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VIRAL ENCEPHALITIS

VIRAL ENCEPHALITIS. Irv Salit November 2009. OBJECTIVES To know……. The causes of viral encephalitis in Canada The causes of viral encephalitis world-wide General aspects of Arboviruses Important aspects of Herpes, West Nile infections Differential Diagnosis of viral encephalitis.

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VIRAL ENCEPHALITIS

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  1. VIRAL ENCEPHALITIS Irv Salit November 2009

  2. OBJECTIVESTo know…… • The causes of viral encephalitis in Canada • The causes of viral encephalitis world-wide • General aspects of Arboviruses • Important aspects of Herpes, West Nile infections • Differential Diagnosis of viral encephalitis

  3. Meningitis vs. Encephalitis • The clinical distinction between meningitis and encephalitis is based upon the state of brain function and presence of meningismus • Seizures and postictal states can be seen with meningitis alone and should not be construed as definitive evidence of encephalitis

  4. RATES Data more available on numbers of cases for specific causes 30-80% have unknown etiology Ratio of 1 : 2: 0.5 for Encephalitis : Meningitis : Encephalomyelitis

  5. ENCEPHALITIS MICROBIAL Post-infectious Infectious DIFFERENTIAL Allergic Rasmussen’s: unilateral, kids, seizures Lupus MS Vascular Toxic

  6. ENCEPHALITISInfectious Causes BACTERIAL • Bartonella • Mycoplasma • Listeria • Subacute bacterial endocarditis • Whipple’s PARASITIC • Malaria • Toxoplasmosis • Acanthameba • Naegleria • Bayliascaris procyonis

  7. VIRAL • * Herpes simplex • * Arboviruses • * Enteroviruses • Mumps • Measles • Influenza • VZV

  8. VIRAL • HIV • EBV • HHV-6 • CMV • Rabies, Lyssavirus • LCM • Henipahviruses (Hendra: Australian horse handlers; Nipah: swine contact) • JC virus (PML) • Herpes B (monkey handlers) • Chikungunya (Africa) • Hepatitis C

  9. DIAGNOSIS Suspected diagnosis is based on: • Season • Geography • Animal contacts • Clinical features

  10. SEASONAL VARIATION IN ENCEPHALITIS

  11. West Nile

  12. CANADA

  13. SURVEILLANCE FOR VIRAL ENCEPHALITIS • 188 patients were tested • 60 patients (32%) met suspect case definition • 34 (57%) had discharge diagnosis of encephalitis • agents: herpes simplex (n = 8), varicella (n = 2), Powassan (n = 1), echovirus 30 (n = 1) group B Streptococcus (n = 1); WNV (=0) CMAJ 166(1):29-35, 2002 Jan 8

  14. ENCEPHALITIS • 145 patients admitted to HSC with encephalitis-like illness • death, 2% (1) • motor difficulties, 26% (13) • global neurological deficits, 16% (8) • mental status changes, 14% (7) Clinical Infectious Diseases. 26(2):398-409, 1998

  15. ENCEPHALITIS Confirmed or probable etiology identified in 20 (40%): • Mycoplasma pneumoniae (9 cases) • M. pneumoniae and enterovirus (2) • Herpes simplex virus (4) • Epstein-Barr virus (1) • HHV-6 (1) • HHV-6 and influenza type A (1) • influenza virus type A (1) • Powassan virus (1)

  16. ENCEPHALITIS • possible pathogen: was identified in 13 (26%) including M. pneumoniae in nine

  17. Mycoplasma pneumoniae in 50/159 (31%) children (Bitnun. CID 32(12):1674, 2001)

  18. Mycoplasma Encephalitis • 58 cases (22 female, 36 male; median age 10 years) from 38 reports • 76% had respiratory symptoms prior to neurologic disease • 40% presented with pulmonary infiltrates • Thirty-three (57%) recovered without sequelae, 20 (34%) had minor to major sequelae and 5 (9%) died Journal of Child Neurology. 19(11):865-71, 2004

  19. NEWER INFORMATION on ENCEPHALITIDES

  20. Enterovirus 71 (EV71) • Hand, foot and mouth disease • High mortality in brainstem encephalitis complicated by pulmonary edema, particularly in children <5 • autonomic nervous system dysregulation • intravenous IgG and milrinone (phosphodiesterase III inhibitor) associated with significantly decreased mortality by attenuating sympathetic activity and cytokine production Expert Review of Antiinfective Therapy. 7(6):735-42, 2009 Aug

  21. INFLUENZAEncephalopathic Syndromes • Spanish flu: encephalitis • Post-encephalitic Parkinson’s • Reye syndrome • MERS: mild encephalopathy with promptly reversible splenial lesions • Other syndromes: Acute necrotising encephalitis, ADEM, AESD, etc. Amin et al. PIDJ 2008; 27 (5): 390 Tada et al. Neuropediatrics 2008; 39(2): 134 American Journal of Neuroradiology. 25(5):798-802, 2004 Biological Chemistry. 385(6):487-92, 2004 Jun. NishaThampi, ID Rounds, Nov 12, 2009

  22. EPIDEMIOLOGY • Japan 1:100,000 in children <15 yo • HSC: 4% of encephalitis • Abnormal MRI • Age <2yo Amin et al. 2008. PIDJ; 27 (5): 390

  23. INFLUENZAEncephalopathy -Mechanisms • Direct virus infection of ependymal cells, vascular endothelium, neurons (rarely found in CSF) • Mini-plasmin modifies the brain capillaries to create permissive state in some • Cytokine-mediated destruction of blood-brain barrier • Autoantibody production Frankova et al. 1977. Arch Virol; 53: 265 Studahl 2003. J Clin Virol 28: 225 Toplak, Avcin 2009. Ann NY Acad Sci; 1173: 619

  24. NEUROANATOMIC LOCALIZATION OF EPSTEIN-BARR VIRUS ENCEPHALITIS 1. Cerebral hemisphere 2. Cerebellum and basal ganglia • If isolated hemispheric gray or white matter: good recovery • Thalamus: ~ 50% have sequelae • Brainstem: highest mortality Journal of Child Neurology. 24(6):720-6, 2009 Jun.

  25. HEPATITIS C VIRUS INFECTION AND THE BRAIN • Significant neurocognitive impairment in HCV infection • Reports of HCV-associated cerebral vasculitis • HCV in brain samples or CSF • Viral sequences in the brain often differed from those in the liver • Trojan horse hypothesis: HCV-infected mononuclear blood cells enter the brain Metabolic Brain Disease. 24(1):197-210, 2009 Metabolic Brain Disease. 19(3-4):383-91, 2004

  26. NIPAH VIRUS • Henipavirus (Hendra + Nipah) - a Paramyxovirus • Emerged in Malaysia and Singapore in 1998-99 • close contact with infected pigs • Some person-to-person spread • Contamination of pig swill by bat excretions

  27. mortality rate: 40% - 70% • relapses and long-term neurological defects. • vasculitis-induced thrombosis and direct neuronal involvement

  28. HERPES SIMPLEX

  29. HERPES SIMPLEX • Most common cause of encephalitis at any time of the year • HSV-1 causes more than 95% of cases • age distribution is biphasic: peaks at 5 to 30 and > 50 years of age

  30. HERPES SIMPLEX ENCEPHALITISSigns • personality change, hallucinations, and aphasia • Suggests temporal lobe localization typical of that infection

  31. HERPES SIMPLEX • The most helpful finding on standard tests is CSF red blood cells in the absence of a traumatic lumbar puncture • CSF PCR for viral DNA is highly accurate: 98% sensitive and 100% specific. May be negative in first 72h • Untreated cases: mortality= 70%; 2.5% overall (11% of survivors) regain normal brain function

  32. Acyclovir has lowered the mortality rate to 19% with 38% of treated patients returning to normal function • significantly poorer outcome: • Glasgow coma score of less than 6 • Age greater than 30 years • Duration of encephalitis greater than four days

  33. MRI • Diffusion-weighted MRI is most sensitive test • May be diagnostic when PCR is negative (<72 hours) • Typical findings in 86% of PCR+ subjects

  34. ARBOVIRUSES

  35. ARBOVIRUSES(AR=arthropod and BO=borne)

  36. clinical manifestations are indistinguishable • Signs of encephalitis appear on day 2-3 • minimal alterations in mental status to coma

  37. The majority of human infections are asymptomatic or flu-like syndrome • insidious or sudden onset • fever, headache, myalgias, malaise and occasionally prostration. • may lead to encephalitis with a fatal outcome or permanent neurologic sequelae. • only a small proportion progress to frank encephalitis

  38. Viral transfer from the blood to the CNS through the olfactory tract has been suggested

  39. CYCLE • Arthropod (mosquitoes or ticks) • Virus • Birds • Mammals

  40. WNV

  41. SURVEILLANCE • dead birds • sentinel chickens • mosquito pools • human infection • human disease

  42. ARBOVIRAL ENCEPHALITIS UNITED STATES Cumulative : 1964-2005 • *** St. Louis encephalitis (SLE) (4600) • ** California Group (La Crosse) (3200) • ** West Nile (2800) • Western equine encephalitis (640) • Eastern equine encephalitis (215) • Powasssan (2)

  43. most transmitted by mosquitoes • only ~150 cases/year in U.S. • Have been uncommon in Canada although outbreaks have occurred (including WNV in 2002-2003)

  44. CANADA

  45. ARBOVIRUSES IN CANADA THAT HAVE • CAUSED HUMAN DISEASE • Virus Family Occurrence Vertebrate Arthropod • WEE Togaviridae BC,AB,SK,MB,ON Wild birds Mosquitoes • EEE Togaviridae ON,QC Wild birds Mosquitoes • SLE Flaviviridae SK, ON,QC Wild birds Mosquitoes • WNV Flaviviridae ON,NS,QC,MB,SK Wild birds Mosquitoes • POW Flaviviridae BC,AB,ON,QC, NS Wild mammals Ticks • SSH Bunyaviridae ALL provinces, YT,NWT Wild mammals Mosquitoes • JC Bunyaviridae NWT,SK,MB,ON,QC,NF Wild mammals Mosquitoes • CTF Reoviridae BC, AB Wild mammals Ticks

  46. WEE • Pre-WNV had been the most important cause of human disease • outbreaks in Canada each decade since the 1930's • in the Prairies in 1941: 1094 human cases (= most of the cases until 1990) • U.S. : 15 / year

  47. mortality rate = 8 to 15% • Children more likely to get disease than adults • Horses can suffer severe, often fatal disease

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