Encephalitis. S. Sears, MD. Herpes simplex virus type 1. Most common cause of fatal sporadic encephalitis HSV infection of the CNS Immediate CNS invasion From the trigeminal nerve or olfactory tract Follows an episode of primary HSV-1 of the oropharynx
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Herpes simplex virus type 1 Most common cause of fatal sporadic encephalitis HSV infection of the CNS • Immediate CNS invasion • From the trigeminal nerve or olfactory tract • Follows an episode of primary HSV-1 of the oropharynx • CNS invasion after recurrent HSV-1 infection • Represents viral reactivation with subsequent spread • CNS infection without primary or recurrent HSV-1 infection • Represents reactivation of latent HSV in situ within the CNS
Pathogenesis Necrosis occurs in the temporal lobe • Direct viral-mediated inflammation • Extent of viral load may be directly related to severity of disease • Indirect immune-mediated CNS damage • Not more common in immunocompromised patients
Clinical features Focal neurologic findings are acute (< 1 week) • Altered mentation - level of consciousness • Focal cranial nerve deficits • Hemiparesis • Dysphasia • Aphasia • Ataxia • Focal seizures Fever Later in the clinical course • Diminished comprehension • Paraphasic (word substitution) spontaneous speech • Impaired memory • Loss of emotional control
Behavioral syndromes Hypomania • Inflammation of the temporal - limbic system • Elevated mood • Excessive animation • Decreased need for sleep • Inflated self-esteem • Hypersexuality Kluver-Bucy syndrome • Psychic blindness • Loss of normal anger and fear responses • Inappropriately oral and sexual States of amnesia
Investigations Imaging • CT • Predominantly unilateral temporal lobe lesions • May be associated with mass effect • MRI • More specific than CT • Brain perfusion studies demonstrate hyperperfusion early in disease
Diagnosis Gold standard • PCR • Detects HSV DNA in the CSF • Positive early in the course of the disease • Detectable 2-4 weeks after the onset of illness If PCR negative • Patient clinically deteriorates on therapy • Brain biopsy • Still the only accurate way for certain diagnosis CSF antigen and antibody determinations not helpful Viral culture rarely positive
Treatment Acyclovir 10mg/kg IV q8hrs for 21 days • Infuse slowly and with fluid to prevent crystalluria and renal failure Shorter courses have been associated with relapse Treat early • Before loss of consciousness • Within 24 hours onset symptoms • Glasgow Coma Scale 9-15 Discontinue therapy • Low probability of encephalitis • Normal imaging, CSF, mental status • Negative CSF PCR Continue therapy • High risk patient • Abnormal imaging, CSF, mental status,seizures, abnormal EEG • Look for alternative why PCR negative • Early testing, antiviral therapy, PCR inhibitors (bloody CSF)
Rabies Neurotropic RNA viruses • Belong to the family Rhabdoviridae Human infections • From rabid animals through a bite • In developing countries • Dogs account for 90 percent of reported cases • In the United States • Four major animal reservoirs • Bats • Raccoons • Skunks • Foxes • Unusual transmission • Organ donor died of encephalitis-unknown cause • All recipients were diagnosed with rabies
Pathogenesis Viruses deposit in peripheral wounds • Exposed skin vs bite through clothing • Face and head vs peripheral site (distance from CNS) • Amount of virus in the saliva • Degree of innervation at the site of bite • Host immunity
Clinical manifestations Classic forms • Encephalitic • Hydrophobia • Aerophobia • Pharyngeal spasms • Hyperactivity • Paralytic • Quadriparesis • Mimics Guillain-Barre • Cerebral involvement is late in the course
Clinical manifestation Non-classic form • Bat-associated rabies • Neuropathic pain • Sensory/motor deficits • Choreiform movements of the bitten limb • Cranial nerve palsies • Myoclonus • Seizures
Clinical manifestation Five general stages • Incubation period • Prodrome • Acute neurologic syndrome • Coma • Death
General stages of disease Incubation period • One to three months • Can be days to one year Prodrome • Lasts days-not more than a week • Flu-like symptoms • Malaise • Anorexia • Irritability • Low grade fever • Sore throat • Headache • Nausea • Vomiting • Viral site of entry • Paresthesias • Pain • Pruritus • Percussion myoedema
General stages of the disease Acute neurologic syndrome • Lasts two to seven days after prodrome • Encephalitic rabies • Paralytic rabies • Atypical rabies Coma • Generalized flaccid paralysis • Respiratory failure • Vascular collapse Death • Two weeks after the onset of coma
Diagnosis Clinical presentation Investigations • Samples • Saliva • Reverse transcriptase PCR • Viral culture • Neck biopsy • Full thickness • At the hairline • Cutaneous nerve • Follicle • RT/PCR • Immunofluorescence staining for viral antigen • Serum and CSF • Antibody titers • Brain biopsy • RT/PCR • Immunofluorescence staining for viral antigen
Treatment Rabies vaccine • Multiple site intradermal injections • To accelerate the immune response Human rabies immune globulin • Total dose 20 IU/kg • Intramuscular • Infiltrated around the wound • To promote clearance of the infection Ribavirin • Intravenous and intraventricular IFN-alfa • Intravenous and intraventricular Ketamine • Intravenous infusion • Inhibits rabies virus replication Vaccine • For patients not previously vaccinated
Prevention Rabies vaccine • Preexposure • Rabies research lab workers • Rabies biologics manufacturing workers • Veterinarians • Animal control workers • Wildlife workers • Postexposure • Any patient not previously vaccinated
West nile virus encephalitis West nile virus Most widely distributed of all the arboviruses • From the group of flavivirus Distribution • Now North America • Was from • Africa • Middle East • Europe • Russia • South Asia • Australia Carried by wild birds Transmitted • By the mosquito bite from the Culex species • Transfused blood • Transplanted organs
Clinical manifestation Incubation ranges from 2-14 days West nile fever • Fever • Malaise • Back pain • Myalgias • Anorexia Persists for 3-6 days Most frequent symptom • Maculopapular rash • Involves • Chest • Back • arms
Diagnosis Serology • IgM antibody capture enzyme-linked immunosorbent assay • Within first 8 days of illness • Convelescent-phase serum as well • Viral nucleic acid CSF • IgM antibody
West Nile fever Treatment • Supportive Prognosis • Increased risk • Older age • Immunosuppressed Long-term sequelae
St. Louis encephalitis Acute mosquito-borne illness Virus is a single-stranded RNA flaviviridae Vector -Culex mosquito Second leading cause of encephalitis after West nile virus Principally occurring • Ohio-Mississippi valley • Eastern Texas • Florida • Southeastern Canada • Northern Mexico
St. Louis encephalitis Human infection • Inoculation of the virus into human host • Spread via lymphatics and blood • Reaches the choroid plexus • Results in lymphocytic encephalitis Most severely affected regions • Hypothalamus • Cerebellum • Cerebral cortex • Basal ganglia • Brainstem • Cervical spinal cord Incubation period • 4-21 days
Clinical features Prodromal symptoms • Four to five days • Fever • Severe headache • Photophobia • Nausea • Vomiting • Malaise • Myalgias
Investigations Laboratory • Increased ALT and CPK • Hyponatremia CSF • Increased lymphocytes • Increased protein • Normal glucose • Negative gram stain Imaging • No specific abnormalities EEG • Diffuse slowing
St. Louis encephalitis Diagnosis • Serum • CSF • IgM antibodies • Acute and convalescence Treatment • No specific antiviral therapy • Supportive • Interferon alfa-2B • Reduced likelihood after first week in hospital • Quadriplegia • Quadriparesis • Respiratory insufficiency
Outcome Death in the first two weeks • 20 percent • From direct brain injury Poor prognosis • Sustained high fever • Convulsions • Advanced age • Severely depressed state of consciousness Convalescence • Weeks to months • Residual • Headaches • Irritability • Memory deficits • Persistent tremor
Dengue virus infection Dengue virus • Member of the family flaviviridae • Distribution in every continent • Except Europe and Antarctica Transmitted by • Mosquito-Aedes aegypti • Breed in or close to houses
