Sunteți pe pagina 1din 20

Chapter 3 Myelination of PNS: ONE Schwann cell myelinates ONE axon, myelination stops at Node of Ranvier.

Major Dense Line: fusion of inner protein layers of schwann cell because cytoplasm disappears. Minor Dense Line: fusion of outer protein layers, results in thin layer in the middle of a tight lipid bilayer. Mesoaxon: double layer of external plasma membrane around the axon. Incisures of Schmidt-Lanterman: major dense line not formed because cytoplasm persists, continuous spiral of cytoplasm from outermost to deepest layer. Provides pathway for metabolites from surface to deep axon. Node of Ranvier: two adjacent Schwann cells terminate, high concentration of Na and K channels Saltatory Conduction! Myelination of CNS: ONE interfascicular Oligodendrocyte myelinates ~ 60 axons, myelination stops at Node of Ranvier. No basement membrane, no mesoaxon, Schmidt-Lanterman and Ranvier Nodes are present! Un-myelinated Nerves: PNS fine axons carrying slow pain (Type IV fibers) and post-ganglionic axons of ANS (Class C fibers). No Node of Ranvier. CNS small axons of CNS and olfactory nerve. No relationship with OGDs. Peripheral Nerve Structure: Nerve Fiber: axon covered by endoneurium (CT) innermost o Blood Nerve Barrier: formed by endothelial cells of capillaries in endoneurium. Tight junctions isolate nerves from blood. Tetanus toxin spreads to spinal cord from peripheral nerves via endoneurial spaces. Bundle of Axons: fascicle covered by perineurium (CT) middle Bundle of Fascicles: nerve covered by epineurium (CT) outermost o Epineurium has plexus of lymph and blood vessels! Blood/Lymphatics of Nerves: Blood supply of nerves (vasa nervosa): peripheral nerves receive blood from nearby arteries.blod vessels from anastamosic plexus in the epineurium so that occlusion of a single vessel does not produce ischemia. o Clinical: Diabetic Neuropathy is due to small vessel disease of vasa nervosa. Mononeuritis Multiplex is due to vasculitis of peripheral nerves. Lymphatics: plexus of lymph vessels in epineurium sheath and drains into regional lymph nodes. If nerve is within subarachnoid space it drains CSF too. Nerve Fiber Classification: Cross Section Diameter of Axon: Alpha to Gamma, B and C thickest to thinnest. o Thicker local anesthetics act slowly o Thinner local anesthetics act quicker and last longer Sensory: Roman numerals (Ia, Ib, II, III, IV) Functional: Sensory, Motor, Autonomic Pre/Post Ganglionic A-Alpha: Thickest, 1 motor, 2 sensory. Carries motor fibers to extrafusal muscle fibers from large alpha motor neurons in ventral gray horn of spinal cord (LMN)

Type Ia: sensory from neuromuscular spindle (intrafusal muscle fibers) Type Ib: sensory from neurotendinous spindles (Golgi Tendon Organ) o Both unconscious A-Beta: Type II, 2nd thickest, only sensory, carries spinal cord dorsal column sensations conscious A-Gamma: 3rd thickest, only motor, carries motor fibers to intrafusal muscle fibers from small gamma motor neurons in ventral gray horn (LMN) A-Delta: Type III, 4th thickest, only sensory, carries spinal cord spinothalamic sensations (FAST sharp pain, cold) conscious B: thinner than A, only autonomic, carries pre-ganglionic autonomic fibers. C: thinnest, unmyelinated, carries post ganglionic ANS fibers. Type IV carries spinal cord Spinothalamic sensations (SLOW dull pain, warm) conscious Receptors: Mechanoreceptors: Respond to mechanical deformations Baroreceptor: Respond to systemic arterial pressure changes Thermoreceptors: Respond to changes in temperature Nociceptors: Respond to potentially harmful stimuli that can damage tissues; Nociceptors are Nonadapting Electromagnetic: Rods / Cones; respond to changes in light intensity and wavelength (visible electromagnetic radiation) Chemoreceptors (CR): Taste, Smell (Chemical changes associated with taste, smell); Carotid body (Peripheral CR; pO2 of blood); Medulla (Central CR; pH, pCO2 of CSF) Exteroceptors: respond to stimuli from external environment Non-encapsulated: o Free nerve endings: detects pain, crude touch, pressure, tickle, temp o Merkels discs: slowly adapting touch receptor, light touch, indicates degree of pressure on skin o Hair follicle receptor: rapidly adapting mechanoreceptor, when bent hair is released activated, hair remains bent receptor is silent Encapsulated: o Meissners corpuscle: rapidly adapting mechanoreceptor, fine touch, 2 point discrimination, low frequency vibration Decreases in # as you get older sensory disequilibrium Krauses end-bulb genital corpuscles: fine touch in lips and genitals o Pacinian corpuscle: rapidly adapting mechanoreceptor, deep pressure rapid high frequency vibration Golgi-Mazzoni corpuscles ~ to Pacinian but in subcutaneous o Ruffinis corpuscle: slowly adapting stretch receptor, slipping of object from fingers Ruffini and Merkel are slowly adapting, all others are rapidly adapting, nociceptors and chemoreceptors and non-adapting. Proprioceptors: detect and responds to stimuli from within body Neuromuscular Spindles (intrafusal fibers): convey unconscious proprioception to spinal cord, mediates stretch reflex, causes reflex muscle contraction (deep tendon reflex). Located within skeletal muscle belly. o Sensory: informs CNS about change and rate of muscle length o Motor: controls muscle activity (reflex, tone, posture) Regular muscle fibers outside this capsule are extrafusal fibers. o Nuclear Bag Fibers: concerned with dynamic response (velocity of contraction) o Nuclear Chain Fibers: concerned with static response of muscle

o A-Gamma motor neurons innervate intrafusal fibers o A-Alpha motor neurons innervate extrafusal fibers Jendrassiks maneuver: increased A-gamma discharge o Stretch Reflex: elongation of intrafusal fibers in NM spindle stimulates annulo-spiral endings and flower-spray endings. Ia carries unconscious proprioception via medial division of dorsal root of spinal nerve and synapses with A-alpha motor neurons in ventral gray horn. A-alpha motor neurons carry impulses via ventral root to extrafusal fibers and the skeletal muscle contracts. Ia afferents also inhibit the antagonist muscles via interneurons. Neurotendinous Spindles (GTO): convey unconscious proprioception, mediates inverse stretch reflex, causes muscle relaxation. Located in tendon and innervated by sensory Ib afferents. Nerve endings activated when squeezed by adjacent tendon fibers during muscle contraction. o Inverse Stretch Reflex: increased muscle tension during contraction stimulates GTO. Ib fibers reach spinal cord through medial division of sensory root and synapse with inhibitory interneurons in ventral gray horn which inhibit A-alpha motor neurons relaxing the same extrafusal muscle fibers and relieving tension. Protects against rupture. Joint Receptors (capsules, ligaments): conveys conscious proprioception about joint position and movement. o Encapsulated: Conscious: pacinian and ruffini give information about position and movement. Unconscious: Golgi Tendon Organ Loss of joint proprioception leads to ataxia (unsteadiness) o Un-encapsulated: Free nerve endings: conveys pain impulses from excessive movements. Myotomes: Segmental innervation of muscles, most innervated by more than 1 spinal nerve. Refer to chart! Deep Tendon Reflex is absent in LMN lesions and exaggerated in UMN lesions. Motor Unit: single A-alpha motor neuron and all the extrafusal muscle fibers it innervates. Fine muscles (hand) have fewer motor units, coarse muscles (glutes) have way more. Increasing activity recruits more motor units and reduces activity of antagonist motor units. Smaller motor units are recruited first, as contraction increases, larger units are recruited. Muscle fatigue occurs due to reduction of ATP within muscle fibers. Muscle Tone: the partial state of contraction of every skeletal muscle even under resting conditions. Higher CNS Control of Reflex Tone Posture: Secondary Motor Cortex: send extrapyramidal tracts to A-gamma and A-alpha LMN in ventral gray horn. Increased A-gamma increases muscle tone of intrafusal fibers. EPT exerts a net inhibitory influence on muscle tone. Jendrassiks maneuver overcomes A-gamma inhibition, increasing muscle tone by increasing A-gamma discharge. Cerebral Cortex: sends pyramidal tract to A-alpha LMN in ventral gray horn then to extrafusal fibers, increasing muscle tone by recruiting motor units. A-alpha LMN receives feedback inhibition from Renshaw inhibitory interneurons in ventral gray horn.

Chapter 3: Clinical Notes Demyelinating diseases: Multipler Sclerosis, Metachromatic Leukodystrophy, Progressive Multifocal Luekoencephalopathy, Central Pontine Myelinolysis, Guillain-Barre Syndrome. Neuronal Reaction to Injury: (trauma, ischemia, disease) Sub-Lethal Injury: changes occur within 6-12 hours and due to intracellular edema (failure of Na-K ATPase) o Neuron and nucleus both swell and get displaced to periphery of cell o Chromatolysis: Nissl substance becomes fine, granular, loses stain and gets dispersed to periphery of cytoplasm o During reparative process, all changes get reversed. Lethal Injury: cell death imminent o Cytoplasm takes up dark stain with basic dyes Hyperchromatic o Nuclear structure becomes unclear due to RNAases and DNAases Karyolysis o Degeneration of entire neuron CNS: debris fragments phagocytosed by microglia, replacement gliosis by astrocytes PNS: debris fragments phagocytosed by macrophage, replacement scar by collagen from fibroblasts Recent Cell Death: Cytoplasm becomes vacuolated, organelles disintegrate o Nucleus fragments Karyorrhexis, due to rupture of membrane Chronic Injury: cell body size decreases, cytoplasm becomes hyperchromatic o Pyknosis Nucleus shrinks, DNA condenses into shrunken basophilic mass Injury to Neuronal Process (Axon): Changes in Distal Segment of Axon: Wallerian Degeneration due to loss of anterograde axon transport. o CNS: destruction phagocytosis astrogliosis No attempt at regeneration of neuron, disappears completely, phagocytized by microglia, gliosis by astrocytes o PNS: destruction phagocytosis Debris digested by Schwann cells and macrophages and replaced by collagen from fibroblasts Changes in Proximal Segment of Axon: retrograde degeneration of axon until first Node of Ranvier Changes in Associated Neuron: retrograde degeneration due to loss of retrograde axon transport, cell derived of trophic factors from distal end

o o o o

Cell body swells, nucleus swells and moves to periphery, chromatolysis The closer the injury to cell body, the more severe. Peripheral axon lesion causes degeneration of DRG and central axon lesion does not! Synaptic Stripping: synaptic terminals withdraw from cell body/dendrites and sites are replaced by microglia/astrocytes in CNS or Scwhann cells in PNS

Anterograde Transneuronal Degeneration: damage to 1 neuron causes degeneration to another group of neurons distally Retinal Ganglion Cell Axon lesion ganglion cells in retina LGB neurons visual cortex neurons Retrograde Transneuronal Degeneration: neuron synapsing with damaged neuron proximally may also degenerate Cell Body Recovery: if sublethal injury in PNS, then there are attempts at axon and cell body recovery but may take months Nissl structure is reconstituted, polyribosomes reappear, nucleus moves to center of cell, nucleolus moves to periphery of nucleus, cell body swelling decreases o Changes indicate edema of cell is subsiding and protein synthesis is being accelerated in preparation for axonal regeneration PNS Axonal Recovery: Schwann cells bulge out of proximal cut end of endoneurial sheath tube and proliferate into several parallel cords filling the space within basal lamina o Band Fibers (Endoneurial tube + Schwann cell cords): bridge gap between cut axon and progress until first Node of Ranvier and end organ distally. o Schwann cells in distal stump secrete chemotropic factors to attract sprouting axons from proximal stump. Multiple axons can sprout (Multiple Axon Sprouting) or only 1 axon can sprout and persist and re-innervate end organ (Single Axon Regeneration) o Recovery starts at site of lesion and progresses distally o Final diameter is 80% of the original conduction velocity is lower, o Each motor axon innervates more muscle fibers less precise control o Requirement: Endoneurial sheath tubes with basal lamina, band fibers, chemotropic factors to attract proximal sprouting axon filaments, growth stimulating factors, laminin/cell-adhesion Ig to stimulate axon growth, and inhibitory factors in perineurium to prevent axons from leaving nerve fascicle and growing outwards

CNS Neuron Recovery: recovery is poor after injury and damage due to: Absence of: endoneurial sheath tubes, nerve growth factor, laminin/cell-adhesion Ig. Presence of: scar tissue by astrocytes, nerve growth inhibitory factor by neuroglia, myelin in CNS. Peripheral Nerve Injury Classification: Seddon Grade Neuropraxia: pressure on nerve (Sunderland grade 1) o Temporary functional neve block, mild sensory loss and weakness, recovery is complete and quick Axonotmesis: crushing, tractions, compression of nerve (Sunderland 2-4)

o Axon cut but CT sheaths are partially intact, more severe manifestations, recovery is possible and could take months Neurotmesis: transection of nerve (Sunderland grade 5) o Nerve trunk completely cut including epineurium, complete loss of nerve function and recovery is very poor and slow

Neurotmesis Manifestations: Motor Changes: due to skeletal muscle denervation (LMN to muscle and Ach at NMJ is required for muscle activity) o Altered Response to Ach: first manifestation Fasiculation: initial visible twitches of muscle fibers Fibrillation: later invisible 1-5ms contractions o Reaction of Degeneration: faradic current (no response after 4-7 days) and galvanic current (weak response to larger strength after 10 days) o Denervation Super-sensitivity: 2 weeks later, Ach applied to sites other than NMJ muscle contracts due to formation of new Ach receptors o Afterwards wasting of sarcoplasm, loss of myofibrils, flaccid paralysis, loss of DTR, atrophy, contracture. Sensory Changes: o Peripheral sensation: total loss of inner zone cutaneous sensation, partial loss of outer zone due to overlap of nerve fibers, light touch lost over larger area than pain and temperature o Cutting sensory nerve from taste buds causes atrophy of taste buds, new taste buds develop when sensory nerve regenerates Vasomotor Changes: post-ganglionic sympathetic loss, skin red/warm initially, blue/cold in cold weather later. Sudomotor Changes: loss of secretomotor fibers to sweat glands dry skin Trophic Changes: poor peripheral circulations, disuse of limb leads to decalcification of bone Causalgia: impulses in sympathetic post-ganglionic fivers evoke ascending pain impulses in afferent fibers at site of injury Neurotmesis Recovery: First recovery: deep sensation (pain on deep pressure) Next: superficial cutaneous pain and vasomotor control Then: temperature sensations return Last: light touch/sensory discrimination takes months and only partial o Tinels sign (Distal segment hypersensitivity): distal part of nerve trunk becomes sensitive to mechanical stimulation Motor recovery occurs if cut ends are sutured before muscle degenerates o Faradic (interrupted current) returns first in muscles o Voluntary motor action: proximal muscles recover first, then distal o Muscles changes according to innervation (slow or fast fiber) and axon innervates more muscles less precise control Nerve Repair: Direct Repair: up to 10cm gap can be repaired by direct suture Nerve Grafting: usually sural nerve (sensory) is used to repair facial nerve (motor) Nerve Recovery: Crush injury (Axonotmesis): moderate recovery when endoneurial intact

Complete nerve cut (Neurotmesis): poor recovery, sprouting axon may reach wrong destination Mixed nerve cut (Neurotmesis): poor recovery, growing axon reaches wrong destination Gap > few mm (Neruotmesis): very poor recovery, gap fills with fibrous tissue, forms tangled mass (amputation neuroma) Infection: greatly decreases chance of regeneration Poor Physiotherapy: paralyzed muscles will atrophy before nerve regeneration occurs

Phantom Limb: following amputation, severe pain at imagined site of absent limb due to pressure on the cut end of nerve fibers at the amputation stump by prosthesis. When a sensory pathway is stimulated, Cerebral cortex always refers the perception of sensation to the site of receptor, regardless if the actual receptor was stimulated or if its even there! Brain doesnt know if a part is missing so it will continue to refer pain to that area. Chapter 4 Spinal Cord Embryology: Cavity of neural tube: Forms the Central Canal of Spinal Cord Neuroepithelial layer/Ventricular zone Ependymal layer Mantle layer/Intermediate zone central gray matter o Alar plate of mantle layer dorsal (sensory) column o Basal plate of mantle layer ventral (motor) column o Roof and Floor plates have no mantle layer Marginal layer/zone peripheral white matter (Funiculi) of spinal cord Neural crest cells: Dorsal root ganglion and nerve roots, peripheral nerves 8th week IUL: Spinal cord is as long as Vertebral column At birth: Spinal cord ends at L3 Adult: Cord ends at lower border of L1 Spinal Cord Enlargements: Cervical (C3-T2) and Lumbosacral (L1-S3) enlargements are due to larger mass of ventral gray matter for upper and lower limb innervations. Filum Terminale Syndrome: Thick short FT adherent to coccyx, traction on brainstem can cause it to herniate through foramen magnum (Tethered Cord Syndrome) Meninges: Dura mater, Arachnoid mater and Pia mater. Meningeal Spaces: Epidural Space: True space, contains fatty areolar tissue and internal vertebral venous plexus Subdural Space (Dura-arachnoid Interface): not a true space, potential subdural space Subarachnoid Space: true space, contains arachnoid trabeculae and CSF Lumber Cisterns: part of Subarachnoid space between L2 and S2, contains cauda equine and filum terminale. Spinal Cord White Matter: Anterior and Lateral Funiculi between ventral and dorsal gray horns Posterior Funiculi either side of posterior median sulcus Anterior and Posterior Commissure A/P to central canal Spinal Cord Gray Matter:

Rexeds Laminae: divides spinal cord gray matter into 10 laminae based on cytological features of its neurons Dorsal Gray Column/Horn Rexed Laminae I - VI, dorsal to ventral Ventral Gray Column/Horn Rexed Laminae VII IX Lateral gray Column/Horn Rexed Laminae VII o At junction beteen dorsal and ventral gray horns, has both sensory and motor outflow nuclei Commisures (A/P) Rexed Laminae X o Commisures connect both sides of gray horns H shape, divided by central canal.

Ventral Gray Horn (Motor): has Lower Motor Neurons (LMN), they are the final common pathway to all muscles. Alpha (A-alpha) LMN large multipolar golgi type 1 to extrafusal skeletal muscle fibers Gamma (A-gamma) LMN small multipolar to intrafusal muscle fibers (NM Spindles) o Topographic Organization of IX: flexors are dorsal to extensors, proximal muscles are medial to distal muscles. Dorsal Gray Horn (Sensory) Dorsomarginal nucleus (Rexed 1) + Substantia Gelatinosa of Rolandi (Rexed II) full length of spinal cord, golgi type II neurons, Rolandi is continuous with spinal nucleus of trigeminal of brainstem. o Receives pain, temperature, crude touch, pressure sensation from periphery, and receives inputs from supraspinal levels o Gives rise to Spinothalamic Tract Nucleus Proprius (Rexed III-IV) full length of spinal cord o Receives conscious proprioception, 2 point discrimination, vibration from periphery o Gives rise to Intersegmental Tracts Nucleus Dorsalis (Clarkes, Rexed VII) C8-L4 segments o Receives unconscious proprioception (NM spindles, GTO) from lower limbs o Gives rise to Dorsal Spinocerebellar Tract Cooper-Sherrington Spinal Border Cells (Rexed VII) L2-S3 segments o Receives unconscious proprioception from whole body o Gives rise to Ventral Spinocerebellar Tract Visceral Afferent Nucleus T1-L2 segments o Receives afferent sensation (pain, stretch) from all thoraco-abdominal viscera o Gives rise to Visceral Afferent Tract Intermedio-Lateral Gray Horn (Sympathetic, Rexed VII) o T1 to L2 pre-ganglionic sympathetic fibers (GVE) o T1 to T2 pre-ganglionic sympathetic fibers to eye General Rules: Large ventral gray horns C3-T1 and L2-S2 Septum in dorsal white funiculus T5 upwards Lateral gray horn T2-L2

Cervical fibers are closer to center of cord in Corticospinal Tract and Spinothalamic Ascending Tracts Organization: 1st order neurons: peripheral process brings impulses from peripheral receptors, pseudounipolar cell body in DRG. Central process enters spinal cord and synapses with a 2nd order neuron in sensory nucleus in dorsal gray horn. 2nd order neuron: cell body is in sensory nucleus in dorsal gray horn of spinal cord, axons cross midline to opposite side (in spinal cord or brainstem) and travel rostrally, synapses in a nucleus in thalamus. 3rd order neurons: in sensory nucleus in thalamus, axons travel through posterior limb of internal capsule and corona radiate and terminate in broadman areas 3, 1, 2 for conscious awareness. o Spinocerebellar tract is the notable exception to these rules. To brainstem ascending reticular activating system for wakefulness and arousal To motor neurons in ventral gray horn of spinal cord for modifying deep tendon reflex arcs Lateral Spinothalamic Tract: Sensations: Sharp fast pain, cold temperature A-delta fibers. Dull slow pain and warm temperature class IV fibers. 1st order neuron Central process enters via Lateral Division of Dorsal root of spinal cord and travel in a white column behind dorsal gray horn called Dorso-Lateral tract of Lissauer. 2nd order neurons are in the substantia gelatinosa of Rolandi and Dorso-marginal nucleus. Axons cross slightly obliquely in spinal cord within one spinal segment in anterior commissure. o Sacral fibers are lateral, cervical fibers are medial, pain fibers are anterior to temperature fibers In Brainstem in medulla, it travels near lateral surface between inferior olivary nucleus and spinal nucleus of trigeminal joined by anterior spinothalamic and spinotectal tracts called Spinal Lemniscus. In pons, ascends through poster part of pons and then in midbrain it ascends through tegmentum lateral to medial lemniscus. In thalamus it synapses with 3rd order neurons in Ventral Posterolateral (VPL) nucleus. 3rd order neurons: axons from VPL nucleus of thalamus (crude pain and temperature appreciated here) go through posterior limb of internal capsule/corona radiate and end in Broadmann area 3, 1, 2 in post-central gyrus and to motor and parietal association areas.

o PET scan shows that nociceptive information reaches post central gyrus, cingulate gyrus and insular cortex. Cingulate gyrus interprets emotional aspects of pain Insular cortex interprets pain from internal organs Anterior Spinothalamic Tract: Sensations: crude touch, pressure Same as Lateral Spinothalmic Tract except 2nd order axons cross very obliquely in ventral commissure over several spinal segments. Ascend in opposite anterolateral funiculus as anterior spinothalamic tract. Merges in lower medulla with lateral spinothalamic tract Spinal Leminiscus. 3rd order axons in VPL thalamus, gross awareness of touch and pressure, end in cortex 3, 1, 2. Visceral Sensation: Sensations: distension, stretch, torsion, ischemic pain from thoraco-abdominal viscera travel in peripheral process via White Ramus Communicans. Central process enters via DRG, some participate in visceral reflex arc, others synapse with 2nd order neurons in Visceral Afferent Nucleus in Dorsal Gray Horn at T1-L2. 2nd order neurons cross and travel with spinothalamic tract and synapse with 3rd order neurons in VPL thalamus. 3rd order neurons terminate in post central gyrus (3,1,2) and insular cortex. Dorsal Column ML Tract: Fasciculus Gracilis: afferents from lower limb and lower trunk (T7 down) Fasciculus Cuneatus: afferents from upper limb, upper trunk (T6 up) o Cuneatus carries conscious and unconscious proprioception Sensations: discriminative touch, 2 point discrimination, conscious proprioception, pressure, vibration Whole tract from spinal cord to brainstem Dorsal Column Medial Leniscal 1st order neurons: pseudo-unipolar cells in DRG o Peripheral processes are myelinated, central processes enter spinal cord via medial division of dorsal root. o Pass directly to posterior funiculus on same side of spinal cord and divide into short (ascending, descending)/long (ascending) fibers Short fibers synapse with cells in nucleus proprius in dorsal gray horn. Interneurons and ventral gray horn cells mediate intersegmental reflexes. Long ascending fibers constitute dorsal column, fibers synapse with 2nd order neurons in nucleus cuneatus and nucleus gracilis on dorsal aspect of medulla. o 2nd order neurons: in the medulla, axons from 2nd order neurons in nucleus cuneatus/gracillis constitute internal arcuate fibers. These fibers sweep anteromedially around central canal of medulla, cross midline, criss-cross with similar fibers from opposite side great Sensory Decussation. After crossing in medulla, fibers travel on opposite side of medulla, pons, and midbrain as a bundle Medial lemniscus. Synapse with 3rd order neurons in VPL thalamus. o 3rd order neurons: in thalamus, 3rd order neurons from VPL follow same course as spinothalamic and reach areas 3, 1, 2 of cortex. Summary of Conscious Tracts: 1) Pain & temperature & 2) light touch and pressure free nerve endings, 1st is DRG, 2nd is Sunstantia Gelatinosa

3rd is VPL nucleus of thalamus Lateral (1) and Anterior (2) Spinothalamic pathways Posterior central gyrus Discriminative touch, vibratory sense, conscious muscle joint sense Meissners, Pacinian, muscle spindles, GTO 1st is DRG 2nd is Nuclei gracilis/cuneatus 3rd is VPL nucleus of thalamus DC-ML pathway Posterior central gyrus Spinocerebellar Tracts: 1. Dorsal SC: Lower limb and lower trunk 2. Ventral SC: Upper limb, lower limb and trunk 3. Cuneo-cerebellar: Upper limb and upper trunk 2 order neuron chain, uncrossed or double crossed, carry unconscious proprioception, travel in lateral funiculus of spinal cord and ends in cerebellum (no awareness) Posterior Spinocerebellar Tract: Peripheral process (Ia, Ib) carry unconscious proprioception from NM/NT spindles of lower limb Central process enters spinal cord via medial division of dorsal root Synapse in Nucleus Dorsalis (Clarkes Column) present only in C8-L4. Axons entering below L4 travel up and synapse in Clarkes column at L4 segment. 2nd order neurons: axons from Clarkes column travel up in posterior aspect of lateral funiculus on same side. Tract travels through Inferior Cerebellar Peduncle in Medulla to Cerebellum. In the cerebellum axons go to ipsilateral cortex as mosy fibers Function: information about muscle stretch, tendon tension, joint movements used by cerebellum for coordination of movements and posture maintenance Anterior Spinocerebellar Tract: 1st order neurons: Ia/Ib fibers carry unconscious proprioception from trunk, upper/lower limb (whole body) 2nd order neurons: Cooper-Sherrington spinal border cells, only in L2-S3. Most cells cross to opposite side in spinal cord and travel up in opposite antero-lateral funiculus. Some stay on same side of spinal cord. Fibers ascend through medulla, pons and midbrain. Enter opposite cerebellar cortex via superior cerebellar peduncle, then cross back! Cuneo-Cerebellar Tract: 1st order neurons: Ia/Ib fibers carry unconscious proprioception from NM/NT spindles in upper trunk/upper limb. Central process enters via medial division of dorsal root and travels in fasciculus cuneatus of same side. No synapse yet, synapses with 2nd order neurons in nucleus cuneatus in dorsal part of medulla. In medulla, axons constitute cuneo-cerebellar tract (Posterior external arcuate fibers) and enter ipsilateral cerebellar cortex via inferior cerebellar peduncle. o Fasciculus cuneatus carries both conscious and unconscious proprioception from upper limb to nucleus cuneatus. Conscious goes to Medial lemniscus Unconscious goes to cerebellum

Minor Ascending Tracts (know origin, termination, function) 1) Spino-tectal Tract: 1st order neurons: pain, thermal, tactile information for spino-visual reflexes 2nd order neurons: unknown, cross to opposite antero-lateral funiculus, travel as spinotectal tract. Join lateral/anterior spinothalamic tracts in medulla Spinal Lemniscus. Synapse with 3rd order neurons in superior colliculus (tectum) of midbrain. 3rd order neurons travel dows as tectospinal/tectobulbar tracts for visual body reflex Function: provides afferent info for spino-visual reflexes brings about movement of eyes and head towards source of stimulation 2) Spino-olivary Tract: 1st order neurons: carry afferent information from cutaneous and proprioceptive organs. 2nd order neurons: cross to opposite side, travel in junction between anterior-lateral funiculus, adjacent to anterior spinocerebellar tract. Synapse with 3rd order neurons in Inferior Olivary Nucleus in medulla. 3rd order neurons: from ION cross midline of medulla, through inferior cerebellar peduncle, to opposite cerebellar cortex as climbing fibers Function: provides indirect pathways for afferent info from cutaneous and proprioceptive organs to cerebellum. 3) Spino-reticular Tract: 1st order neurons: carry afferent pain information from muscles, joint, skin 2nd order neurons: cross in spinal cord, travel in lateral funiculus, mixed with lateral spinothalamic tract. Tract synapses with 3rd order neurons in Brainstem Reticular Formation. 3rd order neurons: from BRF go to thalamic intralaminar nuclei 4th order axons: from thalamic intralaminal nuclei project diffusely to cerebral cortex where pain reaches conscious level and promotes response Function: provides afferent pathway for reticular activation in influencing level of consciousness, promotes behavioral arousal to conscious pain perception Descending Tract Organization: 1st order neuron: multipolar golgi type 1 usually in cerebral cortex. Axons descend through corona radiate, posterior limb of internal capsule, then through brainstem and decussate with opposite side and synapse with 2nd order neuron 2nd order neuron: interneuron (golgi type 2) in ventral gray horn and synapse with 3rd order neuron 3rd order neuron: multipolar golgi type 1 (LMN) in ventral gray horn, exists through ventral gray motor root and innervates skeletal muscles Pyramidal Corticospinal Tract Origin: axons of pyramidal cells (golgi type 1) in layer 5 of cerebral cortex, myelinated but relatively slow fibers o From pre-central gyrus (2/3) 1/3 from primary motor cortex (area 4) 1/3 from pre-motor cortex (area 6) o From post-central gyrus (1/3) From primary sensory cortex (areas 3, 1, 2) o Homunculus: representation of human body on cortex, size of representation depends on skill and functional importance of body part

Sub-cortical white matter: descending axons converge in corona radiate, pass through posterior limb of internal capsule, pass through middle 3/5 of basis pedunculi in midbrain, then through basilar part of pons. Tract is broken into smaller bundles by transverse pontine fibers. In the medulla, fibers are grouped in anterior part in 2 columns called medullary pyramids. 90% of fibers cross midline at medulla-spinal cord junction in Pyramidal Decussation. In the spinal cord, travel in lateral funiculus as lateral corticospinal tract and terminate in ventral gray horn. Small fibers synapse with interneurons that synapse with large Aalpha/small A-gamma LMN. Large fibers synapse directly with A-alpha LMN. 10% of fibers continue in anterior funiculus corticospinal tract and cross midline in cervical/thoracic segments. Function: fine, rapid, skilled voluntary movements of opposite side.

Exrapyramidal Tracts Origin: from brainstem nuclei, which are regions of intermediate motor processing, or provide feedback motor information Reticulospinal Tract: Reticular formation: groups of scattered nerve cells and fibers in brainstem Pons: pontine RST, uncrossed and descend in anterior funiculus Medulla: cross/uncrossed, descend in lateral funiculus Functions: facilitate and inhibit A-alpha/A-gamma LMN, and voluntary movement or reflex Contains tracts for higher control of para/sympathetic outflow o Descending Autonomic Tract (Horners, Hypothalamo-spinal) From hypothalamic nuclei, uncrossed in brainstem, travels in lateral funiculus, synapses with pre-ganglionic autonomic neurons in parasympathetic nucle of CN 3,7,9,10 and S2-S4 and also sympathetic pre-ganglionic neurons in lateral column of T1-L2. Function: higher CSN control of autonomic Lesion: produces central Horners syndrome Destination: alpha and gamma motor neurons Tectospinal Tract: Origin: superior colliculus (tectum) of midbrain o Crosses immediately in midbrain Descends close to midline in brainstem, joins middle longitudinal fasciculus, descends in anterior fasciculus and synapse with interneurons in ventral gray horn in upper cervical spinal cord Functions: visual body reflex, reflex movements in response to visual stimulus, and pupillary dilatation. Destination: alpha and gamma motor neurons Rubrospinal Tract: Origin: Red nucleus located in midbrain tegmentum and receives connections from cerebral cortex/cerebellum integrates information Starts from red nucleus, crosses midline in ventral tegmentum of midbrain, and descends through pons and medulla in central tegmental tract. Descends in lateral funiculus and synapses with interneurons in ventral gray horn. Function: facilitates flexor muscles, inhibits extensor and anti-gravity muscles.

Pathway for indirect control of A-alpha/A-gamma LMN by cortex/cerebellum

Vestibulospinal Tract: Origin: Vestibular nuclei in pons, medulla in floor of 4th ventricle. Receives connections from inner ear and cerebellum. Uncrossed, descends through medulla in medial longitudinal fasciculus and joined by tectospinal tract. Descends in anterior funiculus and synapses with interneurons in ventral gray horn. Functions: facilitate extensor and inhibit flexor muscles, maintain balance in association with inner ear. Cerebellum coordinates head, neck, and eye movements. Medial VST controls neck muscles, Lateral VST controls back. Destination: alpha and gamma motor neurons Olivospinal Tract: Origin: inferior olivary nucleus in medulla Crosses in brainstem, descends in anterior funiculus of spinal cord. Influences A-alpha/Agamma motor neurons. o Doubtful existence Destination: alpha and gamma motor neurons Reflex Arcs: Reflex is an involuntary response to a stimulus Components: Stimulus, receptor, afferent, efferent, effector, response Monosynaptic Arc: central process of afferent neuron are large, rapid conduction, synapses directly with efferent neuron in ventral gray horn and gives a quick response. Polysynaptic Arc: afferent fibers gives many collateral in spinal cord and each branch synapses with interneuron which synapse with the efferent neuron. This prolongs the stimulus producing prolonged asynchronous response. Also spreads afferent impulses to different spinal segments via inter-segmental tracts. Inter-segmental tracts: short ascending/descending tracts composed of A-beta (class II) fibers from medial division of dorsal root. Starts from 1 spinal segment and ends in another. Function: reflex arcs are important for muscle tone and body posture Muscle Tone: depends on A-alpha LMN, stretch reflex (neuromuscular spindle, Ia, A-alpha), inverse stretch reflex (GTO, Ib, A-alpha), A-gamma and higher control by pyramidal/extra-pyramidal tracts. Posture: position of body adopted within environment maintained by high basal tone of erector spinae Renshaw LMN Inhibition: A-alpha LMN axons give off collateral before emerging from the ventral root of spinal nerve, these collaterals synapse and produce Ach-mediated stimulation of inhibitory Renshaw inter-neurons in ventral gray horn. Renshaw cells receive input from A-alpha and synapse back with the same LMN. Use glycine as inhibitory transmitter opens Cl channels and generates IPSP hyperpolarization Chapter 4: Clinical Notes Death Receptor Chain Reaction: following spinal cord injury, there is a sudden influx of ATP into injured site. ATP binds to P2X7 receptor (death receptor) which leads to death of healthy cells in spinal cord, worsening the injury. Injecting oxidized ATP into spinal cord prevents this reaction, but not clinically feasible.

Agents that enhance functional recovery of damaged neurons: methylprednisolone (benefits 15%, suppresses response of microglia and astrocytes), GM Ganglioside, BBG dye, stem cell transplants, olfactory ensheathing glial transplants.

Spinal Shock Syndrome (SSS): following acute severe injury to spinal cord, or immediate spinal cord compression. Lasts 24 hours 4 weeks. Anal sphincter reflex (S2, 3, 4) is absent. All spinal cord functions are lost below spinal segment level of lesion. Hypotension: if injured high up (T1-L2) Atonic bladder: detrusor muscles is completely relaxed, sphincter vesicae is contracted due to loss of CNS inhibition, external urethral sphincter is flaccidly paralyzed. No bladder filling sensation, overflow incontinence, no voluntary control over micturition. SSS Recovery: anal sphincter reflex is the 1st sign of recovery. Segmental spinal reflexes gradually return, gamma rigidity causing increased muscle tone. Spastic paraplegia in flexion: lesion below vestibular nuclei, reflexes are mainly flexor in nature, low extensor tone due to severance of all descending tracts.

Acending Tract Lesions in Spinal Cord Lateral spinothalamic o Contralateral loss of Pain, Temperature o 1-2 segments below segmental level of lesion Anterior spinothalamic o Contralateral loss of Crude touch, Pressure below segmental level of lesion o Fine (Discriminative) touch present Fasciculus cuneatus/gracilis (Dorsal column) o Ipsilateral joint position, postural sensibility lost below level of lesion o Impaired muscle control, Jerky, ataxic movements o Ipsilateral astereognosis: Discriminative touch ve o Rombergs sign +ve (sways with eyes closed) o Ipsilateral loss of vibration sense (Apallesthesia) o Ipsilateral loss of 2-point tactile discrimination

Descending Tract Lesions in Spinal Cord Pyramidal tract (CST) lesions o Paralysis: Fine skilled voluntary movement lost o Babinski +ve: Extension at 1st MTP, fanning of others o Superficial reflex: Abdominal / Cremasteric absent Extrapyramidal tract (EPT) lesions o Spastic paralysis: Severe paralysis with increased tone o Gamma Rigidity (Spasticity) o DTR Exaggerated: Clonus (repetitive response after initial stimulus) may be present o Clasp-knife Reaction: Because of Spasticity, there is initial resistance to passive movement; When Tendon threatens to rupture, GTO-mediated Inverse Stretch Reflex causes sudden muscle relaxation o Disuse atrophy occurs later; No direct muscle atrophy Ventral Gray Horn Lesions (LMN lesion) Altered response to ACh: 1st manifestation Fasciculation: Initial twitches of groups of muscle fibers, visible to the naked eye Fibrillation: Later invisible 1-5 ms contractions, recordable only by Electromyogram (EMG) Reaction of degeneration: LMN lesion Faradic (interrupted) current: No response after 4-7 day Galvanic (continuous) current: Weak response to larger strength after 10 days Denervation super-sensitivity: 2 weeks later; ACh applied to sites other than NMJ muscle contracts; due to new ACh receptors Others: Flaccid paralysis; DTR lost; Direct neurotrophic atrophy; Fibrosiscontracture Complete Cord Transection Syndrome Manifestations: Bilateral LMN palsy at segmental level of lesion Bilateral spastic palsy (Paraplegia in Flexion) below segmental level of lesion Bilateral loss of ALL sensation below segmental level of lesion Anterior Cord Syndrome (ASA): blood supply to anterior part is interrupted Severe Hypotension: T4 and L1 segments more prone to ischemia Traumatic: Damage to Spinal arteries following nerve block procedures; Fractured vertebra pressing on ASA Aortic Surgery: Occlusion of Intercostal and Lumbar arteries feeding Segmental and Radicular branches Thoracic Aorta Dissecting Aneurysm: Blocks Posterior intercostal arteries, which give off Segmental Medullary and Radicular arteries in Thoracic region Abdominal Aorta Leaking Aneurysm: Aneurysm pressing on Lumbar arteries, which give off Segmental Medullary and Radicular arteries in Lumbar region Manifestations: Ventral Gray Horns: Bilateral LMN palsy at segmental level of Spinal Cord lesion Bilateral CST (Anterior / Lateral ) / Extrapyramidal Tracts: Bilateral spastic paraplegia below segment level of lesion Antero-Lateral ST Tract: Bilateral loss of pain, temp, crude touch below Spinal segmental level of lesion Automatic UMN Neurogenic Bladder: Loss of Bladder sensation / Voluntary control, Bladder functions reflexly, Uncoordinated voiding due to disconnection from Pontine Micturition Center Dorsal Column: All preserved

Central Cord Syndrome: hyper extension of spine, whiplash injury Bilateral LMN palsy at segmental level of lesion Bilateral spastic palsy below segmental level of lesion, with sacral sparing Bilateral loss of pain, temp, crude touch below segmental level of lesion, with sacral sparing Hemisection of Cord (Brown-Sequard) Ventral Gray Horn: Ipsilateral LMN palsy at segmental level Dorsal Gray Horn: Ipsilateral band of all sensory loss at segmental level of lesion CST: Ipsilateral spastic palsy below level of lesion; Ipsilateral Babinski +ve DC-ML: Ipsilateral loss of Dorsal Column sensations (fine touch etc) from just below segmental level of lesion ST Tract: Contralateral loss of ST sensations (temperature, pain) from 1-2 segmental levels below lesion downwards Anterior Commissure: Bilateral loss of temperature / pain at level of lesion, because crossing pain, temperature fibers are cut in Anterior White Commissure Poliomyelitis: Poliovirus travels by retrograde axon transport and infects LMN in ventral gray horn and motor nuclei of cranial nerves. Destruction results in skeletal muscle denervation and Post-polio Residual Paralysis. Flaccid paralysis, areflexia, muscle atrophy, fasciculations Progressive Infantile Muscular Atrophy/Werdnig-Hoffman Syndrome/SMA Type 1: Degeneration of ventral horn cells resulting in Spinal Muscular Atrophy due to Survival Motor Neuron gene mutation. Charcot-Marie-Tooth Disease: aka Hereditary Motor-Sensory Neuropathy, most commonly inherited peripheral neuropathy. Lower limb muscle weakness, atrophy, foot drop, upper limb later Touch, conscious proprioception lost more than pain sensation Demyelinating optic neuritis Amyotrophic Lateral Sclerosis: aka Lou Gehrigs disease, UMN and LMN neuro-degeneration. Autosomal dominant missense mutation of Cu-Zn SOD1 gene on Chromosome 21. Pathology: Thin anterior roots of spinal cord; Precentral gyrus atrophic in very severe cases; Reduced Ventral Gray Horn neurons in Spinal cord; Reactive gliosis; Loss of Ventral root myelinated fibers; Denervated skeletal muscles show neurogenic atrophy; Similar changes in CN12, Ambiguus, CN5 Motor nuclei; Rest of neurons contain Bunina Bodies (PAS-positive cytoplasmic inclusions); Destruction of UMN leads to degeneration of myelin in CST, resulting in pale staining Lateral Funiculi Pathophysiology: Typically begins at Cervical segment; progress up / down; May start in other regions Cervical / Thoracic Cord: Asymmetric weakness of hand; Dropping objects; Fine motor difficulty (buttoning, writing); Cramping; Fatigue Lumbosacral Cord: Clumsiness while walking / climbing stairs Respiratory weakness: Due to Cervico-thoracic cord; Features similar to Obstructive Sleep Apnea (OSA) Bulbar (CN9,10): Hoarseness, Dysarthria, Dysphagia Others: Weight loss; Depression (Very common) Tabes Dorsalis: Dorsal softening, seen in tertiary neuro-syphilis. Degeneration of dorsal rots but not pseudo-unipolar cells in DRG. Secondary degeneration bilateral dorsal columns.

Bilateral DC signs below lesion: Loss of Conscious Proprioception, Vibration, Joint passive movements; 2-point discrimination, Deep muscle sensation, Posture appreciation; Astereognosis Mixed sensory features: Hypersensitive to touch, temperature; Anesthesia in parts of trunk, LL; Analgesia on side of nose, medial forearm, lateral leg, inter-nipple; 3-second delayed pain perception after pinprick 3 Ps: Paroxysmal pains (severe stabbing lightning pains in LL due to dysesthesia); Paresthesia/numbness in LL; Polyuria Motor manifestations: Ankle / Knee DTR lost early; Hypotonia (NM spindle afferents lost) Gait manifestation (conscious proprioception lost) High step stride: Unsure of ground height Staggering gait: Due to sensory ataxia of LL (compensated by vision) Rombergs sign +ve: Patient sways with eyes closed, not with eyes open (Distinguish from cerebellar lesion) Autonomic manifestations: Urinary Incontinence (loss of bladder fullness sensation), Impotence, Constipation, pupillary reflex absent Rx: Penicillin

Subacute Combined Systems Degeneration: chronic vitamin B12 deficiency, pernicious anemia, HIV/AIDS. Pathophysiology: B12 is Cofactor for methyl-transferases, which play role in fatty acid metabolism and myelin synthesis. B12 deficiency Abnormal fatty acid accumulation Extensive patchy Demyelination / Axonal degeneration Sites of involvement: peripheral nerves, dorsal column, CST, spinocerebellar tracts. Peripheral Neuropathy: Initially; Distal paresthesia, then distal numbness, leading to Stocking and Glove anesthesia hand and foot involvement due to long nerves being most susceptible Dorsal Column Sensory ataxia, manifested as staggering gait / gait difficulty, bilateral loss of touch, vibration; SC tract Ataxia CST involvement Distal weakness along with Spastic para-paresis, DTR in LL and Babinski +ve Serology: Antibodies against Intrinsic Factor Differential Diagnosis: Friedreichs Ataxia Rx: Vitamin B12 Syringomyelia: aka Arnold-Chiari Malformation. Cavitation and gliosis in central canal. Lower cervical and upper thoracic spinal cord, brainstem. Structures progressively involved: ST fibers: Decussating in Anterior gray / white Commissure 1st involved Initially, pain / discomfort bilateral UL Next, bilateral pain / temperature loss at segmental level of lesion (Cervical segment) Shawl-like / Cape-like distribution: Chest, Upper limbs; Neck above and below Scapula are spared (LL fibers cross in LS segment below syrinx) Accidental burning of hand without realizing Ventral Gray Horn: Syrinx expanding LMN palsy in both UL: Initially, small hand muscles in C8 T1 segment (Claw hand); Later, arm / shoulder muscles CST: Syrinx in lateral funiculus, Bilateral spastic paresis of LL, exaggerated DTR, Bilateral Babinski +ve Brainstem: CN12 nucleus in Floor of 4th ventricle may be involved Tongue paralysis

Descending Autonomic: In RST in Lateral funiculus; innervating pre-ganglionic sympathetic neurons in lateral horns of T1 to T2 segments Central Horners (Ptosis, Miosis, Anhidrosis ipsilateral body) Lateral Horn of T1: Pre-ganglionic Horners (Ptosis, Miosis, Anhidrosis ipsilateral face)

Multiple Sclerosis: autoimmune demyelination of CNS. Pathophysiology: Oligodendrocyte myelin is slowly destroyed; Focal patchy demyelin-ating plaques occur at different times / locations within CNS; Microglia scavenges, Astrocytes form glial scar Impulse transmission impeded: Velocity of action potential (AP) , ultimately blocked Warm duration of AP; Cold AP conduction Remissions are due to number of voltage-gated Na+ channels Progressive MS: Axonal damage also Manifestations: Triad: Scanning speech, Intention tremor, Nystagmus Most common: Weakness of limbs Remissions / Exacerbations: Waxing and waning; Manifestations separated by Time and Location (transitory, scattered); Most have relapses every few years; Always follows variably progressive course Uhthoffs phenomenon: Symptoms worsen with body temperature / hot bath / exercise; Cold improves symptoms Miscellaneous: Focal abnormalities; Chronic fatigue; Old deficits worsened by underlying illness (e.g., UTI, URI); Symptoms appear after Stress periods, Infections Paroxysmal symptoms: Tonic muscle spasms; Trigeminal neuralgia Spinal Cord Manifestations: Transverse myelitis-like features: Distinct level of somatic sensory loss; Neurogenic bowel / bladder: Urgency, dribbling CST signs: Spastic paraplegia (partial/complete), Spastic gait or Wheel-chair bound Dorsal column (DC) signs: Patchy Anesthesia / Paresthesia / Dysesthesia Lightning pains due to Dysesthesia Lhermitte sign: sudden sensation of electric shock down spine and along arms when patient flexes neck. Ataxia; Impaired Vibration / Joint position sense MRI Brain in MS: periventricular plaques demyelinated areas appear as round areas. Dawsons Fingers finger shaped projections running perpendicular to periventricular white along vascular pathways. CSF shows normal pressure, increased CSF IgG index. Cauda Equina Syndrome: pressure on spinal nerve roots in cauda equine from L3-coccyx (LMN). Can be due to: Lipoma of terminal S. cord; Ependymoma; Nerve root tumor; Dermoid; Herniated nucleus pulposus; HIV Lymphoma. Gradual onsent, unilater side affected, severe pain, marked atrophy of lower limb, DTR absent, bladder and sexual function normal. Filum Terminale Syndrome: short thick filum terminale attached to coccyx. Weakness, sensory loss in lower limb, neurogenic LMN bladder. Conus Medullaris Syndrome: pressure on spinal cord segments S3-coccyx in conus medullaris. Sudden onset, bilateral sides affected, mild pain, no marked atropy, normal DTR in lower limb, incontinence and impotent.

Epiconus Syndrome: pathology in L4-S2 segnments. Autonomic: Automatic neurogenic (UMN) bladder and rectum, with loss of voluntary control (Lesion is above Parasymp S2-4) Motor: Severe; Lateral rotation / Extension of thigh most affected (Gluteus Maximus (L5-S2)); Ankle reflex (S1, 2) absent Types of Paralysis: Hemiplegia: Paralysis of one side of body Monoplegia: Paralysis of one limb Diplegia: Paralysis of either both upper or lower limbs Paraplegia: Paralysis of lower part of trunk (variable), including both lower limbs Quadriplegia: Paralysis of all 4 limbs Paresis: Partial paralysis Muscle Tone Abnormalities: Hypotonia / atonia: / absent muscle tone LMN lesion: Interruption of any part of reflex arc Cerebellar disease influence on gamma motor neurons from cerebellum Hypertonia (Rigidity, Spasticity): tone Supraspinal level: Lesion of EPT but not CST Spinal segmental level: Local sensory excitation of stretch reflex; E.g. herniated disc spasm of back muscle; abdominal muscle spasm in peritonitis Spasms: Sudden involuntary contractions of large muscle groups In paraplegia due to EPT but not CST lesions

S-ar putea să vă placă și