Encephalitis Flashcards
Pathogenesis of Encephalitis
Virus or infected leukocyte localizes in blood vessel
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it then leaves the blood vessel
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T cell sensitized to virus or host component releases cytokines
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Cytokines induce infiltrations of mononuclear cells (lymphocytes, NK cells, & macrophaes)
At the same time neural cells are also infected
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Infection is finally controlled, but it causes immunopathology
Further viral spread → destruction of infected neural cell
Clinical Characteristics of Encephalitis
- Brain substance affected (damage) → signs of cerebral dysfunction → Abnormal behavior, AMS, seizures and altered consciousness
- Nausea and vomiting
- Fever
DDx of Encephalitis
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Viral causes:
- HSV1
- HSV2
- Rabies virus
- Japanese Encephalitis virus and other arboviruses
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Protozoal causes:
- T. gondii
- *T. *brucei
- __Immune-mediated causes:
- NMDA-receptor antibody-associated encephalitis
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- NMDA-receptor antibody-associated encephalitis
HSV Encephalitis (HSE)
- HSV = ds, linear, enveloped, DNA virus w/ an icosahedral nucleocapsid
- MC form of severe sporadic acute focal encephalitis
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Neonates:
- From a mother shedding HSV2 in the genital tract during vaginal delivery.
- Prevention: c-section in infected mothers
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Other children & adults:
- Viral reactivation of HSV-1 in the trigeminal ganglia
- Infection then may spread via cranial nn to the brain → focal necrotic lesions in the temporal lobe of the brain → inflammation → encephalitis
- Other herpesviruses (VZV, CMV, HHV6) less commonly cause encephalitis
HSE Diagnosis
- Temporal lobe enhancement on CT and/or MRI
- HSV DNA detection on PCR of CSF
- Electroencephalogram
Other HSV diagnosis:
- Multinucleate giant cells on Tzanck smear of skin cells
- Eosinophilic Cowdry intranuclar inclusion bodies on skin biopsy
HSE Treatment
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IV acyclovir for 21 days
- course is important since relapse can occur
- early and prolonged tx ⇣70% mortality rate significantly
Rabies Virus General Characteristics
- Rhabdoviridae Lyssavirus
- negative, ss, non-segmented, enveloped RNA virus w/ a helical nucleocapsid
- “Bullet-shaped” on EM
- Glycoprotein spikes bind to ACh receptors and are important in rabies virulence
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CP:
- Incubation period of 4-13 weeks (longest 6 months) with no symptoms
- Muscle spasms
- “Foaming of the mouth” due to inability to clear saliva b/c of painful spasms of pharyngeal mm on swallowing. As a result patients avoid drinking ↓
- Hydrophobia
Rabies Virus Pathobiology
- Virus excreted in the saliva of infected dogs or other mammals (wolves, skunks, vampire bats, etc.)
- Transmission to humans via animal bite → localization to bite site for days to months → binds ACh receptors and enters peripheral nn → travels proximally to CNS (distance determines incubation time) → infection (& dysfxn) of neurons of brainstem and brain → cytoplasmic inclusion bodies (negri bodies) form → cell necrosis → cranial nerve palsies and encephalitis → dysphagia, agitation, & seizures → coma → death
Rabies Virus Dx
- Identify Negri bodies in neurons and other infected cells
- PCR for Rabies Virus RNA
- Viral antigen by immunofluorescence
- Serology
Rabies Virus Tx
- Wash wound immediately (alcholic iodine, debridement)
- Human Rabies Immune Globulin (HRIG) antibodies for passive immunity
- Given IM around wound site
- “While the virus is travelling up the axons of motor or sensory neurones, there is no detectable antibody or cell-mediated immune response, possibly because antigen remains sequestered in infected muscle cells. Hence, passively administered rabies immunoglobulin may be given during the incubation period.” -Mims
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Human Diploid Cell Vaccine: live-attenuated virus (often administered after the bite)
- Only vaccine administered after viral exposure
- Works by boosting the immune system during the long incubation period
- Vaccine and HRIG must never be administered at the same anatomical site
- Prevention:
- Immunize domesticated and wild animals
Japanese Encephalitis Virus and other Arboviruses General Characteristics
- Flaviviridae Flavivirus
- Positive, ss, nonsegmented, enveloped RNA viruses w/ an icosahedral nucleocapsid
- Types of Flaviviruses:
- Hemorrhagic fevers:
- Yellow Fever
- Dengue Fever (fever, myalgia, & rash)
- Encephalitis viruses:
- Tickborne encephalitis
- St. Louis Encephalitis (California)
- Japanese Encephalitis (common in India)
- West Nile Virus
- Hemorrhagic fevers:
Japanese Encephalitis Virus and other Arboviruses Pathobiology
- Normal resevoir in monkeys, birds, or humans → transmission by mosquito bite →enters bloodstream w/ transient viremia and infects:
- Hepatocytes (Yellow Fever) → necrosis → hepatitis, jaundice
- Macrophages (Dengue Fever) → acute inflammation → pyrogens and pain mediators released → “breakbone fever”
- CNS (St. Louis or Japanese Encephalitis) → direct damage to neurons, inflammation → neurological abnormalities
Japanese Encephalitis Virus and other Arboviruses Dx and Tx
- Dx:
- Isolate virus from infected tissue (CSF in encephalitis)
- Serology
- Tx:
- No Antivirals
- Vaccine for:
- Tickborne encephalitis
- Yellow Fever virus = live-attenuated
- Japanese Encephalitis = formalin-killed
- Prevention:
- Monitor mosquito counts in an area
Toxoplasma gondii Gen Cha
- Protozoan that causes systemic infection, especially in immunocompromised patients (e.g., AIDS)
- MCC of encephalitis in AIDS pts
- Crescent-shaped trophozoites w/in macrophage
- One of the TORCHES infections:
- Pregnant mothers w/o previous exposure should avoid cats
- Only those w/ active primary infection can result in congenital toxoplasmosis
- Previous infections mount an immune response that protects the fetus
- Pregnant mothers w/o previous exposure should avoid cats
*Toxoplasma gondii *Pathobiology
Cysts ingested from undercooked meat or cat feces
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In small intestine, cysts release invasive form and penetrate the intestinal wall
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Macrophages phagocytose and disseminate them
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This infects & damages cells at distant sites
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Host response can contain infections → mononucleosis-like symptoms → invasive forms become dormant and contained w/in cyst
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If become immunocompromised cyst ruptures
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Release of invasive form
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Encephalitis, chorioretinitis
