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Medical Grand Round

Medical Grand Round. Dr. Lucy Strens Consultant Neurologist UHCW. Nov 24 th 2009. Viral encephalitis. Causes Typical presentation Investigations Treatment Prognosis. Terminology. Encephalopathy Clinical syndrome of reduced consciousness Many causes, incl. viral encephalitis

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Medical Grand Round

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  1. Medical Grand Round Dr. Lucy Strens Consultant Neurologist UHCW Nov 24th 2009

  2. Viral encephalitis • Causes • Typical presentation • Investigations • Treatment • Prognosis

  3. Terminology • Encephalopathy • Clinical syndrome of reduced consciousness • Many causes, incl. viral encephalitis • Encephalitis • Acute, diffuse, inflammatory process affecting brain parenchyma • Most commonly viral • Meningitis: meningeal inflammation • Myelitis: spinal cord inflammation • Radiculitis: nerve root inflammation

  4. Causes of encephalopathy • Hypoxic/ischaemic • Metabolic (liver and renal failure, diabetes) • Toxic (alcohol, drugs) • Vascular (vasculitis, SLE, SAH, SDH, stroke, Behcet’s) • Epileptic (non-convulsive status) • Nutritional deficiency • Systemic infections (malaria) • Traumatic brain injury • Malignant hypertension • Mitochondrial cytopathy (Reye’s and MELAS syndromes) • Hashimoto’s encephalopathy • Paraneoplastic limbic encephalitis • Neuroleptic malignant syndrome…….. (and more!)

  5. Causes of acute viral encephalitis Sporadic causes (not geographically restricted) • Herpes viruses • HSV-1, HSV-2, VZV, CMV, EBV, HHV6, HHV7 • Enteroviruses • Coxsackie, echoviruses, enteroviruses 70/71, parechovirus, poliovirus • Paramyxoviruses • Measles, mumps • Others (rarer causes) • Influenza viruses, Adenovirus, parvovirus, lymphocytic choriomeningitis virus, rubella virus, rabies Geographically restricted causes • Arboviruses — Japanese B, St Louis, West Nile, Eastern equine, Western equine, Venezuelan equine, tick borne encephalitis viruses • Bunyaviruses — La Crosse strain of California virus • Reoviruses — Colorado tick fever virus

  6. Non-viral causes of infectious encephalopathy

  7. Pathogenesis of viral encephalitis • Depends on the virus • direct viral destruction of cells • Para or post-infectious inflammatory or immune-mediated response • Most viruses primarily infect brain parenchyma and neuronal cells • Some cause a vasculitis • Demyelination may follow infection

  8. Herpes simplex encephalitis • HSV encephalitis (HSE) most common cause of viral encephalitis in industrialised nations • Annual incidence 1 in 250,000-500,000 • 90% HSV-1 • HSV-2 more common in immuno-compromised, neonates

  9. HSV-1 • Primary infection occurs in oral mucosa • 30% people get clinically apparent cold sores • 90% healthy people have been infected with HSV-1 • Virus then travels along trigeminal nerve to ganglion in most (if not all) those infected • 70% cases of HSV-1 encephalitis already have antibody present suggesting reactivation of virus most common mechanism • Why HSV-1 reactivates not known • In children, HSV-1 encephalitis occurs during primary infection

  10. HSV-2 • Transmitted via genital mucosa • Genital herpes in adults • USA, 20% of adults sero-positive for HSV-2 • HSV-2 may cause • Meningitis (esp. recurrent meningitis) • Encephalitis (esp in neonates) • Lumbosacral radiculitis • Neonates can be infected during delivery: neonatal herpes (disseminated infection often with CNS involvement)

  11. Case example • 57 yr old female • 4 days N&V, severe headache, loss of appetite • Confused, ‘unable to find right word’ • O/E • Temp 39oC, dysphasic, no focal neuro signs (upgoing plantars) • WCC 11.7, CRP 4

  12. Case 2 • CSF • WCC 36 (80% lymphocytes), RCC 2 • Normal glucose, protein 0.91g/l • HSV-1 PCR positive

  13. Viral encephalitis – clinical presentation • Typical presentation • Acute flu-like prodrome • High fever, severe headache, N&V • Altered consciousness (lethargic, drowsy, confused, coma) • (Seizures) • (Focal neurological signs) • Recent study of HSV-1 encephalitis* • 91% febrile on admission • 76% disorientated • 59% speech disturbances • 41% behavioural change • 33% seizures *Raschilas et al 2002 Clin Infect Dis

  14. Clinical presentation • More subtle presentations now recognised • Low grade fever • Speech disturbances (dysphasia, aphasia) • Behavioural changes • Subacute and chronic presentations can be caused by CMV, VZV, HSV (immuno-compromised) • Any adult with seizure + fever or seizure from which they do not recover must be investigated for possible CNS infection

  15. Encephalopathy vs encephalitis?

  16. Clues in history • Recent rashes • Vaccination history • Travel history • Recent animal/insect bites, contact with sick animals • Immunosuppression (HIV, transplant) • Drugs, alcohol

  17. Clues on examination • Skin rashes, bites, injection sites • Examine chest, abdo, ears, genitals, urine for infection • Meningism, subtle motor seizures, focal neuro signs • NB ‘cold sores’ not diagnostic!

  18. Investigations • General • Haematological and biochemical blood screen • Serology, blood cultures, HIV • Drug screen, urine analysis • CXR • Neurological • CT head, MRI brain • LP (if not contraindicated on cranial imaging) • EEG • ((brain biopsy))

  19. MRI brain (T2W image): right temporal lobe high signal in a patient with herpes encephalitis

  20. Axial DWI: restricted diffusion in the left medial temporal lobe consistent with herpes encephalitis.

  21. CSF examination • Opening pressure • Send samples for • Cell count and differential • Protein, glucose (plasma glucose) • Gram stain and culture • Viral PCRs (HSV 1*,HSV2, VZV, EBV, CMV, enteroviruses) • Other tests as appropriate (discuss with micro!) *HSV-1 CSF PCR still positive in 80% pts after one week of treatment (may be negative in first few days) PCR tests for HSV have overall sensitivity and specificity >95%

  22. Typical CSF findings in CNS infections Bloody tap: subtract 1 WBC for every 700 RBCs subtract 0.1g/l protein for every 1000 RBCs

  23. Management of viral encephalitis • O2, fluids, NG feed?, ITU? • Aciclovir • Start as soon as suspect viral encephalitis • iv aciclovir 10mg/kg tds • 14-21 day course in confirmed HSE • Monitor renal function • Only stop if definite other diagnosis made • Antibiotics too if delay in getting CSF/imaging • Management of complications (brain swelling, seizures)

  24. Prognosis in HSE • Mortality > 70% if untreated (20% with Rx) • Poor prognostic factors • Age > 60 yrs • GCS < 7 • Delay in starting aciclovir (esp > 2 days) • 2/3 rds pts have neuropsychiatric sequelae • 69% memory impairment • 45% personality/behaviour change • 41% dysphasia • 25% epilepsy www.encephalitis.info

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