A 13-year-old Bahraini girl initially presented to a private hospital with a two day history of agitation and new onset of severe continuous bitemporal headache associated with slurring of speech. She had no history of fever, trauma, drug intake or migraine. She had no other past medical history of significance. Her birth and developmental histories were normal. She always performed well in school. Her mother had a long history of a generalized seizure disorder, which was controlled with medication. Her other family members were healthy. She was investigated for a possible cranial lesion and/or seizure, with a brain CT scan and an electroencephalogram (EEG) performed, both of which were normal. The following day she reported both vague auditory and visual hallucinations as well as fatigue. She was seen by a psychiatrist and prescribed antipsychotics for psychosis. Over the following few days, her condition worsened with a new onset of generalized tonic clonic seizures lasting for two minutes. She then presented to the emergency department at our hospital and required pediatric intensive care unit admission for monitoring and further work up. Upon examination, she was afebrile. Her blood pressure, heart rate and saturation were within normal limits. She was opening her eyes spontaneously and obeying simple commands with occasional inappropriate speech. Her Glasgow Coma Scale was 13. Her pupils were constricted bilaterally with sluggish reaction to light. Fundoscopy was normal. Her muscle tone was decreased with generalized diminished deep tendon reflexes. Her plantar responses were equivocal. Her gait was normal. She had no signs of incoordination. Other systems examination were unremarkable. She developed further seizures with shallow breathing, for which she was intubated and started on midazolam infusion, intravenous phenytoin and phenobarbitone. Her EEG showed generalized delta rhythm with sharply contoured waves over the left frontotemporal region. Valproic acid, levetiracetam and clonazepam were all needed for seizure control. She was worked up for causes of neuropsychiatric diseases such as infectious and autoimmune encephalitis with extensive laboratory investigations including complete blood counts, ANA, anti-dsDNA, C3, C4, serum copper, ceruloplasmin, urine porphobilinogen and all were normal pending the result of anti-NMDAR-Ab. Her serological tests for herpes, influenza, EBV, CMV and RSV were negative except for mycoplasma IgM. She was started empirically on IV acyclovir and ceftriaxone along with oral clarithromycin. She received 1 g/kg/dose of intravenous immunoglobulins (IVIG) once daily for two days. Cerebrospinal fluid (CSF) analysis showed pleocytosis with WBC count of 60 cells/high power field (normal 0-5 cells/high power field) and 96% lymphocytes (normal 60-70% lymphocytes) with normal glucose and protein concentrations. CSF oligoclonal bands were negative. Polymerase chain reaction (PCR) analysis of the CSF for enterovirus, CMV, herpes, EBV and mycoplasma was negative. The antibiotics were discontinued when her blood and CSF cultures returned negative. Acyclovir was then discontinued upon obtaining negative PCR viral study of her CSF. Her brain and entire spine magnetic resonance imaging (MRI) scans showed a non-sectoral lesion that was of a high signal intensity in both tbl2 and FLAIR involving the grey and white matter of the left cerebellar hemisphere with no spinal involvement, suggestive of ADEM and less likely of an infectious process (Fig. 1). Having excluded infection and presuming "autoimmune etiology" we proceeded with an empiric trial of steroids and intravenous pulse methyl prednisolone 30 mg/kg/dose every six hours for five days which was given followed by maintenance with oral prednisolone. Anti-NMDAR-Ab assay from CSF, IgG isotype result was 1:16 (reference value 1:1). It was obtained by qualitative indirect immunofluorescence testing done at Bioscientia Institut fur Medizinische Diagnostik (Ingelheim am Rhein, Germany). The result was obtained three weeks after admission. Anti-NMDAR-Abs were not identified in her serum. High anti-NMDAR-Abs confirmed our suspicion of anti-NMDAR-Ab encephalitis. She was extubated around that time and noted to be in a catatonic state; mute, with reduced level of communication and poor appetite for food with periods of occasional agitation. She was responsive to pain, turning in bed with dystonic posturing, some choreoathetoid movements of the limbs and facial grimacing. She was accordingly started on trihexyphenidyl for dystonia and haloperidol for chorea and periodic agitation. Despite ongoing physiotherapy over a period of four weeks, she developed spasticity in her lower limbs for which baclofen was added. Her dystonia and choreoathetosis did not improve; accordingly she was given five sessions of plasmapheresis over ten days. A repeat MRI scan of her brain and entire spine showed complete resolution of the signal abnormality in the left cerebellar hemisphere with no spinal involvement (Fig. 2). She developed paralytic ileus with abdominal distension and was investigated with repeated ultrasound and CT scans of her abdomen, but neither showed any evidence of a tumor. Her family refused a follow up CSF study for anti-NMDAR-Abs.
A multidisciplinary team approach was needed. During the acute stage of the disease, the intensivists' role was focusing on patient stabilization and intubation together with the neurologists for seizure control. Other specialist roles were involved in managing complications and rehabilitation including psychiatrists, physiotherapists, occupational therapists, speech therapists and nutritionists. Each specialists' individualized evaluation and recommendations were obtained regularly as well as a general consensus on patient care. Over the following two months, she showed signs of improvement with seizure control, decreased spasticity and improved speech. She continued to have occasional choreoathetoid movements. Her Modified Rankin Scale scored 4 (moderately severe disability, unable to attend to own bodily needs without assistance, and unable to walk unassisted). Anticonvulsants were weaned off over the following six months. She was followed up in the outpatient clinic and noted to improve remarkably with disappearance of the extrapyramidal symptoms, regaining normal functional mobility with good recall and fluent speech. Her Modified Rankin score reduced to stage 1 (no significant disability, able to carry out all usual activities, despite some symptoms) in one year and reached stage 0 (no symptoms) in two years time. She continued to have no evidence of malignancies.