Key Facts

Encephalitis is a neurological emergency. HSV encephalitis is the most important treatable cause and empirical aciclovir must be started at the earliest suspicion. Autoimmune encephalitis is increasingly recognised and requires immunotherapy.

Epidemiology

Encephalitis incidence: approximately 2-8 per 100,000 children per year in the UK. HSV encephalitis accounts for ~10% of cases but is the most common identifiable cause. Enterovirus is the most common overall viral cause. Autoimmune encephalitis (particularly anti-NMDA receptor) is now recognised as equally or more common than infectious causes.

Aetiology

Infectious:

• HSV-1 (most common treatable cause; temporal lobe predilection)
• Enterovirus, parechovirus (neonates)
• VZV, EBV, CMV, influenza, adenovirus
• Mycoplasma pneumoniae (post-infectious encephalitis)

Autoimmune:

• Anti-NMDA receptor encephalitis (most common autoimmune; may follow HSV encephalitis)
• Acute disseminated encephalomyelitis (ADEM) — post-infectious demyelination

Pathophysiology

In viral encephalitis, the virus directly invades brain parenchyma causing neuronal damage, inflammation, and oedema. HSV-1 has a tropism for the temporal lobes (via olfactory or trigeminal nerve). In autoimmune encephalitis, antibodies target neuronal surface antigens (NMDA, LGI1, CASPR2), causing neuronal dysfunction through receptor internalisation. ADEM involves perivenous demyelination triggered by molecular mimicry.

Clinical Features

• Altered consciousness (confusion → drowsiness → coma)
• Behavioural change/personality change
• Seizures (often focal/temporal in HSV)
• Fever (may be absent in autoimmune)
• Focal neurological signs (dysphasia, hemiparesis)
• Movement disorder (anti-NMDA receptor encephalitis — orofacial dyskinesia)

HSV Encephalitis

• Fever + altered consciousness + temporal seizures
• Rapid deterioration over days
• Temporal lobe changes on MRI

Anti-NMDA Receptor Encephalitis

• Psychiatric symptoms (psychosis, catatonia)
• Seizures, movement disorder
• Autonomic instability
• More common in females; may be associated with ovarian teratoma (rare in children)

Red Flags

• Rapidly declining consciousness — urgent CT, consider raised ICP
• Refractory seizures — may need PICU and continuous EEG
• Focal neurological signs — structural lesion (abscess, tumour) must be excluded
• Post-HSV autoimmune encephalitis — movement disorder developing 2-6 weeks after HSV encephalitis; treat with immunotherapy

Bedside

• GCS: Serial monitoring
• Blood glucose: Exclude hypoglycaemia

Bloods

• FBC, CRP, U&Es, LFTs: Baseline; SIADH screening
• Blood cultures: Exclude sepsis
• Autoimmune panel: NMDA-R antibodies, VGKC, other neuronal antibodies
• Mycoplasma serology/PCR: If suspected

CSF

• PCR: HSV-1/2, enterovirus, VZV, parechovirus
• Cell count: Lymphocytic pleocytosis (may be normal early)
• Protein/glucose: Mildly raised protein, normal glucose (viral)
• NMDA-R antibodies: In CSF — more sensitive than serum

Imaging

• MRI brain: Investigation of choice — temporal lobe signal change (HSV), multifocal white matter lesions (ADEM), normal or subtle changes (autoimmune)
• CT head: If MRI not immediately available; to exclude raised ICP before LP

Special Tests

• EEG: May show PLEDs in HSV; continuous EEG for refractory seizures
• Pelvic/abdominal imaging: USS/MRI for ovarian teratoma in anti-NMDA receptor encephalitis

Pharmacological

• IV aciclovir: 500mg/m² TDS (children >3 months) or 20mg/kg TDS (neonates) — start immediately; continue for 14-21 days if HSV confirmed; minimum 14 days
• Seizure management: Buccal midazolam → IV lorazepam → IV phenytoin/levetiracetam per APLS
• Autoimmune encephalitis: IV methylprednisolone 30mg/kg (max 1g) for 3-5 days; IVIG 2g/kg over 5 days; plasma exchange; rituximab for refractory cases
• ADEM: IV methylprednisolone 30mg/kg for 3-5 days; IVIG if steroid-refractory

Non-pharmacological

• PICU: For GCS ≤8, refractory seizures, respiratory failure
• Raised ICP management: Head elevation, mannitol/hypertonic saline, neurosurgical consultation
• Rehabilitation: Early multidisciplinary input — physiotherapy, OT, SALT, neuropsychology

Referral Criteria

• All suspected encephalitis — urgent paediatric neurology and infectious diseases
• GCS ≤8 — PICU
• Refractory seizures — PICU, continuous EEG
• Suspected autoimmune encephalitis — paediatric neurology, immunology

• HSV encephalitis with treatment: Mortality ~20%; ~50-60% survivors have neurocognitive sequelae
• HSV encephalitis without treatment: Mortality ~70%
• Autoimmune (anti-NMDA receptor): ~80% good outcome with immunotherapy; may relapse
• ADEM: Generally monophasic with good recovery; ~20% have residual deficits
• Viral (non-HSV): Generally good prognosis; enteroviral usually self-limiting
• Post-HSV autoimmune encephalitis: Increasingly recognised; responds to immunotherapy

Encephalitis Investigation Priority

HSV vs Autoimmune Encephalitis