Weekly Wednesday departmental presentation

1. ACUTE VIRAL ENCEPHALITIS
Dr. Thomas O. Oricha
Department of Medicine, FTH, Gombe
1st February, 2017

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

3. 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

4. Introduction
• Definition of terms
Panencephalitis
Polioencephalitis
Leukoencephalitis
Rhombencephalitis
Meningoencephalitis
Meningoencephalomyelitis
Meningoencephaloradiculitis
Encephalomyeloradiculitis

5. 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

6. 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

7. Aetiology
NOT GEOGRAPHICALLY RESTRICTED (SPORADIC CAUSES)
Herpes viruses HSV 1&2, VZV, EBV, CMV, HHV 6&7
Enteroviruses Coxsackie viruses, echoviruses,
enteroviruses 70&71, parechovirus,
poliovirus
Paramyxoviruses Measles virus, mumps virus
Others
(rarer causes)
Influenza viruses, adenovirus, parvovirus,
lymphocytic choreomeningitis virus,
rubella virus

8. Aetiology
GEOGRAPHICALLY RESTRICTED
The 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

9. 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

10. Risk factors
RISK FACTOR POSSIBLE VIRUSES
Insect
contact
Mosquitoes EEEV, WEEV, VEEV, St. Louis encephalitis
virus, MVEV, JEV, WNV
Ticks Tickborne encephalitis virus, Powassan virus
Occupation Laboratory workers West Nile virus
Physicians and
health care workers
VZV, HIV, influenza virus, measles virus
Veterinarians Rabies virus
Recreational
activities
Camping/hunting All agents transmitted by mosquitoes and ticks
Spelunking Rabies virus
Swimming Enteroviruses
MSP HIV

11. Pathogenesis
Entry
• Respiratory/olfactory, GI, GU, skin, conjunctiva, blood
Entry into the CNS
Hematogenous dissemination
Intraneural spread
Neurovirulence
Direct cytopathic effect
Immune-mediated injury

12. Pathogenesis
Histopathologic Changes
• Perivascular infiltration of mononuclear inflammatory cells
• Reactive astrocytosis
• Formation of glial nodules
• Neuronophagia

13. 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

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

15. Clinical manifestation
• Severity of deficits range from very mild to extreme
• Progressive constellation of symptoms evolves over a period of days
Acute febrile illness
Frequent meningeal involvement (headache, neck stiffness)
Brain parenchymal involvement

16. Clinical manifestation
• 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

17. Clinical manifestation
• Extraneural features
Parotitis (mumps)
Pharyngitis & lymphadenopathy (EBV)
Dermatomal rash (VZV)
Herpangina (Coxsackie virus)
Pneumonitis (LCMV)

18. 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

19. 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

20. Investigations/Diagnosis
Investigations
• Specific
Cerebrospinal fluid analysis
Pathogen-specific assays
Culture of other body fluid specimens
HIV
Electroencephalography
Neuroimaging studies
Brain biopsy
• Nonspecific: CBC, E/U/Cr, LFT, coagulation studies, & CXR

21. Investigations/Diagnosis

22. Investigations/Diagnosis

23. Investigations/Diagnosis

24. Investigations/Diagnosis
Diagnostic Criteria for Acute Encephalitis
Major Criterion (required):
Altered mental status (decreased/altered level of consciousness,
lethargy or personality change) ≥24hrs, no alternative cause identified
Minor Criteria
• 2 for possible encephalitis
• ≥3 for probable or confirmed encephalitis

25. Investigations/Diagnosis
Minor Criteria
Documented fever ≥38° C within 72hrs before or after presentation
Generalized/partial seizures not fully attributable to preexisting
seizure disorder
New onset focal neurologic findings

26. Investigations/Diagnosis
Minor Criteria
CSF WBC count ≥5/mm³
Neuroimaging suggestive of encephalitis either new from prior studies
or appears acute in onset
Abnormality on EEG consistent with encephalitis and not attributable
to another cause

27. Differential diagnosis

28. Treatment
• 3 “Es”: emergent issues, epilepsy, and etiology
Emergent issues
ABC of resuscitation
Consider admission to ICU
Fluid restriction
Avoidance of hypotonic intravenous solutions
Suppression of fever
Management of raised ICP

29. Treatment
Hyperventilation to pCO2 30+/-2mmHg & MAP ≥60mmHg
Mannitol 0.25-1g/kg bolus every 4-6 hours
Hypertonic 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)

30. Treatment
Seizures
Aetiology
• 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

31. Treatment
Algorithm for Mgt of Acute Viral Encephalitis

32. Treatment
Algorithm for Mgt of Acute Viral Encephalitis contd

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

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

35. Rehabilitation
• Periodic neuropsychiatric evaluation
• Speech therapy
• Physiotherapy
• Occupational rehabilitation

36. 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

37. 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

38. 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