Encephalitis

Contents

Overview

Encephalitis is inflammation of brain parenchyma, clinically manifest as altered consciousness, seizures, or focal neurological deficits. It is distinct from meningitis (inflammation confined to the meninges), though both may coexist as meningoencephalitis. The condition is a neurological emergency: delayed treatment, particularly of herpes simplex encephalitis, causes avoidable death and disability.

Aetiology

Infectious Encephalitis

Herpes simplex virus (HSV-1) is the most common cause of sporadic viral encephalitis in adults in the UK. It typically affects the temporal and frontal lobes through reactivation of latent virus in the trigeminal ganglion or direct spread along olfactory pathways.

Other viral causes include:

  • VZV: May cause encephalitis, particularly in immunocompromised patients and the elderly
  • CMV and EBV: In the immunocompromised host
  • Enteroviruses: More common in children and young adults
  • Arboviruses: Japanese encephalitis, West Nile virus — consider travel history

Bacterial encephalitis: Listeria monocytogenes causes rhombencephalitis (brainstem encephalitis) in elderly, pregnant, or immunocompromised patients. TB encephalitis and cerebritis should be considered in high-risk groups.

Fungal: Cryptococcal meningoencephalitis in HIV (CD4 <100) and other immunocompromised states.

Autoimmune Encephalitis

Autoimmune encephalitis is immune-mediated inflammation directed against neuronal surface antigens. It can be paraneoplastic or idiopathic.

Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. It predominantly affects young women and is associated with ovarian teratoma (remove surgically as part of treatment). In men, testicular tumours have been described. A paraneoplastic aetiology should always be sought.

Other antibody-associated encephalitides:

  • LGI1 (leucine-rich glioma inactivated 1): faciobrachial dystonic seizures (brief, stereotyped), hyponatraemia, predominantly older men; no consistent tumour association
  • CASPR2: limbic encephalitis, peripheral nerve hyperexcitability; associated with thymoma
  • GABA-B: refractory status epilepticus; associated with small cell lung cancer
  • AMPA receptor: limbic encephalitis, psychiatric features; associated with lung and breast tumours

Clinical Features

The classic triad of encephalitis is fever, headache, and altered consciousness. Additional features include:

  • Seizures (focal or generalised) — often the presenting feature
  • Focal neurological deficits
  • Psychiatric symptoms (particularly prominent in autoimmune encephalitis)
  • Autonomic instability (anti-NMDAR encephalitis)

HSV encephalitis typically presents with temporal lobe features: anterograde amnesia, aphasia, olfactory hallucinations, and personality change, progressing over hours to days to reduced consciousness and seizures.

Anti-NMDAR encephalitis has a characteristic progression: psychiatric prodrome (psychosis, agitation, anxiety) → movement disorder (orofacial dyskinesias, choreoathetosis) → reduced consciousness → autonomic instability. This syndrome is often initially referred to psychiatry.

Investigations

Lumbar puncture is performed urgently unless contraindicated by raised ICP, coagulopathy, or haemodynamic instability. Always perform CT head first if there are focal neurological signs, papilloedema, or immunocompromise.

CSF analysis in viral encephalitis: lymphocytic pleocytosis (10–1000 cells/mm³), mildly elevated protein, normal glucose. Red cells may be present in HSV (haemorrhagic necrosis).

CSF PCR: HSV, VZV, CMV, EBV, enterovirus — sensitivity for HSV is 98% after the first 24 hours. A negative early HSV PCR does not exclude HSV; repeat LP at 3–7 days if clinical suspicion remains.

MRI brain: The most sensitive imaging modality. HSV typically shows T2/FLAIR hyperintensity in the temporal lobes and insular cortex, often unilateral initially. Autoimmune encephalitis may show limbic or cortical signal change, or may appear normal.

EEG: Shows non-specific slow wave activity. Periodic lateralised epileptiform discharges (PLEDs) in the temporal regions are characteristic of HSV encephalitis. Also identifies subclinical seizures.

Autoimmune antibody panel: Sent on both serum and CSF. CSF has higher sensitivity for anti-NMDAR antibodies. Include LGI1, CASPR2, GABA-B, AMPA, and paraneoplastic antibodies (Hu, Yo, Ri).

Tumour screen: CT chest/abdomen/pelvis; pelvic ultrasound and MRI in women of reproductive age (ovarian teratoma); testicular ultrasound in men.

Management

Empirical Treatment

Aciclovir must be started immediately on clinical suspicion of encephalitis, before confirmation of HSV by PCR. Dose: 10 mg/kg IV every 8 hours (adjusted for renal function). Do not delay for MRI or LP results.

Dexamethasone should be added if bacterial meningitis is also a possibility (purulent CSF, bacterial antigen positivity, or clinical features suggesting bacterial meningitis), pending LP results.

Specific Treatment

HSV encephalitis: Aciclovir for 14–21 days. A repeat CSF PCR near the end of treatment confirms viral clearance.

VZV encephalitis: Aciclovir at the same dose; duration depends on immune status.

Bacterial or fungal meningitis: appropriate targeted antimicrobials.

Supportive Care

  • Airway protection if GCS ≤8 — early intubation is preferable to emergency intubation after deterioration
  • Seizure management: lorazepam for acute seizures; levetiracetam or valproate as maintenance
  • ICP management if cerebral oedema develops (head elevation, controlled PaCO2, osmotherapy)
  • Fever control (antipyretics; cooling if required)

Autoimmune Encephalitis

Autoimmune encephalitis requires immunotherapy. The standard initial approach is:

  • Methylprednisolone 1 g IV daily for 3–5 days
  • IVIG 2 g/kg over 5 days
  • Plasma exchange if no response

Second-line therapy for refractory cases: rituximab (anti-CD20) or cyclophosphamide.

Tumour removal is essential where a paraneoplastic cause is identified — this often leads to partial or complete neurological recovery.

Response to treatment in autoimmune encephalitis is often slow; recovery may continue over 12–18 months. ICU admission may be required for mechanical ventilation, management of autonomic instability, and seizure control in refractory cases.

Viva Questions

What is the immediate management of suspected encephalitis in a patient presenting with seizures and reduced GCS?

The immediate priority is airway assessment. A patient with a GCS of 8 or below, ongoing seizures, or a deteriorating trajectory requires urgent intubation for airway protection — delay risks aspiration, hypoxia, and further neurological injury. While preparing for intubation, active seizures should be treated with IV lorazepam. A blood glucose must be checked to exclude hypoglycaemia. Aciclovir 10 mg/kg IV must be started without delay, as the most common treatable cause is HSV encephalitis and delay worsens outcomes. Empirical antibiotics (ceftriaxone 2 g IV) and dexamethasone 0.15 mg/kg should be added if bacterial meningitis cannot be excluded. Blood should be taken for culture, FBC, metabolic panel, and autoimmune antibody panel. CT head is performed before LP if there are focal signs, papilloedema, or reduced GCS. Once safe, LP is performed for CSF analysis, PCR, and autoimmune antibodies. MRI brain should follow as soon as logistically possible.

How does anti-NMDA receptor encephalitis present and how is it treated?

Anti-NMDAR encephalitis presents in a characteristic phased pattern. The initial phase is a psychiatric syndrome — psychosis, agitation, paranoia, and mood disturbance — which is often misidentified as a primary psychiatric illness. This evolves over days to weeks into a movement disorder characterised by orofacial dyskinesias, choreoathetosis, and stereotyped movements. Consciousness then deteriorates, and in severe cases the patient develops autonomic instability with labile blood pressure, tachycardia, and hyperthermia. Status epilepticus and the need for mechanical ventilation are common in severe cases. MRI may be normal; EEG shows a characteristic delta brush pattern in about a third of patients. Diagnosis is confirmed by anti-NMDAR antibodies in serum and CSF. Treatment requires tumour removal if an ovarian teratoma or other tumour is identified — this alone can produce recovery. First-line immunotherapy is methylprednisolone and IVIG or plasma exchange. Second-line therapy with rituximab or cyclophosphamide is used if there is no response. Recovery is possible even after prolonged ventilation, but can take months to years.

What CSF findings would you expect in HSV encephalitis, and how long do you treat for?

The CSF in HSV encephalitis typically shows a lymphocytic pleocytosis, usually 10–500 cells/mm³. Protein is mildly to moderately elevated. Glucose is normal. Red blood cells may be present in up to half of cases, reflecting the haemorrhagic necrosis of temporal lobe tissue characteristic of HSV. The CSF can occasionally appear normal in the first 24–48 hours of illness. PCR for HSV DNA is the definitive diagnostic test, with sensitivity above 95% after the first day of symptoms. A negative early PCR should not terminate aciclovir if clinical suspicion remains high — a repeat LP at 3–7 days is recommended. Treatment duration for confirmed HSV encephalitis is 14–21 days of IV aciclovir at 10 mg/kg every 8 hours, adjusted for renal function. A repeat CSF PCR near the end of the course confirms clearance before discontinuing treatment. Oral valaciclovir suppressive therapy for 90 days after the acute course has been studied in an attempt to reduce neurological sequelae, with some evidence of benefit.