VIRAL ENCEPHALITIS

Encephalitis refers to acute inflammatory injury of the brain parenchyma, while the term Encephalopathy denotes generalized cerebral dysfunction due to non-inflammatory causes, e.g.

Acute encephalitis syndrome (AES) is a term coined by WHO for surveillance purpose, specially in context of Japanese encephalitis, to include any case irrespective of the age or season with acute onset of fever with change in mental status and/or new onset of seizures (Table 18.31).

Etiology: Encephalitis may be infective or non-infective in origin. While non-infectious encephalitis is usually of autoimmune eiology (Ch 18.12.4), infective encephalitis is mostly viral in origin, caused in India by:

• Enteroviruses in gt;80% cases, during epidemics.

• Herpes simplex (HSV₁) - commonest cause of sporadic encephalitis.

• Arboviruses-Japanese B encephalitis, as small outbreaks.

Other viral illnesses, e.g., mumps, measles, varicella, dengue, rubella, EBV, influenza viruses and rabies are responsible for sporadic cases. CMV infections cause encephalitis in neonates or immunocompromised hosts.

TABLE 18.31: Causes of acute encephalitis syndrome

Infective

• Viral: HSV, JE, enteroviruses, measles, ARBO viruses

• Bacterial: BM, TBM, enteric fever

• Spirochetal: Leptospirosis

• Others: Rickettsial fevers, toxoplasmosis

Autoimmune encephalitis

• Acute disseminated encephalopathy (ADEM)

• ANMDAR encephalitis

Metabolic

• Reye syndrome

• Hepatic/renal failure

• Diabetic ketoacidosis

• Dyselectrolytemia, lactic acidosis, IEM

Toxic: Poisonings, e.g. lead, carbon monoxide

Hypoxic-ischemic encephalopathy

Vascular: Hypertension, strokes

Traumatic: Head injury

Hereditary: Mitochondrial encephalopathies

HSV: Herpes simplex; JE: Japanese encephalitis; ARBO: Arthropod- borne; ANMDAR: Anti-n-methyl-d-aspartate receptor encephalitis; IEM: Inborn errors of metabolism

Epidemiology of viral encephalitis is essentially the epidemiology of causative viral disease, which may be sporadic or epidemic.

Pathogenesis: Neurological damage in encephalitis may be due to—(a) direct invasion and destruction of neural tissues by actively multiplying viruses, or (b) hypersensitivity reaction to viral antigens, leading to demyelination and perivascular destruction.

Clinical features: Despite the variable etiology, viral encephalitis usually presents after a short non-specific prodromal viral illness with acute onset of: (a) high fever, (b) altered sensorium with progressive coma, (c) recurrent seizures or status epilepticus, and (d) signs of raised ICP, e.g. vomiting, headache, papilledema. Focal neurological signs are uncommon, except in HSV encephalitis.

Milder cases may have a more gradual onset with altered behavior and speech, ataxia and abnormal movements, e.g. tremors or choreo-athetoid movements. Exanthems often precede or accompany the CNS signs in viral encephalitis.

Diagnosis is essentially clinical, after exclusion of other CNS infections, e.g. meningitis, cerebral malaria, etc. and non-viral encephalopathies (Table 18.31). Supportive investigations include:

• Normal CSF examination except elevated pressure and mild pleocytosis,

• Gross cerebral edema on CT/MRI and,

• Abnormal EEG with diffuse slowing (focal in HSV encephalitis).

Etiological diagnosis is difficult in resource-poor settings, requiring detection of causative virus on CSF culture or PCR. Viral antibody titers turn positive after many weeks with little use in clinical practice, except for epidemiological purpose.

Some useful diagnostic clues include presence of focal signs (HSV), ataxia (VZV), rash (Measles or VZV), diarrrhea (Enteroviruses), respiratory illness (Influenza, adenovirus), parotitis (Mumps) and retinitis (CMV). Treatment is largely supportive and includes:

• Hospitalization with constant monitoring.

• Resuscitation and life-support measures.

• Correction of fluid and electrolyte disturbances.

• Management of cerebral edema.

• Anticonvulsant therapy.

• Prophylactic antibiotic therapy for suspected bacterial etiology.

Role of Specific antiviral therapy is limited, except acyclovir therapy in HSV encephalitis. Immunotherapy with steroids or IVIG must be considered only in cases with suspected autoimmune etiology.

Outcome depends on clinical severity of the disease, age of the patient and efficacy of supportive therapy. Mortality in severe cases may be as high as gt;50%, while survivors may be left with residue like-(a) seizure disorder, (b) deafness/blindness, (c) mental retardation, (d) motor deficits, and (e) behavior disorders.

Some important causes of viral encephalitis in childhood are as follows:

Japanese encephalitis (JE) has emerged as a major public health problem in India during last two decades, with many seasonal outbreaks in different parts of country, specially in Northern India.

Epidemiology: JE virus is a RNA virus, transmitted by Culex - a night-biting mosquito. Children are more affected than adults.

Clinically, apart from other signs of acute encephalitis, two important characteristics of JE are: (a) rapidly changing CNS signs, i.e. alternating hyper/hyporeflexia or extensor/ flexor planters, and (b) frequent presence of concomitant proteinuria.

Diagnosis depends on epidemiological risk and serology with elevated specific IgM titers in CSF or serum. Viral isolation or detection by PCR from CSF is possible but with very low sensitivity.

Treatment is supportive and non-specific. Prognosis is poorer in children than in adults, with 30-40% mortality and ~40% late neurological sequelae.

Prevention is possible with JE vaccine with two doses at least one-month apart, provided under NIS to all children residing in endemic districts at the age of 9-12 months and 16-24 months, with catch-up immunization (two doses at one month interval) till 15 years of age or even more in some states (Ch 9.2.2).

Herpes encephalitis (HSVl) is the commonest cause of sporadic encephalitis in Indian children, frequently but not essentially, characterized by—(a) localizing signs including focal seizures, (b) focal slowing with periodic lateralized discharges on EEG, (c) focal temporal lobe involvement of CT/MRI and (d) presence of RBCs in CSF.

Specific antiviral therapy with acyclovir (IV 20 mg/ kg/dose TDS for 21 days) is highly effective in reducing the mortality and morbidity of these cases.

18.12.3