Encephalitis

Encephalitis is inflammation of the brain parenchyma. It is distinguished from meningitis by altered mental status, seizures or focal neurological deficit, reflecting direct parenchymal involvement. It is most commonly caused by viral infection.

Herpes simplex virus is the most important treatable cause. Specific effective antiviral therapy exists, and delayed treatment has severe consequences.

Aetiology

Herpes simplex virus type one is the commonest identified cause of sporadic viral encephalitis in immunocompetent adults. It has a characteristic predilection for the temporal and frontal lobes.

Other causes include:

• Varicella zoster virus.
• Enteroviruses.
• Arboviruses, with specific geographical distribution according to vector prevalence.
• Autoimmune or paraneoplastic encephalitis, including anti N methyl D aspartate receptor encephalitis. This is an increasingly recognised and important non infectious differential diagnosis with a distinct management pathway.

Fever, headache and altered mental status (ranging from mild confusion to coma) characterise the core presentation and distinguish encephalitis from meningitis. Seizures (focal or generalised) and focal neurological deficit (dysphasia, hemiparesis) are common, particularly with herpes simplex encephalitis given its characteristic temporal lobe involvement.

Behavioural and personality change can be the earliest and most prominent feature, particularly in herpes simplex encephalitis. It can be subtle initially and easily misattributed to a psychiatric cause if not carefully assessed alongside other features.

A preceding or concurrent history of mucocutaneous herpetic lesions is present in only a minority of herpes simplex encephalitis cases. Its absence should not lower clinical suspicion where the presentation is otherwise compatible.

Autoimmune encephalitis, particularly anti N methyl D aspartate receptor encephalitis, presents with a characteristic evolving pattern, often over days to weeks:

• Psychiatric symptoms and memory disturbance.
• Seizures.
• Movement disorder (orofacial dyskinesia).
• Autonomic instability.

Consider it particularly in younger patients, notably young women (with an associated ovarian teratoma in a proportion), where infective causes have been reasonably excluded.

Lumbar puncture with cerebrospinal fluid analysis typically shows a lymphocytic pleocytosis, mildly raised protein and normal or mildly reduced glucose in viral encephalitis.

Polymerase chain reaction testing for herpes simplex virus is the essential specific diagnostic test. Test for other relevant viruses according to clinical context and geographical exposure. A negative result in the first 24 to 48 hours of illness does not fully exclude herpes simplex encephalitis. Consider repeat testing if clinical suspicion remains high.

Magnetic resonance imaging of the brain is more sensitive than computed tomography for detecting the characteristic changes of encephalitis. In herpes simplex encephalitis it shows temporal and frontal lobe signal change and, sometimes, haemorrhage. It is an important component of the diagnostic workup alongside cerebrospinal fluid analysis.

Electroencephalography can show characteristic periodic lateralised epileptiform discharges over the temporal region in herpes simplex encephalitis, supporting the diagnosis. It is also useful for detecting subclinical seizure activity contributing to altered consciousness.

Send autoimmune and paraneoplastic antibody panels (on serum and cerebrospinal fluid) where autoimmune encephalitis is suspected. Screen for an associated underlying tumour where relevant to the antibody identified, using computed tomography or magnetic resonance imaging of the chest, abdomen and pelvis, or pelvic ultrasound in young women.

Start intravenous aciclovir 10 mg per kg every 8 hours immediately on clinical suspicion of herpes simplex encephalitis, without waiting for confirmatory testing. Adjust for renal function, and ensure adequate hydration to reduce the risk of crystalline nephropathy.

Early treatment substantially reduces mortality and morbidity. Any delay carries a significant risk of permanent severe neurological sequelae or death.

Continue treatment for 14 to 21 days for confirmed herpes simplex encephalitis. The longer duration is generally used for immunocompromised patients or where there has been a slower clinical response. Some protocols consider repeat cerebrospinal fluid polymerase chain reaction testing at the end of treatment to confirm viral clearance before discontinuing therapy, particularly in immunocompromised patients.

Aciclovir may be discontinued if herpes simplex virus polymerase chain reaction testing is negative on an adequately timed sample and an alternative diagnosis is identified or the clinical picture is more consistent with a different cause. Make this decision cautiously, given the consequences of stopping treatment prematurely in a case that is in fact herpes simplex encephalitis.

Supportive care is an essential component of management alongside specific antiviral treatment:

• Seizure management with standard anticonvulsant therapy.
• Careful fluid and electrolyte management, given the risk of inappropriate antidiuretic hormone secretion.
• Intensive care support for significantly reduced consciousness or status epilepticus.

Treat autoimmune encephalitis with immunotherapy, under specialist neurology guidance. First line treatment is:

• High dose corticosteroids: methylprednisolone 1 g intravenously once daily for 3 to 5 days.
• Combined with intravenous immunoglobulin (0.4 g per kg once daily for 5 days, or 2 g per kg given as a divided dose over 2 to 5 days) or plasma exchange.

Consider second line agents (rituximab, cyclophosphamide) for refractory disease. Identify and treat any underlying associated tumour where relevant.

Rehabilitation input, including neuropsychology assessment, is an important component of longer term management. Persistent cognitive, behavioural and neurological sequelae are possible, particularly following herpes simplex encephalitis, regardless of how promptly treatment was initiated.