CNS Infections

Dr. Taha Kamel

Types Of CNS Infections:

Based on the time, course, etiological agent and site of involvement: 1-Menengitis: acute bacterial (pyogenic) or viral (aseptic) infections affecting CSF and leptomenengies. 2-Brain abscess: acute bacterial infections of the subdural space (subdural empyema) or CNS parenchma. 3-Menengioencephalitis:chronic bacterial infection of the brain and memengies. 4-Encephalitis:Acute,subacute or chronic viral infection of the brain. 5-Fungal or parasitic infections.

Bacterial infections reach the intracranial structures : by hematogenous spread by extension from juxtacranial structures from an iatrogenic source Bacterial pathogens can cause pyogenic meningitis, brain abscess, septic thrombophlebitis, epidural abscess, or subdural empyema.

Bacterial Infections

Definition
It is as an inflammatory response to bacterial infection of the pia, archnoid and CSF of the subarachnoid space. Extends throughout the cerebro-spinal axis.

Epidemiology

Three main pathogens, H. influenzae, S.pneumoniae, and N. meningitidis, account for 75-80% of cases after the neonatal period. E. coli , L. monocytogenes, and group B streptococci [ neonatal meningitis]

Clinical Features
The classical clinical presentation of adults comprises headache, fever, and neck stiffness, often with signs of cerebral dysfunction Nausea, vomiting, myalgia, and photophobia are also common. Cerebral dysfunction is manifested by confusion, delirium, and a declining level of consciousness that ranges from lethargy to coma. Seizures may occur

Diagnosis
suspected bacterial meningitis requires blood cultures and urgent LP. CT MRI with contrast [ before LP is indicated when focal findings or clinical evidence of raised ICP are present ]. Empiric antibiotic therapy administered appropriate to the clinical setting.

Diagnosis
CSF examination reveals - elevated pressure (200-500 mm H2O) - elevated protein (100-500 mg/dL) - decreased glucose (<40% serum glucose ) - marked pleocytosis (100-10,000 WBC/QL) with predomnant PMN leukocytes.

The CSF Gram stain and CSF culture Other tests, CSF culture, latex particle agglutination and counter-immuno-electrophoresis testing of CSF for bacterial antigens.

Diagnosis
Parameter (normal) OP (<170 mm CSF) WBC (<5mononuclear) %PMNs (0) Glucose (>40mg/dL) Bacterial >300mm >1000 >80% <40 Viral 200mm <1000 1-50% >40 <200 _ _ Neoplastic 200 <500 1-50% <40 >200 + Fungal 300mm <500 1-50% <40 >200 _ +

Protein (<50mg/dL) >200 Gram stain (-) Cytology (-) + _

Differential diagnosis

viral, rickettsial, tubercular, fungal & parasitic meningitis subarachnoid hemorrhage carcinomatous meningitis

When meningeal signs are less prominent there are additional DD ; cerebral or epidural abscess subdural empyema viral encephalitis

Empiric therapy is initiated Ampicillin or penicillin G + a third generation cephalosporin are typical first-line agents. Ampicillin covers most pneumococcus, meningococcus, and Listeria Third-generation cephalosporin, such as cefotaxime, ceftriaxone, or ceftazidime covers gram-negative organisms and ampicillin-resistant H. influenzae . cefepime (Maxipime), Cefdinir ( Omnicef), Cefixime ( Suprax), Cefotaxime (Claforan), Ceftriaxone (Rocephin). Cefoperazone (Cefobid), Ceftazidime (Fortum).

Treatment

Parenteral antibiotics are administered for #7-10 days for meningococcal and H. influenzae meningitis #10-14 days for pneumococcus #14-21 days for L. monocytogenes and Group B streptococci #21 days for gram-negative bacilli other than H. influenzae .

Adjunctive Therapy

Corticosteroids have a beneficial effect by -inhibiting the synthesis of pro-inflammatory cytokines at the level of mRNA -decreasing CSF outflow resistance -stabilizing the BBB.

Management Algorithm for Adults

Suspicion of bacterial meningitis

YES
new onset seizure, papilledema, altered level of consciousness, or focal neurological deficit or delay in performance of diagnostic L.P

NO
Blood c/s & Lumbar puncture
Dexamethasone + empirical Abx CSF is abnormal

YES
B/C stat
Dexamethasone + empirical Abx -ve CT-scan of the head Perform L.P

YES
+ve CSF gram stain

NO
Dexamethasone + empirical Abx

YES
Dexamethasone + targeted Abx

Local:

Complications
4.Subdural effusions 5.Obstructive hydrocephalus

1.Focal cerebral signs such as hemiparesis : -arteritis -septic venous thrombophlebitis -cerebritis 2.Meningeal inflammation can cause cranial neuropathies. 3.Cranial nerve VI palsy and a deteriorating level of consciousness within the first 48 hours usually indicate an increase in ICP.

Systemic:
Septicemia may lead to acute adrenal insufficiency

Prophylaxis for meningococcal meningitis: A 2-day course of oral RIF is given in doses of 600 mg every 12 hours for adults. Alternatives include ceftriaxone IM, recommended for pregnant and lactating women or children younger than 2 years (250 mg for adults, 125 mg for children), or minocycline or ciprofloxacin. Haemophilus Influenzae For all household members under 4 years of age. The doses are the same as for meningococcal prophylaxis, but treatment is given for 4 days

Imaging , What Are We Looking for?

Evidence of meningitis. Complications: Meningoencephalitis Abscess formation Empyema Hydrocephalus Brain edema

CT:
5

mm , C+

MRI:
Contrast

, T1 axial, coronal and sagittal. Axial T2. Pre and post Gd. FLAIR Diffusion / ADC

meningitis

Brain Abscess

contiguous infected cranial site (ear, sinus, or teeth). Classifying brain abscesses Other causes include by entry point of infection; open head trauma Frontal abscesses arise most often from paranasal neurosurgical procedures sinus infection Hematogenous spread; pulmonary disorders as lung temporal or cerebellar abscesses from an abscess, bronchiectasis or otogenic source AV fistula. multiple abscesses from a remote site

It is a focal suppurative process of brain parenchyma. -develops most frequently by spread from a

Once infection is established, the abscess passes through the stages of -cerebritis -central necrosis -capsule development -maturity over a period of about 2 weeks.
Types of Abscesses: Acute: Shaggy irregular necrotic wall surrounded by a zone of congestion and filled with pus Chronic: the wall is smouth formed of thick fibrous tissue

CLINICAL MANIFESTATIONS
OF BRAIN ABSCESS Headache 70%

Fever 50 Altered mental status 50-60 Focal neurologic findings 50 Nausea/vomiting 25-50 Seizures 2535 Nuchal rigidity
Papilledema

25
25

LABORATORY TESTS
BRAIN ABSCESS

Aspirate: Gram/AFB/fungal stains & cultures, cytopathology (+/-PCR for TB) WBC
Normal in 40% ( only moderate leukocytosis in ~ 50% & only 10% have WBC >20,000)

CRP ESR BC
LP

almost invariably elevated

Usually moderately elevated

Often negative BUT Should still be done
Contraindicated in patients with known/suspected brainabscess Risk of herniation 15-30% If done, may have normal CSF findings, but: Usually elevated CSF protein & cell count (lymphs) Unremarkable glucose & CSF cultures rarely positive

IMAGING STUDIES

MRI

CT scan 99m Tc brain scan

more sensitive for early cerebritis, satellite lesions, necrosis, ring, edema, especially posterior fossa & brain stem

very sensitive; useful where CT or MRI not available Skull x-ray : insensitive, if air seen, consider possibility of brain abscess

Axial T2-weighted MRI in a patient with a right frontal abscess. Note the mass effect and surrounding edema. The wall of the abscess is relatively thin (black arrows).

Axial T1-weighted MRI in a patient with a mature cerebral abscess of the right frontal lobe of the brain. Note the thick wall of the abscess with enhancement (black arrow). The central content of the abscess is dark on T1-weighted imaging with no enhancement (double white arrows.)

Mixed infections are present in 30-60% of the cases, In immunocompetent patients: aerobic organisms are the -hemolytic and nonhemolytic streptococci (S. aureus, and Enterobacteriaceae. Other important pathogens include -anaerobes (Bacteroides, Fusobacterium,

Pathogens

Peptostreptococcus, and Propionibacterium) -gram-ve bacteria (Eikenella, Actinobacillus, and Haemophilus) -enteric gram-ve bacteria (E. coli, Klebsiella, and Pseudomonas).

Differential Diagnosis
In the febrile patient with headache, altered mentation and lateralizing findings, the DD includes: subdural empyema epidural abscess viral encephalitis bacterial or acute aseptic meningitis septic thrombophlebitis endocarditis with septic embolism or mycotic aneurysm rupture

Differential diagnosis; Tuberculomas frequently cause SOL in countries with high TB prevalence. Amebae, toxoplasmosis, cysticercosis, or other helminths as schistosomal species, Paragonimus, trichinosis, sparganosis, and echinococcosis cause parasitic cerebral abscesses. Fungal abscess

Treatment
Current recommendations for empiric therapy, based on location of abscess and inferred source of infection are metronidazole with either penicillin or a thirdgeneration cephalosporin for frontal abscesses penicillin, metronidazole and ceftazidime for temporal or cerebellar abscesses nafcillin, metronidazole and cefotaxime for multiple (metastatic) abscesses nafcillin and cefotaxime for penetrating wounds vancomycin and ceftazidime for postoperative abscesses

Adjunctive medical therapy includes corticosteroids for mass effect hyperosmolar agents for worsening cerebral edema and raised ICP prophylactic or symptomatic anticonvulsants There is decreased mortality from brain abscesses reflecting improvements in neuroimaging and neurosurgical techniques. One half of survivors recover completely.

PARASITIC BRAIN ABSCESS

Toxoplasmosis Neurocysticercosis Amebic Echinococcal

FUNGAL BRAIN ABSCESS

(Aspergillus, Mucor ...)

IMMUNOCOMPROMISED Poor inflammatory response, less enhancement on CT. May present w much more advanced disease (seizure, stroke more common) High mortality Rx: aggressive surgery + antifungal

INTRACRANIAL EPIDURAL ABSCESS

Less common & less acute than Spinal epidural abcess Rounded, well-localized (because dura is firmly adherent to bone) Rx: Surgery + abx

SUBDURAL EMPYEMA

It is a collection of pus between the dura and arachnoid. 15-20 % of all focal intracranial infections Motly a complication of sinusitis, otitis media, mastoiditis.

Clinical features

Fever Headache Focal Neuro defects Vomiting Mental status changes Seizures Mass effect Stiff neck Rapid clinical deterioration

Frontal sinusitis, empyema and abscess formation in a patient with bacterial meningitis This T2-weighted axial MRI shows frontal sinusitis, a bone defect (arrow) with adjacent cortical edema (arrowhead), and right occipitoparietal subdural fluid collection (empyema).

Septic Venous Sinus Thrombosis

Septic thrombosis of cerebral veins or venous sinuses may complicate meningitis or epidural or subdural abscesses or develop during the intracranial spread of infection from extracranial veins.

Clinical Features
Thrombosis may develop in the cavernous, superior sagittal or lateral sinuses, depending on the site of primary infection. Specific presenting features vary with the site involved and include: -headache -altered mentation -seizures -cranial neuropathies -fluctuating focal deficits -nonarterial distribution strokes -increased ICP

Cavernous sinus thrombosis is indicated by

-ipsilateral proptosis and facial edema -retinal vein engorgement, retinal hemorrhages or papilledema -clinical involvement of the third, fourth, sixth, and ophthalmic division of the fifth cranial nerves

Lateral (transverse) sinus thrombosis is associated with

-papilledema -extension to the jugular bulb with involvement of cranial nerves IX, X, and XI -extension to petrosal sinuses with involvement of cranial nerves V and VI.

Sagittal sinus thrombosis is associated with

-papilledema -focal or generalized seizures -leg weakness -aphasia -cortical sensory deficits

Diagnosis

CT or MRI may demonstrate the primary infection or clot within the sinus. Clot within the sinus may appear as hyperdensity in the sinus on non-contrast CT, but may be missed by MRI as acute thrombus may appear hypointense on T2weighted images. MRV or cerebral angiography with venous phase studies may be necessary to confirm the diagnosis.

Treatment
Treatment is directed toward the primary infection. Empirical therapy is directed to gram+ve organisms, including staphylococci, aerobic gram -ve bacilli and anaerobes. Anticoagulants.

Spinal Epidural Abscess

American Family Physician April 1, 2002

COMMON PREDISPOSING MICROBIOLOGY CONDITIONS SPINAL EPIDURAL ABSCESS HEMATOGENOUS SPREAD: The most common pathogens from remote infections & w are: IVDU Staph aureus >60% DIRECT SPREAD: Vertebral Streptococci 18% osteomyelitis, diskitis, 13% decubitus ulcers, penetrating Aerobic GNR Polymicrobial 10% trauma, surgery, epidural catheters (Note: TB may cause up to 25% in some areas) Via paravertebral venous plexus: from abdominal/pelvic infections

CLINICAL MANIFESTATIONS
SPINAL EPIDURAL ABSCESS

Four clinical stages have been described: 1. Fever and focal back pain; 2. Nerve root compression with nerve root pain; shooting pain 3. Spinal cord compression with accompanying deficits in motor/sensory nerves, bowel/bladder sphincter function; 4. Paralysis (respiratory compromise may also be present if the cervical cord is involved).

DIAGNOSIS

SPINAL EPIDURAL ABSCESS (Thinking of it is key, in a pt with fever, severe, focal back pain)

MRI, CT scan Blood cultures Routine Labs rarely helpful

ESR,CRP usually elevated, BUT non-specific WBC may or may not be elevated

LP contraindicated

Differential diagnosis
transverse myelitis spinal osteomyelitis Herpes zoster Less commonly spinal subdural empyema epidural hematoma or metastases primary spinal tumors spinal artery syndromes

TREATMENT

SPINAL EPIDURAL ABSCESS

Early surgical decompression/drainage (preferably within first 24h)

Antibiotics

Empiric abx should cover Staph, strep, & GNR Duration of Rx : 4-6 weeks

Tuberculosis Meningitis

Clinical Features
TB meningitis has a subacute course with - low-grade fever - headache - intermittent nausea and vomiting followed by -more severe headache -neck stiffness -altered mentation -cranial (usually III, but also II, VII, and VIII) nerve palsies

Diagnosis
CSF examination demonstrates : normal or elevated opening pressure elevated protein (80-400mg/dL) low glucose (<40 mg/dL) pleocytosis (averaging 200-400 WBC/QL with lymphocytic predominance). PCR technique is now routinely available for the diagnosis of TB meningitis, with reported sensitivities of 70-75%. Cranial CT or MRI showing basal meningeal and sylvian exudates and enhancement with hydrocephalus.

CT scan in a patient with TB meningitis demonstrating marked enhancement in the basal cistern and meninges with dilatation of the ventricles.

Differential Diagnosis
-1] Untreated or partially treated bacterial meningitis -2] Other granulomatous meningitides (spirochetes, Brucella, most fungi and parasites as Amoeba, Toxoplasma and trypanosomes) -3] Subacute or chronic granulomatous ; CNS sarcoid, lupus, Behcet's, granulomatous Angiitis -4] Lymphomatous or carcinomatous meningitis -5] TB should be considered when suspected bacterial meningitis fails to resolve with antibacterial therapy.

Tuberculomas
-It is the parenchymal form of TB -occur as single or multiple brain or spinal cord lesions and present with S/S of SOL. -Tuberculomas are conglomerate caseous foci surrounded by fibrous capsule within the substance of the brain. -Centrally located, active lesions may reach considerable size without producing meningitis. -With poor resistance ---focal areas of cerebritis or frank abscess formation.

Vasculitis involving arteries and veins occurs On CT or MRI scan, the lesions may be of low or high intensity, with ring enhancement. Miliary disease is characterized by multiple small (1-2 mm) lesions. Open or stereotactic biopsy may be necessary if definitive diagnosis of TB cannot be made at an extraneural site.

T1-weighted gadolinium-enhanced MRI in a patient with multiple enhancing tuberculomas in both cerebellar hemispheres.

Spinal Tuberculosis
The most common site of involvement by TB of the spine is in midthorax region. Back pain is the main complaint and paraspinal muscle spasms or kyphotic deformity of the spine (from collapse of vertebra) may be found on examination. The intervertebral disc is almost always involved with the spread of the disease to the adjacent vertebra. A cold abscess develops, either as a paraspinal abscess in the dorsal and lumbar regions or as a retropharyngeal abscess in the cervical region.

The best modality is MRI.

The DD of vertebral bacterial diseases includes: -Infections with staphylococci, streptococci, typhoid and other gram-negative bacilli -Paratyphoid disease -Brucellosis

T2-weighted MRI of the thoracic spinal cord of a patient with 2 hyperintense intramedullary tuberculomas.

T2-weighted MRI of right parietal tuberculoma. Note the lowsignalintensity rim of the lesion and the surrounding hyperintense vasogenic edema.

T1-weighted gadolinium-enhanced MRI in a child with a TB abscess in the left parietal region. Note the enhancing thick walled abscess.

Treatment

Corticosteroid therapy has been generally accepted for specific indications: (1) increased ICP (2) complicated meningitis with hydrocephalus, vasculitis or arachnoiditis (3) very high CSF protein with impending spinal block (4) tuberculoma with surrounding edema

Leprosy (Hansen's Disease)

Diagnosis
Mononeuritis multiplexia: -transient, recurrent or persistent numbness or paresthesias -when a chronic, asymptomatic, atypical skin rash does not respond to standard treatments Palpable nerves include -greater auricular nerve in the neck -ulnar at the elbow -median at the wrist -terminal branch of the radial near the wrist -peroneal at the head of the fibula or in front of the ankle -posterior tibial below the inner malleolus -sural on the lateral foot

Nerve Conduction studies demonstrate focal or multifocal neuropathy in tuberculoid cases more diffuse sensory neuropathy in lepromatous cases Radial nerve sensory conduction study is one of the more sensitive indicators of disease Demonstrating M. leprae in skin, nasal mucous membrane or nerve biopsy establishes the diagnosis. The slit-scrape method :smears of scrapings from skin lesions are stained for AFB. Nerve biopsy is performed in purely neural cases or when a skin biopsy has not been diagnostic.

Treatment
Multibacillary leprosy is treated with -RIF 600 mg once a month -dapsone (a folate antagonist)100 mg daily -clofazimine 50 mg daily plus 300 mg once a month for a minimum of 2 years, or until skinsmear results are ve about 5 years.

Viral Infections of the CNS

Effects of viruses

Hundreds of viruses show tropism for the central and peripheral nervous system. Direct effects Acute Meningitis Chronic mrningitis Acute encephalitis Chronic encephalitis Myelitis Ganglionitis Polyradiculitis Immune mediated effects ADEM Role in chronic illnesses

RNA viruses Pico RNA viruses Enteroviruses Polio, Echo, Coxsackie Arboviruses Alpa viruses: Western, Eastern and Venezuelan equine Bunya viruses: La Crosse and California Encephalitis Ritf Valley Fever Flaviviruses: CNS specific: Japanese E, tick borne E, West Nile E Non CNS specific: Yellow fever, Dengue Reoviridae : Clorado Tick Fever

Classification RNA viruses

Classification RNA viruses

Rhabdoviruses : Rabies virus Paramyxoviruses Measles Mumps Rubella Influenza Para influenza Arena viruses: Lymphocytic Choriomeningitis Virus Retroviruses: HIV, HTLV Others: Rota viruses, Corona viruses

Classification DNA Viruses

DNA viruses

Herpes viruses Parvoviruses: B19 Papoviruses: JC, BK Pox viruses

Poliomyelitis Clinical Picture

Incubation Period: 7 -14 days Gastroenteritis or flu like symptoms Meningeal syndrome:

Fever Headache Meningeal irritation Disturbed conscious level Seizures in infants

Non Polio Enteroviruses Post polio Syndrome Viral meningitis

Clinical manifestations: Meningeal irritation No focal deficits Pharyngitis GIT upset Skin Rash (hand foot mouth disease: enterovirus 71)

Non Polio Enteroviruses Post polio Syndrome Meningioencephalitis

Most cases caused by enterovirus strain 70 Seen in patients with hypogammaglobulinemia Clinical manifestations

Focal deficits generalized manifestations

Non Polio Enteroviruses Post polio Syndrome Diagnosis

CSF:

Elevated cell count

Type and number differ according to specific virus

Virus isolation
PCR Culture: more difficult

Non Polio Enteroviruses Post polio Syndrome Treatment

Supportive measures Pleocanil:

Specific anti-viral that blocks cell/receptor interaction and entry to host cells Tried in more severe cases of enterioviruses Only minor improvement

Post polio Syndrome Arboviruses

Viruses transferred to humans through mosquito or tick bites They are the leading cause of viral encepahlitis world wide More than 100 viruses are known to cause human disease Show marked seasonal and geographical specificity based on life cycle or arthropod vector

Arboviruses Post polio Syndrome Examples

St. Louis encephalitis: The most common in the USA Japanese encephalitis: Widely spread in Asia The most frequent cause of viral encephalitis in the world Eastern Equine encephalitis: The most severe with mortality of 50-70% Tick born encephalitis: Widely spread in Central Europe and former Soviet Union

Arboviruses Post polio Syndrome West Nile Virus

Most widely distributes arboviruse Seen in Africa, West Asia, Middle East, Eastern Europe and Australia Vector: Culex mosquito Amplifying hosts: wild birds and horses Person to person transmission seen in: Blood and blood product transmission Organ transplantation Transplacental infection

Post polio Syndrome Encephalitis or meningioencephalitis

West Nile Virus

Diagnostic clues include: GIT upset Maculopapular rash (up to 5 to 50%) Cranial neuropathies (20% of cases): Most commonly bilateral peripheral facial palsy Optic neuropathy may occur Movement abnormalities: Postural or kinetic tremor Rigidity Myoclonus

Other Clinical Manifestations Brain stem encephalitis Cerebellitis Cranial neuropathiess Polyneuropathy/ radiculoneuropathy Optic neuritis

West Nile Virus Post polio Syndrome Diagnosis

CSF: Pleocytosis characterized by Prolonged predominance of PMNL Abnormal appearing reactive lymphocytosis Specific IgM Abs PCR Other lab investigations: IgM or IgG in serum Elevated CK Hyponatremia

MRI (variable): Signal alteration in cortex, corona radiata, basal ganglia, cerebellum or brain stem Normal studies associated with good prognosis

West Nile Virus Post polio Syndrome Treatment

Supportive measures: Specific measures:

Ribavarin: limited clinical utility Mortality is about 10% up to 35% in elderly

Outcome:

Arboviruses Post polio Syndrome Rift Valley Fever

Disease is found in Egypt, Sudan, east Africa, Mauritania Clinical picture: Influenza like illness Eye manifestations: Retro-orbital pain Macular retinitis with diminution of vision Meningioencephalits Hepatitis No specific treatment

Rabies Post polio Syndrome Introduction

Rabies is found enzootic almost all of the world except for Australia, Great Britain, Ireland and Japan Reservoir hosts include:

Dogs Wild carnivores Bats Bites Aerosoal exposure rarely reported

Transmission:

Rabies Post polio Syndrome Clinical picture

Incubation period: Variable from 1-2 months Shorter with head and neck bites Prodromal phase: Headache High grade fever Pain and paresthesia the site of the bite

Acute neurological phase: Hydrophobia: Spasms in pharngeal or nuchal muscles lasting from 1-5 minutes Triggered by swallowing attempts or sensory stimuli Seizures Autonomic hyperactivity

Rabies Post polio Syndrome Clinical picture

Behavioral changes: Furious rabies: Agitation and hallucinations predominate May proceede to coma Dumb rabies: Seen in 20% of cases Most commonly associated with bat rabies Paresthesia and weakness at site of the bite that proceeds to quadriplegia

Rabies Post polio Syndrome Prevention& Management

Pre-exposure prevention: Human deploid cell rabies vaccine Post exposure prevention: Wash wound with soap and water followed by povidone iodine Immediate administration of vaccine Human rabies immune globulin administered as soon as possible Vaccine may cause: GBS,ADEM

Handling of the animal: Animal can be either killed or kept under observation for 10 days Treatment can be stopped if animal is healthy after period of observation or its brain is negative for rabies No active treatment available Mortality is 100% if patient becomes symptomatic

Measles Post polio Syndrome Introduction

A highly contagious respiratory borne disease Causes four CNS disorders:

Acute encephalitis Post viral encephalitis Measles inclusion body encephalitis SSPE

Measles Post polio Syndrome 1. Acute encephalitis

Occurs as a complication of acute measles infection Most likely to occur in children under the age of 2 Other features of acute measles are seen including Fever Conjunctivits Kopliks spots Maculopapular rash EEG abnormalites are seen in 50% of patients with acute measles in absence of encephalitis

Measles Post polio Syndrome 2. Post infectious encephomyelitis

Affects children above the age of 2 with normal immunity Seen in 1 per 1000 infections Pathology (not specific): Autoimmune mediated demyelinating disease Perivascular demyelination, cuffing and gliosis Hemorrhagic changes in severe cases

Onset: 2 weeks after rash Main manifestations: Encephalopathy Focal pariesis Ataxia Myoclonus Seizure Rarely, pure myelitis

Measles Post polio Syndrome Post infectious encephomyelitis

Management:

Steroids Plasma pharesis Mortality is up to 15% untreated Residual neurological deficits may occur

Outcome:

Measles Post polio Syndrome 3. Inclusion body encephalitis

A rapidly progressive dementing illness developing 1 to 6 months after measles infection in individuals with impaired cell mediated immunity Pathology: Diffuse inflammatory changes in the brain Eosinophilic inclusion bodies within nuclei of neurons Virus antigen can be detected in brain tissue

Clinical picture: Behavioral changes Myoclonus Refractory focal and generalized seizures Altered consciousness Coma and death in a few months

Measles Post polio Syndrome Inclusion body encephalitis

Investigations:

CSF :normal Serology: negative due to immune supression Neuroimaging:Unremrakable

Mainly supportive Reverse immune suppression of possible Passive immune globulin therapy

Treatment:

Subacute sclerosing Post polio Syndrome panencephalitis (SSPE)

A rare, late complication of measles caused by persistent non productive measles infection of neurons and glia. Incidence:

1 per 10 000 cases of measles Not reported after vaccination Male to female ratio is 2.5: 1 More likely if infection is in the first year of life

SSPE Post Clinical polio Syndrome picture

Onset: median 8 years after measles infection Early stage: Behavioral or personality changes Declining school performance Second stage: Myoclonus Seizures Spasticity Choreoathetoid or ballistic movements Ataxia Chorioretinitis

Final stage: Optic atrophy Quadriparesis Autonomic instability Akinetic mutism Coma Acute symptoms and increased intracranial pressure, are poor prognostic signs

SSPE Post polio Syndrome Investigations

Serology:

High titer antimeasles Ab in serum and CSF. The CSF/serum antibody ratio is pleocytosis is absent Glucose is normal Total protein is normal or elevated.

CSF:

SSPE PostInvestigations polio Syndrome

Early (A and B):

Focal abnormality in the subcortical white matter Diffuse cortical atrophy

Late (C and D)

SSPE PostInvestigations polio Syndrome

SSPE Post polio Syndrome Treatment

Some patients have improved or stabilized after one or several 6-week treatments with intraventricular interferon- There have also been reports of response to intravenous ribavirin in combination with intrathecal interferon-. Symptomatic treatmen:
Anticonvulsants Antipsychotics for uncontrolled behavior

Measles and chronic CNS Post polio Syndrome disease [ slow virus ]

Measles virus has been suggested, but not proved to play a role in the pathogenesis of
Multiple sclerosis Autism Chronic active hepatitis Osteosclerosis Crohns disease

Rubella Post polio Syndrome

Post infections encephalomyelitis Complicate 1 of 6000 cases Onset :1-6 days after the appearance of the rash.

Congenital rubella

80% have CNS involvement Manifestation include

Mental retardation Sensorineural hearing loss Motor and posture abnormalities Pigmentary retinopathy

Mumps

Mumps virus causes a mild childhood illness characterized by parotitis In unimmunized populations, mumps is a common cause of aseptic meningitis and encephalitis
Postinfectious encephalomyelitis was also reported

Mumps Post polio Syndrome Mumps meningioencephalitis

Incidence markedly declined after introduction of vaccination Onset: 5 days after onset of parotitis In 40-50% meningitis may precede parotitis May occur without salivary Manifestations: Meningeal irritation Disturbed conscious level

Complications: Seizures Deafness from labyrinth membrane and sensory transducer damage Myelitis Hydrocephalus following viral replication in choroidal and ependymal cells

Influenza

Neurological complications include:

Myositis Reye syndrome Acute encephalitis:

High rate of mortlaity

Post infectious encephalopathy

Good prognosis

Encephalitis lethargica

Arena viruses Lymphocytic choriomeningitis virus

Aseptic meningitis: the most common Encephalitis: (5-34% ) Ascending or transverse myelitis Bulbar syndromes Parkinsonism Sensorineural hearing loss. Hydrocephalus may arise as a sequelae of ependymitis or ventriculitis

Diagnosis: CSF : cell counts of 10-500 WBC Viral culture and serology IgM antibody to LCMV is present in serum and/or CSF during acute meningitic disease Treatment: ribavirin

Retroviruses

The Retroviridae is a large family of viruses including:

HTLV-bovine leukemia group: Human T-cell lymphotropic virus (HTLV) types I and II. Lentivirus group: HIV 1 and 2

HTLV associated spastic myelopathy (HAM)

Incubation period : approximately 20 years Onset: Gradual progressive spastic paraparesis or myeloneuropathy. Neurological findings: Lower extremity weakness and spasticity that is usually symmetric Impotence Urinary and fecal incontinence Generalized hyper-reflexia except in cases of concomitant sensory neuropathy

Other neurological manifestations: Cerebellar ataxia Vertigo Deafness Optic neuritis Inflammatory myositis Peripheral neuropathy

HTLV associated spastic myelopathy (HAM)

Differential diagnosis: Primary progressive spinal MS Hereditary spastic parapresis Vitamin B 12 defeciency Other causes of tropical paraparesis HIV associated myelopathy

CSF: Mild elevations of lymphocytes and proteins Oligoclonal bands Elevated CSF AB levels PCR can be positive Serology MRI: Spine: Diffuse hyperintense signal in T2 images Atrophy in late cases Brain: Periventricular gray or white matter lesions

HTLV associated spastic myelopathy (HAM)

Treatment:

Steroids: pulse followed by oral therapy for 2 months IVIG if failed Best chance of improvement if treatment started in the first year

Outcome:

DNA Viruses

Herpes viruses Parvoviruses: B19 Papoviruses: JC, BK Pox viruses

Herpes Encephalitis

Symptoms and signs

Focal neurologic findings are usually acute (<1 week ) and include altered mentation and level of consciousness, focal cranial nerve deficits, hemiparesis, dysphasia, aphasia, ataxia, focal seizures , or aseptic meningitis . Over 90% of patients will have one of the above symptoms plus fever. Later in the clinical course, patients may have diminished comprehension, paraphasic spontaneous speech, impaired memory, and loss of emotional control, and behavioral syndromes.

Laboratory abnormalities
CSF typically shows a lymphocytic pleocytosis, increased number of erythrocytes (in 84 % of patients), and elevated protein. A normal cerebrospinal fluid (CSF) profile can occur early in the course of the disease. Repeat testing can be helpful when the clinical suspicion is high. Low glucose is uncommon and may suggest an alternative diagnosis.

MRI

Upper panels: MR images of the brain at two day after admission. Abnormal signals were seen in the right temporal lobe and insular cortex. Lower panels: MR images showing that abnormal signals had spread to the left side at 15 days after admission.

EEG
Focal EEG findings occur in >80 percent of cases, typically showing prominent intermittent high amplitude slow waves (delta and theta slowing), and, occasionally, continuous periodic lateralized epileptiform discharges in the affected region. Many EEG findings are nonspecific.

Differential diagnosis
Encephalitis from other viral etiologies such as togavirus infections (West Nile encephalitis, St. Louis encephalitis, Western equine encephalitis, California encephalitis, Eastern equine encephalitis), other herpesviruses (CMV, EBV, VZV) and other miscellaneous viruses (enteroviruses, influenza A, mumps, adenovirus, lymphocytic choriomeningitis virus, progressive multifocal leukoencephalopathy caused by the JC virus). Brain abscess or subdural empyema caused by a variety of organisms including bacteria, mycobacteria, fungi, rickettsiae, mycoplasma, or protozoa.

Acute disseminated encephalomyelitis.

Primary or secondary brain tumors. Other noninfectious causes such as subdural hematoma, systemic lupus erythematosus, adrenal leukodystrophy, vasculitis, neuro-Behcet's and toxic encephalopathy.

Treatment
HSV encephalitis is a devastating infection of the CNS. Even with early administration of therapy after onset of disease, nearly twothirds of survivors will have significant neurologic deficits. Acyclovir was shown to be the treatment of choice for the reduction of mortality and morbidity from HSV encephalitis in the mid-1980s.

Etiologies of Viral encephalitis

Echo virus Coxsakie and Enteroviruses Herpes Simplex West Nile virus Un identified etiology 32- 75% Herpes Encephalitis is NOT SEASONAL

sporadic

THERAPY FOR ENCEPHALITIS Etiology Therapy HSV Acyclovir VZV Acyclovir CMV Ganciclovir + foscarnet HHV-6 Ganciclovir or foscarnet HIV HAART JC virus HAART

DNA Viruses JC virus: PML

PML is a subacute, demyelinating disease of the CNS caused by infection of oligodendrocytes by papovavirus Pathogenesis: Most people acquire infection in childhood leading to asymptomatic persistant infection In states of immune defeciencythe virus can cross the blood-brain barrier and infects oligodendrocytes subsequently, glial cells. When activated it results in asymmetric multi focal white matter involvement. Natalizumab- induced PML . Subacute onset In non-AIDS-associated PML: early affection of subcortical white matter of the occipital lobes, causing visual field deficits or cortical blindness Other manifestations Motor weakness Cognitive and behavioral changes Cerebellar ataxia Sensory abnormalities Dysarthria

PML Investigations

PML

131

PML
MRI during the course of PML and IRIS. Axial reconstructions from 3D Flair acquisition. Routine MRI 1 year before PML diagnosis (A), when PML was diagnosed (B) and subsequent scans directly after plasma exchange (C), 1 week (D), 2 weeks (E), 4 weeks (F), 5 weeks (G), 1.5 months (H), and 2.5 months (I) after plasma exchange. Arrows indicate the PML lesions.

PML Treatment

PLEX , mirtazepine , immuneabsorption, mefloquine [ natalizumab- induced PML ] Cytarabine, Interferon- and Cidofovir tried Improvement of the immune deficiency lead to regression of the PML lesions

Viral Menigitis

85% secondary to
Echo Coxsackie Entero

Also consider HSV, and EBV Neutrophils may predominate in the CSF in the first 24 hours Consider starting ATBs until cultures come back (-)

Viral Encephalitis

Infection of brain parenchyma Presents of neurological abnormalities distinguish it from meningitis Incidence is 1/10 of bacterial meningitis HSV-1, zoster, EBV,CMV, rabies, arbo Arbo SEE(St Louis)-20% mortality in elderly WEE(Western)- causes seizures in 90% of infected infants, permanent neuro deficits in 50% EEE(Eastern)- most devastating, mortality 70% WNV(West Nile)

Neurosyphilis
Presenting Signs and Symptoms

Can be asymptomatic Headache, fever, photophobia, meningismus seizures, focal findings, cranial nerve palsies

Tabes dorsalissharp pains, parasthesias,

decreased DTRs, loss of pupil response General paresis memory loss, dementia, personality changes, loss of pupil response Meningovascular strokes, myelitis Ocular syphilisiritis, uveitis, optic neuritis

Diagnostics
CT Scan/MRI: Aseptic meningitismay show meningeal enhancement. General paresiscortical atrophy, sometimes with infarcts. Meningovascular syphilis deep strokes. May present like dementia. CSF: Protein45-200/ml WBCs5-100 (monos)

VDRL positivesensitivity 65%; specificity 100% positive Serum VDRL and FTA-ABS are clue in >90%; false neg serum VDRL in 5-10% with tabes dorsalis or general paresis Definitive diagnosis: positive CSF, VDRL (found in 6070%)

Management and Treatment

Give Aq penicillin G, 18-24 mil units/day x 10-14 days Follow-up VDRL every 6 months until negative Indications to re-treat:
CSF WBC fails to decrease at 6 months or CSF still abnormal at 2 years Persisting signs and symptoms of inflammatory response at 3 months Four-fold increase in CSF VDRL at 6 months

HIV

HIV