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Encephalitis

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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Encephalitis

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  1. Encephalitis S. Sears, MD

  2. 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

  3. 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

  4. 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

  5. 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

  6. Recurrent brainstem encephalitis Upward gaze Facial numbness Signs of involvement • Corticospinal tract • Spinothalamic tract • Cerebrellar pathways

  7. Investigations Laboratory • CSF • Lymphocytic pleocytosis • Increased RBC • Elevated protein • Normal glucose • PCR-diagnostic confirmation Electroencephalogram (EEG) • Nonspecific • Continuous periodic lateralizing epileptiform discharges

  8. 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

  9. HSV encephalitis

  10. Differential diagnosis Arthropod viruses Other herpesviruses (CMV,EBV,VZV) Viral Meningitis Brain abscess Post-infectious Reye syndrome Acute disseminated encephalomyelitis Vasculitis Neurosyphilis Primary or secondary malignancy Toxic encephalopathy

  11. 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

  12. 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)

  13. Prognosis Fatality • 70 percent Survivors • Serious neurologic deficits • Significant neuropsychiatric difficulties • Significant neurobehavioral issues

  14. 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

  15. 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

  16. Pathogenesis Retrograde passage of virus • Peripheral nerve • Dorsal root ganglia • To brain Viral replication in CNS • Localizes • Brainstem • Thalamus • Basal ganglia • Spinal cord Spread from CNS • Heart • Skin • Salivary glands

  17. Clinical manifestations Classic forms • Encephalitic • Hydrophobia • Aerophobia • Pharyngeal spasms • Hyperactivity • Paralytic • Quadriparesis • Mimics Guillain-Barre • Cerebral involvement is late in the course

  18. Clinical manifestation Non-classic form • Bat-associated rabies • Neuropathic pain • Sensory/motor deficits • Choreiform movements of the bitten limb • Cranial nerve palsies • Myoclonus • Seizures

  19. Clinical manifestation Five general stages • Incubation period • Prodrome • Acute neurologic syndrome • Coma • Death

  20. 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

  21. 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

  22. 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

  23. Rabies-negri body in neuron

  24. Rabies-under electron microscope

  25. 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

  26. Prevention Rabies vaccine • Preexposure • Rabies research lab workers • Rabies biologics manufacturing workers • Veterinarians • Animal control workers • Wildlife workers • Postexposure • Any patient not previously vaccinated

  27. 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

  28. Culex pipiens pipiens-northern house mosquito

  29. 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

  30. West nile fever - rash

  31. Neuroinvasive disease Increased risk • Older age • Alcohol abuse • Diabetes • Immunocompromised Encephalitis • Most common • Presents with • Headache • Fever • Nausea • Vomiting • Associated with muscle weakness and flaccid paralysis

  32. Neurologic disease Tremor Myoclonus Parkinsonian features • Rigidity • Postural instability • Bradykinesia Cranial nerve palsies • Facial weakness • Vertigo • Dysarthria • Dysphagia Acute flaccid paralysis syndrome • Anterior horn cell process (like polio) Seizures Cerebellar ataxia Optic neuritis Weakness • Brachial plexopathy • Radiculopathy • Demyelinating peripheral neuropathy

  33. Other clinical features Ocular manifestations • Chorioretinitis • Vitritis • Uveitis Rhabdomyolysis Myocarditis Hepatitis Pancreatitis Central diabetes insipidus Palpable purpura

  34. Diagnosis Investigations • LP • CSF • Increased lymphocytes • Increased protein • Normal glucose • Imaging • CT • Usually normal • MRI • Hypertensity • Leptomeninges • Periventricular • Basal ganglia • Thalamus • Caudate nuclei • Brainstem • Spinal cord

  35. 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

  36. West Nile fever Treatment • Supportive Prognosis • Increased risk • Older age • Immunosuppressed Long-term sequelae

  37. 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

  38. 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

  39. Clinical features Prodromal symptoms • Four to five days • Fever • Severe headache • Photophobia • Nausea • Vomiting • Malaise • Myalgias

  40. Clinical features Neurologic signs • Rapid onset • Alerted sensorium • Tremors • Eyelids • Tongue • Lips • Extremities • Cranial nerve dysfunction • Unilateral facial motor weakness • Oculomotor dysfunction • Dysarthria • Myoclonus • Opsoclonus • Nystagmus • Ataxia

  41. Investigations Laboratory • Increased ALT and CPK • Hyponatremia CSF • Increased lymphocytes • Increased protein • Normal glucose • Negative gram stain Imaging • No specific abnormalities EEG • Diffuse slowing

  42. 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

  43. 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

  44. Prevention No available vaccine Mosquito control

  45. 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

  46. Aedes aegypti mosquito

  47. Clinical presentation • Asymptomatic infection • After incubation period 3-14 days • Self-limited dengue fever • Dengue hemorrhagic fever with shock

  48. Asymptomatic infection • Seen in children under the age of 15 in endemic areas

  49. Dengue fever-classic Acute febrile illness • Headache • Retroorbital pain • Marked muscle and joint pain • Fever-lasts 5-7 days • Biphasic • Second febrile phase for 1-2 days Rash- in 2-5 days after fever Hemorrhagic manifestations • Spontaneous bleeding • Melena • Purpura

  50. Classic dengue Physical exam • Conjunctival injection • Pharyngeal erythema • Lymphadenopathy • Hepatomegaly • Maculopapular rash Laboratory • Leukopenia • Thrombocytopenia • Serum aspartate transaminase elevated • Virus often found in high concentration in the liver

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