14th June 2023

Encephalitis

Clinical presentation

Encephalopathy refers to altered consciousness persisting for longer than 24 hours, including lethargy, irritability or change in personality or behaviour. Encephalitis is defined as encephalopathy with evidence of CNS inflammation, demonstrated by at least two of:

• Fever
• Seizures or focal neurological findings attributable to the brain parenchyma
• CSF pleocytosis – more than 4 white cells/µL
• EEG findings suggestive of encephalitis
• Neuroimaging finding suggestive of encephalitis

Other clinical features include:

• Photophobia and neck stiffness
• Features of raised intracranial pressure including severe headache, nausea and vomiting
• Focal neurological deficits
• Non-specific viral prodrome symptoms (fever, myalgia, arthralgias)
• Rashes may be seen in varicella, hand-foot-mouth disease, rickettsia.
• Lymphadenopathy and hepatosplenomegaly may be seen in Ebstein Barr virus, varicella zoster virus, and cytomegalovirus infections.
• Features of parkinsonism if basal ganglia involvement in Japanese encephalitis.

The most common aetiology of encephalitis are viral causes, as outlined below, with Herpes Simplex Virus type 1 being the most common cause. More rarely, bacteria, fungi or parasites can cause encephalitis.

Aetiology

Viral causes of encephalitis

Non-viral cases of encephalitis

Investigations

Initial investigations consist of blood tests, imaging and CSF analysis.

Bloods

Routine bloods tests, including full blood count, urea and electrolytes, liver function tests, CRP, glucose and coagulation, can be useful in the first instance to investigate for a cause of the patient’s symptoms. A lymphocytosis may be seen in viral encephalitis. Serum microbiological cultures, serology and PCR may be useful in determining a causative organism.

In some cases, it may be necessary to rule out toxic causes, in which case bloods for paracetamol, salicylates, tricyclics and heavy metals may be required.

Specialist neurological blood tests may be required in some cases to rule out autoimmune or inflammatory causes. These may include complement levels, lupus anticoagulant, cardiolipin antibodies, thyroglobulin, thyroperoxidase antibodies, ferritin, fibrinogen, triglycerides, voltage-gated potassium channel complex and NMDA receptor antibodies.

Imaging

CT brain is normally the first neurological imaging performed as it is quick to arrange and can help to exclude other causes of symptoms such as brain tumour or abscess. CT brain may appear normal, although in some cases of herpes simplex encephalitis, a low attenuating area in the temporal lobes with surrounding oedema may be seen.

MRI brain is the imaging of choice in suspected viral encephalitis. Typical features of herpes simplex encephalitis include focal oedema of the temporal lobes, insular cortex, and inferolateral frontal lobes.

CSF analysis

Once brain imaging has ruled out evidence of raised intracranial pressure, a lumbar puncture to obtain CSF for analysis is important in supporting the diagnosis and ruling out other differentials, such as bacterial meningitis.

In viral causes of encephalitis, there is typically lymphocytic pleocytosis with a normal glucose and normal or mildly elevated protein. CSF culture and viral PCR can help identify a causative organism.

Other investigations

Electroencephalogram (EEG) can be useful in the diagnosis as well as monitoring of encephalitis and can be useful if distinguishing between encephalitis and metabolic encephalopathy.

In rare cases, brain biopsy may be performed.

Treatment

General management of encephalitis is supportive. In certain cases, treatment for seizures may be required, or in cases of severely raised intracranial pressure, therapy with steroids or mannitol may be required.

Specific treatment for encephalitis depends on the cause found and may include antivirals (e.g. IV acyclovir in the case of herpes simplex or varicella zoster encephalitis), antibiotics, antifungals, IV immunoglobulin or plasmapheresis (e.g. anti-NMDA encephalitis.