Encephalitis
Encephalitis is inflammation of the brain parenchyma. It most commonly has an infectious cause, particularly viral encephalitis, but autoimmune encephalitis is also an important cause.
Updated UKMLA guide to encephalitis, which covers causes, risk factors, symptoms, diagnosis, and management.
Causes and Risk Factors
Despite advances in diagnostic testing, the underlying cause of encephalitis remains unidentified in 37–62% of cases. [Ref1][Ref2]
| Category | Causes | Associated risk factors |
|---|---|---|
| Viral (most common) |
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| Autoimmune | Key antibodies are formed against:
|
Autoimmune encephalitis is often paraneoplastic
NMDAR encephalitis is strongly associated with:
VGKC-complex / LGI-1 encephalitis is associated with:
Anti-Hu is associated with small cell lung cancer; anti-Ma is associated with testicular cancer |
| Bacterial, parasitic, fungal (least common) |
|
|
The most common cause of viral encephalitis is HSV; and the most common cause of viral meningitis is enteroviruses (e.g. Coxsackie virus)
Clinical Features
Viral Encephalitis
Typically acute onset of:
- Fever – hallmark sign
- Altered mental status (e.g. lethargy, drowsiness, disorientation, confusion, reduced consciousness)
- Change in personality, behaviour, cognitive
- New-onset seizures (seen in 1/3 HSV encephalitis cases)
- New focal neurological deficits
Meningitis vs encephalitis:
- Meningitis = inflammation of the meninges
- Classically causes headache, fever, neck stiffness/meningism and photophobia
- Consciousness may be normal early, but can become reduced in severe disease
- Encephalitis = inflammation of the brain parenchyma
- Classically causes “brain dysfunction” features: altered behaviour, confusion, personality change, seizures, focal neurology or reduced consciousness
Autoimmune Encephalitis
Autoimmune encephalitis often presents more subacute (over weeks or months) and is strongly associated with:
- Fever is more likely to be absent
- Intractable seizures
- Faciobrachial dystonic seizures (brief arm and face spasms)
- Movement disorders (e.g. choreoathetosis, orofacial dyskinesia)
Investigation and Diagnosis
Standard Work-Up
Initial tests:
- Blood culture
- White blood cell count, CRP
- Blood glucose (important for CSF analysis)
- HIV test
1st line investigation: lumbar puncture
- CSF PCR (specifically for HSV-1, HSV-2, VZV, and enteroviruses) – most important
- Typical CSF analyses (opening pressure, white cell count and differential, red cell count, protein and glucose, bacterial microscopy and culture)
Do NOT perform a lumbar puncture if there are signs of raised ICP or possible space-occupying lesion, as it increases the risk of brain herniation.
In such cases, perform urgent neuroimaging (usually CT head) prior to a lumbar puncture
- Lumbar puncture is only safe to perform if imaging shows no structural contraindications (e.g. mass effect, midline shift, impending herniation)
- However, a normal CT does not automatically make lumbar puncture safe, the decision should be made with senior clinical input
Gold standard (all patients): MRI brain
- Abnormal in ~90% cases of HSV encephalitis within 48 hours of admission
- Classic MRI findings in HSV encephalitis: hyperintensity and gyral oedema localised to the medial temporal lobes and cingulate gyrus
- Autoimmune encephalitis can yield a normal MRI, or discrete, often bilateral high signals in the hippocampus and medial temporal lobes
CSF Analysis
Typical CSF pattern in viral encephalitis:
- ↑ White cell count, predominantly lymphocytes
- Protein: normal to mildly or moderately elevated
- Glucose: normal
- Opening pressure: normal to moderately elevated
- Appearance: normal (“gin clear”)
Cause-specific CSF patterns:
- HSV encephalitis can be haemorrhagic: ~50% cases have ↑ red cell count in the CSF
- Autoimmune encephalitis would have -ve CSF PCR
Further Investigations
If autoimmune encephalitis is suspected:
- Paired serum and CSF antibody testing
- Hyponatraemia is associated with autoimmune encephalitis
Other tests:
- EEG – if there is seizure activity or changes in behaviour where it is difficult to distinguish between organic and psychiatric causes
- Repeat lumbar puncture 24-48 hours after – if the first result is -ve for HSV but clinical suspicion remains (initial PCR can sometimes be falsely -ve in early illness)
- Brain biopsy – last resort
Management
Viral Encephalitis
1st line immediate empirical management: IV aciclovir
- Start empirically if viral encephalitis is suspected, especially to cover HSV/VZV
- If HSV or VZV encephalitis is confirmed → continue treatment
Routine corticosteroids are NOT recommended unless advised by a specialist.
Autoimmune Encephalitis
Management is less standardised than viral encephalitis and should be guided by a specialist.
Key acute management:
- 1st line therapy: high-dose corticosteroids
- If the patient is acutely unwell or not improving → IVIG or plasma exchange
Long-term management:
- Whole-body tumour screening with CT TAP or PET (e.g. ovarian teratoma for NMDAR encephalitis)
- Tumour removal if an associated tumour is identified
- Long-term immunosuppression (e.g. azathioprine) may be required for NMDAR encephalitis as relapse can occur in ~30% cases
- VGKC-complex encephalitis is typically monophasic, and relapse is uncommon, so a tapering steroid dose over 12 months is typically sufficient