Table of contents
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Encephalitis Introduction
- Definition:
- Inflammation of brain parenchyma + neurologic dysfunction
- Meninges are frequently involved ("encephalitis" and "meningoencephalitis" used interchangeably).
- Most common causes in US: ( >100 different agents)
- Herpes Simplex Virus Type I
- Reactivation of latent virus in 2/3 of cases.
- Clinically: fever, temporal lobe seizures.
- Diagnose with CSF polymerase, treat with acyclovir.
- West Nile Virus
- Mosquito-borne infection worldwide.
- Cases in US started 1999, peaked in 2003, then variable (up and down).
- Clinically: Acute flaccid paralysis, encephalitis, myoclonus.
- Dx: IgM of CSF for West Nile Virus.
- 50% cause not identified despite many investigations.
- Other Types:
- Eastern Equine Encephalitis, HHV 6, JC virus, PML, rabbies, St. Lous encephalitis virus.
- Herpes Simplex Virus Type I
- Another approach to causes:
- Arthropod-borne
- Mosquitoes
- Arboviruses (alphavirus, flavivirus, bunyavirus)
- West Nile
- Crows susceptible - finding dead crows = investigation.
- ***Mosquito protection*** is #1
- Mosquitoes
- Person-to-Person
- MUMPs
- Measles
- Varicella
- HHV-6
- HSV1 (not HSV2)
- Other Rare (EBV, Enterovirus, CMV)
- Animal-to-Person
- Rabies (bats and animals)
- Arthropod-borne
- Rarely: bacteria, protozoa, helminths
- Herpes Simplex Encephalitis
- Acute, necrotizing, asymmetrical hemorrhagic process with lymphocytic and plasma cell reaction (medial temporal and inferior frontal lobes).
- Often HSV1, but can be HSV2.
- Symptoms:
- Defined as:
- Altered Mental Status lasting >24hrs. (memory, confusion, agression, hallucinations --> temporal lobe effects)
- Decreased LOC (can be anywhere from mild confusion to coma).
- Seizures (up to 40% of patients)
- Other Symptoms:
- Hallucinations
- Ataxia
- Cranial Neuropathies
- Focal neurologic findings (if focal neuro area involved).
- Meningeal involvement (meningoencephalitis):
- hemicranial headache, nuchal rigidity.
- Cerebral cortex: hallucinations, peculiar motor functions (placing underwear over pants)
- Clinically cannot tell between viruses. They all present the same, except rabies:
- brainstem involvement, nucleus ambuguus, and medulla, resulting in:
- Pt's get "hydrophobia", attemping to swallow = paryngeal spasms.
- Rapid, short respirations
- Hyperactivity/autonomic dysfunction, rarely ascending paralysis.
- brainstem involvement, nucleus ambuguus, and medulla, resulting in:
- Defined as:
- Investigations:
- Standard of care for encephalitis includes:
- 1. LP
- 2. MRI
- 3. EEG
- LP for CSF
- Lymphocytic pleocytosis, but CSF can be acellular.
- LP be normal in 5-10% of patients in viral encephalitis
- Test CSF for PCR HSV1 + other organisms based on edidemiologically relevant (seasons, geography, exposures, rash, etc..)
- West Nile IgM
- MRI is needed to detect encephalitis (more sensitive than CT)
- Can also do CT and EEG based on sx.
- Standard of care for encephalitis includes:
- See specific causes of encephalitis below for more specific signs/symptoms/treatment.
HSV1 Encephalitis
- Most common in US, mostly affects young and elderly patients.
- Organism:
- HSV1 >90%, and HSV2 10%.
- More than 2/3 due to re-activation of latent HSV1 rather than primary infection.
- Mortality rate 15-30%, and those that survive commonly have neuropsychiatric sequelae.
- Symptoms:
- mostly headache, fever, mental status change (present within a week).
- <10% of pts have oral/labial herpetic lesions.
- Partial complex seizures can occur (involves temporal lobes).
- If not recognized, progress to bilateral temporal lobe hemorrhagic necrosis --> severe
- mostly headache, fever, mental status change (present within a week).
- Labs:
- LP demonstrates lymphocytic pleocytosis, but normal in ~5%
- Diagnosis:
- PCR HSV (Sn >95%, Sp ~100%), --> diagnostic!
- PCR can be negative early in infection. IF PCR negative, but suspect encephalitis treat anyway and repeat LP 3-7d later. (should remain positive >7 days).
- NOTE: viral cultures insensitive, and serologic studies are non-specific.
- Can biopsy in extreme cases.
- Presence of RBC in CSF without trauma can suggest HSV.
- EEG: Periodic latererlizing epileptiform discharges (PLEDs), localize to temporal lobes.
- Neuroimaging: Localize lesions to one or both temporal lobes.
- Treatment:
- IV acyclovir (begin empiric IV acyclovir before PCR results).
- If PCR positive, continue IV acyclovir for 14-21 days.
- NOTE: Oral antivirals (i.e. valacyclovir) have poor CSF penetration, MUST use IV acyclovir.
- Can discontinue if negative PCR and suspision becomes low.
- IV acyclovir (begin empiric IV acyclovir before PCR results).
West Nile Virus
- First detected in 1999.
- Spread by bite of a mosquito, peak in late summer and early fall.
- Symptoms (3 possibilities)
- Asymptomatic (80%)
- Symptomatic fever (20%)
- Fever, fatigue, rash, headache, anorexia, back pain, myalgia.
- Neuroinvasive disease (<1%)
- Typically adults > 50y affected.
- Meningitis, encephalitis, myelitis (often overlapping).
- Objective finding of Focal Weakness - IMPORTANT CLUE, characteristic.
- Manifests as an acute flaccid paralysis, can even involve diaphragm (similar to polio).
- Extrapyramidal signs: tremors, bradykinesia (as in Parkinsons).
- Rash (possible, but uncommon in neuroinvasive. Typically sign of symptomatic fever group).
- Labs:
- Lumbar Puncture:
- Lymphocyte dominant pleocytosis, but more neutrophils than other viral CNS infections.
- Send CSF for West Nile Virus IgM = diagnostic
- Reliably detected within 9 days of onset of fever, and persists for >1yr.
- Some cross-reaction to other flavi-viruses (st. louis encephalitis, Japanese encephalitis, dengue, yellow fever - false positives.
- PCR gives false negatives, likely because brief period of viremia in WNV.
- MRI:
- Bilateral enhancement of thalamus and basal ganglia on T2 MRI images.
- Lumbar Puncture:
- Treatment
- Supportive
- Evaluating roles of aminotherapy, some unpublished studies with IVIG.
- Prevention is most important by mosquity protection.
Rabies
- Wash bite wound with 20% soap
- irrigate with virucidal agent (i.e. povidone iodine).
- Inject Rabies Ig (20 IU/kg) around the wound (via IM)
- Rabies vaccine: on days 0, 3, 7, 14, 28
Non-Infectious Encephalitis
-
Anti-NMDA Receptor Encephalitis
- Paraneoplastic Syndrome
- Often associated with ovarian teratomas
- Symptoms:
- Usually a prodomal flu-like syndrome
- Followed by:
- Memory Disturbance
- Personality Change
- Psychosis
- Encephalopathy
- Seizures
- Oral Dyskinesia (involuntary mouth movements)
- Findings:
- Usually MRI FLAIR - shows signal in temporal lobes.
- CSF can be normal, but usually mild lymphocytic pleocytosis with mild elevated protein.
- Diagnosis:
- Finding Anti-NMDA receptor antibodies in CSF or serum
- Treatment:
- Treat Teratoma (i.e. Oophorectomy)
- Cover for HSV encephalitis until cause known.
- Paraneoplastic Syndrome
-
Anti-Hu (Anti-ANNA-1)
- Paraneoplastic Syndrome (autoantibody)
- Usually older patients
- Associated with: Small Cell Lung Ca
- Symptoms (MOTOR or SENSORY)
- Paraneoplastic Syndrome (autoantibody)
Prognosis
- HSV1: 50-60% mortality
- Rabies mortality: 100%
- Eastern equin encephalitis 70%
- West Nile - > often mild and subclinical disease (worse in elderly --> flaccid paralysis).
- Venezuelan equine encephalitis --> mild
- Japanese encephalitis --> varies
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