metabolic!rate!
! Hypotension:! SE!does!Not!cause!Hypotension!
! ! ! ! Sepsis!may!precipitate!SE!and!cause!Hypotension!
! ! ! ! AED!may!cause!Hypotension!

! Page!721!
Neuro! Status! Epilepticus!
! ↑ICP:! ! (Metabolic!Acidosis,!Hypoxemia,!CO2!retention)!
Mortality:!! ! 3O20%;! Higher!M&M!in!Prolonged!Seizure!&!Identified!Acute!Brain!Insult!
Acute!Mx!(Time!is!Critical!factor):!
! Resuscitation:! Check!ABC!
! ! ! ! Airway!Protection:! Intubation!+!Ventilatory!Support!if!necessary!(low!threshold)!
! ! ! ! Oxygen,!IV!line!&!fluid,!Maintain!BP!
! ! ! ! Observe!Vital!signs!closely;!Monitor!BP/P,!Oximeter!&!ECG;!Turn!Lateral!to!prevent!Aspiration!
! ! (Correct!obvious!underlying!causes:!
! ! ! ! Thiamine/Dextrose!for!Alcoholic!disease!
! ! ! ! Glucose!for!Hypoglycemia!
! ! ! ! O2!for!Cyanosis)!
! Drug!Tx:!
! ! Stop!Seizure:!
! ! ! ! IV!Benzodiazepine!(Lorazepam/Diazepam)!bolus:!
! ! ! ! ! IV!Lorazepam!(Ativan)!2O4!mg,!up!to!8!mg!(1st!line!nowadays)!
! ! ! ! ! ! Pros:!Longer!duration!of!action!
! ! ! ! ! ! ! Less!likely!to!have!Resp!depression/Hypotension!when!additional!drugs!needed!
! ! ! ! ! IV!Diazepam!(Valium)!5O10!mg,!up!to!20!mg!
! ! ! ! ! ! Pros:!Rectal!route!available,!useful!if!No!IV!access;!(Rectal!Valium!common!in!Paedi)!
! ! ! ! (If!IV!line!unsuccessful,!consider!Rectal!Diazepam,!IM!Midazolam)!
! ! Prevent!Further!Seizure:!
! ! ! ! IV!Phenytoin/Fosphenytoin!infusion:!
! ! ! ! ! Phenytoin:! Loading!15O20!mg/kg,!ie.!50!mg/min!
! ! ! ! ! ! ! ! Then!Maintenance!5!mg/kg/day!(usually!100!mg!Q8H!iv)!
! ! ! ! If!above!agents!unsuccessful!(Refractory!Seizures),!urgently!consult!ICU!
! ! ICU:! ! Add!on!other!AED,!eg.!
! ! ! ! ! Phenobarbital!(1st!line)!
! ! ! ! ! IV!Midazolam!infusion!(better!for!Hemodynamically!Unstable!Pt)!
! ! ! ! ! IV!Propofol!infusion!
! ! ! ! ! GA!(Barbiturate!Coma!–!last!resort)!
! Lab!Ix:! ! H’stix!(eg.!Hypoglycemia),!Electrolytes!(Na,!Ca,!Mg),!CBC,!ABG,!Serum!AED!level,!Toxicology!
! ! ! ! Monitor!BP/P,!Oximeter!&!ECG!(esp!during!Phenytoin)!&!Document!further!Seizures!
! ! ! ! (Others:! EEG:!! Only!if!Dx!of!SE!uncertain!
! ! ! ! ! ! LP:! ! If!Meningitis/Encephalitis!is!suspected!
! ! ! ! ! ! ! ! For!Recurrent!Seizure!
! ! ! ! ! ! ! ! Not!routine!practice!
! ! ! ! ! ! CT!Brain:! If!SE!is!1st!presentation!of!Seizure!
! ! ! ! ! ! ! ! Focal!Seizures)!
! Prevent!Systemic!Cx!
! Continuous!EEG!Monitoring!
! Evaluate!for!&!treat!Underlying!causes!of!SE!

! Page!722!
Neuro! Status! Epilepticus!
Drugs:!
! Diazepam!(Valium):! ! Bolus!Injection,!Short!duration!of!action!
! Midazolam!(Versed):!! Loading!then!Maintenance!Infusion!
! Phenytoin!(Dilantin):! ! Loading!then!Maintenance!(Risk!of!Hypotension!in!Elderly!–!don’t!too!fast)!
! ! ! ! ! ! (Useful:!90%!stops!within!1h)!
! Phenobarbital:! ! ! High!risk!of!Respiratory!Depression/Arrest!after!Benzodiazepines!
! Propofol:! ! ! ! Loading!then!Maintenance!Infusion!(Rarely!Pancreatitis)!
! Thiopental:! ! ! Loading!then!Maintenance!Infusion!(Barbiturate!–!Last!resort)!

! ! !
!

! Page!723!
Neuro! Status! Epilepticus!
 Neuro&Unsteady&Gait&
Human!Gait:! ! Unique!features!of!Bipedalism:!
! ! ! ! ! Upright!carriage!of!body!in!spinally!Erect!posture,!Body!segments!Balanced,!Base!width!
! ! ! ! Diversity!of!Erect!Locomotion:!
! ! ! ! ! Walking,!Running,!Transient!Unstable!position!(Skipping/Jumping/Kicking/Throwing…)!
Skeletal!changes:! Elongation!of!Hind!limbs,! ! ! Shortening!+!Broadening!of!Pelvis,!
! ! ! ! Rotation!of!Pelvis,! ! ! ! Dominating!Gluteus!Maximus,!
! ! ! ! Curvature!of!Vertebral!Column,!! Articulation!between!Skull!&!Cervical!spine,!
! ! ! ! Reshape!of!Foot!
Neural!Adaptation:! AntiOGravity!Tone:! Vestibulospinal!ouput!(vs!Rubrospinal)!
! ! ! ! ! (Animals!have!well!developed!Rubrospinal>!Flexor!posture)!
! ! ! ! Synergy!&!Rhythm!of!Locomotion:!
! ! ! ! ! Corticospinal!output,!Brainstem!&!Spinal!centres,!Reticulospinal!output!
! ! ! ! Proprioception/Vestibular/Visual!Input,!Cerebellar!
! ! ! ! Spinal!Reflex!&!Inhibitory!pathway!
Physiology!of!Gait:! Locomotor!tasks:! ! ! Initiate/Arrest,!Maintain!Rhythm,!
! ! ! ! ! ! ! ! ! ! Pattern!(eg.!Direction,!Speed,!Stepping!surface)!
! ! ! ! Postural!Control!&!Balance:! Orientation!with!respect!to!Environment!&!Gravity,!
! ! ! ! ! ! ! ! ! ! Maintain!Equilibrium!
! Locomotor!Tasks:!
! ! ! ! Execution:!! ! Premotor!&!Motor!Cortices!
! ! ! ! Synergy:! ! ! Subcortical!Centres!(MLR,!SLN)!
! ! ! ! ! ! ! ! ! (MLR:!Midbrain!Locomotor!Region)!
! ! ! ! ! ! ! ! ! (SLN:!Spinal!Locomotor!Network)!
! ! ! ! Force!Production:! PNS,!MSK!system!
! ! ! ! Regulatory:! ! Basal!Ganglia,!Cerebellum!
! ! ! ! ! ! ! ! Vestibular!&!Proprioceptive!inputs!

! ! ! ! !
Unsteady!Gait:! ! Major!Neurological!Origins:!
! ! ! ! ! Motor!Deficit:! UMN!(Spasticity),!LMN!(Amyotrophy),!Muscular!disorder!
! ! ! ! ! Movement!disorder,!Sensory!Ataxia,!Cerebellar!Ataxia,!Vestibular!disorder,!
! ! ! ! ! Parkinsonian!syndromes,!Normal!Pressure!Hydrocephalus,!Frontal!Lobe!Lesions!
Gait!Disorder:! ! Ataxic!Gait!(Cerebellar,!Sensory),!Apraxic!Gait,!Antalgic!Gait,!Cautious!Gait,!High!Stepping!Gait,!
! ! ! ! Hemiplegic/Diplegic/Spastic!Gait,!Parkinsonian!Gait,!Myopathic/Waddling!Gait,!
! Page!724!
Neuro! Unsteady! Gait!
! ! ! ! Gait!seen!in!other!Extrapyramidal!disorders!including!Chorea!&!Dystonia!
Level!of!Gait!Disorder:!
! Lowest!Level:! MSK,!Peripheral!Nerve!diseases!
! Middle!Level:! Brainstem,!Cerebellum,!Sensorimotor!tract!lesion!
! ! ! ! Ataxic!Gait,!Hemiplegic/Diplegic/Spastic!gait!
! Middle!to!Highest:! Gait!Bradykinesia!from!Parkinsonism!
! Highest!Level:! CorticoOBasal!GangliaOThalamocortical!abnormalities!
! ! ! ! Defective!Corrective!actions!leading!to:!
! ! ! ! ! Postural!Instability,!Inappropriate!Foot!Placement/Postural!Synergy,!
! ! ! ! ! Gait!Execution!Failure!(Hesitation,!Freezing)!
! ! ! ! Gait!Execution/Organization!function:! Initiation,!Select!Appropriate!Rhythm!&!Tempo!
! ! 3!types:! Diffuse!Involvement:!! Gait!Apraxia!
! ! ! ! Corticospinal!pathway:! Pyramidal!
! ! ! ! Basal!Ganglia:! ! ! Extrapyramidal!
Gait!Apraxia:! ! Diffuse!disease!of!Cerebral!cortex:!
! ! ! ! ! Eg.!NPH,!Alzheimer,!Syphilis,!Ischemic!Subcortical!Encephalopathy!
! ! ! ! Difficult!to!Initiate!Gait:!
! ! ! ! ! “Walking!through!Mud”!–!Appear!like!Stuck!to!Ground;! Poor!Stability!&!Correction!
Hemiplegic!Gait:! Shoulder!Adduction!&!IR,!Elbow!Flexion,!Forearm!Pronation,!Wrist!&!Fingers!Flexion!
! (Decorticate)! Hip!slight!Flexion,!Knee!Extension,!Plantar!Flexion,!Foot!Inversion!
Cautious!Gait:! ! Gait!in!Normal!Aging!(Senile!Pt),!(or!other!NonOspecific!medical!condition)!
! ! ! ! Slightly!Widened!Base,!Shorten!Stride,!Slowness,!↓Synergistic!Arm!&!Trunk!movement,!
! ! ! ! Mildly!Defective!Postural!Correction/Balancing,!Normal!Rhythm!&!Foot!Clearance!
Falls:!! ! ! Usually!caused!by!Environmental!Hazards!&!Error!in!Judgment,!
! ! ! ! ! on!top!of!Underlying!Neurological,!Visual!or!Vestibular!diseases!
! ! ! ! Common!Predisposition!in!Elderly:! Previous!Stroke,!PD,!Arthritis,!Dementia/Delirium,!
! ! ! ! ! ! ! ! ! ! ! Chronic!Vestibular!Insufficiency,!Poor!Vision,!
! ! ! ! ! ! ! ! ! ! ! DrugOinduced!Orthostatic!Hypotension/Sedation!
!

! Page!725!
Neuro! Unsteady! Gait!
 Neuro&Ataxia&
Proprioceptive!Impairment:!
! ! ! ! Sensory!Ataxia,!HighOStepping!Gait!

! ! ! ! !
Cerebellum:!
! Archi/Vestibulocerebellum:!
! ! ! ! Body!Equilibrium,!Eye!Movement!
! ! Lesion:! Truncal!Instability,!Nystagmus!
! Paleo/Spinocerebellum:!
! ! ! ! Gross!Motor!function!of!Axial/Large!Limb!Muscles,!Gait!Control!
! ! Lesion:! Gait!Ataxia,!Ipsilateral!Impairment!
! Neo/Pontocerebellum:!
! ! ! ! Skilled!Motor!function,!Fine!Motor!Skills,!Speech!
! ! Lesion:! Abnormal!Spatial!Coordination!(Dysmetria),!Delayed!Check!(Overshooting),!
! ! ! ! Failed!Repetitive!Movement!(Dysdiadochokinesia),!Kinetic!Tremor,!Dysarthria!
Signs:! ! ! Ataxia!&!BroadObased!Gait,!Truncal!Ataxia!(Vermis!lesion),!Dysmetria,!Dysdiadochokinesia,!
! ! ! ! Hypotonia,!Intention!Tremor,!Dysarthria,!Nystagmus,!Pendular!Tendon!Reflex!(Poor!Damping)!
! Cerebellar!Ataxic!Gait:!
! ! ! ! Incoordination!of!movement!+!Unsteady!Balance!of!trunk!
! ! ! ! BroadObased!with!tendency!to!Stagger!&!Lurch!from!side!to!side!
! ! ! ! Walk!relatively!Quickly;!Steps!are!Irregular!in!Length!&!Synergy!
! ! ! ! Ataxia!Exacerbated!during!Rapid!Postural!adjustment!(eg.!Turning!corner)!
! ! ! ! May!combine!with!other!Gait!disorders!depending!on!underlying!pathology:!
! ! ! ! ! Eg.!Spastic!gait!in!MS,!HighOStepping!gait!in!Tabes!Dorsalis!
! ! ! ! Subtle!Cerebellar!Ataxia!may!be!Unmasked!by!HeelOToe!walking!or!Tandem!gait!
! Limb!Ataxia:! Combined!effect!of!Dysmetria,!Tremor!&!Dysdiadochokinesia!
! ! ! ! Test!for!Limb!Ataxia!is!difficult!to!Interpret!if!Weakness/Sensory!Impairment!
! ! Dysmetria:! ! ! Error!in!Range!&!Force!of!movement>!Under/OverOshooting!
! ! Intention/Kinetic!Tremor:! Exaggerated!by!Maximizing!ROM!tested!
! ! Dysdiadochokinesia:! ! Decomposition!of!Fine!Repetitive!movement!
! Page!726!
Neuro! Unsteady! Gait! –! Ataxia!
! ! ! ! ! ! ! NOT!Specific!for!Cerebellar!lesion!
! ! ! ! ! ! ! Can!be!seen!in!all!Neurological!condition!affecting!limb!motor!control!
! Hypotonia:! Often!Not!apparent!clinically!
! Dysarthria:! Cerebellar!Dysarthria/Ataxic!Dysarthria:! Explosive!Speech/Scanning!Speech/Slurred!Speech!
! ! ! ! Incoordination!of!Speech!&!Respiration!
! ! ! ! ! >!Speech!Volume!&!Rate!vary!from!word!to!word!(Explosive!Dysarthria)!
! ! ! ! Scanning!Dysarthria:! Explosive!Dysarthria!+!Slurred!Cerebellar!Speech!
! Nystagmus:! Jerkiness!of!SmoothOPursuit!Eye!movement!with!disrupted!Fixation!(Ocular!Dysmetria)!
! ! ! ! Typically!GazeOevoked!&!Horizontal!
! ! ! ! For!Unilateral!lesion,!Fast!phase!of!Nystagmus!toward!Affected!side!
Cause:!
! Acute:! ! Drug!Intoxication!(Alcohol,!Sedative…),!Wernicke!Encephalopathy,!
! ! ! ! VertebroObasilar!Ischemia,!Cerebellar!Hemorrhage,!Infection/Inflammation!(except!Virus)!
! Chronic:! ! MS,!Alcoholic!Cerebellar!Degeneration,!Tumor,!HypoT,!Drugs!(AntiConvulsant),!
! ! ! ! Degenerative!diseases!(Friedreich's!Ataxia,!Ataxia!Telangiectasia),!CJD,!Vascular!Malformation!
! Children:! ! Congenital!Maldevelopment!(ArnoldOChiari,!DandyOWalker),!Metabolic!disorder,!
! ! ! ! Infection!(Chickenpox!Encephalitis),!Tumor!(Cystic!Astrocytoma,!Medulloblastoma),!
! ! ! ! Hereditary!Degenerative!disorder!
! AdultOOnset:! Degenerative:! Alcoholism!
! ! ! ! ! ! ! Hereditary:! Spinocerebellar!Ataxia!(AD),!Friedreich’s!Ataxia!(AR)!
! ! ! ! Stroke,!Demyelination!(MS),!Tumor!(Direct!involvement/Paraneoplastic)!
! ! ! ! Metabolic!disorder!(HypoT),!Drug!overdose!(AntiConvulsant,!AntiHistamine)!
! ! ! NB:! AutoAb!in!Paraneoplastic!Cerebellar!degeneration:!
! ! ! ! ! Predominantly!asso!with!Cerebellar!degeneration:!
! ! ! ! ! ! AntiOYo:! ! Gyne!Cancer,!Breast!Cancer!
! ! ! ! ! ! Others:! ! AntiOTr!(HL),!AntiOmGluR1!(HL),!AntiOZic4!(SCLC)!
! ! ! ! ! Sometimes!asso!with!Cerebellar!degeneration:!
! ! ! ! ! ! AntiOHu:! ! SCLC,!etc!
! ! ! ! ! ! AntiORi:! ! Breast!Cancer,!Gyne!Cancer,!SCLC!
! ! ! ! ! ! AntiOVGCC:! SCLC,!Lymphoma!
! ! ! ! ! ! Others!
Cerebellar!Infarct:! Supplied!by!3!arteries:! SCA!(also!supply!Midbrain),!AICA!(also!Pons),!PICA!(also!Medulla)!
Misc:!
Spinocerebellar!Ataxia:!
! Multiple!types:!
! ! SCA!3:! 21%;!UMNL;!Muscle!weakness!&!Atrophy!
! ! SCA!2:! 15%;!Areflexia;!Slow!Eye!movement,!sometimes!Dementia!
! ! SCA!6:! 15%;!Very!Slow!Worsening!of!Sx!
! ! SCA!1:! 6%;!UMNL!
Friedreich’s!Ataxia:! Degeneration!of!mainly!SC!&!Peripheral!nerves,!with!some!Cerebellar!degeneration!too!
! Neuro:! ! Motor:! LMNL!(Peripheral!Neuropathy!pattern:! Areflexia,!Distal!weakness)!

! Page!727!
Neuro! Unsteady! Gait! –! Ataxia!
! ! ! ! ! ! UMNL!(SC!involvement:! Upgoing!Plantar!response)!
! ! ! ! Sensory:! Glove!&!Stocking!(Peripheral!Neuropathy),!Posterior!column!
! ! ! ! Cerebellar!Ataxia!
! ! ! ! Others:! Scoliosis,!Pes!cavus!
! Others:! ! Cardiac!involvement!(eg.!Cardiomyopathy),!DM!
!

! Page!728!
Neuro! Unsteady! Gait! –! Ataxia!
 Neuro&Movement&Disorder&
Movement!Disorder:!Due!to!disorder!of!Basal!Ganglia!(Extrapyramidal)!
! ! ! ! More!concerned!with!Slow!(Ramp)!than!Rapid!(Ballistic;!Controlled!by!Cerebellum)!movement!
! ! ! ! Akinesia!(Loss!of!movement)!vs!Dyskinesia!(Excessive!Abnormal!Involuntary!movement)!
! ! ! ! Always!look!for!underlying!cause,!although!usually!Idiopathic!
! Hyperkinetic:! Tremor,!Chorea,!Athetosis/Choreoathetosis,!Dystonia,!Tics,!Myoclonus,!
! ! ! ! Hemiballismus/Ballismus,!Tardive!Dyskinesia!
! Hypokinetic:! Parkinsonism!
Tremor!
! ! ! ! Rhythmic!Oscillating!movement!of!a!segment!of!Limb!or!Head!
! ! ! ! Produced!by!Alternating/Synchronous!Contraction!of!Reciprocally!innervated!Antagonistic!M!
! ! ! ! Relatively!Fixed!Periodicity,!though!Waveform!&!Amplitude!can!vary!with!Physio/Psycho!
Factors!
! ! ! ! Enhanced!by!Emotional!Stress;!Disappear!during!Sleep!
! ! ! ! Clinically!important:! Parkinsonian!Rest!tremor,!Cerebellar!Kinetic!tremor,!Essential!tremor!
! Type:! ! Postural!Tremor:! Occur!during!Sustained!Posture!(eg.!Outstretched!Hands)!
! ! ! ! ! (Test:! ! ! 1.!Stretch!out!2!hands!with!fingers!spread!apart!
! ! ! ! ! ! ! ! 2.!Mimic!posture!of!testing!Shoulder!Abduction)!
! ! ! ! Intention!Tremor:! Occur!during!Movement!but!Absent!at!Rest!
! ! ! ! Resting!Tremor:!! Occur!when!the!body!is!at!Rest!
! Origin:! ! Postural:! Physiological!Tremor:! ! ! 8O12Hz!
! ! ! ! ! ! Enhanced!Physiological!Tremor:!
! ! ! ! ! ! ! ! Old!Age,!Anxiety,!Exercise,!Sleep!Deprivation,!
! ! ! ! ! ! ! ! Drugs!(Lithium,!Valproate,!TCA!...),!Alcohol,!Thyrotoxicosis,!
! ! ! ! ! ! ! ! Poisoning!(Mercury,!Lead,!Arsenic,!CO)!
! ! ! ! Intention:! ! ! 3O6Hz;!Terminal!Accentuation!is!common!
! ! ! ! ! ! ! ! Cerebellar!involvement,!Lesion!of!Superior!Cerebellar!Peduncle!
! ! ! ! ! ! ! ! No!satisfactory!Tx!
! ! ! ! Rest:!! ! ! Parkinsonism!(4O6Hz),!Heavy!Metal!Poisoning,!Wilson’s!disease!
! ! ! ! Rubral!Tremor:! ! Resting!+!Kinetic!Tremor;!Pathology!in!Midbrain!Red!Nucleus!
! ! ! ! Essential!Tremor:! 5O10Hz;!Resemble!Exaggerated!Physiological!Tremor!(But!Not!the!same)!
! ! ! ! ! ! ! ! ActionOinduced!(Action!Tremor)!(Can!have!Postural!component!too)!
! ! ! ! ! ! ! ! Often!Symmetrical,!Predominantly!affect!Hands,!Can!affect!Head!&!Voice!
! ! ! ! ! ! ! ! Exact!cause!Not!wellOdefined;!Some!with!FHx!+ve!
! ! ! ! ! ! ! ! Worsen!by!Stress,!Progress!with!Age!
! ! ! ! ! ! ! ! Alcohol!can!improve!Transiently!(but!maybe!the!trigger!in!some!Pt)!
! ! ! ! ! ! ! ! Medical!Tx!indicated!if!Disabling:! BB/Primidone!
Chorea!
! ! ! ! Irregular,!Jerky,!NonORepetitive,!Involuntary,!Unpredictable!
! ! ! ! Affect!different!body!parts!in!random!sequence;!Limbs,!Head,!Face,!Tongue!can!be!involved!
! ! ! ! Voluntary!movement!disturbed!(Hand!Grip)!
! Page!729!
Neuro! Unsteady! Gait! –! Movement! Disorder!
! ! ! ! QuasiOpurposive:! May!try!to!incorporate!Voluntary!“masking”!gesture,!
! ! ! ! ! ! ! ! ! to!convert!Chorea!into!seemingly!Purposive!movement!
! ! ! ! Stance!&!Gait!are!affected!with!tendency!to!Sway!&!Jerk!
! ! ! ! No!Weakness!but!Irregular!&!Unsteady!Gait!(Dancing!apart)!
! ! ! ! Muscle!tone↓!
! ! ! ! Irregular!&!Explosive!Speech!
! ! ! ! Chorea↑!with!Stress,!but!Disappear!during!Sleep!
! Lesion:! ! Corpus!Striatum!&!related!structures!
! Causes:! ! Hereditary:! ! ! Huntington's!disease,!Benign!Hereditary!Chorea,!etc!
! ! ! ! Cerebral!Palsy:! ! ! Perinatal/Antenatal!
! ! ! ! Rheumatic!Fever!(Sydenham’s!Chorea,!reactivate!as!Chorea!Gravidarum!during!Pregnancy)!
! ! ! ! Drug!Toxicity!(Levodopa)!
! ! ! ! Metabolic!disorder:! ! SLE,!Wilson’s!disease,!Kernicterus!(BilirubinOinduced;!Rare!now)!
! ! ! ! Inflammatory!disorder:! Thyrotoxicosis!
! ! ! ! Cerebrovascular!disorders!(eg.!AVM)!
! Huntington:! Onset!Age!30O50!(Mean!40);!Chorea!&!later!Dementia!
! ! ! ! Hereditary!disease,!AD,!Chromosome!4!(Psychi!2010!MCQ!12),!CAG!repeats!
! ! ! ! Atrophy!of!Caudate!&!Putamen!(Loss!of!Medium!Spiny!Neurons)!
! ! ! ! Juvenile!onset!most!Disabling!(usually!from!Father)!
! ! Signs:! Irritability,!Moodiness,!Abnormal!Behavior!leading!to!Dementia!
! ! ! ! (Behavioural!problem:! Personality!Change,!Affective!disorder,!Frank!Psychosis)!
! ! ! ! Abnormal!Choreic!movement;!Others:!Dysarthria,!Dysphagia,!Apraxia!
! ! ! ! Stiffness,!Rigidity!in!some!cases!(Akinetic!form,!mimick!PD)!
! ! MRI/CT:! Cortical!&!Caudate!Atrophy!
! ! Tx:! ! No!Cure;!Death!within!10O12(15)!years!
! ! ! ! Symptomatic!Tx!by!Neuroleptic!drugs!(Haloperidol),!Clonazepam/Tetrabenazine!
! Wilson:! ! Hepatolenticular!Degeneration;!Copper!accumulate!in!Liver!&!BG!
! ! ! ! AR;!Defect!in!CopperOtransporting!ATPase!coded!on!Chromosome!13!
! ! Neuro!S/S:!Begin!in!Childhood/Young!Adulthood!
! ! ! ! Dyskinesia/Parkinsonism!&!Psychiatric!problems!
! ! Ix:! ! SlitOlamp!examination:!
! ! ! ! ! Cerebral!involvement!is!almost!always!associated!with!KayserOFleischer!rings!
! ! Tx:! ! Untreated!Pt!die!from!Cirrhosis/Neurological!Cx!within!10!years!after!manifestation!
! ! ! ! Symptomatic:! Penicillamine!(Copper!Chelation)!or!Liver!Transplant!(Copper!Removal)!
! ! ! ! Presymptomatic:! Zinc!Sulphate!(Compete!for!Absorption)!
! ! ! ! ! ! ! ! Detect!by!Family!Screening!
Athetosis!&!Dystonia:!
! Athetosis:!! Slow,!Coarse,!Sinuous,!Writhing!movement!of!Extremities!
! ! ! ! Release!of!Alternating!Gasp!&!Avoidance!Reaction,!caused!by!Corticostriatal!fibre!Degeneration!
! ! ! ! Abnormal!Limb!Posturing:!
! ! ! ! ! Typically!Adducted!&!IR!at!Shoulder,! SemiFlexed!at!Elbow,!
! Page!730!
Neuro! Unsteady! Gait! –! Movement! Disorder!
! ! ! ! ! Flexed!at!Wrist!&!MCPJ,! ! ! Extended!at!IPJ!
! ! ! ! This!posture!is!disrupted!by!Slow!Writhing!movement!of:!
! ! ! ! ! Flexion!&!Extension!at!Wrist/Finger/Elbow,! ! Retraction!&!IR!at!Shoulder!
! ! ! ! If!Unilateral!involvement,!Pt!may!grasp!affected!limb!with!Normal!hand!to!Restrain!movement!
! ! ! ! LL!less!affected!
! ! ! ! UMN!signs!may!also!be!present!
! ! Cause:! Usually!due!to!Neonatal!Cerebral!Hypoxia!or!Kernicterus!
! Dystonia:! ! Kind!of!‘Frozen!Athetosis’;!Sporadic/Familial!
! ! ! ! Sustained!Postural!Distortion!due!to!Excessive!Muscle!Tone!in!Antagonistic!M!
! ! ! ! Abnormal!Posturing!can!be!distorted!by!Repetitive!Spasmodic!Twisting!movement!
! ! Location:! *Focal!Dystonia!(Localized!Muscle!groups),!Segmental!Dystonia!(eg.!2!connected!body!parts),!
! ! ! ! Generalized!Dystonia!(Most!of!Body)!
! ! ! ! (Hemidystonia:!1!side;! Multifocal!Dystonia:!Different!parts)!
! ! ! Focal!Dystonia:!
! ! ! ! Cervical!Dystonia!(Spasmodic!Torticollis;!Neck!tilt!to!1!side!upon!Chewing),!Blepharospasm,!
! ! ! ! Foot!Dystonia!(eg.!Inversion!Dystonia,!in!Advanced!PD),!Writer’s!Cramp!
! ! Specific:! PostureO,!ActionO!or!TaskO!Specific!
! ! ! ! Absent!during!Sleep!(2006!MCQ!X21),!Enhanced!by!Stress!&!Voluntary!activity!
! ! Cause:! If!related!to!Focal!Brain!Lesion:! BG!or!Rostral!Midbrain!usually!involved!
! ! ! ! Reversible!causes:! Wilson,!Focal!BG!Tumor,!DrugOinduced!
! ! Tx:! ! AntiCholinergic,!Levodopa,!Benzodiazepine,!Local!injection!of!Botulinum!Toxin!
! Etiology:! ! Cerebral!Palsy,!Idiopathic!Torsion!Dystonia,!HD!&!PD,!Levodopa!Tx,!
! ! ! ! Toxins!(Methanol,!Manganese),!Progressive!Supranuclear!Palsy…!
Hemiballismus!
! ! ! ! Proximal!Large!Amplitude!Chorea!(Hemiballismus!=!affect!1!side,!cf!Ballismus)!
! ! ! ! Irregular,!NonORepetitive,!Violent!Excursions!of!affected!Limbs!
! ! ! ! Particularly!Violent!because!Proximal!muscles!of!limb!are!affected!
! ! ! ! Due!to!a!Vascular!lesion!(Stroke)!of!Contralateral!Subthalamic!Nucleus!
! Tx:! ! ! Tetrabenazine!(Block!Dopamine!Uptake)!
! ! ! ! Usually!disappear!several!weeks!after!onset!
Tics!
! ! ! ! Sudden,!Rapid,!Stereotypic,!Coordinated!Involuntary!movement,!repeated!at!Irregular!intervals!
! ! ! ! Usually!at!Head/Arms!
! ! ! ! Can!be!Suppressed!Voluntarily!but!only!Temporarily;!Inner!Urge!to!resume!movement!
! Type:! ! *Transient!Simple!Tics:! Very!common!in!Children,!usually!resolve!Spontaneously!before!20!
! ! ! ! Chronic!Simple!Tics:! ! Usually!Begin!during!Childhood,!often!do!Not!Regress!
! ! ! ! Persistent!Multiple!(Simple)!Tics:! Begin!before!15!yo,!associated!with!Vocal!Tics!
! ! ! ! ! ! ! ! ! ! ! Complete!Remission!can!occur!in!Adulthood!
! ! ! ! Tourette’s!syndrome:! ! Chronic!Multiple!Motor!&!Vocal!Tics!
! ! ! ! ! ! ! ! ! Also!Compulsive!behavior,!Obsessive!Rumination,!ADHD!
! ! ! ! ! ! ! ! ! Sporadic,!sometimes!Familial;! M>F;!! Rare!
! Page!731!
Neuro! Unsteady! Gait! –! Movement! Disorder!
! ! ! ! ! ! ! ! ! Onset!at!Childhood,!Worst!at!Late!Adolescence,!
! ! ! ! ! ! ! ! ! ! then!Tendency!to!improve!with!Age!
! ! ! ! ! ! ! ! ! Tx:! Clonidine,!Haloperidol!
Myoclonus!
! ! ! ! Myoclonic!Jerks:! Sudden,!Rapid,!TwitchOlike!(ShockOlike)!movement!
! ! ! ! Variable!Intensity;!Jerks!can!be!Repetitive/Paroxysmal!
! ! ! ! Unlike!Chorea/Athetosis,!Myoclonus!movement!is!Always!Simple!in!nature!
! ! ! ! Repetitive!Myoclonus!differ!from!Tremor!by!being!Less!Rhythmic!with!Visible!Pauses!
! ! ! ! ! (Hence,!Flapping!Tremor!resemble!Myoclonus!more!than!Tremor)!
! ! ! ! Spontaneous/Triggered!by!Sensory!stimulation!
! ! ! ! Generalized!or!Segmental!(Focal);!Broad!Ddx!
! Clinical!&!Etiological!Classification:!
! ! ! ! Physiological:! Nocturnal,!Hiccups!
! ! ! ! Essential:! ! Sometimes!Inherited!
! ! ! ! Epileptic:! ! Sometimes!difficult!to!Dx!
! ! ! ! Symptomatic:! Numerous!causes!
! Generalyzed!Myoclonus:!
! ! ! ! Usually!due!to!Abnormal!Cortical!activities:!
! ! ! ! ! Epilepsy!syndrome,!Neurodegenerative!diseases!(eg.!Alzheimer),!CJD,!
! ! ! ! ! Mitochondrial!disease,!Cerebral!Anoxia!
! ! Degenerative:!
! ! ! ! Dentatorubro!Thalamic!Atrophy,!Alzheimer,!Wilson,!Huntington!
! ! Infection:! CJD,!AIDS!Dementia!Complex,!Viral!Encephalitis!
! ! Metabolic:! Drug!Intoxication!(Penicillin,!Bismuth…)!
! ! ! ! Encephalopathy!(Hyperglycemia,!Uremic,!Hepatic...)!
! ! ! ! Brain!damage!(Traumatisms,!Stroke…)!
! ! ! ! Anoxia!
! Segmental!Myoclonus:!
! ! ! ! Lesion!of!Cerebral!Cortex,!Brainstem,!SC;! Stroke,!Tumor,!MS!
! ! ! ! Focal!Myoclonus!due!to!BG!disorder!often!affects!Muscles!in!Neck,!Arm!or!Shoulder!
! ! ! ! Dystonia!&!Myoclonus!can!sometimes!Coexist!
! Tx:! ! ! Common!AntiOMyoclonic!drug:! Benzodiazepine,!Piracetam,!AntiConvulsant!(eg.!Valproate)!
! ! ! ! ! Valproic!acid,!500!mg!Q3D!
! ! ! ! ! Clonazepam!0.5!mg!Q3D!(at!the!beginning)!
! ! ! ! ! 5OHydroxytryptophan!(Anoxic!Myoclonus)!
DrugVinduced!
DrugOinduced!Movement!Disorder:!
! ! ! ! Parkinsonism,!Acute!Dystonic!Reaction,!Tardive!Dyskinesia!
Acute!Dystonic!Reaction:!
! ! ! ! Usually!in!Young!Pt!a!few!hours!after!AntiODopaminergic!
! ! ! ! ! Eg.!Prochlorperazine,!Metoclopramide!
! Page!732!
Neuro! Unsteady! Gait! –! Movement! Disorder!
! ! ! ! Dystonia!can!affect!Cranial,!Cervical,!Axial!muscles;!May!also!has!Oculogyric!Crisis!
! Tx:! ! ! IV!AntiCholinergic!(Procyclidine,!Benztropine,!Diphenhydramine)!or!Benzodiazepine!
Tardive!Dyskinesia:! Affect!~20%!Pt!taking!Long!term!AntiPsychotic,!esp!Elderly!
! ! ! ! DopamineOreceptor!Hypersensitivity!is!probably!responsible!
! ! ! ! Continuous!Stereotypic!movement,!more!pronounced!in!Orolingual!region!
! ! ! ! ! Include!Chewing!&!Smacking!of!Mouth!&!Lips,!Rolling!of!Tongue!in!mouth,!
! ! ! ! ! ! or!Pushing!against!the!inside!of!Cheek!with!Periodic!Protrusions!
! ! ! ! ! This!contrast!with!Irregular!&!Random!Nature!of!Chorea!
! ! ! ! Gait!is!Unaffected!
! Tx:! ! ! Difficult!to!treat!
! ! ! ! Withdrawal!of!responsible!drug!may!produce!Remission,!
! ! ! ! ! But!Abrupt!Withdrawal!might!Paradoxically!Precipitate!Tardive!Dyskinesia!
!

! Page!733!
Neuro! Unsteady! Gait! –! Movement! Disorder!
 Neuro&Parkinsonism&
Parkinsonism:! ! Clinical!features!seen!in!PD!(ie.!TRAP);!Not!Exclusive!for!PD!
! *Idiopathic:! Idiopathic!PD!(Sporadic)!
! Familial!Parkinsonian!Syndrome!(Familial!PD):!
! ! ! ! 5O10%!of!the!cases;!>10!genetic!loci;!(Almost!certainly!will!develop!PD,!except!LRRK2)!
! ! ! ! ! Park!1:! SNCA!(αOSynuclein)!(1stdiscovered;!Involved!in!Pathogenesis!of!Lewy!body)!
! ! ! ! ! Park!2:! PRKN!(Parkin)!
! ! ! ! ! Park!8:! LRRK2!(Most!common)!(Can!also!be!a!RF!for!Sporadic!PD)!
! Parkinson!Plus!Syndrome:!
! ! ! ! Widespread!Neurodegeneration!
! ! ! ! Aggressive!course!(Worse!Prognosis!than!PD),!Poor/No!response!to!Levodopa!
! ! ! ! Typically!Symmetrical!(except!CBD),!No!Resting!Tremor,!Early!Gait/Speech/Dysphagia!
! ! Diseases:! Multiple!System!Atrophy,!Progressive!Supranuclear!Palsy,!
! ! ! ! Corticobasal!(Ganglionic)!Degeneration,!(Lewy!body!Dementia!–!Part!of!Parkinson!Plus?)!
! ! MSA:!! MSAOP:! MSA!with!predominant!Parkinsonism;!Old!term:!StriatoNigral!Degeneration!
! ! ! ! MSAOC:! MSA!with!Cerebellar!features;!Old!term:!Sporadic!OlivoPontoCerebellar!Atrophy!
! ! ! ! (MSAOA):! Parkinsonism!with!Pronounced!Autonomic!Failure!(eg.!Orthostatic!Hypotension)!
! ! ! ! ! ! Now!Not!used;!Old!term:!ShyODrager!syndrome!
! ! ! ! Relatively!Symmetrical;!Often!with!Autonomic,!Cerebellar,!Corticospinal!dysfunction!
! ! ! ! MRI!may!show!Putaminal!Rim!in!MSAOP,!or!Pontine!‘Hot!Cross!Buns’!sign!in!MSAOC!
! ! PSP:! ! Vertical!Gaze!Palsy:! Initially!Downward!palsy,!then!Upward!palsy!
! ! ! ! ! ! ! ! Voluntary!impaired!but!Not!Reflexive!impaired!
! ! ! ! SquareOwave!Jerks!(Due!to!Saccadic!movement,!cf!Nystagmus),!Upright!Posture!(Hyperextend),!
! ! ! ! Pseudobulbar!Affect!
! ! ! ! Relatively!Symmetrical;!Often!with!Early!Falls!in!1st!year!
! ! ! ! MRI!may!show!Hummingbird!sign!on!Midsagittal!film!(Midbrain!Atrophy!with!preserved!Pons)!
! ! CBD:!! (Uncommon,!Difficult!to!diagnose,!often!after!ruling!out!others)!
! ! ! ! Cortical!Sensory!abnormalities!(Limb!Apraxia,!Agnosia,!Alien!hand!syndrome),!
! ! ! ! Coarse!Unilateral!Tremor!(Dystonic),!Early!Dementia!
! ! ! ! Very!Asymmetrical!
! ! LBD:! ! Early!Dementia,!Visual!Hallucination!
! ! ! ! (RH:! More!responsive!to!Dementia!drugs!than!Alzheimer!
! ! ! ! ! Avoid!AntiPsychotics!–!↑Risk!of!NMS)!
! Vascular!(Pseudo)Parkinsonism:!
! ! ! ! Due!to!Cerebrovascular!disease;!(Now!may!call!Subcortical!PD)!
! ! ! ! ‘Lower!body!Parkinsonism’!–!Often!presents!as!Gait!dysfunction!
! ! ! ! May!be!Acute,!or!Stepwise!(Accumulated!Stroke!mimicking!Progressive!picture)!
! ! ! ! Ddx:! No!Resting!Tremor,!Cortospinal!signs,!Early!Gait!Instability,!(Dementia)!
! Secondary:! DrugOInduced:! DA!Antagonist!–!AntiPsychotic!(Phenothiazine),!AntiEmetics!(Metoclopromide)!
! ! ! ! ! ! ! Others:! Major!Tranquillisers,!AntiHistamine,!Methyldopa,!Tetrabenazine!
! ! ! ! ! ! ! (Usually!Symmetrical!involvement,!Less!likely!to!have!Resting!Tremor)!

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! ! ! ! Toxin:! Cu!(Wilson),!CO!(Ischemic!injury),!MPTP!Drug!user,!Manganese,!Carbone!disulfide!
! ! ! ! PostEncephalitic!(PostOEncephalitis!Lethargica;!Very!Rare!now,!due!to!Influenza!Pandemic!
1918)!
! ! ! ! ! (Nowadays,!JE!may!have!potential!too!because!it!preferentially!affect!BG)!
! ! ! ! NPH,!Alzheimer,!Head!Trauma!(Chronic!Head!Injury:!PunchODrunk!Syndrome;!eg.! ),!
! ! ! !! Neoplastic!(Parasagittal!Meningioma),!CJD!
! ! Others:! Leucodystrophy,!Familial!Olivopontocerebellar!Atrophy,!DenataoORubroOPallidoOLuysian!
Atrophy,!
! ! ! ! HallevordenOSpatz!disease!(Neurodegeneration!with!Brain!Iron!Accumulation,!usually!
Pediatric),!
! ! ! ! Westphal!variant!of!Huntington’s!disease,!Guam!variant!of!Motor!Neuron!disease!
Parkinsonian!Gait:! Flexed/Stooping!Posture!
! ! ! ! ↓Arm!Swing!
! ! ! ! Slow,!Narrow!Base,!Small!steps!Shuffling!(Marche!á!petit),!Poor!Foot!Clearance!
! ! ! ! Trunk!appear!Stiff,!Turning!require!Multiple!Steps!(‘En!bloc’!turning)!
! ! ! ! Tendency!to!Fall!Backward!(Retropulsion)!
! Advanced:!! Difficulty!in!Initiating!steps>!Appear!to!‘Freeze’!with!feet!stuck!to!floor!
! ! ! ! Initiate!Gait!by!Leaning!Forward,!then!Festinating!(Progressively!Shortened,!Accelerated!steps)!
! ! ! ! ! (Rapidly!advance!with!Small!Steps!to!catch!up!with!Shift!in!Centre!of!Gravity)!
! ! ! ! Falls!tend!to!be!Late!features!
Parkinson’s!disease:! aka!Paralysis!agitans!
! ! ! ! Occur!in!All!Ethnic!groups;!0.3%!general!population,!Prevalence!1!in!1,000!
! ! ! ! Related!to!Aging;!Up!to!3%!>65;!Age!of!Onset!50O60!(Rare!<40!&!>65)!
! ! ! ! LifeOexpectancy:!Mortality!2O5x!of!ageOmatched!controls!
! ! ! ! Average!Time!from!Dx!to!Severe!Disability!14!years!
Genetics:! ! ! PD!is!Sporadic;! But!if!FHx!+ve,!2x!risk!of!PD!
! ! ! ! LRRK2:! Found!in!both!Familial!PD!&!0.5O2%!of!Sporadic!LateOonset!cases;!Susceptible!loci?!
Dx:! ! ! ! Clinical,!No!Confirmatory!Test;! Ix!mainly!for!evidence!of!other!Parkinsonian!Syndrome!
! ! ! ! Cardinal!Features!–!TRAP,!usually!but!Not!always!present!
! ! ! ! ! Upper!Body!Akinesia!is!essential!for!Dx!of!Idiopathic!PD!(+!Any!1!of!other!3!features)!
! ! ! ! ! (Medscape:!Any!2!of!Tremor,!Rigidity,!Bradykinesia;!Postural!instability!usually!Later)!
! ! ! ! Involvement!often!Asymmetrical!
Signs:! ! ! (Classical!signs!descriptions!are!based!on!Idiopathic!PD;!Other!Parkinsonism!can!be!Atypical)!
! Tremor:! ! 4O6Hz,!Coarse,!Rest!(↓with!Action,!↑with!Stress)!
! ! ! ! ! (Postural!ReOemergent!Tremor!may!be!seen:!Postural!Tremor!after!a!Latency!of!~5s)!
! ! ! ! Begin!in!Hand/Foot,!classically!‘PillOrolling’!(Note!Thumb!&!Index!finger)!
! ! ! ! ! (In!Early!stage!may!need!Distraction!to!check!Resting!Tremor,!eg.!Count!10,!9,!8…)!
! ! ! ! UL!affected!more!than!LL;!Head!Tremor!uncommon;!(Voice!may!exhibit!Kinetic!Tremor)!
! ! ! ! ! Fingers/Thumb:!! MCPJ!movement!
! ! ! ! ! Wrist:! ! ! Flexion/Extension,!Lateral!Displacement,!Pro/Supination!
! ! ! ! ! Usually!Little!movement!above!Wrist!

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! ! ! ! (Most!common!presenting!Sx!of!Idiopathic!PD)!
! Rigidity:! ! ↑Resistance!to!Passive!movement!
! ! ! ! 2!Types:! Leadpipe!Rigidity!(Uniform!throughout!ROM)!
! ! ! ! ! ! Cogwheel!Rigidity!(Leadpipe!Rigidity!+!Tremor>!Jerky!Resistance)!
! ! ! ! ↑Tone!usually!Equal!in!Flexors!&!Extensors,!best!seen!with!Slow!Passive!move!
! ! ! ! ! (May!see!UL!Flexed!at!Elbow/Wrist/MCPJ,!Extended!at!IPJ)!
! ! ! ! ! May!be!made!more!obvious!with!Pt!actively!moving!the!opposite!limb!
! ! ! ! ! Contrast!with!Distribution!(Extensor)!&!VelocityOdependent!nature!of!Spasticity!
! ! ! ! Axial!Flexor!Tone!slightly!Greater!than!Extensor!
! ! ! ! ! Slightly!Flexed,!Stooping!“Simian”!posture;!Head!tilt!Forward!and!Body!Stooped/Kyphotic!
! Bradykinesia:! Slowness!&!↓Amplitude!of!Voluntary!movement,!↓Spontaneous/Automatic!movement!
! ! ! ! Lack/Fixity!of!Facial!Expression!(MaskOlike!face,!aka!Facial!Amimia/Hypomimia)!
! ! ! ! Lack!of!EyeOblinking!(Reptilian!eyes)!
! ! ! ! ↓Voice!(Soft!&!Monotonous!Speech)!
! ! ! ! Small!hand!Writing!(Micrographia!–!Handwriting!gradually!↓!in!Size)!
! ! ! ! Clumsiness!with!Rapid!Repetitive!movement!(Dysdiadochokinesia)!
! ! ! ! Gait!with!Small!&!Shuffling!steps/Turning!difficulties,!↓Arm!Swinging!
! Postural!Instability:!
! ! ! ! Usually!emerge!Later!in!Idiopathic!PD!
! ! ! ! Pull!Test!for!Retropulsion!(May!close!eyes!to!test!it;!Taking!1O2!steps!back!is!still!acceptale)!
! ! ! ! ! (May!test!HeelOtoe!walking!first!to!see!how!bad!the!Postural!Instability!is)!
! ! ! ! Timed!Up!&!Go!Test!may!help!evaluation!of!risk!of!Fall!(Overall!functional!assessment)!
! ! ! ! ! (PYNEH!Geri:!Normal!15s,!Abnormal!25s,!Borderline!15O24s)!
! Others:! ! Blepharospasm!(Can!be!due!to!Rigidity,!or!due!to!S/E!of!AntiOParkinsonian!drugs)!
! ! ! ! Sustained!Blink!responses!on!Glabellar!Tap!(Sustained!Glabellar!Reflex!–!Myerson’s!Sign)!
! ! ! ! ! ! (Test:! Stand!at!Back!of!Pt,!Tap!Glabella!~1/s;!Not!too!Low!to!trigger!Menace!Reflex)!
! ! ! ! ! ! ! Normal!Adults!only!blink!for!first!few!taps!
! ! ! ! ! ! ! Primitive!reflex!in!Infants;!Also!as!a!Frontal!releasing!sign!in!other!pathology)!
! ! ! ! Cognitive!Decline!
Clinical!Red!Flags:! Rapid!Progression,!Early!Instability!&!Falls!
! ! ! ! Poor!response!to!Levodopa!(>70%!PD!has!Excellent!Initial!response!to!LOdopa)!
! ! ! ! ! (KW!Fong:!If!Poor!response!despite!dose!↑!to!1g,!consider!other!ddx)!
! ! ! ! LL>UL!involvement!(Vascular:!Gait!&!Postural!Instability!more!affected!than!UL)!
! ! ! ! Early!&!Prominent!Dementia!(eg.!Lewy!Body!Dementia)!
! ! ! ! Pyramidal!signs,!Cerebellar!signs,!Autonomic!Failure!(MSA)!
! ! ! ! Gaze!Palsy!(PSP)!
! ! ! ! Young!onset!with!+ve!FHx!(Must!rule!out!Wilson’s!disease!in!Young!onset!Parkinsonism)!
Other!Problems:! Degeneration!in!PD!Not!only!confined!to!BG!Motor!Loop,!but!involve!Multiple!pathways!
! ! ! ! ExtraOmotor!manifestations!do!Not!respond!to!Dopaminergic!therapy!( other!pathways)!
! ! ! ! Usually!Mild!until!Advanced;!Suspect!other!Parkinsonian!syndromes!if!Early/Prominent!
! ! ! ! (PreOmotor!features:! Olfactory!deficit,!REM!sleep!behavior!disorder,!Constipation,!Depression)!

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! Dysautonomia:! Constipation,!Orthostatic!Hypotension,!Detrusor!Instability!
! ! ! ! Salivation!may!↑!and!prone!to!Sialorrhea!(Drooling)!due!to!↓Spontaneous!Swallowing!
! ! ! ! ↑Risk!of!Seborrheic!Dermatitis!
! Postural!&!Motor!Execution!dysfunction:!
! ! ! ! Freezing,!Impaired!Postural!Correction,!‘Fall!like!a!Log’!
! Sensory:! ! Hyposmia!(Can!be!a!very!Early!sign!of!PD;!May!affect!Appetite)!
! ! ! ! Pain!&!Paresthesia!
! Cognitive!deficit:!
! ! ! ! Slowness!of!Thought,!Poor!Memory!Retrieval,!Lack!of!Motivation,!Blunting!of!Drive!
! ! ! ! Dementia:!! ! ! Atypical!in!Early!disease,!but!eventually!develop!in!20%!Pt!
! ! ! ! Depression!&!Anxiety:! Common!
! ! ! ! Pt!with!Cognitive!deficits!are!More!prone!to!Psychi!S/E!of!AntiOParkinsonian!Tx!
(Dx:! ! ! ! Clinical!Dx,!eg.!with!Queen!Square!Brain!Bank!criteria)!
(Neuroimaging:!
! MRI:!! ! Subtle!abnormalities,!found!only!in!20%!Pt!
! ! ! ! T2W:!! Atrophy!of!area!separating!Red!nucleus!&!SNr!from!SNc,!
! ! ! ! ! ! ! Correlated!with!↓Width!of!Hyperintense!band!in!Midbrain!in!Advanced!PD!
! ! ! ! Mainly!for!picking!up!Atypical!Parkinsonism!
! SPECT:! ! DAT!(Dopamine!Transporter)!scan!most!commonly!used!
! ! ! ! ! Can!help!diagnose!Parkinsonism!but!can’t!rule!out!other!causes!of!Parkinsonism!
! PET!
! Transcranial!Sonography)!
(Olfactory!Tests:! ! May!be!used!as!Screening!test;!But!Not!done!clinically!as!No!useful!diseaseOmodifying!Tx)!
Staging:! ! ! Hoehn!&!Yahr!Staging!of!PD!
! ! ! ! ! Stage!1:! Sx!Unilateral,!Mild,!Inconvenient!but!Not!Disabling,!
! ! ! ! ! ! ! Usually!presents!with!Tremor!of!1!limb,!
! ! ! ! ! ! ! Friends!have!noticed!changes!in!Posture,!Locomotion!&!Facial!Expression!
! ! ! ! ! Stage!2:! Sx!Bilateral,!Minimal!Disability,!Posture!&!Gait!affected!
! ! ! ! ! Stage!3:! Significant!Slowing!of!body!movement,!
! ! ! ! ! ! ! Early!Impairmen!of!Equilibrium!on!Walking/Standing,!
! ! ! ! ! ! ! Generalized!dysfunction!that!is!Moderately!Severe!
! ! ! ! ! Stage!4:! Sx!Severe,!Can!still!walk!to!a!limited!extent,!
! ! ! ! ! ! ! Rigidity!&!Bradykinesia,!No!longer!able!to!live!alone,!
! ! ! ! ! ! ! Tremor!may!be!Less!than!earlier!stages!
! ! ! ! ! Stage!5:! Cachetic!stage,!Invalidism!Complete,!Cant!stand/walk,!
! ! ! ! ! ! ! Require!constant!Nursing!care!

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! ! ! ! ! !

Pathology:!! ! Loss!of!MelaninOcontaining!Dopaminergic!neurons!in!Substantia!nigra!pars!compacta!
! ! ! ! ! Features!appear!if!60O80%!Nigrostriatal!neurons!degenerated,!with!90%↓of!Striatal!DA!
! ! ! ! (Loss!of!neurons!in!Brainstem,!Pallidum,!Putamen)!
! ! ! ! Intraneuronal!Lewy!bodies!Inclusions!
Tx:! ! ! ! No!Cure,!essentially!Palliative!
! By!Purpose:! Restorative!Therapy,!Neuroprotective!Therapy,!
! ! ! ! Symptomatic/Palliative!Therapy!(Dopaminergic,!AntiOInhibitory)!
! By!Form:! ! Drug:! ! AntiCholinergic,!Dopamine!agonist!(Bromocriptine,!Ropinirole…),!Amantadine,!
! ! ! ! ! ! ! Levodopa!+!Carbidopa,!Tolcapone!(COMTI),!Selegiline!(MAOBI),!Apomorphine!
! ! ! ! Surgery:! ! Thalamotony!(mainly!useful!for!Tremor),!Pallidotomy,!DBS,!Cell!Transplantation!
! ! ! ! ! ! ! (Inactivate!HyperOexcitable!Subthalamic!Nucleus!or!Medial!Globus!Pallidus,!
! ! ! ! ! ! ! ! By!Thermolytic!Ablation!or!Implanting!Programmable!Electrodes)!
! ! ! ! Physical!Therapy,!Daily!Living!Aid!
Levodopa:!! ! Always!combined!with!DopaODecarboxylase!Inhibitor:!
! ! ! ! ! Sinemet!(Levodopa!+!Carbidopa)!or!Madopar!(Levodopa!+!Benserazide)!
! ! ! ! ! Purpose:! ↓Peripheral!conversion!to!Dopamine!(↑CNS!concentration)!
! ! ! ! ! ! ! ↓Peripheral!Dopaminergic!S/E!
! ! ! ! Stable!reversal!of!almost!all!manifestations!at!Initial!stage,!typically!last!for!5!years!
! ! ! ! Gradual!Loss!of!Dopaminergic!terminals!↓Capability!to!synthesize/store/release/reuptake!DA!
! ! ! ! ! >!Levodopa!benefit!↓gradually!(Lesser!&!Shorter!effect),!Motor!Fluctuation!occur!
! ! ! ! Eventually!most!Pt!experience!DrugOinduced!Choreiform!Dyskinesia,!
! ! ! ! ! Due!to!Overshoot!Sensitivity!of!Postsynaptic!receptor!to!Dopamine!
! ! ! ! LOdopa!induced!Cognitive!&!Neuropsychiatric!Cx!common!in!Elderly!(Hallucination,!Psychosis)!
! ! ! ! ! Mx!by!↓Levodopa!dose!at!expense!of!Motor!Deterioration,!
! ! ! ! ! Or!Add!Atypical!Neuroleptic!with!Low!Propensity!for!inducing!Extrapyramidal!S/E!
! ! ! ! ! ! Eg.!Clozapine,!Olanzapine,!Quetiapine!
! S/E:! Peripheral:!N/V,!Postural!Hypotension!
! ! ! NB:! Treat!N/V!by!Domperidone!(2011!MCQ!67);!Don’t!use!Metoclopromide,!Prochlorperazine!
! ! Neuropsychiatric:!
! ! ! ! Daytime!drowsiness,!Confusion,!Psychosis,!(Punding)!
! ! Motor!Cx:!Motor!fluctuations:! End!of!dose!(wearingOoff)!
! ! ! ! ! ! ! ! Unpredictable!motor!fluctuations!(onOoff!phenomenon)!
! ! ! ! ! ! ! ! Dose!failures!&!‘DelayedOon!
! ! ! ! Dyskinesia:! ! Early!AM!dystonia,!Peak!dose!Dyskinesa,! !

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! ! ! NB:! 50%!Pt!have!LOdopa!induced!Motor!Cx!after!5!years!of!Levodopa!Tx!
! ! ! ! Pathophysiology:! Poorly!understood!
! ! ! ! ! ! ! ! ?!Pulsatile!Dopaminergic!stimulation!
! ! ! ! Continuous!Dopaminergic!Stimulation!(CDS)!may!help!↓Motor!Cx!
Other!Drugs:! ! Dopamine!Receptor!Agonist:! Bromocriptine,!Pergolide,!Apomorphine!
! ! ! ! AntiMuscarinic!(Benzhexol):! ↓Excessive!Striatal!Cholinergic!activity!
! ! ! ! MAOBI!(Selegiline,!Rasagiline):! ↓Breakdown!of!Dopamine!by!Monoamine!Oxidase!
! ! ! ! COMTI!(Entacapone):!! ! ↓Peripheral!Breakdown!of!LOdopa!to!3OOOMethyldopa!
! ! ! ! Amantadine!(NMDA!Blockade)!
! Use:! ! ! No!Consensus!
! ! ! ! AntiMuscarinic/Selegiline!may!be!sufficient!in!Early!stage!
! ! ! ! ! (Selegiline!may!be!Neuroprotective,!but!Efficacy!in!Symptomatic!Tx!limited!
! ! ! ! ! ! Thus!may!be!used!in!Young!Pt)!
! ! ! ! ! (AntiCholinergic!good!for!Tremor,!but!avoid!in!Elderly!due!to!Confusion)!
! ! ! ! Dopamine!Agonist/COMTI!are!useful!Adjunct!to!Levodopa!in!Late!stage!
! ! KH!Chan:! In!Early!onset!Parkisonism,!may!use!DA!agonist!rather!than!LOdopa!(Less!Dyskinesia)!
! ! ! ! Apomorphine!is!given!SC,!can!rescue!Freezing!
! ! ! ! Amantadine!only!gives!Mild!symptomatic!benefit!in!Early!PD!
! ! ! ! ! More!commonly!used!to!↓Dyskinesia!from!LOdopa!in!Advanced!PD!
! ! ! ! COMTI!can!be!added!to!DA!agonist/LOdopa!to!prolong!action!in!Advanced!PD!
! ! ! ! AntiMuscarinic!has!lots!of!S/E,!Not!commonly!used!
Problems!with!LT!Dopaminergic!Therapy:!
! Loss!of!Therapeutic!Efficacy!(Last!~10!years)!
! Motor!Fluctuation:! End!of!dose!Wearing!off,!Dyskinesia,!Unpredictable!onOoff!response!
! Psychiatric!Cx:! ! Pt!with!Previous!Cognitive!dysfunction/Psychiatric!disorder!are!more!Susceptible!
! ! ! ! ! Memory!deficits!(AntiCholinergic!agents)!
! ! ! ! ! Confusion!&!Psychosis!(Dopaminergic):!
! ! ! ! ! ! Agitation,!Hallucination,!Paranoia,!Vivid!dreams!
DA!agonist:! ! Direct!actions!on!Striatal!Dopamine!receptors!
! ! ! ! Current!clinical!practices!almost!exclusively!uses!NonOergot!DA!
! ! ! ! ! Ie.!Pramipexole,!Ropinirole!(Oral),!Rotigotine!(Transdermal)!
! ! ! ! ! Due!to! !
! ! ! ! Less!Motor!Cx,!but!also!Less!Efficacy!
DBS:!SurgicalOrelated!Cx:!
! ! ! ! ICH,!Cerebral!infarct,!Seizures,!Infection!of!Implantation!site!
! HardwareOrelated!Cx:!
! TargetOrelated!Cx:!
! ! ! ! Behavior:! ! Eg.!Depression!
! ! ! ! NonObehavior!
Tx!Algorithm:!

! Page!739!
Neuro! Parkinsonism!
! ! ! ! !
PE!Checklist:!
BP:! ! ! ! Postural!Hypotension!(Autonomic!dysfunction)!
Head:! ! ! Mask!Face!(Lack!of!Facial!Expression)!(Sad!Face!due!to!Depression!also!possible)!
! ! ! ! Titubation!(ToOandOfro!movement!of!Head!&!Trunk:!Cerebellar!Ataxia)!
! ! ! ! ! (Essential!Tremor!may!have!Head!Tremor!too:! YesOYes!or!NoONo!movement)!
! ! ! ! Glabellar!Tap!
! Eye:! ! ! Lack!of!Blinking!
! ! ! ! Brow!for!Seborrhea!(Autonomic!dysfunction)!
! ! ! ! Blepharospasm!
! ! ! ! Test!EOM!for!PSP:! Downward!Gaze!Palsy!±!Upward!Gaze!Palsy!
! Nose:! ! Anosmia/Hyposmia!
! Mouth:! ! Drooling!(Autonomic!dysfunction)!
! ! ! ! Soft!Monotonous!Speech!
! Higher!Mental:! Cognitive!dysfunction,!Depression!
UL:! Tone:! ! Wrist!&!Elbow!Tone:! Cogwheel!or!Leadpipe!Rigidity!
! Power:! ! Weakness!can!give!misleading!results!in!Coordination!
! ! ! ! Check!Pronator!Drift!for!Weakness!&!Rebound!for!Cerebellar!signs!too!
! Tremor:! ! Resting!Tremor!with!relaxed!arms!(May!worsen!with!Distraction)!
! ! ! ! FingerONose:! Tremor↓!(vs!Essential!Tremor,!which!↑!with!movement)!
! ! ! ! ! ! ! Possibility!of!MSA!if!Ataxia!present!
! Bradykinesia:! (Any!test!of!Repetitive!movement!for!Dampening!–!Progressive!↓!in!Amplitude!&!Speed)!
! ! ! ! Hand!Clapping!(Like!testing!Dysdiadochokinesia)!
! ! ! ! Finger!Pinching!(Progressively!Smaller)!
! ! ! ! ! (KH!Chan:!If!Pt!has!RA/Finger!Joint!problems,!Can!rub!abdomen!circumferentially!instead)!
! ! ! ! Hand!drawing:! Micrographia!
LL:! Reflex:! ! Babinski!sign!+ve!may!suggest!Vascular!Parkinsonism,!etc!
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Neuro! Parkinsonism!
! ! ! ! Upgoing!Big!Toe!without!Fanning!may!be!seen!in!MSA,!Advanced!PD!
! Foot!Tapping:! Bradykinesia!
Gait:!Standing:! ! Test!Retropulsion!
! Walking:! ! Freezing,!Difficulty!initiating!movement!(Bradykinesia)!(Rising!from!chair,!Taking!1st!step)!
! ! ! ! Shuffling!gait,!Festination!
! ! ! ! ‘En!bloc’!turning!
! ! ! ! ↓Arm!swing!
! HeelOToe:! ! Difficult!HeelOtoe!walking!
!

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 Neuro&CNS&Infection&
CNS!Infection:! ! Meningitis,!Encephalitis,!Myelitis,!Brain/SC!Abscess,!Epidural/Subdural!Empyema!
! ! ! ! Very!Common!&!Important,!High!M&M!
! ! ! ! Formulate!Dx!&!Start!Empirical!Tx!asap;! Lumbar!Puncture!if!No!Contraindication!
! ! ! ! Quick!Septic!workup!including!Blood!Culture!before!starting!Antibiotics!
! Tx:! ! ! High!dose!Parenteral!Antibiotics:! Cefotaxime,!Ceftriaxone,!Meropenem,!Penicillin!
! ! ! ! Oral!Chloramphenicol,!Cotrimoxazole,!Metronidazole!with!good!CSF!Penetration!
! ! ! ! Intrathecal!admin!Not!required!
! ! ! ! Corticosteroid!Controversial:! Useful!in!Childhood!Meningitis!or!Severe!Inflammation!
Approach!to!Pt!with!Fever!&!Confusion:!
! Ddx:! ! ! CNS!Infection:! Meningitis,!Encephalitis,!Brain!Abscess!
! ! ! ! Others:! ! Systemic!Infection!with!Toxic/Metabolic!Encephalopathy!
! ! ! ! ! ! ! CTD!with!CNS!Involvement!
! Hx:! ! ! Hx!of!Travel,!Systemic!Infection,!Chronic!illness,!Immunization!
! ! ! ! Age,!Immunological!status,!Onset!&!Duration!of!Sx,!Progression,!Previous!Tx!(esp!Antibiotics)!
! PE:! ! ! Fever,!Higher!Mental!Function,!Focal!Neurological!Signs,!Neck!Stiffness,!Kernig’s!Sign,!GE!
! Ix:! ! ! Septic!workup,!CXR,!CBC!with!DC,!ESR,!PT!&!APTT,!RG/FG,!LRFT,!ABG,!Toxicology!Screen,!
! ! ! ! CT/MRI!Brain,!LP!&!CSF!Analysis,!EEG!
! ! NB:! ! BG!should!be!obtained!Before!doing!LP!
! (Empirical!Tx!for!uncertain!CNS!Infection!according!to!Jasper!Chan:!
! ! ! ! IV!Penicillin!G,!Cefotaxime,!Metronidazole!to!cover!Brain!Abscess,!Acyclovir!to!cover!HSV)!
LP:! CSF:! ! ! Production!(500!ml/day),!Circulation!(Ventricular!Volume!150!ml),!
! ! ! ! Absorption!(Across!Arachnoid!Villi!by!ValveOlike!Mechanism)!
! ! Function:! Mechanical!Support,!Protective!Water!Jacket,!Regulating!Ionic!Composition,!
! ! ! ! Immunological!Isolation,!Removal!of!Metabolite,!Protection!from!Sudden!Pressure!change!
! Analysis:! ! Opening!Pressure!(may!also!test!Closing!P)!
! ! ! ! Biochemistry:! Protein,!Glucose!(+!paired!BG)!(DM!Pt!can!have!High!CSF!Glucose)!
! ! ! ! Microbiology:! Routine!Microscopy,!Gram!Smear,!Culture!&!Sensitivity!
! ! ! ! ! ! ! Fungal!Smear!&!Culture,!Indian!Ink!
! ! ! ! ! ! ! PCR!for!HSV!&!TB!DNA!
! ! ! ! ! ! ! Serological!Test!(Cryptococcal!Ag,!Viral!Ab)!
! Diagnostic:! CNS!Infection,!SAH!(if!CT!–ve),!Inflammatory!disorder!of!CNS!(eg.!CNS!Lupus),!Demyelination,!
! ! ! ! Malignant!disease!of!CNS,!CSF!Pressure!
! Therapeutic:! Analgesia,!Chemo!(Methotrexate,!Cytarabine,!Hydrocortisone),!Baclofen,!
! ! ! ! Contrast!injection,!CSF!Removal!
! Contraindications:!
! ! Absolute:! Signs!of!↑ICP:! Altered!Pupillary!responses,!Absent!Doll's!eye!reflex,!
! ! ! ! ! ! ! Decerebrate/Decorticate!posturing,!Abnormal!Resp!pattern,!Papilledema,!
! ! ! ! ! ! ! HT,!Bradycardia!
! ! ! ! ! (NB:! ! Some!may!still!do!if!very!sure!No!SOL;!Whenever!in!doubt,!don’t!do)!
! ! ! ! Evidence!of!Obstructive!Hydrocephalus,!Cerebral!Edema/Herniation!on!CT/MRI!

! Page!742!
Neuro! CNS! Infection!
! ! ! ! ! Ie.!Unequal!Pressure!between!SupraO/InfraOTentorial!Compartment!(May!Herniate)!
! ! ! ! Local!Skin!Infection!
! ! Relative:! Sepsis/Shock!(Pt!should!be!stabilized!first)!
! ! ! ! Coagulopathy/Thrombocytopenia!(Should!be!corrected!first)!
! ! ! ! Focal!Neurological!deficit!(esp!when!Posterior!Fossa!lesion!suspected)!
! ! ! ! Coma!(GCS!≤8)!
! ! ! ! Seizure!
! ! (Others:! Local!Congenital!lesion!
! ! ! ! Spinal!Shock!
! ! ! ! Spinal!Block:! Leptomeningeal!adhesion!to!SC!
! ! ! ! ! ! ! CSF!taken!downstream!Not!representative;!Risky!to!do!LP!too)!
! ! Paedi:! Also!Strong!suspicion!of!Meningococcal!infection!(typical!purpuric!rash!in!an!ill!child)!
! Cx:! ! ! Headache,!Dry!Tap,!Subdural!Hematoma,!Aneurysmal!SAH,!Brain!Herniation!
! ! KH!Chan:! LP!can!be!Hazardous!in:!
! ! ! ! ! ↑ICP!
! ! ! ! ! Expanding!Mass:! Subdural!Empyema,!Brain!Abscess,!HSV!(Necrotic!Temporal!lobe)!
CSF!Interpretation!of!Meningitis:! (Compiled!from!multiple!charts!from!different!lectures!throughout!MBBS)!
! Appearance! Opening!Pressure! WBC! Protein! Glucose!
3
Normal! Clear! 8O12!mmHg! 0O5/mm !(0O30!in!newborn)! 0.15O0.5!g/L! 2.5O4!mmol/L!
Colorless! Fluctuation!with! >50%!BG!
Odorless! Respiration!
Pyogenic! Turbid,! ↑!(500O20,000/mm3)! ↑!
Meningitis! Cloudy,! Neutrophilic!Pleocytosis!
Purulent! ↓!
Chronic! ICP↑! ↑Mildly!
Meningitis! Clear,!slightly! ↑!(10O500/mm3)!
Aseptic! Turbid! Lymphocytic/Mixed!Pleocytosis! ↑Mildly!(<1)! Normal!
Meningitis!
! ! ! ! RBC:!Normally!Not!seen!
! ! ! ! ! Suspect!Contamination!by!Blood!if!Very!High!Protein!&!RBC!seen!
CSF!Interpretation!Ddx:!
! Meningitis:!
! ! Pyogenic:! Acute!Bacterial!Meningitis!(Pyogenic!organisms),!Early!TB,!Mycotic!Meningitis!
! ! Chronic:! TB!Meningitis,!Fungal!Meningitis,!Partially!treated!Pyogenic!Meningitis,!
! ! ! ! Malignant!Meningitis!(Lymphoma,!Leukemia,!Carcinomatosis)!
! ! Aseptic:! Viral!Meningitis/MeningoEncephalitis!
! Lymphocytosis!+!↑Protein:!
! ! Infection:! Viral!Meningitis/Encephalitis,!TB!Meningitis,!Cryptococcal!Meningitis,!
! ! ! ! Partially!treated!Bacterial!Meningitis,!Cerebral!Abscess,!Listeria!Meningoencephalitis,!
! ! ! ! Neurosyphilis,!Leptospirosis,!Lyme!disease,!Brucellosis,!Toxoplasmosis!
! ! Others:! Cerebral!Lymphoma/Leukemia,!Sarcoidosis,!SLE,!Behcet’s!disease,!MS,!Cortical!Vein!
! Page!743!
Neuro! CNS! Infection!
Thrombosis!
! Lymphocytosis!+!↑Protein!+!↓Glucose:!
! ! Infection:! TBM,!Fungal!Meningitis,!Partially!treated!Bacterial!Meningitis,!Cerebral!Abscess,!
! ! ! ! Brucellosis!(may!be!similar!to!Viral!Meningitis)!
! ! Others:! Cerebral!Lymphoma/Lymphomatous!Meningitis,!Leukemic!Infiltration!into!Brain/Meninges,!
! ! ! ! Carcinomatous!Meningitis!
! Normal!WBC!+!↑Protein:!
! ! ! ! GBS,!SC!Tumor!causing!Spinal!Block!(Froin’s!syndrome),!Acoustic!Neuroma,!
! ! ! ! Lead!Encephalopathy,!SSPE!
Microbiological!tests!on!CSF:!
! Gram!stain:! Rapid!identification;!Sensitivity!60O90%,!Specificity!≥97%!
! Bacterial!Ag:! Limited!Sensitivity;!Helpful!in!those!–ve!in!Gram!stain!&!C/ST!
! PCR:! ! ! High!Sensitivity!&!Specificity;!But!further!refinement!needed!before!routinely!recommended!
IC!Host:! ! ! New!or!Reactivation!of!Latent!infection!
! ! ! ! Hematogenous!spread!is!usual!
! ! ! ! Unusual!Infection!or!Unusual!Presentation!of!Common!Infection!
! ! ! ! Fever,!Headache,!±!Meningism,!Altered!Mental!state,!Focal!Sign!
! ! ! ! Empirical!Tx!of!likely!organisms!in!adequate!dose!
! Asplenism:! (Pneumococcal!Meningitis)!
! ! ! ! PostOSplenectomy,!Sickle!Cell!Anemia,!Celiac!disease!
! Humoral!Immunodeficiency!State:! (Bacterial!&!Viral!Infection)!
! ! ! ! HypoGammaglobulinemia,!CLL,!Myeloma!
! Complement!Deficiency:! (Meningococcal!Infection)!
! ! ! ! Congenital!Complement!Deficiency,!Active!SLE!
! Neutropenia:! (Bacterial!&!Fungal;! Organism!from!Skin,!GIT,!Resp!Tract)!
! ! ! ! Aplastic!Anemia,!Chemo,!Extensive!Irradiation!
! CellOmediated!Immunodeficiency:! (Viral,!Fungus,!Parasite,!Mycobacteria,!Listeria,!or!Reactivation!of!Latent)!
! ! ! ! HIV!(AIDS),!LPD!(eg.!Hodgkin’s!disease),!Immunosuppression!for!AI!disease/Transplant!

! Page!744!
Neuro! CNS! Infection!
Meningitis!
Definition:!
! Meningitis:! Inflammation!of!Leptomeninges:!
! ! ! ! ! Infection,!Neoplastic!Infiltration,!Irritation!by!Drugs,!Contrast!Medium,!Blood!
! Meningism:! Sx!of!Meningeal!Irritation!without!Actual!Inflammation!
Source:! ! ! Local!Spread!from!nearby!structures:!
! ! ! ! ! Sinus,!Middle!Ear,!Mastoid,!Orbit,!Nasopharynx!
! ! ! ! Direct!Spread!via!Skull/Meningeal!Defect!(Head!Injury,!Neurosurgery)!
! ! ! ! Hematogenous!Spread!from!Distant!Septic!Foci:!
! ! ! ! ! Lung!Abscess,!Pneumonia,!IE,!Septicemia,!Bacteremia!
Pathogens:!
! Bacterial:! ! Common:! ! Streptococcus!pneumoniae,!Neisseria!meningitidis,!
! ! ! ! ! ! ! Streptococcus!suis!(Occupational!risk!–!Pig),!TB,!Haemophilus!influenzae!Type!b!
! ! ! ! Less!Common:! Group!B!Streptococcus,!E.coli,!Staphylococcus!aureus,!Listeria!monocytogenes!
! ! Age:! ! Neonate:! ! Enterobacteriaceae!(E.coli),!GBS,!Listeria!
! ! ! ! Infant:! ! H.!influenzae,!Meningococcus,!Pneumococcus,!Salmonella!
! ! ! ! Children/Young!Adult:! Meningococcus,!Pneumococcus!
! ! ! ! Older!Adults:! Pneumococcus!
! ! ! ! Elderly:! ! Pneumococcus,!Gram!–ve!bacilli,!Listeria!
! ! Others!(from!Year!2!CNS!Block):!
! ! ! ! IC:! ! ! Pneumococcus,!Meningococcus,!Gram!–ve!bacilli,!Listeria,!Pseudomonas!
! ! ! ! Dirty!Fresh!water:! Naegleria!fowleri,!other!Free!living!Amoeba;!High!Mortality!
! ! ! ! Head!Trauma/Intrathecal!injection/PostONeurosurgery/PostOShunting:!
! ! ! ! ! ! ! S.!aureus,!S.!epidermidis,!Gram!–ve!bacilli,!Aspergillus,!Propionibacterium!acne!
! ! ! ! RT!for!NPC:! Mixed!Upper!airway!flora,!Gram!–ve!bacilli!
! ! ! NB:! Subacute/Chronic!Meningitis!(Instead!of!Acute/Pyogenic):!
! ! ! ! ! ! ! Treponema!pallidum!(Syphilis),!B.!burgdorferi!(Lyme),!Nocardia!(IC!Pt),!Brucella!
! Viral:!! ! Common:! ! Enterovirus:!Coxsackievirus!A!&!B,!Poliovirus,!Echo!virus,!Enterovirus!type!
68O72!
! ! ! ! ! NB:! ! (FecalOOral!route,!Young!Children,!Warm!Climate,!Poor!Hygiene)!
! ! ! ! ! ! ! (WinterOSpring!time)!
! ! ! ! Less!Common:! Herpes!(HSV,!VZV),!Influenza,!Measles,!Mumps,!EBV,!Lymphochorionic!virus!
! ! ! ! ! NB:! ! HSV!Meningitis!is!usually!by!HSVO2,!while!HSV!Encephalitis!is!usually!by!HSVO1!
! Fungal!(Uncommon):!
! ! ! ! Cryptococcus!neoformans!
! Parasitic!(Rare):!Angiostrongylus!cantonensis!(Eosinophilic!Meningitis!in!SEA;!From!eating!Raw!Mollusk)!
! ! ! ! Toxocara!canis!(Worldwide)!
! Prion!(Rare)!
Clinical:! ! ! Usually!develop!over!24O48h,!vary!with!Age!of!Pt!
! ! ! ! {NB:! %!of!S/S!below!represent!Frequency!in!Bacterial!Meningitis!of!Older!Children!&!Adults}!
! NonOSpecific:! Fever!(75O95%),!Chill!

! Page!745!
Neuro! CNS! Infection!
! ! ! ! Headache!(80O95%)!
! ! ! ! Photophobia!30O50%!
! ! ! ! Nausea/Vomiting!(Vomiting:!10%!Adults,!90%!Children)!
! ! ! ! Malaise/Lethargy!
! Meningeal!Irritation:!
! ! Adults:! Neck!Rigidity!(50O90%):!Neck!Extensor!Spasm!
! ! ! ! Kernig!Sign!(5%):!Hamstrings!Spasm!(Resistance!to!Passive!Knee!Extension!when!Hip!Flexed!
90°)!
! ! ! ! Brudzinski!Sign!(5%)!(Involuntary!Hip/Knee!Flexion!upon!Passive!Neck!Flexion)!
! ! Infants:! Bulging!Anterior!Fontanelle!(if!Euvolemic),!Paradoxical!Irritability!(Cry!when!held)!
! ! ! ! Usually!No!Neck!Stiffness!
! Neurological:! Global:! Poor!Concentration,!Irritability!
! ! ! ! ! ! Drowsiness,!Confusion!(75O85%),!Coma!
! ! ! ! ! ! Seizure!(15O30%)!
! ! ! ! Focal:! 20O30%;!Cx?!
! Special!Features:!
! ! ! ! Meningococcal:!! Young!Adults/Children!
! ! ! ! ! ! ! ! Petechial!Hemorrhage!in!Skin!(Purpuric!Rash)!(10O15%)!
! ! ! ! ! ! ! ! DIC,!Septic!Shock,!Adrenal!Hemorrhage;!High!M&M!
! ! ! ! Streptococcus!suis:! Exposure!to!Raw!Pork;!Sensorineural!Deafness!
! ! ! ! Tuberculous:! ! Other!forms!(Tuberculoma,!Myelopathy,!Radiculopathy,!Arachnoiditis)!
! ! ! ! ! ! ! ! Cx!common!unless!treated!quickly;!Prolonged!Tx!course!
Course:!
! Early!events:!
! ! Phase!1:! Bacterial!invasion>!ProOinflammatory!cytokines!released>!Subarachnoid!space!inflammation!
! ! ! ! Clinical:! Fever,!Headache!
! ! Phase!2:! Subpial!Encephalopathy!induced!by!Cytokines!&!other!Chemical!mediators!
! ! ! ! Clinical:! Meningism,!Confusion,!↓CSF!Glucose!
! ! Phase!3:! Breakdown!in!BBB,!Transendothelial!Emigration!of!WBC!&!Development!of!Cerebral!Edema!
! ! ! ! Clinical:! Impaired!Consciousness,!↑CSF!Pressure,!↑CSF!Protein,!Focal!Sx!
! Intermediate!events:!
! ! ! ! Impaired!CBF,!↑ing!ICP,!Vasculitis!
! ! ! ! Clinical:! Obtundation,!Seizure,!Focal!Neurological!S/S!(eg.!CN!palsy)!
! Late!events:! Focal!Neuronal!injury!
! ! ! ! Clinical:! Paralysis,!Cognitive!impairment!Coma,!Possibly!death!in!untreated!cases!
Ddx!of!Acute!Bacterial!Meningitis:!
! Infection:! ! Other!Infective!Meningitis!&!MeningoEncephalitis:!
! ! ! ! ! Viral,!TB,!Fungal,!Leptospiral,!Primary!Amoebic!
! ! ! ! Viral!Encephalitis!
! ! ! ! Brain!Abscess!
! ! ! ! Spinal!Epidural!Abscess!(Cervical)!

! Page!746!
Neuro! CNS! Infection!
! ! ! ! Parameningeal!Infection!(Cranial!Osteomyelitis,!Subdural!Empyema)!
! Others:! ! Aseptic!Meningitis!(eg.!SLE,!Behcet,!Sarcoidosis)!
! ! ! ! Chemical!Meningitis!(eg.!after!human!IVIG!therapy,!SAH)!
Neuroimaging!(CT/MRI):!
! ! ! ! May!be!Normal,!↑Meningeal!Enhancement!
! Detect!Brain!shift,!in!selected!Pt:!
! ! ! ! NewOonset!Seizure!
! ! ! ! IC!
! ! ! ! Signs!suspicious!for!SOL!(Papilledema)!
! ! ! ! ModerateOSevere!Impairment!of!Consciousness!
Cx:! ! ! ! Meningeal!Adhesion:!! ! Obstructive!Hydrocephalus,!↑ICP,!CN!Palsy!
! ! ! ! ! ! ! ! (NB:! ! TB!often!causes!Basal!Meningitis>!Adhesion>!Hydrocephalus)!
! ! ! ! Arteritis/Thrombophlebitis:! Cerebral!Infarct!
! ! ! ! Seizure/Epilepsy!
! ! ! ! Local!spread!of!Infection:! ! Cerebritis,!Cerebral!Abscess,!Subdural!Effusion/Empyema!
! ! ! ! Systemic:! ! ! ! ! SIADH!
! ! ! ! Paedi:! ! ! ! ! Intellectual!Impairment,!Mental!Retardation,!Cerebral!Palsy!
! ! ! ! Sensorineural!Hearing!Loss!
Tx:! Antibiotics:!
! ! Empirical!Tx!in!suspected!Acute!Bacterial!Meningitis:!
! ! ! ! Initiation:! Don’t!delay!in!initiating!Antibiotics!(Can!result!in!Poor!outcome)!
! ! ! ! ! ! ! Association!between!delay!>6h!after!arrival!in!AED!&!Death!
! ! ! ! ! ! Timing:! If!planning!Neuroimaging!before!LP:! Start!before!doing!Neuroimaging!
! ! ! ! ! ! ! ! If!do!LP!without!Neuroimaging:! ! Start!after!LP!
! ! ! ! Regimen:! Old!regimen:! 3rd!Gen!Cephalosporin!+!BroadOspectrum!Penicillin!
! ! ! ! ! ! New!regimen:! 3rd!Gen!Cephalosporin!+!Vancomycin!±!Ampicillin!(depends!on!Age)!
! ! ! ! Agents:! Cephalosporin:! Can!cover!most!except!Listeria!
! ! ! ! ! ! ! Dose:! Cefotaxime!2!g!(Children!50!mg/kg)!IV!Q6H!
! ! ! ! ! ! ! ! ! Ceftriaxone!2!g!(Children!50!mg/kg)!IV!Q12H!
! ! ! ! ! ! ! ! Alt:! Meropenem!2!g!Q8H!
! ! ! ! ! ! ! ! ! Chloramphenicol!1g!Q6H!
! ! ! ! ! ! Vancomycin:! Cover!Penicillin/CephalosporinOResistant!Streptococcus!(↑ing)!
! ! ! ! ! ! ! Dose:! Medicine:!60!mg/kg/day!(adjust!for!CrCl)!after!Loading!15!mg/kg!
! ! ! ! ! ! ! ! ! Paedi:! 500O1000!mg!Q6O12H!
! ! ! ! ! ! Penicillin:! ! Ampicillin!is!used!to!cover!Listeria!(consider!Age!group)!
! ! ! ! ! ! ! Dose:! Amoxicillin/Ampicillin!2O3!g!(Children!50!mg/kg)!IV!Q4O6H!
! ! ! ! ! ! ! ! Alt:! Benzylpenicillin!1.8!g!(Children!60!mg/kg)!IV!Q4H!
! ! ! ! Dose:! High!dose!(Meningitic!dose)!
! ! Pathogen!Specific!Tx!when!Organism!&!Sensitivity!are!known:!
! ! ! ! Pneumococcal:! Cephalosporin!&!Vancomycin;!May!add!Rifampin!if!poor!control!
! ! ! ! H.!influenzae:! Cephalosporin!

! Page!747!
Neuro! CNS! Infection!
! ! ! ! Meningococcal:!Penicillin;!Cephalosporin!is!acceptable!alternative!
! ! ! ! Listeria:! ! Ampicillin!+!Aminoglycoside!
! ! Duration:! Adults!(EFNS!guidelines!2008):!
! ! ! ! ! ! Meningococcal:!! ! ! 5O7!days!
! ! ! ! ! ! Hib:! ! ! ! ! ! 7O14!days!
! ! ! ! ! ! Unspecified,!Pneumococcal:! 10O14!days!
! ! ! ! ! ! Listeria:! ! ! ! ! 21!days!
! ! ! ! ! ! Gram!–ve!Bacilli,!Pseudomonal:!21O28!days!
! ! ! ! Paedi:! 7O10!days!
! ! Monitoring!Tx!response:!
! ! ! ! Response!to!Tx!is!expected!within!a!few!days!
! ! ! ! If!Clinical!condition!does!Not!improve!by!48h!after!starting!Antibiotics,!consider:!
! ! ! ! ! Dx:! ! Incorrect!Dx!
! ! ! ! ! Cause:! Persistence!of!source!of!Primary!Infection!(Pneumonia,!IE,!Mastoiditis,!Otitis…)!
! ! ! ! ! Cx:! ! ↑ICP!from!Cerebral!Edema/Obstructive!Hydrocephalus!
! ! ! ! ! ! ! Vascular!Cx!(Arteritis,!Venous!sinus!Thrombosis)!
! ! ! ! ! ! ! Seizure!(eg.!NonOConvulsive!Status!Epilepticus)!
! ! ! ! ! ! ! Metabolic!Cx!(eg.!SIADH>!HypoNa)!
! ! ! ! ! Tx:! ! Inappropriate!Antibiotics!
! ! ! ! ! ! ! Poor!Antibiotic!Penetration!(eg.!Vancomycin!if!Pt!on!Dexamethasone)!
! ! ! ! CT/MRI:!Areas!of!Ischemia/Infarct,!Brain!Abscess,!Subdural!Empyema,!Venous!sinus!thrombosis!
! Steroid!(usually!Dexamethasone):! (Not!routinely!done!in!QMH)!
! ! Indication:!Adults:! Recommended!for!Pneumococcal!Meningitis;!Controversial!
! ! ! ! ! ! ! (RTF!Cheung!claims!often!Not!given:!
! ! ! ! ! ! ! ! Empirical!Tx!is!usually!good!enough!with!response!seen!in!24O48h!
! ! ! ! ! ! ! ! Steroid!may!mask!Sx!leading!to!a!False!image!of!response!to!Empirical!Tx)!
! ! ! ! Children:! Recommended!for!Hib!Meningitis,!Controversial!for!Pneumococcal!Meningitis!
! ! ! NB:! Adjuvant!Dexamethasone/Prednisone!is!often!recommended!in!CNS!TB!
! ! Evidence:! Adults:! ↓Mortality!only!in!Pneumococcal,!but!Not!Hib!or!Meningococcal!
! ! ! ! ! ! ↓Hearing!Loss!&!ShortOterm!Neurologic!sequelae!in!Pt!in!HighOincome!countries!
! ! ! ! Children:! ↓Severe!Hearing!Loss!in!Hib!
! ! Timing:! Start!shortly!Before!or!Simultaneously!with!1st!dose!of!Antibiotics!
! Neurosurgery:! For!Hydrocephalus:! Relieve!Hydrocephalus!via!temporally!CSF!Diversion!
! ! ! ! ! ! ! ! ! >!Obtain!CSF!for!Dx>!Permanent!CSF!Diversion!(Shunting)!
Isolation:! ! ! Required!for!suspected!Meningococcal!Infection!
Chemoprophylaxis!&!Immunoprophylaxis!of!Contact:!
! Meningococcal!Meningitis:!
! ! Chemoprophylaxis:!
! ! ! ! Rifampicin!10!mg/kg!(Max!600!mg/day)!Q2D!for!4!days!(5!mg/kg!Q2D!for!Infant!<1!month)!
! ! ! ! Not!for!Pregnant!Female!
! ! ! ! For!all!Household!contact,!other!contact!of!Oropharyngeal!secretions,!

! Page!748!
Neuro! CNS! Infection!
! ! ! ! ! Close!contact!in!Child!care!Facility,!Recent!Close!contact!in!Camps!
! ! ! ! Alternative:! Ceftriaxone!2!g!(Children!50!mg/kg)!IMI!Once!
! ! Immunoprophylaxis:!
! ! ! ! Meningococcal!Vaccine!recommended!in!Health!Officials!under!special!circumstances!
! Haemophilus!influenzae!Type!b!Meningitis:!
! ! Chemoprophylaxis:!
! ! ! ! Rifampicin!20!mg/kg!(Max!600!mg/day)!daily!for!4!days!(10!mg/kg/day!for!Infant!<1!month)!
! ! ! ! Not!for!Pregnant!Female!
! ! ! ! For!Index!case!&!all!Household!contact,!
! ! ! ! ! All!Close!contact!(including!Staff)!who!are!Not!Fully!Vaccinated,!
! ! ! ! ! If!Index!case!attend!Child!care!Facility!with!other!Children!<2!yo!for!>18h!per!week!
! ! ! ! Alternative:! Ceftriaxone!1!g!(Children!50!mg/kg)!IMI!daily!for!2!days!
! ! Immunoprophylaxis:!
! ! ! ! Haemophilus!influenzae!Type!b!(Hib)!Vaccine!after!Recovery!if!Index!case!<2!yo,!
! ! ! ! ! and!for!Unvaccinated!contact!<5!yo!
CNS!TB:! ! ! Brain:! Meningeal:! TB!Meningitis!(TBM)!
! ! ! ! ! ! Parenchymal:! Tuberculoma,!etc!
! ! ! ! SC!
TBM:!! ! ! Most!common!&!serious!form!of!Extrapulmonary!TB!
! Clinical:! ! Headache,!Nausea,!Apathy,!Bizarre!behavior!
! ! ! ! Fever!&!Meningism!Not!always!present!
! ! ! ! Unilateral/Bilateral!CN!palsy!
! ! ! ! Hemiparesis!
! ! ! ! Chorea,!Hemiballismus,!Athetosis,!Myoclonus!
! ! ! ! Cerebellar!Ataxia!
! ! Clinical!Staging:!
! ! ! ! Stage!1!(Early):! ! ! NonOspecific!
! ! ! ! Stage!2!(Intermediate):! Lethargy,!Meningeal!irritation,!CN!palsy!
! ! ! ! Stage!3!(Advanced):! ! Convulsions,!Stupor/Coma,!Paresis!
! ! Fundoscopy:!
! ! ! ! Choroidal!Tubercles:! Yellow!with!distinct!borders!
! ! ! ! ! ! ! ! Present!in!>50%!Miliary!TB!
! ! ! ! ! ! ! ! Present!in!~10%!TBM!without!Miliary!TB!
! ! ! ! Papilledema!
! Modified!British!Medical!Research!Council!Clinical!Criteria!for!Severity:!
! ! ! ! Grade!I:! Alert!&!Orientated!without!Focal!Neurological!deficit!
! ! ! ! Grade!II:! GCS!10O14,!or!GCS!15!with!Focal!Neurological!deficit!
! ! ! ! Grade!III:! GCS!<10!(Coma/Delirium)!
! Ix:! Lab:! ! Routine!Lab!tests!Not!very!helpful:!
! ! ! ! ! WBC/DC,!ESR!
! ! ! ! SIADH:! HypoNa,!HypoCl!
! Page!749!
Neuro! CNS! Infection!
! ! CXR:!! Abnormalities!in!25O50%!Adults!
! ! ! ! Miliary!disease,!Apical!Scarring,!Calcified!Ghon!complexes,!Nodular!Upper!lobe!disease!
! Cx:! ! ! Acute!Hydrocephalus,!Cerebral!Infarction!(due!to!Endarteritis!Obliterans),!CN!palsy,!
! ! ! ! Spinal!Block,!Tuberculoma,!Tuberculous!Brain!Abscess!
! ! Tuberculoma:!
! ! ! ! Plain!CT!Brain!
! ! ! ! MRI!Brain:!T2!&!PD,!GadoOT1!
Tx:! AntiOTB!Drugs:! ±!Pyridoxine!(Prevent!IsoniazidOinduced!Neuropathy)!
! ! Penetration!of!AntiOTB!agents!into!CSF:!
Agents! Usual!daily!dose!mg/kg/day! Range!of!mean!peak!conc,!mcg/ml!
Serum! CSF,!Normal! CSF,!Inflamed!
Meninges! Meninges!
Isoniazid! 5O10! 3O5! 0.6O1.6! 2O3.2!
Rifampicin! 10O20! 0.4O12! 0! 0.4O1!
Ethambutol! 15O25! 1O7.7! 0! 0.5O2.5!
Pyrazinamide! 25O30! 35O50! 30! 30O50!
Streptomycin! 15O40! 25O50! Trace! 2O9!
! ! ! NB:! Streptomycin:! Only!effective!in!Acute!stages!when!there!is!↑Blood!supply!to!meninges!
! ! ! ! Ethambutol:! May!be!used,!though!relatively!poor!BBB!penetration!
! ! ! ! Both!should!be!avoided!for!Infants,!Elderly,!or!those!with!impaired!Consciousness!
! ! ! ! ! They!can’t!report!adverse!reactions!
! ! DrugOresistant!CNS!TB:!
! ! ! ! May!be!Primary/Secondary!due!to!Poor!Drug!compliance,!Inappropriate!dosing!
! ! ! ! ↑ing!Frequent!in:! Pt!treated!previously,!HIVOinfected!Pt,!IVDU!
! ! ! ! Strategy:! ! Broad!Empirical!AntiOTB!Tx!for!initial!6O12!weeks!
! ! ! ! ! ! ! Regimen!tailored!according!to!Sensitivity!pattern!
! ! ! ! ! ! ! At!least!2!potent!agents!continued!for!18O24!months!
! Steroid:!
! ! Indication:!Extreme!Neurological!compromise!
! ! ! ! ↑ICP!
! ! ! ! Impending!Intracerebral!herniation!
! ! ! ! Established!Spinal!block!
! ! ! NB:! Some!recommend!giving!Steroid!regardless!of!Age!or!Disease!Severity,!in!Pt!without!HIV!
! ! ! ! TB!Clerkship!Booklet:!Recommended!for!Stage!2O3!(ie.!↓GCS!or!Focal!Neuro!signs)!
! ! Dose:! Prednisolone!1!mg/kg/day!in!divided!doses!(or!Dexamethasone!with!converted!dose)!
Cryptococcal!CNS!Infection:!
Cryptococcus!neoformans:!
! ! ! ! Encapsulated!Yeast,!Worldwide!distribution!
! ! ! ! Found!in!Soil,!Bird!excreta,!Animals;!Can!even!colonize!Human!
! ! ! ! Via!inhalation!of!Small!Yeast!forms!from!environment!

! Page!750!
Neuro! CNS! Infection!
! ! ! ! Once!in!Host,!develop!Large!Polysaccharide!Capsules!that!strongly!resist!Phagocytosis!
! ! ! ! Most!Pulmonary!Infections!are!Asymptomatic!
! ! ! ! Remain!Dormant!in!Lungs!&!LN!for!Long!periods;!Reactivate!when!Host!immunity!weakened!
! ! ! ! Spread!from!Lungs!&!Intrathoracic!LN!to!circulate!in!blood>!Distant!Infection!(*CNS)!
! ! ! ! CD4!T!cells!are!essential!in!preventing!Dissemination!&!Recurrence!
RF:! ! ! ! AIDS!(HIV!infection),!other!IC!states!
Clinical:! ! ! Subacute/Chronic!Meningitis!or!Parenchymal!syndromes!
! ! ! ! Most!common!presentation!in!Normal!host:! Meningitis!
! ! ! ! Others:! Cerebral!Abscess!
! ! ! ! ! ! Isolated!Granulomatous!lesion,!Cryptococcoma!
! ! ! ! ! ! Chronic:! Mimic!Progressive!Dementia!
! ! ! ! ! ! Visual!Loss!with!↑ICP>!Poor!Prognosis!
! Meningitis!! Usually!Subacute/Chronic:!>4!weeks!
! ! ! ! Fever,!Headache,!Neck!Stiffness,!N/V,!Weight!Loss!
! ! ! ! Cognitive/Behavioral!changes!
! ! ! ! Focal!Neurological!deficits:!CN!palsy!
! ! ! ! ! ! ! ! ! Apraxia,!Gait!difficulties!
! ! ! ! Hydrocephalus!(esp!with!CN!palsy)!
! ! CSF:! ! ↑Protein,!↓/N!Glucose,!MildOModerate!Mixed!cell!Pleocytosis!(≤500/uL)!
! ! ! ! Indian!ink!stain!for!organism!(50%!+ve)!
! ! ! ! CSF!Culture!(75%!+ve;!100%!in!some!reports)!
! ! ! ! Cryptococcal!Ag!titre:! Polysaccharide!Ag!by!Latex!Agglutination!test!(>90%!Sensitive!&!
Specific)!
! ! ! ! ! ! ! ! Better!Prognosis!if!initial!titre!<1/256!
! Parenchymal!syndromes:!
! ! ! ! Diffuse!Granulomatous!infiltrates!
! ! ! ! Solitary!Abscesses!
! ! ! ! Multiple!Microabscesses/Macroabscesses!
! ! ! ! Meningeal!&!Subarachnoid!inflammation>!Vessel!occlusion!
! ! ! ! Vasculitis/Arteritis!(Cryptococcus):!
! ! ! ! ! Small!vessel!thrombosis!by!Hyphae/Pseudohyphae,!or!Microinfarcts!in!areas!of!Vasculitis!
! ! ! ! Vessel!wall!invasion!&!SAH!due!to!Ruptured!Mycotic!Aneurysm!
! ! ! ! ! (Emboli!from!Cryptococcal!Endocarditis)!
HIVOseroPositive!vs!HIVOseroNegative!Pt!in!Cryptococcal!Meningitis:!
! Sx!duration! Extracranial! Cryptococcomas! Mortality!↑ICP! Indian!ink! CSF!Ag! Serum! CSF!
>2!weeks! involvement! +ve! >1:1024! Ag! Culture!
HIV!+ve! +! ++++! +/–! +++! ++! 80%! ++++! ++++! >90%!
HIV!–ve! ++! +/–! ++! +! +/–! 50%! +! +! 75%!
! CT!findings:! HIV!+ve:! Normal!50%,!Diffuse!Cortical!Atrophy!34%,!Hydrocephalus!9%,!Focal!Masses!11%!
! ! ! ! HIV!–ve:! Normal!50%,!Hydrocephalus!25%,!Gyral!enhancement!15%,!Focal!Mass!15O25%!
Tx!of!Cryptococcal!CNS!infection:!
! Page!751!
Neuro! CNS! Infection!
! Normal!Host:! IV!Amphotericin!B!0.3O0.5!mg/kg/day!+!Oral!Flucytosine!150!mg/kg/day!in!4!divided!doses!
! ! ! ! 4O6!weeks!or!Longer!
! ! ! ! Response!rate!75O85%!
! ! ! ! Monotherapy!with!Amphotericin!B:!
! ! ! ! ! For!10!weeks,!or!until!Blood!&!CSF!culture!–ve!for!at!least!4!weeks!
Tx!of!Cryptococcal!Meningitis:!
! Normal!Host:! Standard:! IV!Amphotericin!B!0.7O1.0!mg/kg/day!+!5OFlucytosine!100!mg/kg/day!for!6O10!weeks!
! ! ! ! Alternative:!IV!Amphotericin!B!0.7O1.0!mg/kg/day!+!5OFlucytosine!100!mg/kg/day!for!2!weeks,!
! ! ! ! ! ! ! followed!by!Fluconazole!400!mg!/day!for!at!least!10!weeks!(Up!to!6O12!months)!
! IC!Host:! ! Induction!with!Amphotericin!B!0.7O1.0!mg/kg/day!+!5OFlucytosine!100!mg!/kg/day!for!2!weeks,!
! ! ! ! ! then!Fluconazole!400!mg/day!for!at!least!10!weeks!
! ! ! ! ! (Dose!can!be!↓!to!200!mg/day!after!10!weeks,!depending!on!clinical!status)!
! ! ! ! Fluconazole!should!be!Continued!for!Life!or!at!least!up!to!time!of!CD4!count!reaches!350/mm3!
! ! ! ! ! (Itraconazole!if!intolerant!of!Fluconazole)!
! ! NB:! ! Fluconazole!Monotherapy:!
! ! ! ! ! More!failures!during!first!few!weeks!of!Tx!than!with!Amphotericin!+!Flucytosine!
! ! ! ! ! Outcome!after!1!year!for!Cryptococcal!meningitis!in!AIDS!Pt!is!similar!for!either!Tx!
! Other!Considerations:!
! ! Renal!impairment:!
! ! ! ! ↓Dose!of!Amphotericin!B!&!5OFlucytosine!
! ! Before!stopping!Tx:!
! ! ! ! Repeat!LP:!
! ! ! ! ! CSF!Glucose!Normal!
! ! ! ! ! CSF!Protein!on!↓ing!trend!
! ! ! ! ! Indian!ink!stain!may!be!+ve!when!CSF!Culture!turns!–ve!(+ve!stain!=/=!Active!disease)!
! ! ! ! If!CSF!still!grows!Cryptococcus:!
! ! ! ! ! Continue!Acute!Tx!+!Consider!Dose!adjustment!or!Addition!of!other!AntiFungal!agents!
! ! Pregnancy:!
! ! ! ! Similar!Tx!
! ! ! ! Both!Amphotericin!B!&!Flucytosine!cross!BloodOPlacental!barrier!
! ! Pt!taking!Steroid!for!underlying!diseases:!
! ! ! ! If!Steroid!Mandatory>!Dose!should!be!↓!rapidly,!as!far!as!underlying!disease!allows!
! ! ! ! A!reasonable!goal:! ↓Dose!to!equivalent!of!Prednisolone!20!mg/day!
! ! ! ! For!at!least!6!weeks!
Immune!Reactivation!Inflammatory!syndrome!(IRIS):!
! ! ! ! Considered!when!Pt!develop!New!Neurological!deficits!with!an!improving!CD4!count!
! ! ! ! Usually!occurs!after!a!few!weeks/months!
! Can!present!as:!Meningitis,!Intracranial!Mass!lesions,!Pulmonary!Cavitation,!Lymphadenitis!
! Tx:! ! ! Steroid,!NSAID!
Prognosis!of!Cryptococcal!Meningitis:!
! ! ! ! Mortality!~10%!(More!in!HIV!+ve!Pt)!

! Page!752!
Neuro! CNS! Infection!
! Poor!Prognostic!Factors:!
! ! ! ! ↓Level!of!Consciousness,!Papilledema,!CN6!palsy,!Hydrocephalus,!↑CSF!opening!pressure,!
! ! ! ! ↓CSF!Glucose,!Initial!Indian!ink!+ve,!CSF!Ag!titre!>1024,!ExtraOCNS!culture!+ve!sites!(eg.!Blood),!
! ! ! ! Lymphoreticular!Malignancy,!Steroid!therapy!
Neurological!sequelae!of!Cryptococcal!Meningitis:!
! ! ! ! Cognitive!impairment!31%,!Visual!Loss!8%,!Motor!impairment!5%,!CN!palsy!3%!
! ! ! ! Relapse!rate!20O25%!in!the!1st!year!after!Tx!
! ! ! ! FU!with!Urine,!Sputum!&!CSF!culture!for!at!least!1!year!after!Tx!
!

! Page!753!
Neuro! CNS! Infection!
Encephalitis!
! ! ! ! Inflammation!of!Brain!Parenchyma;! *Viral!
! ! ! ! Usually!with!Aseptic!Meningitis,!Myelitis!
Types!–!Pathology:!
! Acute!Viral!Encephalitis:!
! ! Epidemic:! Japanese!B!Encephalitis,!Dengue!Fever,!Influenza!
! ! Sporadic:! HSV!Type!1,!Enterovirus!(Coxsackie!virus,!ECHO!virus,!Poliovirus)!(Usually!Children),!
! ! ! ! Herpes!(Cytomegalovirus,!VZV,!EBV),!Mumps,!Measles,!Rubella,!
! ! ! ! Adenovirus,!Lymphocytic!Choriomeningitis!virus,!Rabies,!HIV!
! NonOViral!Infectious!MeningoEncephalitis:!
! ! ! ! Plasmodium!falciparum!(Cerebral!Malaria)!(Important!Ddx!for!any!Fever!after!Traveling),!
! ! ! ! Rickettsia!(Typhus,!Scrub!Typhus,!Rocky!Mountain!Spotted!Fever),!
! ! ! ! Toxoplasma!gondii,!Trypanosomiasis,!Strongyloides!stercoralis!
! PostOInfective!Encephalitis!(ADEM):!
! ! ! ! Common!Viral!infection!(Measles,!Chickenpox,!Childhood!Exanthemata,!Mumps,!Rubella),!
! ! ! ! Vaccinations!(Rabies,!Smallpox,!Influenza,!Pertussis),!Hypersensitivity!reaction!to!Myelin!
! Chronic!Infective!Encephalitis:!
! ! ! ! Slow!virus!(Prion!disease,!eg.!CJD),!Progressive!Multifocal!LeucoEncephalopathy!(Papovavirus),!
! ! ! ! Subacute!Sclerosing!PanEncephalitis!(Measles)!
Types!–!Microbiology:!
! Herpes!Simplex!Encephalitis:! HSVO1!
! ! ! ! Predilection!for!Temporal!&!Frontal!lobe,!(Cingulate,!Insular!cortex)!
! ! ! ! ! Fever,!Confusion!&!Seizures!(typically!Partial!Seizures!±!Generalization)!
! ! ! ! ! Temporal!lobe!signs:! Personality!change,!Hallucinations,!Aphasia,!Anosmia,!TL!Seizures!
! ! ! ! Usually!Abrupt!Onset!
! ! ! ! CSF!PCR!&!Serology!help!in!Dx!
! ! ! ! Level!of!Consciousness!&!Duration!of!Encephalitis!influence!outcome!
! ! Tx:! ! IV!Acyclovir!for!at!least!7!days!(preferably!10O14!days)!
! Japanese!B!Encephalitis:! MosquitoOborne!Flavivirus!related!to!St.!Louis!Encephalitis!virus!
! ! ! ! Subclinical!infection!common,!Endemic!in!Asia!
! ! ! ! Brainstem!involvement,!Parkinsonian!signs,!Meningeal!signs!may!be!striking!
! ! Clinical:! NonOspecific!prodrome,!then!Headache,!Vomiting,!Altered!Mental!state;!Seizure!common!
! ! ! ! Other!characteristics:!Coarse!Tremor,!Dystonia,!Rigidity,!ChoreoAthetosis,!MaskOlike!facies!
! ! Dx:! ! (Usually!by!Serology;!PCR!Not!widely!available)!
! ! ! ! MRI:!Mixed!Intensity!or!Hypodense!lesions,!esp!in!Thalamus!(can!Hemorrhage),!BG,!Midbrain!
! ! Mx:! ! Supportive!Tx!
! ! Prognosis:!Mortality:!30%!
! ! ! ! Morbidity:!75%!survivors!have!severe!Neurological!sequelae!
! ! Prevention:!Vaccine,!Mosquito!control!
! Enterovirus!71:! A!large!outbreak!in!Taiwan!in!1998!
! ! Clinical:! Rhombencephalitis!characterized!by!Myoclonus,!Tremor,!Ataxia,!CN!involvement!

! Page!754!
Neuro! CNS! Infection!
! ! ! ! Brainstem!involvement!(including!Neurogenic!Shock!&!Pulmonary!Edema)!in!Severe!cases!
! ! MRI:!! HighOintensity!lesions!localized!to!Midbrain,!Pons,!Medulla!
! ! Tx:! ! Trial!of!Pleconaril!
! Nipah!Virus!Encephalitis:! Paramyxovirus!
! ! ! ! Outbreak!amongst!Pig!farm!&!Abattoir!workers!in!Malaysia!
! ! ! ! Atypical!Pneumonia!
! ! ! ! Serology!for!IgM!Ab;!Multiple!Discrete!Deep!Cortical!or!White!Matter!lesion!on!MRI!
! ! ! ! IV!Ribavirin;!High!Mortality/Disability!
! Eastern!Equine!Encephalitis!virus:!
! ! Transmission!Cycle:!
! ! ! ! Cycle!between!Culiseta!melanura!Mosquitoes!&!Birds:! Maintain!&!Amplify!virus!
! ! ! ! But!C.!melanura!itself!is!Not!thought!to!be!important!Vector!for!Transmission!to!ppl!
! ! ! ! Instead,!Species!of!Mosquitoes!that!are!Less!particular!about!Blood!Source,!
! ! ! ! ! and!more!Aggressive!Mammal!biters,!
! ! ! ! ! act!as!a!Bridge!Vector!from!Birds!to!Humans!&!other!Mammals!
Presentation:! ! Triad!of!Fever,!Confusion,!Convulsion!(3P:!Pyrexia,!Postictal!Drowsiness,!Partial!Seizure??)!
! Cerebritis:!! Epileptic!Seizure,!Myoclonus,!Chorea/Athetosis,!Limb!Weakness,!Visual!changes,!
! ! ! ! Memory!Impairment,!Aphasia,!Agnosia,!Confusion,!Delirium,!Drowsiness,!Stupor,!Coma,!
! ! ! ! Psychiatric!manifestations!
! ↑ICP!from!Cerebral!Edema!
! NonOSpecific!Systemic!Sx:!
! ! ! ! Fever,!Viral!syndrome,!Headache,!Nausea,!General!Malaise!
Ddx:! ! ! ! Complicated!Bacterial!Meningitis!with!Cerebral!Edema!or!Cerebral!Venous!Thrombosis!
! ! ! ! Toxic!Encephalopathy!due!to!Septicemia,!other!Febrile!illness,!or!Drug/Toxin!Overdose!
! ! ! ! Metabolic!Encephalopathy!caused!by!Hypoglycemia,!Organ!Failure,!Electrolyte!disturbance!
Dx:! ! ! ! CT/MRI!Brain!+!LP!&!CSF!Analysis!+!EEG!
! Imaging:!
! ! CT:! ! Usually!Normal!
! ! MRI:!! May!reveal!abnormalities!in!Gray/White!Matter!
! ! ! ! ! Eg.!Hyperintensity!over!Gray!matter!(Neuronal!bodies)!in!Cortex!in!T2W!
! ! ! ! HSV:!! ! Frontal,!Temporal!
! ! ! ! VZV:!! ! Diffuse/Frontal,!Cerebellum!
! ! ! ! ! NB:! ! VZV!&!CMV!may!show!Ventriculitis,!EncephaloMyeloRadiculopathy!
! ! ! ! Nepah:! ! NonOspecific!
! ! ! ! Enterovirus:! NonOspecific!
! ! ! ! JE!Virus:! ! Thalamus,!also!Basal!ganglia!
! LP!
! EEG:!! ! Diffuse!Slow!waves!&!Spike!activities,!But!may!be!Focal!in!Herpes!Encephalitis!
! ! ! ! HSV:!Periodic!Lateralizing!Epileptiform!discharge!from!Temporal!lobe(s)!
! Microbiological:!Paired!Sera!for!Viral!Titres!
! ! ! ! Urine,!Feces,!Throat!Swab!for!Viral!Culture!(Stool,!Throat,!CSF!rtOPCR!good!for!Enterovirus)!

! Page!755!
Neuro! CNS! Infection!
! Brain!Biopsy:! Seldom!performed!nowadays!
Tx:! ! ! ! Empirical!Tx:! Acyclovir!10!mg/kg!Q8H!IV!10O14!days!–!Effective!for!Herpes!only!

! Page!756!
Neuro! CNS! Infection!
Brain!Abscess!
Source!of!Infection:! *Local!Extension:! Paranasal!Sinus,!Middle!Ear,!Mastoid!(eg.!Dental!infection),!
! ! ! ! ! ! ! ! Orbit,!Cavernous!Sinus,!Scalp!
! ! ! ! Direct:! ! ! Skull/Meningeal!Defect!
! ! ! ! Hematogenous:!! Distant!Focus!
! ! ! ! ! ! ! NB:! Surg!2007!MCQ!47:! Asso.!with!Pulmonary!AV!Fistula!
S/S:! ! ! ! Features!of!↑ICP!
! ! ! ! NonOspecific!Systemic!upset!due!to!Infection!
! ! ! ! Focal!deficit!depending!on!Site!
! ! ! ! Seizure!(up!to!30%)!
Pathogen:!! ! Usually!Mixed!Aerobic!&!Anaerobic!organisms!
! Aerobic!&!Microaerophilic!Bacteria:!
! ! ! ! Streptococcus!milleri,!Pneumococcus,!Staphylococcus!aureus,!Enterobacteriaceae,!
! ! ! ! Pseudomonas!
! Anaerobic!Bacteria:!
! ! ! ! Bacteroides,!Fusobacterium,!Peptostreptococcus,!Actinomyces,!Nocardia!
! Rare:!! ! Cryptococcus,!Aspergillus,!Amoeba,!Toxoplasma,!Angiostrongylus!cantonensis,!
! ! ! ! Taenia!solium!(Cysticercosis),!Echinococcus!(Hydatid!Cyst)!
Dx:! ! ! ! CT!Head!(Plain!&!Contrast)!or!MRI!Head!
! ! ! ! ! MRI:!T1W:!! ! Hypointense!centre!+!Ring!with!similar!intensity!as!parenchyma!
! ! ! ! ! ! T2W:!! ! Hyperintense!centre!+!Hypointense!Ring!
! ! ! ! ! ! T1W+Contrast:! Only!Capsule!is!Hyperintense!(as!intense!as!bone)!
! ! ! ! ! (G!Leung:! Ring!Enhancement!in!Contrast!CT!is!due!to!disrupted!BBB!causing!leakage)!
! ! ! ! Avoid!LP!!
! ! ! ! Microbiological!workup:! Blood!Culture,!Aspirated!Pus!for!Smear!&!Culture!
! ! ! ! Look!for!Septic!foci!by!CXR,!Echo,!XOray!of!Paranasal!Sinus,!Skull!XOray,!ENT!Exam!
! ! ! ! EEG!
Tx:! ! ! ! Empirical!Tx:! Benzylpenicillin!1.8!g!(Children!60!mg/kg)!IV!Q4H!
! ! ! ! ! ! +! Cefotaxime!IV!Q6H!or!Ceftriaxone!IV!Q12H,!2!g!(Children!50!mg/kg)!
! ! ! ! ! ! +! Metronidazole!500!mg!(Children!12.5!mg/kg)!IV!Q8H!
! ! ! ! Tx!for!at!least!6!weeks!(ClinicoOradiological!monitoring)!
! ! ! ! Abscess!complicating!Skull!Injury!or!Neurosurgical!procedures!
! ! ! ! ! need!High!dose!Cloxacillin!or!Fusidic!Acid!to!cover!Staphylococcus!aureus!
! ! ! ! Neurosurgery:! Usually!Not!required!for!Small!&!Multiple!Abscess!
! ! ! ! ! ! ! Close!Monitoring!of!Clinical!status!with!Serial!CT!Head!
! ! ! ! ! ! ! In!Abscess/Empyema:!Drainage!to!establish!Dx!&!Bacteriology,!↓Mass!effect!
! ! ! ! ! Approach:!Stereotactic/US!guided!Aspiration,!Craniotomy!&!Excision!of!Abscess!Cavity!
! ! ! ! AntiEpileptic!medication!
!

! Page!757!
Neuro! CNS! Infection!
 Neuro&Stroke&
Cerebral!Arterial!Supply:!

! ! ! ! ! !
Definition:!! ! Stroke:! Rapid!Onset!Clinical!S/S!of!Focal/Global!disturbances!of!Cerebral!function,!
! ! ! ! ! ! ! due!to!NonOTraumatic!Vascular!causes,!
! ! ! ! ! ! ! Sx!lasting!>24h!or!leading!to!Death!
! ! ! ! TIA:! ! Ischemic!Stroke!but!Sx!<24h!
! ! ! ! Do!NOT!use!Cerebrovascular!Accident/CVA!!
! New!Proposed!Definition!by!AHA/ASA:!
! ! ! ! Stroke!(Ischemic):! Continuing!Sx!>24h,!or!Fatal,!or!Imaging!evidence!of!Acute!Infarct!(MRI)!
! ! ! ! TIA:! ! ! ! Focal!Neurological!Sx!<1h,!without!evidence!of!Acute!Infarction!
Epidemiology:! ! Most!common!Adult!Neurological!disease!
! ! ! ! 2nd!&!3rd!Leading!cause!of!Death!in!China!&!HK;!Major!cause!of!Disability!
Type:!
! Ischemic:! ! Ischemic!Stroke!75O80%:! ! Cortical,!Subcortical,!Posterior!Circulation,!Lacunar!
! ! ! ! ! ! ! ! ! ! Thrombosis,!Embolism,!Hypoxia!(Hypotension)!
! Hemorrhagic:! Intracerebral!Hemorrhage!20%:!Supra/InfraOtentorial;!Hypertensive!
! ! ! ! SAH!<5%:! ! ! ! ! Ruptured!Aneurysm!
Mortality:!! ! From!High!to!Low:! SAH!(50%!at!1!month)!
! ! ! ! ! ! ! ! Intracerebral!Hemorrhage!(40%!at!1!month,!50%!at!1!year)!
! ! ! ! ! ! ! ! Cortical!Infarct!(20%!1!month,!35%!1!year)!
! ! ! ! ! ! ! ! Lacunar!Infarct!
Disability:! ! ! SAH!>!Cortical!Infarct!>!Intracerebral!Hemorrhage!>!Lacunar!Infarct!
! ! ! ! 50%!survivors!with!Severe!Morbidity!
Cause:!
! Ischemic:! ! Atherosclerosis:!! Large!vessel!inOsitu!Thrombosis!(Hypercoagulable!state!may!↑risk!too)!
! ! ! ! ! ! ! ! ArteryOtoOArtery!ThromboEmbolism!(Carotid!bifurcation,!Aortic!arch,!AD)!
! ! ! ! CardioEmbolism:! Valvular!Thrombus!(eg.!MS,!IE,!Prosthetic!valve)!
! ! ! ! ! ! ! ! Mural!Thrombus!(eg.!AF,!MI,!DCM)!
! ! ! ! ! ! ! ! Atrial!Myxoma!

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! ! ! ! Small!Vessel!disease!(Lacunar):! Microatheroma,!Lipohyalinosis,!etc!
! ! ! ! Others:! ! ! Severe!Hypotension,!Vasculitis,!Venous!sinus!Thrombosis,!
! ! ! ! ! ! ! ! Vasospasm!after!SAH,!Blood!dyscrasia!(Sickle!cell,!MM,!PV),!
! ! ! ! ! ! ! ! Drugs!(Cocaine/Amphetamines!can!cause!Vasoconstriction)!
! Intracerebral!Hemorrhage:!
! ! ! ! *HT,!Aneurysm,!Vascular!Malformation!(AVM,!Venous/Cavernous/Capillary!Angioma),!
! ! ! ! Bleeding!Tendency,!Cerebral!Amyloid!Angiopathy!(Congophilic!Angiopathy),!Traumatic,!
! ! ! ! (Hemorrhagic!Transformation!from!Infarct,!Tumor!Bleed)!
! SAH:!! ! Aneurysm,!Vascular!Malformation!
! ! ! ! ! Aneurysm:! Anterior!Circulation!85%:!
! ! ! ! ! ! ! ! ! ACA!30%,!ICA!30%,!MCA!25%!
! ! ! ! ! ! ! ! Posterior!Circulation!15%:!
! ! ! ! ! ! ! ! ! PCA!2%,!Basilar!A!10%,!VertebralOPICA!3%!
RF:! Unmodifiable:! Old!Age,!Male,!Hx!of!TIA/Stroke,!PVD!
! Modifiable:! HT,!Heart!disease,!AF,!DM,!HyperLipidemia,!Smoking,!Alcohol!Abuse,!Carotid!Stenosis,!
! ! ! ! OC!use,!High!Plasma!Fibrinogen,!High!Blood!Viscosity,!Obesity,!Lack!of!Exercise,!
! ! ! ! Homocysteinemia!
Clinical:! ! ! S/S:! Location!&!Extent!of!Damage,!–ve!Features!from!Loss!of!Functions,!Sudden/Rapid!in!
Onset!

! ! ! ! !
! ! ! ! ! Blue!ACA,!Red!MCA,!Green!PCA,!Yellow!AChA!(Anterior!Choroidal!Artery)!
1.!By!Arterial!territory:!
! Anterior!Circulation!–!Carotid!Territory:! ! ! Mainly!by!MCA!&!ICA!
! ! ! ! Hemiparesis!±!Hemifacial!Weakness,!Hemisensory!Loss,!
! ! ! ! Language!disturbance!(Dominant),!Visuospatial!Disorientation!(NonODominant),!
! ! ! ! Visual!disturbance!(Retinal!Stroke!or!Amaurosis!Fugax),!
! ! ! ! Deviation!of!Head!&!Eyes!toward!Lesion!side,!Dysarthria,!Dysphagia!
! ! ACA:!! Cortical!branches:!
! ! ! ! ! Medial!Frontal!&!Parietal!lobes!
! ! ! ! Medial!LenticuloStriate!branches:!
! ! ! ! ! Anterior!BG,!Anterior!limb!of!Internal!Capsule!(FrontoPontine,!ThalamoCortical)!
! ! ! S/S:! Primarily!affect!Frontal!lobe!function!
! ! ! ! ! Disinhibition!&!Speech!perseveration,!Primitive!Reflexes!(eg.!Grasping,!Sucking!Reflexes),!
! ! ! ! ! Altered!Mental!status,!Impaired!Judgment,!
! ! ! ! ! Contralateral!Weakness!(LL!>!UL),!Contralateral!Cortical!Sensory!deficits,!

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! ! ! ! ! Gait!Apraxia,!Urinary!Incontinence!
! ! MCA:! Cortical!branches:!
! ! ! ! ! Lateral!Frontal!&!Parietal!lobes,!Anterior!&!Lateral!Temporal!lobes!
! ! ! ! Lateral!LenticuloStriate!branches:!
! ! ! ! ! BG,!Internal!Capsule!
! ! ! S/S:! Contralateral!Hemiparesis!(UL!&!Face!>!LL),!Contralateral!Hyperesthesia,!
! ! ! ! Ipsilateral!Hemianopia,!Gaze!preference!toward!Side!of!the!lesion,!Agnosia,!
! ! ! ! Receptive/Expressive!Aphasia!(Dominant!hemisphere)!
! ! ! ! Neglect/Inattention/Extinction!of!Double!simultaneous!stimulation!(Some!Nondominant)!
! ! AChA:! Optic!tracts,!Medial!Temporal!lobe,!VentroLateral!Thalamus,!Corona!radiata,!
! ! ! ! Posterior!limb!of!Internal!Capsule!(Corticospinal,!Sensory)!(Supplied!by!MCA!too!–!Redundant?)!
! Posterior!Circulation!–!Vertebrobasilar!Territory:! ! Mainly!by!Basilar!artery!
! ! ! ! Cortical!Blindness,!Homonymous!VF!Defect,!Diplopia,!Nystagmus,!Vertigo,!
! ! ! ! Horner’s!Syndrome,!Dysarthria,!Dysphagia,!Crossed!Hemiparesis,!Tetraparesis,!
! ! ! ! Crossed!Unilateral!Sensory!Loss,!Bilateral!Sensory!Loss,!Ataxia!
! ! PCA:!! Cortical!branches:! ! Posterior!&!Medial!Temporal!&!Parietal!lobes,!Occipital!lobes!
! ! ! ! Perforating!branches:! ! Brainstem,!Posterior!Thalamus!
! ! ! S/S:! Affects!Vision!&!Thought!
! ! ! ! ! Contralateral!Homonymous!Hemianopia,!Cortical!Blindness,!Visual!Agnosia,!
! ! ! ! ! Altered!Mental!status,!Impaired!Memory!
! ! SCA:! ! Superior!Vermis,!Superior!Cerebellum!
! ! AICA:! AnteroLateral!Cerebellum!
! ! PICA:!! Inferior!Vermis,!Posterior!&!Inferior!Cerebellar!hemispheres;!(Come!from!Vertebral!Arteries)!
! Lacunar!Stroke:!Due!to!Occlusion!of!Small!Perforating!arteries!of!Deep!Subcortical!areas;!Mostly!related!to!HT!
! ! Classical!Lacunar!syndrome:! (Just!classical!descriptions;!Nowadays!rely!on!MRI!for!localization)!
! ! ! ! *Pure!Motor,!Ataxic!Hemiparesis,!Pure!Sensory,!Dysarthria/Clumsy!Hand,!Mixed!Motor!Sensory!
! ! ! Ataxic!Hemiparesis:!
! ! ! ! Homolateral!Hemiataxia!&!Hemiparesis!(Homolateral!Ataxia+!Crural!Paresis)!
! ! ! ! Affect!Contralateral!side!of!lesion,!usually!affect!LL>UL!
! ! ! ! May!have!additional!Dysarthria,!Nystagmus,!Paresthesia,!Pain!
! ! ! ! ! Sensory!Loss!indicates!Capsular!involvement!(Posterior!limb)!
! ! ! ! ! Pain!without!other!Sensory!features!indicates!Thalamic!involvement!
! ! ! ! Cause:! Lesions!that!simultaneously!interrupt!Pyramidal!systems!&!FrontoCerebellar!systems!
! ! ! ! ! ! Common!Sites:! Internal!Capsule,!Corona!radiata,!Lentiform!nucleus,!Thalamus!
! (Watershed!Infarcts):!
! ! ! ! BorderOzone!Infarctions!at!most!distal!areas!between!arterial!territories!
! ! ! ! Due!to!Embolic!phenomenon!(eg.!Carotid!occlusion)!or!Severe!Hypoperfusion!

! ! ! ! !
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2.!By!Location!(Cortical!vs!Subcortical):!
! Region:! ! Cortical:! ! Cerebral!cortex!(Frontal,!Parietal,!Temporal,!Occipital)!
! ! ! ! ! ! Eg.! Distal!branch!MCA!occlusion!by!Embolus!from!Heart/Carotid!artery!
! ! ! ! Subcortical:! Internal!capsule,!Thalamus,!BG,!Brainstem,!Cerebellum!
! ! ! ! ! ! Eg.! Lacunar!infarct!by!Small!Penetrating!artery!occlusion!in!Internal!capsule!
! Clinical:!
! ! Motor:! Cortical:! ! Focal/Topographical:!MCA!stroke:! Face/Arm!>!Leg!
! ! ! ! ! ! ! ! ! ! ! ACA!stroke:! Leg!>!Face/Arm!
! ! ! ! Subcortical:! Equal!extent!( Close!proximity!of!Corticospinal!tract!fibres)!
! ! Sensory:! Cortical:! ! Focal/Topographical!
! ! ! ! Subcortical:! HemiOSensory!Loss!(Thalamic!stroke!can!involve!whole!contralateral!hemibody)!
! ! Others:! Cortical:! ! Higher!Mental!functions:!
! ! ! ! ! ! ! ! Dominant:!! ! ! Aphasia,!Alexia,!Agraphia,!Acalculia!
! ! ! ! ! ! ! ! NonOdominant!Parietal:! Neglect,!Visuospatial!disorientation!
! ! ! ! ! ! ! ! Memory!impairment,!Behavioral!change!
! ! ! ! ! ! ! Visual!disturbances!
! ! ! ! ! ! ! ! VF!deficit:!! ! ! Occipital,!Parietal,!Temporal!
! ! ! ! ! ! ! ! Gaze!preference:! ! Frontal!eye!fields!(Horizontal!gaze)!
! ! ! ! ! ! ! ! ! ! ! ! ! ! Preferential!gaze!to!side!of!stroke!
! ! ! ! Subcotical:! Cerebellar!signs:! Nystagmus,!Ataxia,!Intention!Tremor!
! ! ! ! ! ! ! Brainstem!findings:! EOM!deficit,!Diplopia,!Nystagmus,!Dysphagia,!Dysarthria!
Ddx!of!Stroke:! ! Intracranial!Tumor,!Chronic!Subdural!Hematoma,!Encephalitis,!MS,!Seizure,!Hysteria!
Scoring:!
! ABCD2!Score!for!TIA:!
! ! Items:! Age:! ! ! ! ≥60!(1pt)!
! ! ! ! BP:! ! ! ! SBP!≥140!or!DBP!≥90!(1pt)!
! ! ! ! Clinical!Features:! Unilateral!Weakness!(2pt),!or!
! ! ! ! ! ! ! ! Speech!Impairment!without!Unilateral!Weakness!(1pt)!
! ! ! ! Duration!of!Sx:! ! ≥60!min!(2pt),!or!
! ! ! ! ! ! ! ! 10O59!min!(1pt)!
! ! ! ! DM!(1pt)!
! ! Risk!of!CVA!at!2!days:!
! ! ! ! 0O3!points:!! 1%!risk!
! ! ! ! 4O5!points:!! 4.1%!risk!
! ! ! ! 6O7!points:!! 8.1%!risk!
! NIHSS!(National!Institute!of!Health!Stroke!Scale)!for!Stroke:!
! ! ! ! 42Opoint!scale!to!quantify!Severity!of!Stroke!impairment;!Predictor!for!Pt!outcomes!
! ! 11!Items:! Level!of!Consciousness:! LOC!Responsiveness,!LOC!Questions,!LOC!Commands!
! ! ! ! Horizontal!Eye!movement,!VF!test!
! ! ! ! Facial!Palsy!
! ! ! ! Motor!Arm,!Motor!Leg!

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! ! ! ! Limb!Ataxia!
! ! ! ! Sensory!
! ! ! ! Language!(for!Dysphasia),!Speech!(for!Dysarthria)!
! ! ! ! Extinction!&!Inattention!
! ! Score:! 0:! ! No!Stroke!Sx!
! ! ! ! 1O4:! ! Minor!Stroke!
! ! ! ! 5O15:!! Moderate!Stroke!
! ! ! ! 16O20:! ModerateOSevere!Stroke!
! ! ! ! 21O42:! Severe!Stroke!
Cx:! Cerebral:! ! Cerebral!Edema,!↑ICP,!Herniation,!
! ! ! ! ! (eg.! Malignant!MCA!syndrome!
! ! ! ! ! ! Posterior!Cranial!Fossa!Infarct!–!Better!Recovery!than!MCA! Cerebellum!Plasticity)!
! ! ! ! Hemorrhagic!Transformation!(due!to!BBB!breakdown;!Risk!of!Symptomatic!Transformation!
6%),!
! ! ! ! Seizure!
! Systemic:! ! BronchoPneumonia,!Aspiration!Pneumonia,!DVT,!PE,!Pressure!Sore,!UTI,!
! ! ! ! Contracture,!Frozen!Shoulder,!Cardiovascular!disturbance,!Fluid!&!Electrolyte!disturbance,!
! ! ! ! Anxiety!&!Depression!
Ix:! Basic:! ! To!confirm!Clinical!Dx,!Classify!Type!of!Stroke,!Define!underlying!Causes!&!RF,!Reveal!any!Cx!
! ! ! ! CT/MRI!Brain!
! ! ! ! Routine!Blood!test,!ESR,!Fasting!BG,!Fasting!Lipoprotein!pattern!
! ! ! ! ECG,!CXR!
! Further:! ! Test!for!Prothrombotic!state!
! ! ! ! Echo!(TTE/TEE)!
! ! ! ! 24h!Holter!ECG!monitoring!(Esp!if!Arrhythmia!suspected!&!No!other!causes!of!Stroke!found)!
! ! ! ! US!Doppler!(Extracranial/Transcranial)!
! ! ! ! Cerebral!Angioplasty!
! ! ! ! LP!
Neuroimaging:! ! CT/MRI:! Mandatory;!Able!to!delineate!BV!&!Assess!Brain!Perfusion!
! ! ! ! US:! ! For!Neonatal!Brain,!IntraOop!Imaging,!Extracranial!Vascular!Imaging!
! ! ! ! Conventional!Angiography:! Invasive!
! ! ! ! ! ! Reserved!for!Selected!cases,!or!Endovascular!Interventional!therapy!
Evolution!of!Findings! CT! MRI!
NormalO12h! Hyperdense!A,!or!↓Density!of!Lentiform!N! Abnormal!DWI,!or!Vascular!Enhancement!
12O24h! Loss!of!GrayOWhite!Differentiation!or!Insular!Ribbon,! T2W!Hyperintensity!(Edema),!
Sulcal!Effacement! Intravascular!&!Meningeal!
Enhancement!
1O3!days! WedgeOshape! Cytotoxic!Edema,!Hemorrhagic!Transformation! WedgeOshape!T2W!
Hypodensity! Hyperintensity!
4O7!days! Maximal!Cytotoxic!Edema,!Gyral!Enhancement!

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1O8!weeks! Subsiding!Edema!
>8!weeks! Encephalomalacia!(Cerebral!Softening)!
st
! CT:! ! ! 1 !line!(Quick,!Cheap,!Readily!Available)!
! ! ! ! Can!only!pick!up!Hemorrhage!&!Old!Infarct!in!first!12h!
! ! ! ! ! (eg.!Loss!of!GrayOWhite!Junction,!Sulcal!Effacement,!Edema)!
! ! ! ! Seldom!use!Contrast!study,!but!if!use,!can!see!Edema!in!4O7!days!
! ! ! ! (Early!signs!of!Acute!Stroke!on!NCCT:!
! ! ! ! ! Hyperdense!MCA!sign:! Signify!occlusion!of!MCA;!High!Specificity!
! ! ! ! ! Obscuration!of!Lentiform!nucleus!&!Insular!Ribbon!sign:! Signify!Early!Infarction)!
! MRI:!! ! Inclusion!of!DWI!&!T2W!Gradient!Echo!sequences!recommended!(Class!II,!Level!A)!
Interventional!Neuroradiology:!
! ! ! ! Transarterial!Thrombolysis,!Embolotherapy!for!AVM!&!Aneurysm,!
! ! ! ! Angioplasty!±!Stenting!for!Arterial!Stenosis!
General!Mx:! ! Regular!NeuroOobservation!
! ! ! ! Monitor!Arterial!BP,!Avoid!Rapid!Lowering!of!BP!
! ! ! ! Avoid!Electrolyte!Imbalance,!Hypovolemia,!Fluid!Overload!
! ! ! ! Speech!Therapist!for!Dysphagia!or!Speech/Language!problems!
! ! ! ! Ryle’s!Tube!feeding!for!Depressed!Conscious!level!or!Dysphagia!
! ! ! ! Monitor!BG!&!Maintain!Euglycemia!
! ! ! ! Prevent!Pulmonary!Cx!by!careful!Feeding!practice,!Early!Mobilization,!Chest!Physiotherapy!
! ! ! ! Consider!Low!dose!SC!Heparin!for!Prophylaxis!of!DVT!&!PE!
! ! ! ! Treat!any!Infection!vigorously!&!↓Core/Brain!Temp!if!Fever!
! ! ! ! Avoid!Bladder!OverODistension!&!Genitourinary!Infection,!
! ! ! ! ! By!Condom!Catheter!in!Incontinent!M,!and!Indwelling!Catheter!in!Both!Sex!if!necessary!
! ! ! ! ! Use!Intermittent!Catheterization!to!measure!PostOVoid!Residual!Volume!
! ! ! ! Avoid!Constipation,!Fecal!Impaction!&!Soiling!by!providing!High!Fibre!Diet!&!Stool!Softeners,!
! ! ! ! ! But!Not!Laxatives!
! ! ! ! Prevent!Pressure!Sores!by!Repositioning!of!Weak!Limbs,!Frequent!Turning,!Use!of!Cushions,!
! ! ! ! ! EggOCrater!Mattress!&!Air!Mattress!
! ! ! ! Early!PT!&!OT!
! ! ! ! AntiConvulsant!(PostOStroke!Seizure!complicate!11%!Pt!without!Previous!Hx!of!Stroke)!
! ! ! ! Watch!out!for!Depression!
! ! ! ! Avoid!Iatrogenic!Cx!
! ! ! ! Initiate!measures!to!Prevent!Future!Stroke/CV!events;!RF!Identification!&!Control!
! ! ! ! AntiPlatelet!for!NonOCardioembolic!Ischemic!Stroke!
! ! ! ! ! Eg.!Aspirin,!Clopidogrel,!SlowOreleasing!Dipyridamole!
! ! ! ! AntiCoagulation!for!Cardioembolic!Ischemic!Stroke!
! ! ! ! Healthy!Lifestyle,!Regular!Exercise!
Acute!Thrombolytic!Therapy:!
! IV!rOtPA:! ! Appropriate!Pt!selection!is!crucial!
! ! ! ! Dose:! 0.9!mg/kg,!max!90!mg,!with!10%!dose!given!as!bolus,!then!60Omin!infusion!

! Page!763!
Neuro! Stroke!
! ! Efficacy:! IV!rOtPA!(0.9!mg/kg)!within!3h!(Some!recommend!4.5;!HK!still!3)!of!Onset!of!Stroke!is!Effective!
! ! ! ! ! ↑Proportion!of!Pt!with!Minimal/No!disability!by!13O16%!(NNT=6O8)!
! ! ! ! ! ! (If!within!4.5h:! 7%,!NNT=14)!
! ! ! ! ! NonOsignificant!↓!(3.2%)!of!Mortality!
! ! ! ! ! NINDS!study:! Sustained!benefit!of!rtPA!at!1!year!
! ! Risk:!! 6%!risk!of!Symptomatic!Hemorrhagic!Transformation!
! ! ! ! 2!Major!factors!for!ICH:!
! ! ! ! ! Early!Infarct!change!>1/3!of!MCA!territory!(Thus!avoid!if!Large!lesion)!
! ! ! ! ! NIHSS!>20!
! ! ! ! STARS!phase!IV!study:! Mean!Age!69,!Mean!NIHSS=14,!Rate!of!Symptomatic!ICH=3.3%!
! ! NB:! ! If!BP!>185/110!mmHg,!should!be!lowered!before!Thrombolysis!(Class!IV,!GCP)!

! ! ! ! !
! ! ! ! IV!Streptokinase!has!Unacceptable!risk!of!Hemorrhagic!Cx!
! IA!Thrombolysis:!
! ! ! ! May!be!done!in!selected!cases!
! ! ! ! ! Acute!MCA!occlusion!within!6h!time!window!(Class!II,!Level!B)!
! ! ! ! ! Acute!Basilar!occlusion!in!selected!Pt!(Class!III,!Level!B)!
! ! ! ! ! ! IV!Thrombolysis!for!Basilar!occlusion!is!an!acceptable!alternative!even!after!3h!
! ! WM!Lui:! Therapeutic!potential!for!IA!Thrombolysis!is!6h!(50%!Pt!can!achieve!good!outcome)!
! NB:! ! ! Aspirin:! Should!be!given!within!48h!after!Ischemic!stroke!(Class!I,!Level!A)!
! ! ! ! ! ! ! But!if!Thrombolytic!planned/given,!do!Not!initiate!within!24h?!(Class!IV,!GCP)!
! ! ! ! Not!Recommended!in!Acute!Ischemic!Stroke:!
! ! ! ! ! ! Other!AntiPlatelets!(single/combined)!(Class!III,!Level!C)!
! ! ! ! ! ! GPIIbOIIIa!inhibitors!(Class!I,!Level!A)!
! ! ! ! ! ! UFH,!LMWH,!Heparinoids!(Class!I,!Level!A)!
Mechanical!Thrombectomy:!
! MERCI!Retriever:! Mechanical!Embolus!Removal!in!Cerebral!Ischemia!

! ! ! ! ! !

! Page!764!
Neuro! Stroke!
! Alligator!Retrieval!Device:! FDA!approved!for!Peripheral!&!Neurovasculature!Foreign!body!Removal!

! ! ! ! ! ! !
AntiCoagulant!in!Acute!stage:!
! ! ! ! Avoid!if:! Extensive/Hemorrhagic!Infarct,!Active/Unidentified!Bleeding!source,!
! ! ! ! ! ! Lack!of!Monitoring,!Uncontrolled!HT,!IE!
! ! ! ! ! ! (If!Pt!suddenly!deteriorate!after!confirmed!Ischemic!Stroke,!
! ! ! ! ! ! ! Stop!AntiCoagulant!due!to!fear!of!Hemorrhagic!Transformation,!
! ! ! ! ! ! ! And!order!Urgent!CT!again)!
! ! ! ! Clinical!trials!Failed!to!show!any!beneficial!effect!in!Acute!stage!
! ! ! ! Logical!but!Unproven:! 1.!Definite/Probable!Cardiac!Emboli!
! ! ! ! ! ! ! ! ! 2.!Prophylaxis!of!Thrombus!Formation/Propagation,!or!
! ! ! ! ! ! ! ! ! ! Embolism!distal!to!occluded/severely!stenotic!large!cerebral!A!
! ! ! ! Indicated:!Cerebral!Venous!Thrombosis!(may!present!as!Hemorrhagic!Infarct!&!Edema)!
AntiPlatelet!in!Acute!stage:! Aspirin!
! International!Stroke!Trial:!
! ! ! ! Aspirin!(300!mg/D)!in!Ischemic!Stroke!within!48h:! NonOSignificant!benefit!
! Chinese!Acute!Stroke!Trial:!
! ! ! ! Aspirin!(160!mg/D)!in!Suspected!Acute!Ischemic!Stroke!within!48h:!
! ! ! ! ! Significant!14%!Risk!Reduction!in!Mortality!at!4!weeks!
! ! ! ! ! NonOSignificant!11%!Risk!Reduction!in!Death!&!Dependency!upon!Discharge!
Neurosurgery:! ! Carotid!Endarterectomy:! Beneficial!in!Symptomatic!Severe!Stenosis!
! ! ! ! ! ! ! ! ! But!Small!benefit!in!Asymptomatic!Severe!Stenosis!
! ! ! ! –ve!result!of!ECOIC!CoOop!study!for!Extracranial!to!Intracranial!Bypass!
! ! ! ! ! In!Pt!with!Cerebral!Hypoperfusion?!(unproven)!
! ! ! ! Young!Pt!with!Moyamoya!disease!(rare)!may!benefit!from!Synangiosis:!
! ! ! ! ! Myoencephalosynangiosis,!Duroarterioencephalosynangiosis,!
! ! ! ! ! Formal!Superficial!Temporal!A!to!MCA!Bypass!
! ! ! ! Tx!of!↑ICP!is!guided!by!ICP!Monitoring!
! ! ! ! Surgical!Decompression!of!Supratentorial!Infarct:!
! ! ! ! ! QOL!Not!improved;!Consider!in!Young!Pt!with!NonODominant!Infarct!
! ! ! ! Cerebellar!Infarct>!Direct!Brainstem!Compression>!may!lead!to!Acute!Deterioration!
! ! ! ! ! Prompt!Drainage!of!Hydrocephalus,!Infarctectomy,!Posterior!Fossa!Decompression!
! ! ! ! Cerebellar!Hemorrhage:! Neurosurgical!Emergency!
! ! ! ! ! Prompt!CSF!Drainage!&!Clot!Evacuation!
! ! ! ! Hemorrhage!at!BG!often!related!to!HT>!Mortality!improved,!but!Vegetative!Survival↑!
! ! ! ! ! Minimal!Invasive!techniques,!eg.!Endoscopy,!Stereotaxy,!Chemical!Clot!Liquefaction!
! ! ! ! ! ! Proper!Clinical!trials!are!awaited!
! ! ! ! Brainstem!Hemorrhage:! Very!High!Mortality;!Conservative!Tx!
! ! ! ! Diverse!Etiology!for!Lobar!Hemorrhage:!
! ! ! ! ! Evacuation!&!Exam!for!Hematoma!cavity!under!Microscope!recommended,!

! Page!765!
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! ! ! ! ! ! Except!for!Amyloid!Angiopathy!
! ! ! ! Intraventricular!Hemorrhage!&!associated!Hydrocephalus:!
! ! ! ! ! Ventricular!Drainage!&!Chemical!Clot!Lysis!(Streptokinase,!Urokinase,!tPA)!
! For!SAH:! ! 75%!SAH!associated!with!Ruptured!Cerebral!Aneurysm!
! ! ! ! Early!Microsurgical!Clipping:! Standard!Tx!
! ! ! ! Conservative!Tx:! ! ! For!Poor!Grade!Pt!
! ! ! ! Angioplasty!&!IntraOarterial!Papaverine!(AntiSpasmodic)!for!Vasospasm!becoming!Popular!

! Page!766!
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Cerebral!Venous!Thrombosis:!
! ! ! ! Any!Age!
! ! ! ! Most!in!F!associated!with!Puerperium!
! ! ! ! Sx!onset!may!be!Acute/Subacute/Chronic!
Type:! ! ! No!cause!found!in!20%!cases!
! Septic:! ! Most!often!involve!Cavernous!sinus!
! ! ! ! Typical!Cx!of!Facial/Orbital!infection!
! ! ! ! Proptosis,!Chemosis,!Painful!Ophthalmoplegia!
! Aseptic:! ! Dural!sinus!Venous!Thrombosis!(most!commonly!involve!Superior!Sagittal!sinus)!
! ! ! ! Deep!Venous!Thrombosis!
! ! ! ! Superficial/Cortical!vein!Thrombosis!
Mx:! Screen!for!RF:! ANA,!RF,!AntiOENA,!ANCA!
! ! ! ! Lupus!AntiCoagulant!&!AntiOCardiolipin!Ab!
! ! ! ! AntiOthrombin!III!deficiency,!Activated!Protein!C!resistance!(Factor!V!Leiden!mutation),!
! ! ! ! ! Protein!C!&!Protein!S!levels!4!weeks!after!completion!of!AntiCoagulation!
! ↓ICP:! ! IV!Mannitol!
! AntiCoagulant:! Prevent!extension!of!thrombus,!Allow!development!of!Collateral!circulation,!Prevent!PE!
! Interventional!procedures:!
! ! ! ! Transvenous!Thrombolytic!into!Dural!sinus!via!Femoral!route!
! ! ! ! Endovascular!Clot!removal!via!Suction!device!
!

! Page!767!
Neuro! Stroke!
 Neuro&Multiple&Sclerosis&
MS:! ! ! ! ImmuneOmediated!Inflammatory!disease!attacking!Myelinated!axons!in!CNS!
Classification:! ! *RelapsingORemitting!(~85%):!
! ! ! ! ! Recurrent!attacks!in!different!parts,!resolve!almost!completely!with!little!Residual!deficit!
! ! ! ! ! Subgroup:!Clinically!Isolated!Syndrome!
! ! ! ! ! ! ! Benign!MS!
! ! ! ! Secondary!Progressive:!
! ! ! ! ! 50%!Pt!with!RRMS!may!convert!to!SPMS!within!10O15!years!after!onset!
! ! ! ! ! Continued!Progression!over!years!with!↑ing!Disability;!May/May!Not!include!Relapses!
! ! ! ! Primary!Progressive:!
! ! ! ! ! ~10%;!Function!↓!steadily!without!Relapses!
! ! ! ! ProgressiveORelapsing:!
! ! ! ! ! <5%;!Occasional!Relapses!superimposed!on!Progressive!disease!

! ! ! ! !
Clinical:! ! ! Fatigue!
! ! ! ! Optic!Neuritis!(usually!1!eye)!
! ! ! ! ! Mostly!Retrobulbar!(ie.!Normal!Fundus);!Disc!Pallor!often!occur!months!afterward!
! ! ! ! ! (May!have!Pulfrich!phenomenon)!
! ! ! ! Acute!Transverse!Myelitis!(Partial)!
! ! ! ! ! Sensory!Loss/Paresthesia!
! ! ! ! ! Weakness!&!Spasticity!
! ! ! ! ! Urinary!Incontinence,!Constipation!
! ! ! ! CN:! Diplopia!(Horizontal!more!common;!Can!be!due!to!CN!Palsy!or!INO),!Nystagmus!
! ! ! ! ! Bilateral!Facial!Weakness/Trigeminal!Neuralgia!may!occur!
! ! ! ! ! Bulbar!involvement!relatively!uncommon!(eg.!Dysphagia)!
! ! ! ! Cerebellar!Sx:! Charcot!triad!of!Dysarthria,!Ataxia,!Intention!Tremor!
! ! ! ! Pain!(Primary!–!Neuropathic!Pain;!Secondary!–!MSK!Pain!from!Poor!Posture,!Spasticity,!etc)!
! ! ! ! ! Lhermitte!sign:! Shooting!Sensation!from!Back!to!Limbs,!elicited!by!Neck!Flexion!
! ! ! ! ! ! ! ! Due!to!involvement!of!Posterior!columns!
! ! ! ! Depression!
! ! ! ! Cognitive!dysfunction!
! ! ! ! Heat!Intolerance!(Uhthoff's!phenomenon):!

! Page!768!
Neuro! Multiple! Sclerosis!
! ! ! ! ! Worsening!of!Sx!when!exposed!to!High!Temp,!eg.!Hot!Weather,!Hot!Bath,!Exercise,!Fever!
Dx:! ! ! ! Clinically,!Attacks!must!be!compatible!with!pattern!in!MS,!typically!duration!of!days!to!weeks!
! ! ! ! Traditionally!MS!canNot!be!diagnosed!after!only!1!symptomatic!episode!
! ! ! ! ! Repeated!attacks!separated!in!Time!&!Space!
! ! ! ! 2010!McDonald!Criteria:! Combination!of!Clinical,!Imaging!(MRI),!Tests!(CSF,!Evoked!
potentials)!
! ! ! ! ! ! ! ! ! Allows!Dx!after!a!Single!attack!too!
Ix:! MRI!Brain!&!SC:!Typically!Multifocal!areas!of!Demyelination!with!High!T2!Intensity!(Plaques)!with!different!Ages!
! ! ! ! Location:! Periventricular!regions,!Corpus!Callosum!
! ! ! ! ! ! Cerebellum/Cerebellar!Peduncles,!Brainstem!
! ! ! ! ! ! SC:! T2!Hyperintensity:!Partial,!Extend!within!1!Vertebral!segment!
! CSF:! ! ! ↑Protein,!↑IgG,!Oligoclonal!bands!+ve!(90%!Classical!MS)!
! Evoked!Potential:!
! ! VEP:! ! Can!be!Prolonged!without!Visual!Sx,!ie.!Subclinical!Optic!Neuritis!
Tx:!
1.!Acute!Relapse:! 1st!line:! Methylprednisolone!
! ! ! ! 2nd!line:! Plasmapheresis,!(IVIG)!
2.!Immunomodulatory!therapy:!(AAN!Guideline)!
! Indication:!! Mainly!approved!in!RRMS;!Sometimes!CIS,!SPMS,!(PRMS);!No!approved!Tx!in!PPMS!
! ! ! ! Immunomodulatory!therapy!in!CIS!if!High!risk!for!MS:!
! ! ! ! ! Usually!Age!15O50!
! ! ! ! ! Highly!suggestive!Neurologic!syndrome!
! ! ! ! ! ! (eg.!Monocular!Optic!Neuritis,!Incomplete!Transverse!Myelitis)!
! ! ! ! ! Evidence!of!Silent!lesions!on!Brain!MRI!
! ! ! ! ! No!better!explanation!for!presenting!syndrome!
! ! AAN!Guideline!Recommendation:!
Compound! Attack!Rate! ↓Disease!Severity!on!MRI!Disability!Progression!
IFNOβ! Level!A! Level!B!
Glatiramer!Acetate! Level!A! Level!C!
Mitoxantrone! Level!B! NA! Level!C!
Natalizumab! Level!A!
! IFNOβ:!
! ! Agents:! IFNOβ1b!(SC),!IFNOβ1a!(IM)!
! ! Evidence:! Level!A!in!RRMS,!SPMS,!CIS!to!↓Attack!rate!
! ! ! ! ↓Relapse!rate!by!1/3!well!proven!in!multiple!trials!
! ! ! ! Effect!of!INFOβ!on!Disability!progression!stronger!than!for!Glatiramer!acetate!
! ! ! ! ! (Level!B!vs!Level!C)!
! ! ! NB:! For!Pt!with!a!first!event!&!MRI!features!of!MS,!only!IFNOβ!approved!by!FDA!
! Glatiramer!Acetate!(SC):!
! ! Evidence:! Level!A!in!RRMS!
! Mitoxantrone!(IV):!
! Page!769!
Neuro! Multiple! Sclerosis!
! ! ! ! Anthracenedione;!Suppress!T!&!B!cells,!Induce!Apoptosis!in!APC,!Deactivate!MQ!
! ! Evidence:! Level!B!for!SPMS;!Level!C!for!Disease!progression!
! ! ! ! Reserved!for!worsening!RRMS!or!SPMS!(&!PRMS)!unresponsive!to!other!approved!therapies!
! ! ! ! ! DBRCT:! ↓Clinical!Exacerbation!&!Disability!progression!in!worsening!RRMS!or!SPMS!
! ! Indication:!As!Induction!therapy!with!very!active!disease!
! ! ! ! Or!Rescue!therapy!for!Pt!Not!responding!to!IFNOβ/Glatiramer!Acetate!
! ! Serious!S/E:!
! ! ! ! ModerateOSevere!CHF!when!cumulative!dose!>140!mg/m2!(Blackbox!warning!for!Cardiotoxicity)!
! ! ! ! ! Maximum!use!for!3!years!at!current!dose!
! ! ! ! Birth!defects!(When!given!in!Pregnancy!or!during!time!of!Conception!for!both!M!&!F!partners)!
! ! ! ! Sterility!(may!be!permanent)!
! ! ! ! Rarely!asso.!with!Secondary!AML!(Blackbox!warning)!
! Natalizumab!(IV):! (New)!
! ! ! ! Humanized!mAb!vs!α4b1!integrin!
! ! ! ! ! Very!Late!Ag!4!(VLA4)!on!surface!of!activated!Lymphocytes!&!Monocytes!
! ! Evidence:! Level!A!
! ! ! ! Reserved!for!those!who!can’t!tolerate/do!Not!respond!well!to!Immunomodulators!
! ! ! ! ! DBRCT:! ! In!RRMS/Relapsing!SPMS!
! ! ! ! ! ! ! ! ↓No.!of!new!enhancing!lesion,!↓No.!of!Clinical!episodes!
! ! ! ! ! AFFIRM!trial:! Clinically!active!RRMS!
! ! ! ! ! ! ! ! ↓:! Risk!of!sustained!disability!progression!by!42%!(2Oyear),!
! ! ! ! ! ! ! ! ! Clinical!Relapse!rate!by!68%,!Development!of!CEL!by!92%,!
! ! ! ! ! ! ! ! ! New/Enlarging!T2W!lesions!by!83%!
! ! S/E:! ! Slight!↑!risk!of!serious!Infective!Cx:!
! ! ! ! ! Pneumonia,!Urosepsis,!
! ! ! ! ! Progressive!Multifocal!Leucoencephalopathy!(PML)!(~1/1000!Pt!treated!for!~17.9!months)!
! ! ! ! Infusion!reaction!
! ! ! ! Hypersensitivity!reaction!(0.8%!Anaphylactoid!reaction)!
! ! ! ! Persistent!Ab!to!Natalizumab!(6%)>!Loss!of!Efficacy!&!↑Infusion!adverse!reaction!
! Fingolimod!(oral):! (New)!
! ! ! ! Approved!for!Tx!of!MS!in!2010;!1st!line!agent!in!US,!2nd!line!agent!for!active!MS!in!Europe!
! ! Mechanism:!
! ! ! ! Structural!analog!of!intracellular!sphingosine!that!is!phosphorylated!in!vivo!
! ! ! ! Mimics!sphingosineO1Ophosphate!(S1P)!
! ! ! ! >!Binds!to!S1P!receptors!on!lymphocytes!
! ! ! ! >!Internalization!&!Downregulation!of!receptors!
! ! ! ! >!Without!receptor!signals,!T!&!B!cells!are!unable!to!egress!from!secondary!lymphoid!tissues!
! ! ! ! >!Marked!↓T!&!B!cells!in!peripheral!blood!&!↓Recruitment!to!sites!of!inflammation!
! ! Evidence:! Phase!3!FREEDOMS!(compared!to!Placebo):!
! ! ! ! ! ↓Annual!relapse!rate!by!54O60%,!↓Risk!of!Disability!progression,!
! ! ! ! ! Fewer!new/enlarging!T2!lesions!&!CEL,!Less!Brain!volume!loss!

! Page!770!
Neuro! Multiple! Sclerosis!
! ! S/E:! ! Herpes!infection/URTI,!Bradycardia/AVB!during!initiation,!HT,!↑Liver!enzymes,!
! ! ! ! Macular!Edema,!Lymphopenia,!Possible!Malignancy!
! Others!(oral):! Teriflunomide,!Dimethyl!fumarate!
3.!For!Aggressive!MS:!Cyclophosphamide!
!

! Page!771!
Neuro! Multiple! Sclerosis!
NMO:!
Neuromyelitis!optica:!Aka!Devic’s!disease;!Recurrent!Simultaneous!Optic!Neuritis!+!Myelitis!
! ! ! ! AQP4+!NMO!is!an!AI!disease!with!AutoAb!against!Aquaporin!4,!cf!TOcell!mediated!in!MS!
! ! ! ! More!common!in!Asians!than!Caucasians,!cf!MS!more!common!in!White!
Dx:! ! ! ! 2!Absolute!criteria!+!2/3!Supportive!criteria!
! Absolute:! ! Optic!Neuritis!(usually!Bilateral)!(May!require!VEP!for!Dx!if!Subclinical!Optic!Neuritis)!
! ! ! ! Acute!Myelitis!
! Supportive:! Brain!MRI!Not!meeting!criteria!for!MS!at!disease!onset!
! ! ! ! SC!MRI!with!contiguous!T2W!signal!abnormality!extending!over!≥3!vertebral!segments!
! ! ! ! ! (Myelitis!in!NMO!is!typically!more!Longitudinally!Extensive,!cf!MS)!
! ! ! ! NMOOIgG!sero!+ve!status!
Variants:! ! ! Standard!Devic’s!disease!(according!to!above!diagnostic!criteria)!
! ! ! ! Limited!forms!of!Devic’s!disease!
! ! ! ! Asian!OpticOSpinal!MS!(Can!present!CNS!involvement!like!MS)!
! ! ! ! Associated!with!Systemic!AI!disease!
! ! ! ! Associated!with!Lesions!in!specific!brain!areas,!eg.!Hypothalamus,!Periventricular!N,!Brainstem!
! ! ! ! NMOOIgG!–ve!NMO!
Tx:! Supportive!
! Medical!(According!to!RTF!Cheung):!
! ! ! ! Acute:! 1st!line:! Pulse!Steroid!
! ! ! ! ! ! 2nd!line:! Plasmapheresis,!IVIG!
! ! ! ! Chronic:! Steroid!±!SteroidOsparing!agents!
!

! Page!772!
Neuro! Neuromyelitis! optica!
ADEM:!
Acute!Disseminated!EncephaloMyelitis:!
! ! ! ! ImmuneOmediated!inflammatory!demyelinating!condition,!
! ! ! ! ! that!predominately!affects!White!matter!of!CNS!
! ! ! ! Acute!onset!Encephalopathy!with!Multifocal!Neurological!deficits!
! ! ! ! Typically!Self!limiting!(Spontaneous!resolution!quick)!
! ! ! ! Usually!occurs!after!a!Febrile!Prodromal!Viral!illness!or!Immunization!
!

! Page!773!
Neuro! Acute! Disseminated! Encephalomyelitis!
 Neuro&SC&Lesion&
Cause!of!SC!Disorder:!
! Compression!(NonONeoplastic):!
! ! ! ! Trauma,!Spondylosis,!Disk!Herniation,!etc!
! Compression!(Neoplastic):!
! ! ! ! Vertebral!Collapse!from!Bony!Mets!
! ! ! ! Extramedullary!Tumor:!
! ! ! ! ! Meningioma,!NF1/Schwannoma,!Leptomeningeal!Mets,!Secondary!Lymphoma!
! ! ! ! Intramedullary!Tumor:!
! ! ! ! ! Ependymoma,!Astrocytoma!
! NonCompressive:!
! ! ! ! Demyelinating:! MS,!NMO,!ADEM!
! ! ! ! Viral!Transverse!Myelitis!
! ! ! ! SC!Infarction/Hemorrhage!
! ! ! ! AI!(SLE)!
! ! ! ! ST!
! ! ! ! Spirochetal!Infection!(Syphilis,!Lyme’s!disease)!
! ! ! ! Degenerative!disorder:! Spinocerebellar!disorder,!MSA,!ALS,!Vit!B12!Deficiency!
! ! ! ! Paraneoplastic!causes!
Caution:! ! ! Not!all!isolated!LL!UMN!weakness!is!due!to!SC!lesion!
! ! ! ! Examples:!Parasagittal!Meningioma,!ACA!Stroke!
SC!Lesion:!! ! Complete!Transverse!lesion,!BrownOSequard!syndrome!(Unilateral!Transverse),!
! ! ! ! Central!Cord!syndrome,!Anterior!Spinal!A!syndrome,!Posterior!Column!disease!
Complete!Transverse:!
! Acute!–!Spinal!Shock:!
! ! ! ! Total!loss!of!Motor!&!Sensory!function!Below!lesion!
! ! ! ! Loss!of!all!Spinal!reflex!Below!lesion!with!Flaccidity!
! ! ! ! (Autonomic!Dysreflexia!(Sympathetic!overcharge)!may!occur!with!SCI!level!above!T6)!
! ! (Course):! 1st!day:! ! Complete!Areflexia/Hyporeflexia!
! ! ! ! Next!2!days:! Reflex!start!returning!(Polysynaptic!first,!eg.!Bulbocavernosus!Reflex)!
! ! ! ! ! ! ! Monosynaptic!Reflex!like!Deep!Tendon!Reflex!are!Not!restored!until!Phase!3!
! ! ! ! Phase!3&4:! Initial!Hyperreflexia!~1O4!weeks!(Phase!3)!
! ! ! ! ! ! ! Spasticity!~!1O12!months!(Phase!4)!
! ! Cause:! Sudden!Vascular!event!of!SC,!Acute!Compression!of!SC,!Transverse!Myelitis!
! Chronic:! ! As!above!except!Babinski!Sign!&!Brisk!Spinal!Reflex!Below!lesion!level!
! ! Cause:! Benign!Tumor,!Cervical!Spondylosis!
BrownOSequard:! Can!be!Complete!(perfectly!unilateral)!or!Incomplete!
! ! ! ! Check!if!Posterior!Column!lesion!is!at!the!same!side!as!UMNL!
! ! ! ! Unilateral!Transverse!lesion:!Rarely!Pure,!usually!Partial!

! Page!774!
Neuro! SC! Lesion!
! ! ! ! !
! Clinical:! ! Ipsilateral:!! At!level!of!lesion,!All!Sensory!Modality!affected!
! ! ! ! ! ! ! Below!level!of!lesion,!Proprioception/Joint!Position!Sense!affected!&!UMN!
! ! ! ! Contralateral:! Below!level!of!lesion,!Pain/Temp!affected!
! Cause:! ! Trauma!(eg.!Stab,!Bullet)!
! ! ! ! Asymmetrical!Tumor!Compression/Spondylosis!
! ! ! ! Radiation!Necrosis!
Central!Cord:! ! IntraOaxial!lesion!
! Clinical!feature:!Depend!on!Extent!of!lesion!
! ! ! ! ! At!lesion!level:! ! Decussating!Spinothalamic!affected>!Pain/Temp!Sensory!deficit!
! ! ! ! ! If!extend!Anteriorly:! Anterior!Horn!affected>!LMNL!At!lesion!level!
! ! ! ! ! If!extend!Laterally:! Corticospinal!affected>!UMNL!Below!lesion!level!
! ! ! ! ! ! ! ! ! ! (May!have!Sacral!Sparing! Sacral!nerves!are!most!superficial)!
! ! ! ! (Think!of!this!when!see!UL!Motor!involvement!>!LL!Motor!involvement)!
! ! ! ! (Sensory!Loss!below!level!of!lesion!is!variable)!
! Cause:! ! Acute:! Spinal!Hemorrhage,!Trauma!with!Contusion!(eg.HyperExtension),!Transverse!
Myelitis!
! ! ! ! Chronic:! Syringomyelia,!Tumor!
! Syringomyelia:! On!MRI!T2W,!Can!see!Hyperintensity!within!SC!(Central!Canal!Dilated)!
! ! ! ! Usually!Upper!Thoracic/Lower!Cervical;!May!extend!into!Medulla!forming!Syringobulbia!
! ! ! ! Expansion!in!Central!Canal!(eg.!Cyst)!at!Foramen!Magnum>!Press!on!Central!Canal!
! ! Lesion:!
! ! ! Central:!
! ! ! ! Affect!Spinothalamic>!Bilateral!Pain/Temp!Sensory!Loss!At!the!level!
! ! ! ! ! (Because!they!decussate!at!the!level)!(eg.!C5OT1)!
! ! ! Horizontal/Elongated:!
! ! ! ! Spread!horizontally!to!affect!Lateral!tracts!
! ! ! ! ! Dermatomes!(Spinothalamic:!PinOprick/Temp!Loss)!
! ! ! ! ! Affect!Anterior!Horn!Cells>!LMNL!At!the!level!(eg.!C8OT1)!
! ! ! ! ! Affect!Corticospinal!tract>!UMNL!Below!(LL)!
! ! Cause:!
! ! ! ArnoldOChiari!Malformation:!
! ! ! ! Abnormal!Cerebellar!Tonsilar!Herniation!
! ! ! ! May!be!associated!with!Hydrocephalus,!Syringomyelia/Syringobulbia,!
! ! ! ! ! Bony!abnormalities!(eg.!C1!level!Spinal!Bifida)!
! ! ! DandyOWalker!Malformation!(Rare):!
! ! ! ! Ballooning!of!Posterior!Half!of!4th!Ventricle!
! ! ! ! Atresia!of!Foramen!of!Magendie,!Aplastic!Cerebellar!Vermis!
! ! ! ! Obstructive!Hydrocephalus,!Associated!with!Mental!Retardation!

! Page!775!
Neuro! SC! Lesion!
! ! ! Intramedullary!SC!Tumor!
! ! ! SC!Trauma!
Anterior!Spinal!A:! Anterior!portion!of!SC!involved,!esp!at!Vascular!watershed!MidOthoracic!level!
! Clinical:! ! Spinal!Shock!initially,!followed!by!UMNL!later!Below!level!of!lesion!
! ! ! ! Dissociated!Sensory!Loss:! Spinothalamic!Affected,!Posterior!Column!Spared!
! Cause:! ! DM,!AF,!Invasive!Intravascular!procedures,!Hypoperfusion!(Eg.!Aortic!insufficiency!from!AD)!
Combined!Posterior!&!Lateral!Column!disease:!
! Clinical:! ! Dissociated!Sensory!Loss:! Spinothalamic!Spared,!Posterior!Column!Affected!
! ! ! ! UMNL!(May!have!mixed!UMNL!&!LMNL!signs,! Patellar/Ankle!Areflexia!due!to!Sensory!Loss)!
! Cause:! ! Vit!B12!deficiency>!Subacute!Combined!Degeneration!of!Cord!
! ! ! ! Friedreich’s!Ataxia!(Causes!both!Sensory!&!Cerebellar!Ataxia)!
! ! ! ! (Posterior!cord!syndrome!from!Posterior!Spinal!Artery!interruption!is!very!Rare)!
Acute!Transverse!Myelitis!(ATM):!
! ! ! ! Inflammation,!Demyelination>!SC!Neural!Injury!
! Dx:! ! ! Sensory,!Motor!or!Autonomic!dysfunctions!
! ! ! ! Progression!to!Nadir!from!4h!–!21!days!
! ! ! ! Spinal!Compression,!Infarction!&!AVM!need!to!be!excluded!
! Cause:!
! ! Idiopathic:!Parainfectious:!30O60%!with!antecedent!Respiratory/GI!illnesses!
! ! Diseases:! CTD:!! Behcet’s!disease,!Sjogren’s!syndrome,!SLE,!MCTD!
! ! ! ! Infection:! Bacterial:! Lyme’s!disease,!Syphilis,!Mycoplasma!
! ! ! ! ! ! Viral:!! HIV,!HTLVO1,!HSV1/2,!VZV,!CMV,!EBV!
! ! ! ! MS:! ! Relapsing,!Disseminated!
! ! ! ! NMO:! Monophasic/Relapsing!ATM!+!Optic!Neuritis!
! ! ! ! ADEM:! Monophasic!&!Disseminated!
!

! Page!776!
Neuro! SC! Lesion!
 Neuro&Generalized&LMN&Weakness&
Generalized!Weakness:! Weakness!(↓Muscle!Strength)!vs!Fatigue!(Failure!to!maintain!expected!Contraction)!
! ! ! ! ! Weak!muscles!are!always!more!Fatigable!than!Normal!muscles!
! ! ! ! ! In!general:!! Neuropathic!disorders!cause!Distal!Limb!Weakness!
! ! ! ! ! ! ! ! NMJ/Muscle!disorders!cause!Proximal!Weakness!
! Ddx:! ! ! ! Polyneuropathy,!NMJ!disorder,!Myopathy!
! ! Important:! Clinically!Important!Polyneuropathies!
! ! ! ! ! MG!
! ! ! ! ! Inflammatory!Myopathies,!Muscular!Dystrophies,!Muscle!Channelopathies!
! ! ! ! ! Floppy!baby!syndrome!
Clinical!Neurophysiology:! Nerve!Conduction!Studies:!
! ! ! ! ! ! Assessment!of!Large!Fibre!Conduction!function!
! ! ! ! ! ! Analysis!of!Neuronal!signals!generated!by!Electrical!Activation!
! ! ! ! ! Needle!Electromyography!(EMG):!
! ! ! ! ! ! Analysis!of!Bioelectric!Activities!of!muscles!
! ! ! ! ! Special!techniques!for!NMJ!Conduction!functions!
! Electrodiagnostic!(EDx)!studies:!
! ! ! ! ! Objective!Assessment!of!PNS!function!
! ! ! ! ! Generate!Quantitative!&!Reproducible!info!
! ! ! ! ! NonOInvasive!
! ! Indication:

! !
!

! Page!777!
Neuro! Generalized! LMN! Weakness!
 Neuro&Polyneuropathy&
Peripheral!Neuropathy:! Polyneuropathy:! Generalized!involvement!
! ! ! ! ! Focal!Neuropathy:! Traumatic!&!Entrapment!Neuropathy!
! (Wiki:! ! ! Mononeuropathy,!Mononeuropathy!Multiplex,!Polyneuropathy,!Autonomic!Neuropathy,!
! ! ! ! ! Neuritis)!
Nerve!Fibres:!
! Large!Fibres:! Type!A!Fibres!–!Myelinated!Fibres!
! Small!Fibres:! Type!B!Fibres!–!Thinly!Myelinated!Fibres:!
! ! ! ! ! Cutaneous!Cold!&!Pain,!Sympathetic!Preganglionic!
! ! ! ! Type!C!Fibres!–!Unmyelinated!Fibres:!
! ! ! ! ! Cutaneous!Hot!&!Pain,!Sympathetic!Postganglionic!
Mononeuritis!Multiplex:!
! ! ! ! Nerve!Infarction!from!Small!to!Medium!Arterial!disease!
! ! ! ! ! DMOassociated!Atherosclerosis!
! ! ! ! ! Vasculitis!
! ! ! ! ! Syphilis,!HIVOrelated!
! ! ! ! Acute!Pain,!followed!by!Focal!Neuropathy:!! (Can!Progress>!Look!more!like!
Polyneuropathy)!
! ! ! ! ! Focal:! ! Eg.! R!Radial!or!L!Abducens!or!L!Peroneal!
! ! ! ! ! Multifocal:! ! R!Radial!+!L!Abducens!+!L!Peroneal!
! ! ! ! ! Generalized:! ! R!Radial!+!L!Abducens!+!L!Peroneal!+!…!
Polyneuropathy:!
Clinical:! ! ! May!show!Motor,!Sensory,!sometimes!Autonomic!S/S!
! ! ! ! Majority:! Mixed!SensoryOMotor!pattern!
! ! ! ! Some:! Predominant/Exclusive!Sensory!or!Motor!
! ! ! ! Rare:!! Pure!Autonomic!Neuropathy!
! Generally:!! Symmetrical,!Sensory!>!Motor,!LL!>!UL,!Distal!>!Proximal;!ie.!LengthODependent!pattern!
! Motor:! ! LMN!sign:! Fasciculation,!Weakness,!Atrophy/Wasting;! ! Affect!Limbs,!Bulbar,!
Respiratory!
! ! ! ! ! Fasciculation:! Spontaneous!Contraction/Twitch!of!Muscle!Fibres!of!Same!Motor!Unit!
! ! ! ! ! ! ! ! Can!be!Normal!after!Exercise!&!during!Fatigue,!esp!Calves!&!Hamstrings!
! ! ! ! ! Wasting:! ! Denervated!Muscles!will!undergo!Atrophy!
! ! ! ! ! ! Acute!Neuropathy:! Wasting!takes!3O10!weeks!to!become!Apparent!
! ! ! ! ! ! Slowly!Evolving/Arrested!Neuropathy:! Wasting!may!be!Minimal/Absent!
! ! ! ! ! ! ! ! Neurogenic!process!causes!Atrophy!of!Both!type!I!&!II!fibres,!whereas!
! ! ! ! ! ! ! ! Type!II!fibres!are!affected!with!Muscle!Inactivity,!ie.!‘Disuse’!Atrophy!
! Sensory:! ! –ve:! Numbness!(Sensory!Loss)!
! ! ! ! +ve:! Paresthesia!(Sensation!in!the!Absence!of!Normal!Stimulation!of!Receptors)!
! ! ! ! Sensory!Ataxia:!Another!possible!Sign,!though!also!occur!in!Posterior!Column!lesion!
! ! ! ! ! ! ! Proprioception!Impairment>! Rombergism!(Ataxic!Gait!with!Eye!Closure),!
! ! ! ! ! ! ! ! ! ! ! ! ! Postural!Tremor,!PseudoOAthetoid!movement!
! Page!778!
Neuro! Polyneuropathy!
! Tendon!Reflex:! Disturbance!of!either!Afferent/Efferent>!Hyporeflexia/Areflexia;!LengthOdependent!Progression!
! Autonomic:! Postural!Hypotension,!Cardiac!Conduction!abnormalities,!Bladder/Bowel!disturbance,!
! ! ! ! Erectile!Dysfunction,!Alteration!of!Sweating,!Other!Trophic!changes!of!Skin!
! ! ! ! ! CVS:! Tachycardia/Exercise!Intolerance,!Cardiac!Denervation/Painless!MI,!
! ! ! ! ! ! Orthostatic!Hypotension,!Heat!Intolerance,!Alteration!in!Skin!Blood!Flow!
! ! ! ! ! GI:! Esophageal!Dysfunction,!Gastroparesis!Diabeticorum,!
! ! ! ! ! ! Diarrhea,!Constipation,!Fecal!Incontinence!
! ! ! ! ! GU:! Erectile!Dysfunction,!Retrograde!Ejaculation,!Cystopathy,!Neurogenic!Bladder!
Time!Course:! ! Acute!Polyneuropathy:! Reach!Nadir!(Lowest!point)!within!4!weeks!
! ! ! ! ! ! ! ! ! Vasculitis!causing!Nerve!Infarction!might!evolve!Overnight!
! ! ! ! Subacute!Polyneuropathy:!Reach!Maximal!deficit!within!12!weeks!
! ! ! ! *Chronic!Progressive:! ! Impairment!↑ing!over!months!to!years!
! Phase:! ! Monophasic:! Subsequent!Arrest!of!Disease!Progression!
! ! ! ! Polyphasic:! RelapsingORemitting;!Can!occur!but!Uncommon!
Etiology:! ! ! Diverse!(>100);! Cause!can!be!found!in!>90%!cases!
! 7!Categories:! Hereditary,!Metabolic,!Deficiency,!Toxic!&!Iatrogenic,!Infectious,!Dysimune,!Idiopathic!
! Types:! ! Inflammatory!Demyelinating!Neuropathy:! GBS,!CIDP!
! ! ! ! Infectious!&!Granulomatous!Neuropathy:! Leprosy,!Sarcoid,!HIVOrelated,!Lyme!disease!
! ! ! ! Associated!with!Systemic!Disease:!
! ! ! ! ! DM,!CRF,!Vitamin!Deficiency,!Paraproteinemia!&!other!Dysimmune!Neuropathies,!CTD,!
! ! ! ! ! Critical!Illness!Polyneuropathy!
! ! ! ! Ischemic!Neuropathy:! PVD,!Vasculitis!
! ! ! ! Metabolic!Neuropathy!
! ! ! ! Hereditary!Neuropathy!
! ! ! ! Toxin:! ! ! ! Drugs!(eg.!Chemo),!Environmental!Toxins!(eg.!Mercury)!
! ! ! ! ! Neurotoxic!agents:! Alcohol!
! ! ! ! ! ! ! ! ! Solvent!&!other!Industrial!Chemicals!
! ! ! ! ! ! ! ! ! Heavy!Metals!
! ! ! ! ! ! ! ! ! Drugs:! Chemo,!AntiMicrobial!(TB,!HIV),!
! ! ! ! ! ! ! ! ! ! ! Others!(Colchicine,!Thalidomide,!Pyridoxine!Abuse)!
! Classify!by:! Time!Course:! ! ! Acute,!Subacute,!Chronic,!Relapsing!
! ! ! ! Distribution!&!Pattern:! Generalized,!Focal!(Entrapment,!Trauma,!Granulomatous…)!
! ! ! ! Type!of!Functional!Fibres:! Large/Small,!Motor/Sensory/Autonomic/Mixed!
! ! ! ! Primary!Axonal,!Demyelinating,!or!Mixed!
Ix:! Electrophysiology:! Clinical!Neurophysiology!or!Electrodiagnostic!Medicine:! Mostly!NonOInvasive!
! ! Type:! Nerve!Conduction!studies!(NCS):! For!LargeOfibre!functions!
! ! ! ! Needle!EMG:! ! ! ! ! For!Bioelectric!Activity!of!Muscles!
! ! Use:! ! Define!whether!there!is!a!Neurogenic!Process!&!Extent!of!disease!
! ! ! ! Ddx!Axonal!Degeneration!&!Demyelination!
! ! ! ! Subclinical!evidence!of!Motor/Sensory!nerve!Involvement!
! ! ! ! Measure!Degree!of!Neuronal!Degeneration!

! Page!779!
Neuro! Polyneuropathy!
! ! ! ! Assess!NMJ!Conduction!functions!
! ! ! ! Assess!Disease!Activity!of!a!Myopathic!process!
! CSF!Analysis:! Indicated!when!Acquired!Demyelinating!Polyneuropathies!are!suspected!
! ! ! ! ! Eg.!CIDP,!GBS!
! ! ! ! Typical!finding:! ↑Protein!but!Normal!Cell!count!
! Nerve!Biopsy:! Seldom!indicated:! Invasive>!Irreversible!Neurological!deficits!after!procedure!
! ! ! ! Sural!N!or,!less!commonly,!Superficial!Radial!N!can!be!biopsied!
! ! Limitation:! Aim:!Look!for!Reversible!Etiological!factors!
! ! ! ! But!No!Specific!Tx!for!many!Polyneuropathies!other!than!Symptomatic!therapy!
! ! ! ! ! >!Limited!Benefit!from!this!Harmful!Ix!
! ! ! ! Almost!always!Not!helpful!in!Advanced!Neuropathies:!
! ! ! ! ! Histology:!Chronic!Axonal!Degeneration!
! ! ! ! ! (Terminal!event!for!most!Neuropathies,!regardless!of!Etiology)!
! Systemic!Cause!Ix!
! Genetic!Test!
!

! Page!780!
Neuro! Polyneuropathy!
Inflammatory!Neuropathies:!
GBS!
GuillainOBarre!syndrome:! (English!pronunciation:!/ɡiːˈjænbɑrˈeɪ/)!
! ! ! ! Clinical!Syndrome:! Rapidly!Evolving,!Relatively!Symmetrical!Flaccid!Paralysis,!Areflexia,!
! ! ! ! ! ! ! ! ↑CSF!Protein!without!Cells!
! ! ! ! Underlying!process!is!Acute!Polyradiculoneuropathy!
! ! ! ! Pathological!findings:!Lymphocytic!Infiltration!&!MQOmediated!Demyelination!
! ! ! ! Originally!aka!Acute!Inflammatory!Demyelinating!Polyneuropathy!(AIDP)!
! ! ! ! Now!believed!to!be!a!Diverse!disorder,!including!Both!Demyelinating!&!Axonal!forms!
! ! ! ! ! And!AIPD!can!be!caused!by,!eg.!Toxins,!which!wont!be!accounted!as!GBS!
! Types:! ! *AIDP,!AMAN,!AMSAN!(Acute!Motor!Sensory!Axonal!Neuropathy),!MFS!(Miller!Fisher),!
! ! ! ! Ataxic!GBS,!Polyneuritis!Cranialis,!POCOB!Variant,!PanDysautonomia!
! Epidemiology:! Incidence:!1O2!per!100,000!
! ! ! ! Antecedent!URTI/GI!Infection,!esp!Campylobacter!jejuniOrelated,!in!70%!(2/3)!cases!
! ! ! ! ! (Others:! CMV,!EBV,!M.!pneumoniae)!
! ! ! ! Dysimmune!Reaction!to!Preceding!Infection!(Autoimmunity)!
! ! ! ! Mortality:!5O10%!(2O12%),!due!to:! Resp!Failure!(25O30%)!
! ! ! ! ! ! ! ! ! ! ! Autonomic!Dysfunction!(20O30%)!(Arrhythmia,!Labile!BP)!
! ! ! ! 20%!Permanent!Disability,!10%!Severe!
! Clinical:! ! Fairly!Symmetrical!Ascending!Flaccid!Paralysis!(Hypo/Areflexia;!Normal!Reflex!is!Against!the!Dx)!
! ! ! ! Subacute!Onset!Evolving!over!a!few!days,!Progress!over!1O3!weeks,!Nadir!within!4!weeks!
! ! ! ! Monophasic,!Clinical!Improvement!usually!begins!2O4!weeks!after!Progression!Stops!
! ! ! ! ! Good!Clinical!Recovery!in!85%!(Miller!Fisher!has!even!Faster!Recovery)!
! ! ! ! ! (Theoretically,!Recovery!from!Demyelination!is!Fast!
! ! ! ! ! ! But!if!accompanied!by!Axonal!damage!after!Demyelination,!Recovery!takes!Longer)!
! ! ! ! MildOModerate!Sensory!Accompaniment!(Motor>Sensory)!
! ! ! ! CN!involvement!might!be!present!with!Bilateral!Facial!Weakness!&!Ophthalmoplegia!
! ! ! ! ! (Suspect!Miller!Fisher!Syndrome!if!see!this,!though!GBS!can!uncommonly!cause!it!too)!
! ! ! ! Muscle!Ache!in!Back!&!Thighs,!and!Neuritic!Pain!in!Extremities!are!Common!
! ! ! ! Autonomic!Dysfunction!(>2/3!Pt)!
! ! ! ! Sphincter!involvement!is!Uncommon!(5O15%!as!part!of!Autonomic!Failure)!
! ! MFS:!! Triad!of!Ophthalmoplegia!+!Ataxia!(Tend!to!be!out!of!proportion!of!Sensory!Loss)!+!Areflexia!
! ! ! ! Often!also!Bilateral!Facial!Weakness,!Ptosis,!Bulbar!Palsy,!Mild!LL!Weakness!
! ! ! ! Descending!Paralysis;!Serum!AntiOGQ1b!+ve!in!90%!
! ! ! NB:! If!Ophthalmoplegia!+!Ataxia,!but!Drowsiness/Coma/Hyperreflexia,!
! ! ! ! ! think!Bickerstaff’s!Encephalitis!(CNS!involvement,!also!AntiOGQ1b!+ve)!
! Ix:! ! ! Electrophysiology!(Nerve!conduction!study)!(TWH!doctor:!1st!step!to!do!for!initial!Tx!decision)!
! ! ! ! LP!–!CSF!study:! ↑CSF!Protein!without!Pleocytosis!(ProteinOCell!Dissociation),!Oligoclonal!bands!
! ! ! ! (MRI!Brain!if!CN!involvement)!
! ! ! ! (Visual!Evoked!Potential!if!Optic!Neuritis)!
! ! ! ! Serology!for!AntiOganglioside!Ab!esp!if!suspect!MFS!(AntiOGQ1b)!

! Page!781!
Neuro! Polyneuropathy!
! ! ! ! ! (Others):! AIDP:! ! ! ! ! Unknown!Ab!
! ! ! ! ! ! ! AMSAN:! ! ! ! ! GM1,!GM1b,!GD1a!
! ! ! ! ! ! ! AMAN:! ! ! ! ! GM1,!GM1b,!GD1a,!GalNacOGD1a!
! ! ! ! ! ! ! Acute!Sensory!Neuropathy:! GD1b!
! ! ! ! ! ! ! Acute!PanDysautonomia:!
! ! ! ! ! ! ! ! Regional!variants:!
! ! ! ! ! ! ! ! ! Fisher’s!syndrome:! GQ1b,!GT1a!
! ! ! ! ! ! ! ! ! Oropharyngeal:!! GT1a!
! ! ! ! ! ! ! MFS/GBS!overlap!syndrome:! GQ1b,!GM1,!GM1b,!GD1a,!GalNacOGD1a!
! ! ! ! (Microbiology):! Stool!Culture!&!Serology!for!C.!jejuni!
! ! ! ! ! ! ! Stool!Culture!for!Poliovirus!in!Pure!Motor!syndrome!
! ! ! ! ! ! ! Acute!&!Convalescent!Serology!for!CMV,!EBV,!M.!pneumoniae!
! Tx:! Supportive!&!Treat!Cx:!
! ! ! ! Monitor!Resp!&!Hemodynamic!Status:!
! ! ! ! ! ECG,!ABG!(SaO2),!BP,!Pulse!
! ! ! ! ! RR,!Evidence!of!Resp!Distress/Fatigue/Failure!
! ! ! ! ! Bed!side!FVC!
! ! ! ! ! Bulbar!function!
! ! ! ! Resp!support:! ! Mechanical!Ventilation!for!Resp!Failure!(Type!2)!
! ! ! ! Nutritional!support:! NPO!&!Ryle’s!Tube!Feeding!if!Poor!Bulbar!function,!Fluid!Replacement!
! ! ! ! Immobility!care:! Eg.!Passive!Exercise!to!prevent!DVT!
! ! ! ! Physiotherapy:! ! Chest!&!Limb!Physiotherapy!
! ! ! ! Consult!ICU!early!for!Assessment!&!Monitoring!ideally!
! ! Immunotherapy:!
! ! ! ! High!dose!IVIG!(1st!line;!Equivalent!Efficacy!but!Safer,!Easier,!Cheaper);! ! (NOT!Steroid)!
! ! ! ! ! Usually!0.4!g/kg/day!for!5Odays!(RTF!Cheung:!Costs!~10K!in!total)!
! ! ! ! ! (Tx!failure!threshold!–!2!weeks!from!onset)!
! ! ! ! Plasmapheresis!(5!sessions!within!2!weeks,!2L!per!session)!
CIPD!
Chronic!Inflammatory!Demyelinating!Polyradiculoneuropathy:!
! ! ! ! Evolve!over!at!least!8!weeks;!Some!cases!run!a!RelapsingORemitting!course!
! ! ! ! Also!DysimmuneOmediated,!some!Secondary!to!underlying!Paraproteinemia!
! Ix:! ! ! ↑Protein!without!Pleocytosis!in!CSF!
! ! ! ! Evidence!of!Demyelination!with!Electrophysiological!studies!
! ! ! ! (Need!SPEP!&!BM!study!for!underlying!MM/LPD)!
! Tx:! ! ! Important!to!recognize!this!condition!because!it!may!respond!to!Immunotherapy!
! ! ! ! Corticosteroids!(Steroid!can!be!used!in!CIPD!but!Not!GBS),!Plasmapheresis,!High!dose!IVIG!
! ! ! ! Tx!against!underlying!Hematological!disorders!if!present!

! Page!782!
Neuro! Polyneuropathy!
Hereditary!Neuropathies:!
CharcotOMarieOTooth!Disease/Hereditary!Motor!&!Sensory!Neuropathy:!
! ! ! ! Group!of!EarlyOOnset!Slowly!Progressive!Polyneuropathy!
! ! ! ! Considerable!Genetic!Heterogeneity;!Mostly!AD!
! ! ! ! Prevalence!is!5!per!100,000!population;!(Pt!are!often!called!back!for!Med!Final!OSCE)!
! Type:! ! Type!I!(Demyelinating),!Type!II!(Axonal),!Type!X!(XOlinked),!Type!3!(DejerineOSottas!disease),!
! ! ! ! Hereditary!Neuropathy!with!Liability!to!Pressure!Palsy!
! Clinical:! ! Gait:!! ! High!Steppage!gait!(due!to!Foot!drop),!±!Sensory!Ataxic!gait!(Romberg!+ve)!
! ! ! ! Inspection:! Pes!Cavus/High!Arched!Foot (Foot!Drop!can!be!initial!Sx)!
! ! ! ! ! ! ! ! (Indicate!Chronicity!+!Childhood!Onset)!
! ! ! ! ! ! ! ! (Also!seen!in!Friedreich's!Ataxia,!Poliomyelitis,!Cerebral!Palsy,!etc)!
! ! ! ! ! ! ! Marked!Distal!Wasting!(Inverted!Champagne!BottleOshaped!LL)!
! ! ! ! Motor:! ! LMNL:! LL!>!UL,!Distal!>!Proximal!
! ! ! ! Sensory:! ! ↓Vibration/Proprioception,!but!Pain/Temp!often!intact!
! ! ! ! ! ! ! Usually!No!Sensory!complaint!(Pt!never!perceived!normal!sensation!before)!
! ! Severity:! Depends!on!Subtype,!but!most!have!Normal!Lifespan!
SMA/Hereditary!Motor!Neuropathy:! (Details!see!Paediatric!Crashcourse)!
! ! ! ! Group!of!Inherited!diseases!affecting!Only!LMN!
! ! ! ! Onset:! Usually!Infancy/Childhood!
! Prognosis:!! Variable!depending!on!Subtype!of!disease!
! ! ! ! Death!from!Resp!Failure!can!occur!from!Early!Childhood!to!Middle!Age!
! ! ! ! AdultOOnset!form!runs!a!more!Benign!course,!can!be!compatible!with!Normal!LifeOspan!

! Page!783!
Neuro! Polyneuropathy!
MND!
Motor!Neuron!Disease:! (Idiopathic!Motor!Neuropathy)!
! ! ! ! Progressive!Degenerative!of!Both!Corticospinal!tract!neurons!&!Anterior!Horn!cells,!
! ! ! ! ! >!Combination!of!UMN!&!LMN!signs!
! ! ! ! Other!name!for!MND!is!ALS!(Amyotrophy!–!LMN;!Lateral!Sclerosis!–!UMN)!
! ! ! ! Incidence:!1O2!per!100,000!population;!LifeOtime!Prevalence!1!in!1,000!
! ! ! ! Mean!Age!of!Onset:! 60;! ! M:F!=!3:2!
! ! ! ! Cause:! Unknown!
! ! ! ! Minority!are!Familial!(could!be!attributed!to!known!Genetic!Defects):!
! ! ! ! ! 5O10%!have!+ve!FHx!suggestive!of!AD!trait!
! ! ! ! ! ! 20%!have!mutations!of!CopperOZinc!Superoxide!Dismutase!(SOD1)!gene!on!Chr21!
! ! ! ! Majority!are!Sporadic!cases,!with!2%!having!SOD1!gene!mutations,!
! ! ! ! ! 1%!having!Neurofilament!Heavy!Chain!Gene!mutations!
! Clinical:! ! Mixed!UMN!&!LMN!Involvement!
! ! ! ! Fasciculations,!Muscle!Wasting,!Weakness,!Brisk!Tendon!Jerks!with!Upgoing!Plantar!responses!
! ! ! ! Eye!&!Sphincter!control!are!Spared!until!Late!stage!
! ! ! ! Bulbar!&!Respiratory!Muscles!involvement!with!Progression!
! ! ! ! Sensory!component!is!Not!affected!primarily!in!MND!
! Neurophysiology:! Widespread!Motor!Denervation,!but!Preserved!Sensory!responses!
! ! Ddx:! ! Both!UMN!&!LMN!Signs:! Cervical!MyeloRadiculopathy!(Cord!+!Root!involvement)!
! ! ! ! ! ! ! ! ! Subacute!Combined!Degeneration!of!Cord!
! ! ! ! Isolated!LMN!Signs:! ! SMA!
! ! ! ! ! ! ! ! ! Multifocal!Motor!Neuropathy!
! ! Tx:! ! No!Tx!of!Unequivocal!Benefit!to!Reverse/Halt!disease!Progression!
! ! ! ! Nutritional!Care!&!Physical!therapy!to!prevent!Cx!from!Immobility!
! ! ! ! ! Die!from!Resp!Failure!or!Pulmonary!Cx!2O4!years!after!Onset!
! ! ! ! Psychological!Support!to!Pt!&!Family!also!important!
! ! ! ! Assisted!Ventilation!with!Permanent!Tracheostomy!&!Mechanical!Ventilator:!
! ! ! ! ! Prolong!Survival!(as!well!as!Pt!&!Carers’!Sufferings),!or!Euthanasia?!(Controversial)!
!

! Page!784!
Neuro! Polyneuropathy!
 Neuro&NMJ&Disorder&
NMJ!Disorder:! ! Presynaptic!vs!Postsynaptic!
Clinical:! ! ! Fluctuating!Weakness,!Fatigability!
! ! ! ! ExtraOOcular!Muscle!Involvement!(‘Safety!Factor’)!
MG!
Myasthenia!Gravis:! Acquired!AI!NMJ!disorder!(Postsynaptic!disorder)!of!Skeletal!muscles!
! ! ! ! AutoAb!to!Nicotinic!AChR!at!Postsynaptic!membrane>!Dysfunction/Destruction!of!AChR!
! ! ! ! Prevalence!4!per!100,000,!Incidence!0.4!per!100,000!
! ! ! ! Age!of!Onset!30;!M:F=3:4!(1:2);!Young:!F>M!vs!Elderly:!M>F!
Association:! ! Thymic!Pathology:! Thymic!Hyperplasia!70%!
! ! ! ! ! ! ! ! Thymoma!15%!(30%!Invasive)!
! ! ! ! ! ! ! ! ! More!Severe!&!More!likely!related!to!AI!diseases!
! ! ! ! Other!AI!diseases:! AI!Thyroiditis,!AI!Adrenalitis,!RA!&!other!CTD,!Pernicious!Anemia,!IBD,!
! ! ! ! ! ! ! ! Hemolytic!Anemia,!AI!Thrombocytopenia,!Aplastic!Anemia,!
! ! ! ! ! ! ! ! Primary!Ovarian!Failure,!Pemphigus!
Clinical:!
! Weakness:!
! ! Nature:! Fluctuating!(Not!Progressive)!
! ! ! ! Fatigability!(Weaker!with!Activity,!Improve!with!Rest)!
! ! Site:! ! *Ocular!involvement:! ! Present!initially!in!50%!Pt,!eventually!90%!Pt!during!the!course!
! ! ! ! ! Levator!Palpebrae:! Ptosis!
! ! ! ! ! EOM:! ! ! Diplopia!(EOM!weakness!typically!Asymmetric,!thus!Diplopia)!
! ! ! ! ! ! (NB:! ! ! Weakness!of!MR!&!LR!can!produce!“PseudoOINO”!picture)!
! ! ! ! Extraocular!involvement:!
! ! ! ! ! Facial!muscles:! Variable!weakness!
! ! ! ! ! Bulbar!muscles:!Variable!weakness;!Often!with!Neck!weakness!(Flexion/Extension)!
! ! ! ! ! ! ! ! Bulbar!Sx!important!–!Risks!of!Aspiration!
! ! ! ! ! Limb!muscles:! Usually!Proximal;!Often!relatively!Mild!
! ! ! ! ! ! ! ! Isolated!Limb!weakness!as!the!presenting!Sx!is!Rare!(<10%!Pt)!
! ! Exacerbations:!
! ! ! ! May!be!triggered!by!exposure!to:!
! ! ! ! ! Bright!Sunlight,!Surgery,!Immunization,!Emotional!Stress,!Menstruation,!
! ! ! ! ! Intercurrent!illness!(eg.!Viral!infection),!Drugs!
! Course:! ! ! Spectrum:!AntiOAChR!+ve!or!–ve!
! ! ! ! ! ! Thymic!Pathology!present/absent!
! ! ! ! ! ! AntiOMuSK!+ve!if!in!AntiOMuSK!Syndrome!(More!Severe)!
! ! ! ! ! ! Ocular!MG!&!Generalized!MG!
! ! Ocular!MG:!
! ! ! ! Ocular!involvement!only!
! ! ! ! Remains!exclusive!in!16%!Pt!only!in!the!West!(But!Pure!Ocular!MG!quite!common!in!Chinese)!
! ! ! ! If!Ocular!MG!for!long!time!(eg.!3!years),!Less!likely!to!become!Generalized!MG!
! Page!785!
Neuro! NMJ! Disorder!
! ! Generalized!MG:!
! ! ! ! Usually!both!Ocular!&!Extraocular!involvement!
! ! ! ! ! Generalized!weakness!without!Ocular!weakness!is!Rare!
! ! ! ! Progress!from!Mild!to!more!Severe!disease!over!weeks!to!months!
! ! ! ! Weakness!tend!to!spread!from!Ocular!to!Facial!to!Bulbar,!then!to!Truncal!&!Limb!muscles!
! ! ! ! ~87%!Pt!have!Generalized!disease!within!13!months!after!onset!
! ! ! ! ! Interval!from!onset!to!Max!weakness!<36!months!in!83%!Pt!
! ! ! NB:! AntiOMuSK!+ve!MG:! Usually!Generalized!MG;!More!common!to!have!Myasthenic!Crisis!
! ! Myasthenic!Crisis:!
! ! ! ! Severe!cases!of!MG;!Resp!muscles!are!involved>!LifeOthreatening!Resp!Failure!
! ! ! ! Precipitating!factors!(2001!SAQ):!
! ! ! ! ! Infection,!Surgery,!Drug,!(Poor!Drug!Compliance)!
! ! ! ! Vaccination!(Influenza,!Pneumococcus)!may!be!helpful?!
! ! ! Mx:! Stop!AntiCholinesterase!(Reintroduce!after!Stabilization)!
! ! ! ! Monitor!FVC!(More!indicative!of!Muscle!effort,!cf!FEV1!in!Asthma!for!Small!airways)!
! ! ! ! ! Intubation!&!Mechanical!Ventilation!if!necessary!
! ! ! ! Protect!from!Aspiration!(NPO,!NG!tube!if!necessary)!
! ! ! ! IVIG/Plasmapheresis!to!hasten!recovery!
! ! ! ! Treat/Withdraw!Triggers!
! ! Transient!Myasthenia!in!Newborn:!
! ! ! ! Can!follow!Placental!transfer!of!Maternal!AChR!Ab!
Demonstration!of!Fatigability!–!Essential!for!Dx:!
! Hx:! ! ! Worsens!with!Activity/Exercise,!Improves!with!Rest!
! ! ! ! Worsen!towards!End!of!the!day!
! PE:! Ocular:! Ptosis!exacerbated!by!Sustained!Upward!gaze!(for!1!min)!
! ! ! NB:! Cogan’s!Lid!Twitch!sign!may!be!seen!during!testing:!
! ! ! ! ! Pt!may!look!down/close!eyes!shortly!to!alleviate!Fatigability,!
! ! ! ! ! ! then!Upward!Saccade,!sometimes!excessively!causing!Transient!Lid!Retraction,!
! ! ! ! ! ! then!slowly!droop!back!to!Ptotic!position!
! ! Bulbar:! Dysarthria!exacerbated!by!Counting!from!0O100!
! ! ! ! ! May!become!Nasal!speech!
! ! Proximal:!
! ! ! UL:! Sustained!Shoulder!Abduction!(May!measure!Arm!Abduction!Time)!(±!Resistance!by!examiner)!
! ! ! ! ! Pt!either!can’t!hold!up,!or!weakness!becomes!Apparent!on!subsequent!manual!testing!
! ! ! LL!(seldom!tested):!
! ! ! ! Sustained!Leg!Elevation!on!Supine,!or!
! ! ! ! Repeated!arising!from!chair!without!use!of!arms!
! ! ! ! ! May!see!Excessive!LeanOforward,!or!ButtockOfirst!maneuver!
! Ix:! ! ! Confirmed!Electrophysiologically!by!RNS!
Ix:! ! ! ! MG!is!a!Clinical!Dx;!No!Gold!Standard!Confirmatory!test!
! Bedside!Test:! Not!Definitive!Dx!

! Page!786!
Neuro! NMJ! Disorder!
! ! Tensilon!test:!
! ! ! ! Temporary!Improvement!by!IV!10!mg!Edrophonium!(ShortOacting!AChEI,!t1/2!30min)!
! ! ! ! ! (2!mg!initially;!If!No!undesirable!S/E,!then!a!further!8!mg!30s!later)!
! ! ! ! False!–ve/+ve!are!Common!
! ! ! ! (David!Wong:! Can!use!Hess!chart!to!document!ocular!excursion,!so!as!to!objectively!measure)!
! ! ! NB:! (May!need!another!Placebo!with!Saline!infusion!to!keep!the!test!more!objective)!
! ! ! ! Be!prepared!for!possible!Resp!distress!
! ! Ice!Pack!test:!
! ! ! ! Alternative!if!Tensilon!test!can’t!be!performed!(eg.!Pt!with!Cardiac!disease,!Asthma)!
! ! ! ! Ice!pack!on!Closed!Eyelids!for!few!minutes>!Ptosis!reassessed!for!Improvement!
! ! ! ! Mechanism:! Cooling>!↓Activity!of!AChE>!Improve!NM!Transmission!
! Serology:!
! ! AntiOAChR:!Sensitivity:! +ve!in!60O90%!(Sero!+ve!MG)!(60%!in!Ocular!MG,!90%!in!Generalized!MG)!
! ! ! ! ! ! ! Chinese!Pt:! 30O70%!
! ! ! ! Specificity:! High!(up!to!100%)!
! ! Others:! AntiOMuSK:! AntiOMuscle!Specific!Kinase!Ab!
! ! ! ! ! ! ! +ve!in!50%!Pt!with!AntiOAChR!–ve!(Sero!–ve!MG)!
! ! ! ! AntiOSM:! ! AntiOStriated!Muscle!Ab!
! ! ! ! ! ! ! +ve!in!84%!Pt!<40!yo!with!Thymoma!( Check!for!Thymoma!in!<40!yo!if!+ve)!
! ! ! ! ! NB:! ! In!Pt!aged!>40,!AntiOSM!can!be!+ve!without!Thymoma!
! ! ! ! Others:! ! AntiOLRP4!Ab,!AntiOAgrin!Ab!
! Electrophysiology:! Mandatory!for!Sero!–ve!MG!
! ! Repetitive!Nerve!Stimulation!Test!(RNS):!
! ! ! ! Measure!Fatigability!
! ! ! ! Significant!Decremental!response!(cf!Incremental!response!in!LEMS)!
! ! ! ! ! Under!3Hz!stimulation,!Decremental!Response!>10%!by!4th/5th!action!potential!
! ! SingleOfiber!EMG!(SFEMG):!
! ! ! ! Done!if!RNS!in!doubt;!Most!Specific!test!but!Technically!difficult!to!do!
! ! ! ! Jitter!&!Blocking!are!diagnostic!
! Others:!
! ! For!Thymoma!(in!All!Newly!Dx!MG):!
! ! ! ! CXR,!Contrast!CT!Thorax!
! ! For!Asso!AI!diseases:!
! ! ! ! TFT,!etc!
Tx:!
1.!Supportive!
2.!Medical:!
! AntiOCholinesterase:!
! ! ! ! The!only!required!drug!in!Mild!disease!
! ! Agents:! 1st!line:! Pyridostigmine!(Mestinon)!(LongerOacting!than!Edrophonium)!
! ! ! ! 2nd!line:! Neostigmine!(Usually!if!Pyridostigmine!Unavailable)!

! Page!787!
Neuro! NMJ! Disorder!
! ! Cholinergic!S/E:!
! ! ! ! Muscarinic:! Salivation,!Diarrhea,!Abd!cramps!
! ! ! ! ! NB:! ! AntiOMuscarinic!(eg.!Propantheline,!Atropine)!may!help!counteract!these!S/E!
! ! ! ! Nicotinic:! ! Muscle!weakness,!Muscle!Fasciculations!
! ! ! ! ! Cholinergic!crisis:!
! ! ! ! ! ! ! If!overdose,!can!lead!to!Flaccid!Paralysis!
! ! ! ! ! ! ! Ddx!from!Myasthenic!crisis:!
! ! ! ! ! ! ! ! Hx,!PE!(Check!Pupils),!Tensilon!test!(Worsens!Cholinergic!crisis)!
! Immunomodulating!therapy:!
! ! ! ! For!ModerateOSevere!disease/Inadequate!response!to!AntiCholinesterase!
! ! ! ! ! Usually!required!in!Generalized!MG!
! ! Agents:! Steroid!
! ! ! ! Azathioprine!(Mainstay,!usually!after!a!dose!of!Steroid),!Cyclosporin,!Cyclophosphamide,!etc!
! Others:! ! IVIG:!! ! ! Usually!for!ModerateOSevere!MG!worsening!into!Crisis!
! ! ! ! Plasma!Exchange:! Usually!reserved!for!Myasthenic!Crisis!&!Refractory!cases!
3.!Surgery!(Thymectomy):!
! ! ! ! Can!induce!remission!(esp!in!Thymic!Hyperplasia)!
! Indication:!! Thymoma!(Consider!postOop!RT/Chemo!if!Invasive)!
! ! ! ! Young!Pt!(Age!10O55)!with!Generalized!MG!even!without!Thymoma:!
! ! ! ! ! Full!Recovery!in!1/3,!Improvement!in!1/2!
! ! NB:! ! In!Ocular!MG,!should!be!delayed!at!least!2!years!to!allow!for!spontaneous!remission!
! ! ! ! Not!recommended!in!Pt!with!AntiOMuSK!+ve!
! Approach:!! TransOsternal!rather!than!Endoscopic!(Ensure!Complete!Clearance)!
4.!Education:! ! Educated!for!Acute!Deterioration!esp!SOB!&!Dysphagia!(Crisis)>!Attend!A&E!if!notice!Sx!
Drugs!to!avoid:! ! Aminoglycosides!(2008!MCQ!88,!2009!MCQ!68),!Penicillamine,!Sedatives,!
! ! ! ! NonODepolarizing!NMB,!Some!AntiOArrhythmic!(Quinidine,!Lignocaine,!Procainamide,!BB)!

! Page!788!
Neuro! NMJ! Disorder!
Others:!
LambertOEaton!Myasthenic!Syndrome!(LEMS):!
! ! ! ! Rare!disorder!
! ! ! ! ImmuneOmediated!Presynaptic!NMJ!disorder!(VoltageOgated!P/QOtype!Ca!channel!Ab)!
! ! ! ! ! >!Impaired!Ca!channelOmediated!ACh!Release!
! Presentation:! Variable!Weakness!of!Proximal!muscles!(esp!Legs,!cf!MG)!
! ! ! ! Mild!Ocular!involvement,!Limb!Reflexes↓!
! ! ! ! Weakness!Improve!with!repeated!Muscle!use!(Weaker!in!Morning,!Best!at!End!of!Day)!
! ! ! ! ! (Lambert’s!sign:!Improvement!of!Power!on!Repeated!Hand!Grip)!
! ! ! ! Autonomic!involvement!(also!has!P/QOtype!Ca!channel)!
! Association:! EarlyOonset:! Idiopathic!AI!disorder!
! ! ! ! *LateOonset:! Often!SCLC!(Paraneoplastic)!
! Dx:! ! ! Fast!RNS:! Incremental!response!
! ! ! ! AutoAb!to!P/QOtype!VGCC!
! Tx:! ! ! Steroid,!Plasma!Exchange,!3,4ODiaminopyridine,!AntiCholinesterase,!Removal!of!Tumour!
Botulism:! ! ! Rare!
! ! ! ! Endotoxin!by!Clostridium!botulinum!(Heat/DryOResistant!Spores)!
! ! ! ! Botulinum!Toxins!bind!to!Motor!nerve!terminals,!Block!&!Destroy!AChR!
! Source:! ! Food:! Contaminate!Inadequately!Preserved!food,!Eg.!Sausages,!Canned!meat,!Mushroom!
! ! ! ! Wound:! Traumatic!injury!with!wounds!contaminated!with!Soil!
! ! ! ! ! ! Can!appear!in!IVDU!too!
! Presentation:! Acute!Symmetrical!Descending!Flaccid!Paralysis!with!Autonomic!involvement!
! Tx:! ! ! No!specific!therapy!(Botulism!Immune!Globulin!IntravenousOHuman/BIGOIV!not!used?)!
! ! ! ! Supportive!&!Ventilatory!care!while!awaiting!Regeneration!of!Motor!nerve!terminals!
! ! ! ! ! (Spontaneous!Recovery)!
(Congenital!Myasthenia):!
! ! ! ! Heterogeneous!group!of!NonOImmune!disorders;! Mostly!AR!
! ! ! ! Present!at!Birth/Early!Childhood!
! ! ! ! NonOProgressive,!often!Improve!in!Adolescence!
! Types:! ! Presynaptic:! Familial!Infantile!Myasthenia!
! ! ! ! Postsynaptic:! Congenital!NMJ!Acetylcholinesterase!Deficiency,!AChR!Deficiency!
!

! Page!789!
Neuro! NMJ! Disorder!
 Neuro&Myopathy&
Myopathy:!
Old!Definition:! ! Inherited,!All!Sx!due!to!Muscle!Weakness,!Progressive,!
! ! ! ! No!Histopathological!abnormalities!other!than!Degeneration!&!Regeneration!
Clinical:! ! ! Weakness!Onset:! Usually!Gradual!rather!than!Acute!
! ! ! ! Distribution:! ! Symmetrical!
! ! ! ! Proximal!Limb!more!Impaired:! Difficulty!in!Climbing!Stairs,!Rising!from!Sitting!Position,!
! ! ! ! ! ! ! ! ! ! Combing!Hair!
! ! ! ! If!Progressive:! Weakness!of!Neck!Flexors,!Dysphagia,!Voice!changes,!Resp!Failure!may!occur!
! ! ! ! Sensation!&!Sphincter!functions!are!Unimpaired!
! ! ! ! Tendon!Reflexes!are!Preserved!until!Late!stages!of!disease!
! ! ! ! Pain!&!Cramps!occur!in!Inflammatory!Myopathies!
Ix:! Muscle!Enzymes:!CK,!Myoglobin,!AST,!LDH!
! ! ! ! ! ↑or!Not!depend!on!Type!&!Severity!of!Myopathic!process!
! Needle!EMG:! Can!define!Activity,!but!Not!Etiology!
! Muscle!Biopsy:! Not!as!damaging!as!Nerve!Biopsy!(can!regenerate)!
! Genetic!studies!
! Systemic!causes:!Eg.!Endocrinopathies!
Etiology:!
! Acquired:! ! Inflammatory!Myopathies:!! ! Polymyositis,!Dermatomyositis,!Inclusion!body!Myositis,!
! ! ! ! ! ! ! ! ! ! ! InfectionOrelated!
! ! ! ! Complicating!Systemic!Diseases:! ! CTD,!Endocrinopathies,!Sarcoidosis,!
! ! ! ! ! ! ! ! ! ! ! Critical!Illness!Myopathy!
! ! ! ! Toxic!Myopathies!(DrugOinduced)!
! ! ! ! Rhabdomyolysis!
! Inherited:! ! Muscular!Dystrophies:! ! ! Dystrophinopathies,!FacioScapuloHumeral!Dystrophy,!
! ! ! ! ! ! ! ! ! ! ! LimbOGirdle!Dystrophies!
! ! ! ! Metabolic:! ! ! ! ! ! Mitochondropathies,!Glycogenoses,!Lipid!
Myopathies!
! ! ! ! Congenital!Myopathies!
! ! ! ! Channelopathies:! ! ! ! Myotonic!disorders,!Periodic!Paralysis,!
! ! ! ! ! ! ! ! ! ! ! Malignant!Hyperthermia!
Inflammatory!Myopathies:!
! ! ! ! Major!group!of!‘treatable’!Myopathies!
! Types:! ! Infection:! ! Viral!–!Coxsackie,!Echovirus,!Influenza,!HIV!
! ! ! ! ! ! ! Bacterial!–!Leptospirosis!
! ! ! ! ! ! ! Parasitic!–!Toxoplasmosis,!Trichinosis,!Cysticercosis!
! ! ! ! DrugOinduced,!Sarcoidosis,!
! ! ! ! Idiopathic!(Unknown!or!AI!causes;!Majority!of!Clinically!important!Inflammatory!Myopathies)!
Idiopathic!Inflammatory!Myopathies:!
! ! ! ! Chronic!Lymphocytic!&!MQ!Infiltration!in!Muscle!tissue!
! Page!790!
Neuro! Myopathy!
! ! Types:! Polymyositis,!Dermatomyositis,!Inclusion!Body!Myositis!(Uncommon)!
! Polymyositis:! Occur!in!Isolate!or!Associated!with!other!AI!CTD!
! ! ! ! Subacute/Chronic!Onset,!Progressive!
! ! ! ! Incidence!peaks!from!Age!40O60;! *F!
! ! Ix:! ! Muscle!Biopsy:! Endomysial!Infiltration!of!Mononuclear!cells!(TOcell!mediated)!
! ! ! ! ! ! ! Scattered!Muscle!Fibre!Necrosis!
! ! ! ! AntiOJoO1!Ab!found!in!20O30%!of!cases!&!Associated!with!Interstitial!Pneumonitis!
! Dermatomyositis:!
! ! ! ! Affect!Younger!population!than!Polymyositis!
! ! ! ! Mediated!by!Humoral!Factors!against!Capillary!Endothelial!cells!
! ! ! ! ! >!ComplementOmediated!Microangiopathy!
! ! ! ! Muscle!damage!is!Secondary!to!Ischemia!(Vasculitis)!
! ! Association:!15%!of!AdultOOnset!Dermatomyositis!is!TumourOrelated,!ie.!Paraneoplastic!
! ! ! ! ! Ix!for!underlying!Malignancy!is!essential!(eg.!*NPC!in!HK,!GI,!Gynecological)!
! ! ! ! Childhood:! Scarring,!Calcinosis,!Contractures!
! ! ! ! Adult:! ! Malignancy!in!60%!(actually!varies!from!6%!to!60%!for!different!studies)!
! ! Ix:! ! Muscle!Biopsy:! Perivascular!&!Perifascicular!Infiltration!
! ! ! ! Dermatological!manifestations!occur!in!90%!of!cases:!(Rash!can!be!Photosensitive)!
! ! ! ! ! Heliotrope!Rash!(BlueOPurplish!Discoloration)!on!Upper!Eyelids!with!Edema!
! ! ! ! ! Flat!Red!Rash!on!Face!&!Upper!Trunk!
! ! ! ! ! Gottron’s!Papules:! Erythematous!Induration!+!Violaceous!Scaly!Eruption!
! ! ! ! ! ! ! ! ! ! of!Knuckles!(MCPJ)!&!other!Extensor!surface!
! ! ! ! ! Telangiectasia!
! Mx:! ! ! Supportive!Care!+!Immunosuppression!therapy!&!Close!clinical!Monitoring!of!Tx!Response!
! ! ! ! Biochemical!Monitoring!with!CK!is!Not!Reliable!
! ! ! ! ! Level!might!Not!Correlate!with!disease!Activity!
Polymyositis! Endomysial!Infiltration! T!cell!mediated! Asso.!with!CTD!
Dermatomyositis! Perimysial!Infiltration! B!cell/Complement!mediated! Asso.!with!Malignancy!
Rhabdomyolysis:! Acute!Fulminating!Massive!Muscle!Necrosis!
! Cause:! ! Major!Trauma,!Convulsion,!Heat!Stroke,!DrugOinduced/Infective/Metabolic!Myopathies!
! ! Ddx:! ! Muscle!injury/ischemia:!
! ! ! ! ! Trauma,!Pressure!Necrosis,!Electric!Shock,!Burns,!Acute!Vascular!disease!
! ! ! ! Myofibre!Exhaustion:!Seizures,!Excessive!Exercise,!Heat!Exhaustion!
! ! ! ! Toxins:! Alcohol,!Cocaine,!Heroin,!Amphetamines,!Ecstasy,!Phencyclidine,!Snakebite!
! ! ! ! Drugs:! Statins,!Fibrates,!Zidovudine,!Neuroleptic!Malignant!syndrome,!Azathioprine,!
! ! ! ! ! ! Theophylline,!Lithium,!Diuretics!
! ! ! ! Electrolyte!disorders:!HypoPO4,!HypoK,!Excess!Water!shifts!(Hyperosmolarity)!
! ! ! ! Infection:! Viral:!! Influenza,!HIV,!Coxsackievirus,!EBV!
! ! ! ! ! ! Bacterial:! Legionella,!Francisella,!S.!pneumoniae,!Salmonella,!S.!aureus!
! ! ! ! Familial:! McArdle’s!disease,!Carnitine!palmitoyl!transferase!deficiency,!
! ! ! ! ! ! Malignant!Hyperthermia!

! Page!791!
Neuro! Myopathy!
! ! ! ! Others:! HypoT,!Polymyositis/Dermatomyositis!
! Clinical:! ! Widespread!Muscle!Pain,!Weakness,!Dark!Urine!
! ! ! ! Myoglobinuria!is!an!early!feature:! May!lead!to!ARF!
! ! ! ! ! Urine!dipstick!+ve!for!‘Blood’,!but!Microscopy!will!Not!show!RBC!
! ! ! ! Massive!↑CK!
! Cx:! ! ! ARF,!HyperUricemia,!HyperK,!HypoCa,!HyperPO4,!DIC!(Late!Cx)!
! Mx:! ! ! Osmotic!&!Alkaline!Diuresis!to!promote!Excretion!of!Myoglobin!
! ! ! ! Renal!Replacement!therapy!when!indicated!
! ! ! ! Correction!&!Treat!Cx!of!Electrolyte!abnormalities!
Muscular!Dystrophies:!
! Old!Definition:! Inherited!Myopathy,!Progressive,!Sx!due!to!Weakness,!
! ! ! ! No!Histopathological!abnormalities!other!than!Degeneration!&!Regeneration!
! Types:! ! Common:! ! Duchenne!MD,!Becker!MD,!FacioScapuloHumeral!Dystrophy,!LimbOGirdle!MD,!
! ! ! ! ! ! ! (Emery!Dreifuss!Dystrophy)!
! ! ! ! Less!Common:! Congenital!MD,!Distal!MD,!OculoPharyngeal!MD!
! ! ! ! (Myotonic!Dystrophy:!Included,!but!might!be!better!to!consider!it!with!a!different!class)!
! Classification:! Phenotypic!
! ! ! ! Immunohistochemical:! DystrophinOopathy,!SarcoglycanOopathy!(LGMD)!
! ! ! ! ! ! ! ! ! (Laminin,!Caveolin,!Calpain,!Dysferlin)!
! ! ! ! Genetic:! ! DMD/BMD:! Deletion!in!Dystrophin!gene;! XOlinked!(Xp21)!
! ! ! ! ! ! ! FSHD:! ! 4q35;! ! ! ! ! AD!
! ! ! ! ! ! ! LGMD:! ! Many!(at!least!15);! ! ! AD/AR!
! Muscle!Membrane!Protein!Components!Deficiencies:!
! ! ! ! Dystrophin!(Dystrophinopathies)!vs!Sarcoglycan!(Sarcoglycanopathies)!
! ! ! ! ! Dystrophin:!DMD/BMD;! ! Sarcoglycan:!LGMD!(Some)!
! ! ! ! DMD:! Dystrophin!Stain:! No/Few!+ve!Fibres!
! ! ! ! BMD:! Quantitative!method!by!Western!Blot!demonstrates!Partial!Deficiency,!
! ! ! ! ! ! ! or,!more!often,!↓Amount!of!Smaller!MW,!Functionally!Abnormal!Proteins!
! ! ! ! Recently,!Defects!involving!several!membrane!protein!components!were!found!in!other!MD!
! ! ! ! DystrophinOGlycoprotein!Complex:! Components!include!Dystrophin!&!Sarcoglycan!
! ! ! ! ! MembraneOassociated!Protein!Muscle!that!Span!Muscle!Sarcolemma!
! ! ! ! ! Key!role!in!maintaining!Muscle!Membrane!Stability!
! ! ! ! ! Disruption!would!lead!to!a!cascade!of!events!resulting!in!Muscle!cell!Damage!
DMD/BMD:!
! Pathogenesis:! Absence!of!Dystrophin!protein!alter!Structural!&!Biochemical!properties!of!Skeletal!muscle!
! ! ! ! If!mutation!allows!some!production!of!DMD!protein,!Clinical!features!are!Milder!(BMD)!
! DMD:! ! Incidence:!1!in!3,500!male!live!births!in!Caucasian!
! ! Course:! Mild!Delay!in!Motor!Milestones,!Progressive!Weakness!from!Age!3O5!
! ! ! ! ! Begins!to!manifest!at!Early!Childhood!with!Difficulties!in!Running!&!Later!Climbing!stairs!
! ! ! ! WheelchairObound!by!Age!of!9O12,!Resp!Failure!by!Late!Teens!
! ! ! ! Death!in!Late!Teens!or!Early!20s,!from!Resp!&!Cardiac!Cx!
! Page!792!
Neuro! Myopathy!
! ! Clinical:! Knee!&!Hip!Extensor!Weakness!–!Gower’s!sign!in!Children!(Waddling!Gait!in!Adult):!
! ! ! ! ! Climb!up!by!Pushing!Down!on!Thighs!to!Extend!Hips!&!Trunk!
! ! ! ! Pseudohypertrophy!(Enlarged!Calves)!
! ! ! ! Cardiomyopathy!&!ECG!Conduction!abnormalities!are!common!
! ! ! ! Mild!Mental!Impairment!
! ! Ix:! ! CK!level↑!>10x!ULN!until!Late!stage!
! ! ! ! Muscle!Biopsy:! Characteristic!Immunohistological!findings!(No/Few!Dystrophin!+ve!Fibres)!
! BMD:! ! Less!Severe!clinical!manifestations!
! ! ! ! Continue!to!ambulate!beyond!Age!15,!Death!delayed!until!MiddleOAge!(40O60)!
! Variant:! ! Outliers:! Intermediate!variant!
! ! ! ! ! ! Ability!to!walk!is!Retained!after!Age!12,!but!Not!beyond!15!
! ! ! ! Mild!Variants!with!NonOdisabling!LaterOonset!Weakness!also!occur!
! Mx:! ! ! Supportive:! Splinting!&!Physiotherapy,!Corrective!Surgeries,!Ventilatory!care!
(Emery!Dreifuss!Dystrophy):! XOlinked/AD!
! ! ! ! Present!Early!with!HumeroPeroneal!Wasting,!
! ! ! ! ! with!Prominent!Contractures!&!Striking!Cardiac!abnormalities!
FSHD:! ! ! AD;! Disease!Intensity!varies!even!within!Same!family!
! ! ! ! Combination!of!Facial!Weakness!&!Scapular!Winging!is!characteristic!
! ! ! ! (Can!affect!LL!in!some!as!well)!
! ! ! ! Onset!during!Adolescence!
LGMD:! ! ! Prevalence!1!in!100,000;! AD/AR!
! ! ! ! Typical!Presentation!is!Progressive!Proximal!Wasting!&!Weakness!from!Childhood!
! ! ! ! Clinical!presentation!might!Mimic!other!Muscular!disorders!
! ! ! ! (Face!Never!Involved;!Sometimes!can!have!Pseudohypertrophy!of!Calves)!
Metabolic!Myopathies:!
! Cause:!
! ! Glycogen!Storage:! McArdle’s!disease,!Tarui’s!disease,!Pompe’s!disease/Acid!Maltase!Deficiency!
! ! Lipid!Storage:! ! Carnitine!Deficiency,!Carnitine!Palmityl!Transferase!Deficiency!
! ! Disorders!of!Mitochondrial!Resp!Chain!
! Clinical:! ! Exercise!Intolerance,!Cramps,!Rhabdomyolysis,!Progressive!Weakness!
! Related!problems:!
! ! ! ! Polyneuropathy,!Encephalopathy,!StrokeOlike!episodes,!Epilepsy,!Myoclonus,!Retinopathy,!
! ! ! ! Ophthalmoplegia,!Deafness,!Migraine,!Cerebellar!Ataxia,!Cardiomyopathy,!
! ! ! ! Renal!Tubular!defects,!Endocrinopathies,!Short!Stature,!Lactic!Acidosis,!Pancytopenia,!IO!
! Acquired!Metabolic!Myopathies!are!commonly!Secondary!to!Endocrinopathies:!
! ! ! ! Hyper/HypoT,!Cushing!syndrome,!Parathyroid!problems,!Acromegaly,!Vit!D!Deficiency!
! ! ! ! (Usually!LowOgrade,!Presentation!will!be!Mild!Proximal!Weakness!only)!
(Congenital!Myopathies):!
! ! ! ! Rare!Developmental!NM!disorders,!Manifest!at!Birth!as!Infantile!Hypotonia!
! ! ! ! Mostly!NonOProgressive/only!Slowly!Progressive!
! ! ! ! Congenital!Myopathies!are!Not!classified!as!Muscular!Dystrophies!
! Page!793!
Neuro! Myopathy!
! ! ! ! Dx!rely!on!Histopathology!
! Types:! ! 40!different!types!are!Identified!
! ! ! ! Eg:! Central!Core!Disease,!Nemaline,!Rod!Myopathy,!Centronuclear/Myotubular!Myopathy,!
! ! ! ! ! Congenital!Fibre!Type!Disproportion!
Skeletal!Muscle!Channelopathies:!
! ! ! ! Disorders!of!VoltageOgated!Ion!channels!affect!Excitable!tissues!(Muscle,!Nerve,!Renal!Tubules)!
! ! ! ! Myotonia!&!Periodic!Paralysis!are!2!main!disorders!related!to!Skeletal!Muscle!Channelopathies!
! ! ! ! Mechanisms:! Failure!to!Maintain!Muscle!Membrane!in!Refractory!state!due!to!Leaky!
Channel!
! ! ! ! Mostly!AD,!Mutant!(Leaky)!channels!vs!Normal!channels!
! ! ! ! Depolarization!occurs!when!Normal!Resting!Potential!is!disrupted!by!Ion!Leakage:!
! ! ! ! ! Mild!(5O10!mV):!! Minor!Leakage!=!Myotonia!
! ! ! ! ! ! ! ! ! Normal!channels!can!Restore!back!Resting!Potential!
! ! ! ! ! ! ! ! ! >!Muscle!Fibre!can!be!Depolarized!again!via!Mutant!channels!
! ! ! ! ! ! ! ! ! >!Repetitive!Firing!&!Myotonia!
! ! ! ! ! Strong!(20O30!mV):! Major!Leakage!=!Periodic!Paralysis!
! ! ! ! ! ! ! ! ! Normal!channels!canNot!Restore!Resting!Potential!
! ! ! ! ! ! ! ! ! >!Muscle!Fibre!Persistently!Inexcitable>!Flaccid!Paralysis!
! ! ! ! Variable!Clinical!manifestation!&!Disease!Severity!related!to!Ratio!of!Mutant!&!Normal!
channels!
! Types:! ! Na!channel:! Paramyotonia!Congenita,!KOSensitive!Periodic!Paralysis,!KOAggravated!
Myotonia!
! ! ! ! Ca!channel:! HypoK!Periodic!Paralysis,!Malignant!Hyperthermia!
! ! ! ! Cl!channel:! Myotonia!Congenita!
! ! ! ! Possibly!Myotonic!Dystrophy!&!Proximal!Myotonic!Myopathy:! Channel!defects!Not!identified!
Myotonia:!! ! Disruption!of!Muscle!Relaxation!after!Contraction;! (Shake!Hand!to!check!for!it)!
! ! ! ! Improve!with!Repeated!Contractions!(WarmOUp!phenomenon),!except!
! ! ! ! ! Paradoxical!Myotonia!(Paramyotonia)!Worsen!after!Repetitive!Contraction!
! ! ! ! TempOrelated!(may!Worsen!in!Cold),!or!Worsen!after!prolonged!Rest!
! ! ! ! Painless!!(cf!Dystonia)!
! Common!Myotonic!Syndromes:!
! ! ! ! Myotonia!Congenita,!Paramyotonia!Congenita,!Proximal!Myotonic!Myopathy,!
! ! ! ! Myotonic!Dystrophy!
! Clinical:! ! First!3!syndromes:! Restricted!to!Skeletal!Muscles!
! ! ! ! Myotonic!Dystrophy:!MultiOSystemic!disease!
! Myotonic!Dystrophy:!(2003!MCQ!61)!
! ! ! ! Myotonia,!Distal!Myopathy;!Slowly!Progressive!
! ! ! ! AD;!Anticipation!phenomenon!
! ! ! ! Mutation:!Unstable!Expansion!of!a!CTG!Trinucleotide!Repeat!on!Chr19q!
! ! ! ! Age!of!Onset!(15O40)!&!Clinical!Manifestations!correlate!with!Size!of!Expansion!
! ! ! ! Trinucleotide!Repeat!can!also!Enlarge!with!Time:! MidOlife!Onset!&!Progressive!Course!
! Page!794!
Neuro! Myopathy!
! ! ! ! Pathogenic!Mechanism!Poorly!Understood!
! ! Clinical:! Weakness!&!Wasting!of!Distal!muscles,!Temporalis,!SCM,!Facial!muscles!
! ! ! ! Ptosis,!Frontal!Balding!
! ! Systemic:! Heart:! ! Conduction!problems!(Arrhythmia)!
! ! ! ! Respiration:! OSA,!Pulmonary!Hypoventilation!
! ! ! ! GI:! ! ! Smooth!muscle!Dysfunction!
! ! ! ! Endocrine:!! DM,!Gonadal!Atrophy,!Low!Metabolic!rate!unrelated!to!HypoT!
! ! ! ! CNS:!! ! Lack!of!Motivation,!Paranoid!Personality,!Cognitive!Dysfunction!(Low!IQ)!
! ! ! ! Eyes:!! ! Cataract,!Retinal!Degeneration!
! ! ! ! Bone:! ! Skull!Hyperostosis,!Air!Sinus!Enlargement,!Small!Pituitary!Fossa!
Periodic!Paralysis:! Episodic!Weakness!with!Hyporeflexia,!Sparing!Bulbar!&!Resp!function!
! ! ! ! Attacks!can!be!Provoked!by!Rest!following!Exercise!
! ! ! ! Primary/Familial:! HypoK!vs!KOSensitive!forms!(HyperK)!
! ! ! ! Secondary:! ! Systemic!diseases!which!produce!Aberration!of!K!Concentration!
! ! ! ! ! Thyrotoxicosis:! Sporadic!syndrome!similar!to!Primary!HypoK!Periodic!Paralysis!
!

! Page!795!
Neuro! Myopathy!
 Neuro&Data&Interpretation&
Cerebral!Calcification:!
! ! ! ! Incidental!finding!in!0.5%!of!CT!scan!in!Elderly!
! ! ! ! 20O30%!with!Widespread!BG!Calcification!exhibit!Neurological!Signs:!
! ! ! ! ! Parkinsonism,!Chorea,!Epilepsy,!Ataxia,!Dementia!
! ! ! ! Association!of!BG!Calcification!with:!
! ! ! ! ! HypoPTH,!PseudoHypoPTH,!Cerebral!Irradiation,!Mitochondrial!diseases!
Papilledema:! ! Fundi!Exam:! Blurred!Disc!Margin!
! Unilateral:!! Optic!Neuritis,!Anterior!Ischemic!Optic!Neuropathy,!Orbital!Tumor,!
! ! ! ! Others!(Central!Retinal!Vein!Occlusion,!Infiltrative!disorder,!Papillophlebitis)!
! Bilateral:! ! Any!of!the!Unilateral!causes!
! ! ! ! ↑ICP:! Intracranial!Mass/Hemorrhage/Infection,!Parenchymal!Edema,!GBS,!
! ! ! ! ! ! Craniostenoses,!BIH!(Benign!Intracranial!HT),!Venous!Sinus!Occlusion/Disorder,!
! ! ! ! ! ! Systemic!Illness!(Hypercapnia!(2006!MCQ!X23),!Polycythemia,!Behcet!disease)!
Wernicke’s!Encephalopathy:!
! S/S:! Common:! Ocular!abnormalities,!Mental!status!changes,!Incoordination!of!Gait!&!Truncal!Ataxia!
! ! ! ! (Triad!of!Confusion,!Ataxia!&!Ophthalmoparesis)!
! ! Uncommon:!
! ! ! ! Stupor,!Hypotension!&!Tachycardia,!Hypothermia,!Epileptic!Seizure,!Hearing!Loss,!
! ! ! ! Bilateral!Visual!disturbances!&!Papilledema,!Hallucination!&!Behavior!disturbances!
! ! LateOStage:!
! ! ! ! Hyperthermia,!↑Muscle!Tone!&!Spastic!Paresis,!Choreic!Dyskinesia,!Coma!
! Clinical!Setting:! Staple!Diet!of!Polished!Rice!
! ! ! ! Chronic!Alcohol!Abuse!&!Malnutrition!
! ! ! ! GI!Surgery:!
! ! ! ! ! Surgery:! Gastrectomy,!Gastrojejunostomy,!Partial/Subtotal!Colectomy,!
! ! ! ! ! ! ! Gastric!Bypass!Surgery,!Vertical!Banded!Gastroplasty,!
! ! ! ! ! ! ! Therapy!with!an!Intragastric!Balloon!
! ! ! ! ! Disorder:! PU,!Gastric!Cancer,!Colon!Cancer,!UC!with!Megacolon,!Severe!Obesity!
! ! ! ! Recurrent!Omitting!or!Chronic!Diarrhea:!
! ! ! ! ! Pyloric!Stenosis,!PU,!DrugOinduced!Gastritis,!Biliary!Colics,!Crohn's!disease,!
! ! ! ! ! Intestinal!Obstruction/Perforation,!LithiumOinduced!Diarrhea,!Migraine!attacks,!AN,!
! ! ! ! ! Pancreatitis,!Hyperemesis!Gravidarum!
! ! ! ! Cancer!&!Chemotherapy:!
! ! ! ! ! Cancer!&!related:! Gastric!Carcinoma,!NHL,!Myelomonocytic!Leukemia,!
! ! ! ! ! ! ! ! ! Large!BOcell!Lymphoma,!Myeloid!Leukemia,!Allogenic!BM!transplant!
! ! ! ! ! Chemotherapeutics:! Erbulozole,!Ifosfamide!
! ! ! ! Systemic!diseases:! Renal!diseases,!AIDS,!Chronic!Infectious!Febrile!diseases,!Thyrotoxicosis!
! ! ! ! Magnesium!Depletion:! Secondary!to!Chronic!Diuretic,!Intestinal!tract!Resection,!Crohn's!
! ! ! ! Chemical!compounds!&!Drugs:! IV!Infusion!HighOdose!Nitroglycerin,!Tolazamide!
! ! ! ! Unbalanced!Nutrition:!
! Page!796!
Neuro! Data! Interpretation!
! ! ! ! ! Absolute!Deficiency!of!Food/Thiamine:!
! ! ! ! ! ! Dietary!Restrictions!owing!to!Economic!reasons!or!Political!trade!embargoes,! !
! ! ! ! ! ! Psychogenic!food!Refusal,!Fasting!for!ReligiousOPhilosophical!reasons,!
! ! ! ! ! ! Starvation!for!Tx!of!Obesity,!Hunger!Strike,!Neglect!in!Old!Age!or!Alzheimer!
! ! ! ! ! Relative!Deficiency!of!Thiamine:!
! ! ! ! ! ! Unbalanced!Total!Parenteral!Nutrition,!Unbalanced!IV!Hyperalimentation,!
! ! ! ! ! ! ReOfeeding!syndrome,!Use!of!Dietary!Commercial!Formula,!Slimming!Diets,!
! ! ! ! ! ! Excessive!Cooking!of!food,!Chronic!use!of!Sulphites!as!Food!Additives!(dogs),!
! ! ! ! ! ! Chronic!use!of!Food!containing!Thiaminases!or!AntiThiamine!Factors!
! Thiamine!Deficiency:!
! ! ! ! After!4!days:! ↓αOKGDH!activity!in!Astrocytes!
! ! ! ! ! ! ! Cytotoxic!Edema!&!Astrocyte!volume!↑!
! ! ! ! After!7O10!days:!↓Transketolase!activity!in!Astrocytes!+!↑NO!from!Endothelial!cell!dysfunction:!
! ! ! ! ! ! ! ! Low!Intracellular!Glutamate!
! ! ! ! ! ! ! ! High!Extracellular!Glutamate!
! ! ! ! ! ! ! ! Loss!of!Cell!Osmotic!gradients!
! ! ! ! ! ! ! ! Free!Radical!production!&!↑!in!Cytokines!
! ! ! ! ! Results!in:!Cytotixic!&!Vasogenic!Edema!in!Astrocytes/Neurons!+!BBB!breakdown!
! ! ! ! After!14!days:! DNA!Fragmentation!in!Neurons!+!↑Lactate!in!Astrocytes/Neurons!
! ! ! ! ! ! ! +!Low!pH!&!Focal!Acidosis!
! ! ! ! ! Results!in:!Neuronal!Necrosis!+!Irreversible!Structural!lesions!in!specific!areas!of!brain!
! ! NB:! ! Thiamine:! Essential!CoOfactor!in!Carbohydrate!Metabolism!
! ! ! ! ! ! ! For!Transketolase,!Pyruvate!Dehydrogenase,!αOKetoglutarate!Dehydrogenase!
! ! ! ! High!Carbohydrate!Intake!without!Vitamin!supplement!precipitates!WE!!
Pneumocephalus:! Can!occur:!! After!Neurosurgery,!Head!&!Facial!Trauma,!Ear!infection,!Spontaneously!
! ! ! ! Small!amounts!of!Air!usually!Reabsorbed!without!Cx!
! ! ! ! With!↑ing!Air!Entrapment,!Significant!Clinical!Sequelae!may!occur:!
! ! ! ! ! Compression!of!Lateral!Ventricle!&!Adjacent!Sulci!&!Gyri!
! ! ! ! ! Midline!Shift!
! ! ! ! ! Uncal!Herniation!
! ! ! ! ! Brainstem!Rotation/Compression!
Paraneoplastic!Limbic!Encephalitis:!
! Types!of!Ab:! AntiOHu!(ANNAO1):! ! ! SCLC!
! ! ! ! AntiOCV!2!(CRMP5):! ! ! SCLC,!Thymoma,!Testicular!Germ!cell!tumor!
! ! ! ! AntiOMa!(Ma!1,!Ma!2):! ! Testicular!cancer,!Lung!cancer,!Breast!cancer!
! ! ! ! AntiAmphiphysis:! ! ! SCLC,!Breast!cancer!
! ! ! ! ANNAO3:! ! ! ! ! SCLC!
! ! ! ! PCAO2:! ! ! ! ! SCLC!
! ! ! ! AntiOVGKC:! ! ! ! Thymoma,!SCLC!
! ! ! ! ‘Novel’!Ab!against!Neuropil:! Thymoma,!Mediastinal!Germ!cell!tumor,!Thyroid!cancer!
Common!Neurology!Emergencies:!
! Page!797!
Neuro! Data! Interpretation!
! ! ! ! Acute!change!in!Sensorium!(Delirium,!Coma),!Stroke/TIA,!CNS!Infection,!Convulsive!SE,!
! ! ! ! Others!(GBS,!MG!crisis)!

! Page!798!
Neuro! Data! Interpretation!