Appendix e-1:Clinical features of one VGKC Ab encephalitis patient (Case 4)
A 14 year old girl of Vietnamese origin presented with headache and dizziness followed by new onset secondary generalised tonic-clonic seizures (GTCS) and confusion. On examination she was febrile, encephalopathic and combative, but no focal neurologic deficit. She had frequent short lived GTCS every 30-90 minutes without intervening return of consciousness. She was intubated, ventilated and commenced on a midazolam infusion.
Brain MRI at presentation and three weeks into her admission was normal. The initial EEG had left periodic epileptic discharges whilst subsequent EEGs showed generalised slowing and alternating right and left temporal electrical seizures. CSF revealed six white cells, normal protein and glucose, and negative PCR for herpes simplex virus and enterovirus. CSF neopterin was elevated at 87.9 nmol/L (normal 7-28), and oligoclonal bands were negative. Her erythrocyte sedimentation rate was 40 mm/hr (normal <20), and C-reactive protein was 42 mg/L (normal 0-10). There was no hyponatraemia at any stage of the illness.
Her acute VGKC antibody titre was 640 pM (<100). Serology for mycoplasma, cytomegalovirus, Epstein Barr virus, human herpes virus 6, toxoplasma, and cat scratch disease were negative. Anti-nuclear antibody (ANA) titre was elevated at 1:640 with a speckled pattern, although further autoimmune testing was normal. Pelvic ultrasound revealed no ovarian teratoma.
During her 18 days of intensive care she had hyperthermia up to 41.5oC. Despite midazolam infusion, sodium valproate, phenytoin and levetiracetam, she continued to have up to 20 focal and generalised seizures per day. In the third week of her admission her seizures abated and she was extubated and discharged to the ward, although she was emotionally labile and had word finding difficulties. Formal neuropsychology assessment at three months revealed impairments of cognition and higher executive function, including problems with emotional control, attention and complex thinking. In view of the ongoing cognitive concerns three months after discharge, she was given one course of intravenous immunoglobulin and oral steroids for 1 month. At 15 month follow-up, she is back to her pre-morbid functioning according to her family and school, and has been weaned off all anti-convulsants.