Viral Encephalitis Clinical scenario 1 Definitions/Descriptions Viral causes of acute encephalitis/encephalomyelitis Pathogenesis (I)

Viral Encephalitis Clinical scenario 1 Definitions/Descriptions Viral causes of acute encephalitis/encephalomyelitis Pathogenesis (I) www.phwiki.com

Viral Encephalitis Clinical scenario 1 Definitions/Descriptions Viral causes of acute encephalitis/encephalomyelitis Pathogenesis (I)

Richards, Tim, Operations Manager has reference to this Academic Journal, PHwiki organized this Journal Viral Encephalitis Definitions Pathogenesis Epidemiology Clinical findings/diagnosis/treatment Specific examples: HSV-1 Arboviruses/West Nile Rabies Clinical scenario 1 50 yo man in Riverdale awakens from a Saturday afternoon nap in December, puts on his swimsuit, in addition to begins to fill the bathtub with shredded pieces of that day’s newspaper. Although he finds nothing odd about his behavior, he complains of a headache, in addition to his wife convinces him to go to the E.R., where he is found to be febrile (102.4) in addition to extremely lethargic. Definitions/Descriptions Encephalitis vs. Meningitis Viral meningitis Fever, headache, n/v, malaise, stiff neck, photophobia Enteroviruses, herpesviruses, “arboviruses,” acute HIV Viral encephalitis Fever, headache, altered mental status, decreased consciousness, focal neurologic findings Herpesviruses, “arboviruses,” enteroviruses (U.S.) Aseptic meningitis Meningoencephalitis Myelitis

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Typical CSF findings in selected CNS infections Viral causes of acute encephalitis/encephalomyelitis Virus Family Specific viruses (genus)——– Adenoviridae Adenovirus Arenaviridae LCMV (lymphocytic choriomeningitis virus), Lassa Bunyaviridae La Crosse, Rift Valley Filoviridae Ebola, Marburg Flaviviridae St. Louis, Murray Valley, West Nile, Japanese B, Tick-borne complex Herpesviridae HSV-1, HSV-2, VZV, HHV-6, EBV, CMV, Herpes B Paramyxoviridae (Paramyxovirus) Mumps (Morbillivirus) Measles, Hendra, Nipah Picornaviridae Poliovirus, Coxsackie virus, Echovirus Reoviridae Colorado tick fever Retroviridae (Lentivirus) HIV Rhabdoviridae Lyssavirus, Rabies Togaviridae (Alphavirus) Eastern equine, Western equine, Venezuelan equine Pathogenesis (I) Neurotropism Neuroinvasiveness Neurovirulence Outcome dependent on: Viral factors Above plus site of entry, size of inoculum Host factors Age, sex, immune status, genetic factors

Pathogenesis (II) Entry Respiratory, GI, GU, skin, ocular conjunctiva, blood Invasion Entry into central nervous system Hematogenous dissemination Neural dissemination Neurovirulence in addition to Immunopathology Hematogenous Spread Occurs despite blood brain barrier with tight junctions Via choroid plexus Via infection of cerebral capillary endothelial cells Via diapedesis Neural spread

Olfactory spread Pathogenesis (III) Neurovirulence Neuronal infection Latency, subtly altered function, apoptosis, necrosis Anatomic location affects manifestations Oligodendroglial cells JC virus, PML (progressive multifocal leukoencephalopathy) Immunopathology Inflammatory reaction in meninges in addition to in perivascular distribution within brain Acute disseminated encephalomyelitis (ADEM)

Immune Activation Plays a Protective in addition to Pathologic Role Release of Inflammatory Cytokines Inhibition of viral replication Neuronal dysfunction/ injury activated microglia Infected neurons infiltrating inflammatory cells Epidemiology 20,000 cases annually in U.S. Worldwide incidence unknown 10,000 deaths due to Japanese encephalitis 60,000 deaths due to rabies Geographic in addition to temporal niches Iceberg phenomenon Extremes of age in addition to the immunocompromised Altered by +/- routine vaccinations Clinical Features Headache Fever Altered consciousness Confusion, cognitive impairment, personality changes Seizures Weakness in addition to movement disorders PRESENCE OF FOCAL NEUROLOGIC FINDINGS IN ADDITION TO FEVER AND HEADACHES – THINK ENCEPHALITIS Prognosis

Diagnosis in addition to Treatment Diagnosis History in addition to Physical CSF profile Mild-mod lymph pleocytosis, normal or slightly elevated protein, normal glucose Rule out other causes Viral cultures, detection of viral nucleic acid, serology of CSF in addition to serum MRI, EEG Treatment supportive except acyclovir as long as HSV Clinical scenario 1 50 yo man in Riverdale awakens from a Saturday afternoon nap in December, puts on his swimsuit, in addition to begins to fill the bathtub with shredded pieces of that day’s newspaper. Although he finds nothing odd about his behavior, he complains of a headache, in addition to his wife convinces him to go to the E.R., where he is found to be febrile (102.4) in addition to extremely lethargic. HSV encephalitis The major treatable viral encephalitis Most common cause in U.S. of sporadic, fatal encephalitis Usually HSV1 (HSV 2: meningitis) Occurs year-round, kids in addition to adults Reactivation > primary but can be either Retrograde transport into CNS via olfactory or trigeminal nerves Necrotizing encephalitis in addition to hemorrhagic necrosis, particularly temporal lobe

HSV encephalitis – MRI HSV encephalitis Clinical as above, particularly personality changes in addition to bizarre behavior, amnesia, hypomania Sudden onset, no prodrome Diagnosis as above, plus sometimes RBCs in CSF MRI in addition to EEG with temporal lobe findings PCR of CSF 98% sensitive, 94% specific Treatment Acyclovir is well-tolerated in addition to reduces mortality from 70% to 19% in addition to should be started EARLY “ARBOVIRUSES” (arthropod-borne viruses)

Arboviral encephalitis: classification Family Genus Species Togaviridae Alphavirus Western Equine (ssRNA+,env) Eastern Equine Venezuelan Equine Flaviviridae Flavivirus (Japanese B antigenic complex) (ssRNA+,env) Japanese B St. Louis West Nile Murray Valley (Tick-borne antigenic complex) Tick-borne encephalitis Central European encephalitis Russian spring-summer encephalitis Powassan Bunyaviridae Bunyavirus LaCrosse (ssRNA neg, Cali as long as nia encephalitis segmented, env Arboviral encephalitis: Pathogenesis Non-cytopathic in mosquito vectors; cytopathic in most mammalian cells Hematogenous entry into CNS: arthropod bite -> replication in peripheral sites -> viremia -> CNS invasion Neuron is primary target in CNS Neurovirulence due primarily to neuronal dysfunction in addition to neuronal death induced directly by virus Age of host is of paramount importance in determining neuroinvasion/neurovirulence

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Arboviral encephalitis Clinical Short incubation period (4-10 days) Occurs late spring through early fall Wide clinical spectrum: asymptomatic (most), to mild flu-like illness, to aseptic meningitis, to encephalitis (subtle mental status changes to severe confusion, coma) Diagnosis – isolate viral antigen or nucleic acid in CSF, serology Treatment – supportive Clinical scenario 2 66 yo man from Staten Isl in addition to experiences onset in June of fever, chills, headache, nausea, vomiting, muscle aches, fatigue, muscle weakness, dizziness Two weeks later, abrupt onset of double vision in addition to mental status changes West Nile Virus A flavivirus, ssRNA, enveloped

U.S. WNV Activity 2004

Rabies – Clinical features Incubation period 1 week to 1 year+ 100% fatality rate once symptoms occur in an unvaccinated individual (until now) Prodromal phase – 2-10 days Fever, sore throat, headache, paresthesias, pain at site of bite Acute neurologic phase (encephalitic/furious) – 2-10 days Agitation, delirium, stiffness, hypersalivation, hydrophobia Coma, flaccid paralysis, seizures, respiratory in addition to vascular collapse Less commonly, pure ascending paralysis (paralytic) Rabies diagnosis, treatment, prevention Diagnosis – isolate virus or detect nucleic acid in saliva, skin biopsies, CSF; serology Treatment – THERE IS NO EFFECTIVE TREATMENT ONCE SYMPTOMS ARISE Recent exception in Wisconsin teenager Prevention Pre-exposure prophylaxis (rabies vaccine) Post-exposure prophylaxis Wound care, rabies immune globulin, rabies vaccine +/- animal observation x 10 days A few take home points Recognize encephalitis vs. meningitis in addition to know potential etiologic agents Hematogenous vs. neural spread into CNS “arboviral” vs. rabies/HSV Early administration of acyclovir as long as possibility of HSV encephalitis Beware of BATS

Richards, Tim Operations Manager

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