Limbic Encephalitis

Limbic encephalitis is inflammation of the medial temporal lobes and limbic system, either autoimmune or paraneoplastic.

• Antibodies: LGI1 (hyponatraemia, faciobrachial seizures), CASPR2, GABA B (small cell lung cancer), AMPA, GAD65, Hu, Ma2 (testicular germ cell tumour), CRMP5, amphiphysin; seronegative cases.

• Infectious mimics: HSV (most important), HHV-6, syphilis, neuroborreliosis.

• Subacute onset (under 12 weeks).

• Short term memory impairment, confusion, behavioural change, seizures (temporal lobe, often drug resistant), anxiety, depression, hallucinations.

• Faciobrachial dystonic seizures (LGI1) may precede cognitive decline.

• Sleep disturbance, hyponatraemia.

• Graus criteria: subacute memory deficit, seizures or psychiatric symptoms, bilateral medial temporal lobe T2/FLAIR hyperintensity, CSF pleocytosis or EEG temporal slowing/epileptiform activity.

• Serum and CSF neuronal antibodies (LGI1, CASPR2, GABA B, AMPA, GAD65, onconeural panel).

• MRI (may normalise), EEG, CSF with HSV PCR and cultures.

• PET CT and cross sectional imaging for cancer (lung, testis, breast, thymus).

• Exclude infection, neurodegenerative dementia, Creutzfeldt-Jakob disease, structural lesions.

• Empirical IV aciclovir 10 mg/kg every 8 hours until HSV PCR negative.

• Immunotherapy: methylprednisolone 1 g IV daily for 3 to 5 days, then IVIG 2 g/kg or plasma exchange; maintain with oral prednisolone taper.

• Second line: rituximab 1 g x 2 or cyclophosphamide, mycophenolate, azathioprine.

• Treat the cancer (surgery, chemotherapy, radiotherapy).

• Antiseizure medication (levetiracetam, lacosamide, lamotrigine; sodium channel blockers helpful in LGI1/CASPR2); correct hyponatraemia.

• Cognitive rehabilitation and psychiatric support.

• LGI1 and CASPR2 disease respond well; paraneoplastic intracellular antibody disease responds poorly.