acute viral encephalitis

ACUTE VIRAL ENCEPHALITISDr. Thomas O. Oricha

Department of Medicine, FTH, Gombe1st February, 2017

Outline• Introduction• Epidemiology• Aetiology• Risk factors• Pathogenesis• Clinical manifestation• Investigations/Diagnosis• Differential diagnosis• Treatment• Sequelae• Conclusion• References

Introduction

• Encephalitis is defined as inflammation of the brain parenchyma associated with neurologic dysfunction• Acute encephalitis associated with viral infections includes 2 distinct

clinical-pathological diseases. ACUTE VIRAL ENCEPHALITIS Postinfectious encephalomyelitis• Acute viral encephalitis is due to direct effects of acute infections on

the brain

Introduction

• Definition of termsPanencephalitisPolioencephalitisLeukoencephalitisRhombencephalitisMeningoencephalitisMeningoencephalomyelitisMeningoencephaloradiculitisEncephalomyeloradiculitis

Introduction

WHO Clinical case definition of acute encephalitis syndrome • Person of any age, at any time of year, with• Acute onset of fever AND• Change in mental status (including symptoms such as confusion,

disorientation, coma, or inability to talk) AND/OR • New onset of seizures (excluding simple febrile seizures)• Other early clinical findings can include an increase in irritability,

somnolence or abnormal behaviour greater than that seen with usual febrile illness

Epidemiology

• Acute viral encephalitis is of public health concern worldwide because of its high morbidity and mortality• Incidence of 5-10 per 100 000/year• Commoner in children and the elderly• Slight predominance in males• Paucity of data in Nigerian

Aetiology

NOT GEOGRAPHICALLY RESTRICTED (SPORADIC CAUSES)Herpes viruses HSV 1&2, VZV, EBV, CMV, HHV 6&7Enteroviruses Coxsackie viruses, echoviruses,

enteroviruses 70&71, parechovirus, poliovirus

Paramyxoviruses Measles virus, mumps virusOthers (rarer causes)

Influenza viruses, adenovirus, parvovirus, lymphocytic choreomeningitis virus, rubella virus

Aetiology

GEOGRAPHICALLY RESTRICTEDThe Americas WNV, La Cross virus, St Louis encephalitis virus,

Rocio virus, Powassan encephalitis, VEEV, EEEV, WEEV, Colorado tick fever virus, dengue virus (DV), rabies virus (RV)

Europe/Middle East

Tick-borne encephalitis, WNV, Tosana virus, RV, DV, louping ill virus

Africa WNV, RVF virus, CCHF virus, DV, chikungunya virus, RV

Asia JEV, WNV, DV, Murray Valley encephalitis virus (MVEV), RV, chikungunya virus, Nipah virus

Australasia MVEV, JEV, kunjin virus, DV

Risk factors

RISK FACTOR POSSIBLE VIRUSES

Agammaglobulinemia Enteroviruses

Animal contact

Bats Rabies virus, Nipah virus

Birds WNV, EEEV, WEEV, VEEV, St. Louis encephalitis virus, MVEV, JEV

Cats/Dogs Rabies virus

Horses EEEV, WEEV, VEEV

Rodents EEEV, VEEV, tickborne encephalitis virus, Powassan virus, La Crosse virus

Swine JEV, Nipah virus

Immunocompromised VZV, CMV, HHV 6, WNV, HSV

Transfusion and transplantation

CMV, EBV, WNV, HIV, tickborne encephalitis virus

Risk factorsRISK FACTOR POSSIBLE VIRUSES

Insect contact

Mosquitoes EEEV, WEEV, VEEV, St. Louis encephalitis virus, MVEV, JEV, WNV

Ticks Tickborne encephalitis virus, Powassan virusOccupation Laboratory workers West Nile virus

Physicians and health care workers

VZV, HIV, influenza virus, measles virus

Veterinarians Rabies virusRecreational activities

Camping/hunting All agents transmitted by mosquitoes and ticksSpelunking Rabies virusSwimming EnterovirusesMSP HIV

Pathogenesis

Entry• Respiratory/olfactory, GI, GU, skin, conjunctiva, bloodEntry into the CNS Hematogenous dissemination Intraneural spread Neurovirulence Direct cytopathic effect Immune-mediated injury

Pathogenesis

Histopathologic Changes• Perivascular infiltration of mononuclear inflammatory cells• Reactive astrocytosis• Formation of glial nodules• Neuronophagia

Pathogenesis

Immunopathology• Cytotoxic T cells & phagocytic macrophages act as effectors• Interferons (α, β, and γ) and their regulatory transacting proteins may

act to limit CNS virus replication• IL-1β, IL-6, and TNF-α are injurious

Pathogenesis

• Specific sites of viral predilection Temporal and inferior frontal lobes (HSV) Periventricular areas (CMV) Limbic system (RV) Cerebellum (VZV) Basal ganglia (JEV)

Clinical manifestation

• Severity of deficits range from very mild to extreme• Progressive constellation of symptoms evolves over a period of daysAcute febrile illnessFrequent meningeal involvement (headache, neck stiffness)Brain parenchymal involvement


• Seizures, behavioral changes, weakness, altered sensorium coma• Hallucination, agitation, personality change, frankly psychotic state• Focal findings: aphasia, ataxia, UMN/LMN patterns of weakness,

involuntary movements (e.g. myoclonus, tremor), CN deficits• Involvement of hypothalamic-pituitary axis: Temp dysregulation, DI, SIADH


• Extraneural features Parotitis (mumps) Pharyngitis & lymphadenopathy (EBV) Dermatomal rash (VZV) Herpangina (Coxsackie virus) Pneumonitis (LCMV)

Case presentation

• A 35-year-old man presented to A/E with 3 days of low-grade fever• He awoke at 2:00 AM on the fourth day, got dressed, went to the

kitchen, poured cereal onto the kitchen table, added milk, got the car keys, and promptly packed his car across the garage door. At that point, his wife immediately took him to A/E• He had no witnessed seizures• Temp in A/E was 38.5◦C; he was normotensive• On neurologic examination, he had an expressive aphasia• No focal signs of weakness at presentation

Case presentation

oComment• This case is a classic presentation for HS encephalitis• It is now the responsibility of the A/E physician or neurologist to

define a course of action• First, a working differential diagnosis must be established• Numerous diseases mimic HS encephalitis; most are not treatable• Clearly, the expressive aphasia points to focal neurologic process

Investigations/DiagnosisInvestigations• SpecificCerebrospinal fluid analysisPathogen-specific assaysCulture of other body fluid specimensHIVElectroencephalographyNeuroimaging studiesBrain biopsy• Nonspecific: CBC, E/U/Cr, LFT, coagulation studies, & CXR

Investigations/Diagnosis


Diagnostic Criteria for Acute EncephalitisMajor Criterion (required): Altered mental status (decreased/altered level of consciousness, lethargy or personality change) ≥24hrs, no alternative cause identifiedMinor Criteria • 2 for possible encephalitis• ≥3 for probable or confirmed encephalitis


Minor Criteria Documented fever ≥38° C within 72hrs before or after presentationGeneralized/partial seizures not fully attributable to preexisting

seizure disorderNew onset focal neurologic findings


Minor Criteria CSF WBC count ≥5/mm³Neuroimaging suggestive of encephalitis either new from prior studies

or appears acute in onsetAbnormality on EEG consistent with encephalitis and not attributable

to another cause

Differential diagnosis

Treatment

• 3 “Es”: emergent issues, epilepsy, and etiologyEmergent issuesABC of resuscitationConsider admission to ICUFluid restrictionAvoidance of hypotonic intravenous solutionsSuppression of feverManagement of raised ICP

Treatment

Hyperventilation to pCO2 30+/-2mmHg & MAP ≥60mmHgMannitol 0.25-1g/kg bolus every 4-6 hoursHypertonic saline• Active brain herniation: 23.4% saline (30 mL bolus via CV line)• Maintenance 2%-3% saline (250-500 mL boluses or continuous

venous infusion; 3% saline via CV line)

Treatment

SeizuresAetiology• Acyclovir, 10 mg/kg IV q 8 hrs x 14-21 days• Oral acyclovir, famciclovir, and valacyclovir (efficacy against HSV,

VZV, EBV) have not been evaluated in the treatment of encephalitis either as primary therapy or as supplemental therapy• IV ribavirin 15-25 mg/kg/day in divided doses every 8 hrs

TreatmentAlgorithm for Mgt of Acute Viral Encephalitis

TreatmentAlgorithm for Mgt of Acute Viral Encephalitis contd

Sequelae

• Behavioural and psychiatric disturbances• Epilepsy• Post-encephalitic parkinsonism• Memory difficulties• Speech disturbances• Permanent home care

Prognosis

Factors of bad prognosis• Severe neurologic impairment• Older age• High viral load in CSF• Delay in initiation of therapy

Rehabilitation

• Periodic neuropsychiatric evaluation• Speech therapy• Physiotherapy• Occupational rehabilitation

Conclusion

• Acute viral encephalitis is frequently devastating• All patients with a febrile illness and altered behaviour or

consciousness should be investigated promptly for viral encephalitis• Patients suspected need a lumbar puncture as soon as possible• Early institution of therapy improves prognosis

References• Ftichard T. Johnson, Acute Encephalitis, Clinical Infectious Diseases 1996;23:219-26• WHO – recommended standards for surveillance of selected vaccine-preventable diseases.

Geneva: WHO; 2006: http://www.who.int/vaccines-documents/DocsPDF06/843.pdf• DiseaseM.Saminathan, K. Karuppanasamy, S. Pavulraj, A. Gopalakrishnan and R. B. Rai

Acute Encephalitis Syndrome - A Complex Zoonotic Int. J. Livest. Res. 2013; 3(2): 174-177

• Tom Solomon, Ian J Hart, Nicholas J Beeching; Viral encephalitis: a clinician’s guide; Practical Neurology 2007;7;288-305

• Allan R. Tunkel et al, The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America; Clinical Infectious Diseases 2008; 47:303–27

• David Schlossberg, Clinical Infectious Disease 2nd Edition; 2015 Chapter 76

References

• Dennis L. Kasper et al, Harrison’s Principles of Internal Medicine, 19th Edition; 2015, p. 893-898• Venkatesan et al, Case Definitions, Diagnostic Algorithms, and Priorities in

Encephalitis: Consensus Statement of the International Encephalitis Consortium; Clinical Infectious Diseases 2013;57(8):1114–28• Sergio Ferrari et al, Viral Encephalitis: Etiology, Clinical Features, Diagnosis and

Management, The Open Infectious Diseases Journal, 2009, 3, 1-12• Richard J. Whitley, Herpes Simplex Virus Infections of the Central Nervous System,

Continuum (Minneap Minn) 2015;21(6):1704–1713• T. Solomon et al, Management of suspected viral encephalitis in adults-Association of

British Neurologists and British Infection Association National Guidelines; Journal of Infection (2012) 64, 347e373

acute viral encephalitis

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