We report the case of an eight year old developmentally normal and previously healthy girl who presented to our institution for further management of status epilepticus. She started experiencing focal seizures with impaired awareness characterized by staring without concomitant abnormal body movements. These seizures began to occur four days following a febrile gastroenteritis. The initial brain MRI was normal. The initial EEG revealed right temporal electro-clinical seizures. Cerebrospinal fluid infectious studies were taken and the patient was started on empirical antibacterial and antiviral therapy. Her seizures progressed in frequency to multiple daily episodes of staring that failed to respond to antiepileptic drug poly-therapy including lacosamide, levetiracetam, phenytoin, clonazepam, and valproic acid. Repeated brain MRI was also unrevealing. She presented to our institution six days following her initial seizures. On presentation, she was obtunded, disoriented, unresponsive to verbal stimuli with normal power and hyperreflexia.
Extensive infectious and autoimmune serum and cerebrospinal fluid (CSF) evaluation was performed. Initial CSF studies showed pleocytosis, 125 WBCs and the presence of 3 RBCs. CSF protein was normal (0.29 g/L, normal range 0.1-0.5 g/L). CSF glucose was normal (70 mg/dL, normal range 40-70 mg/dL). Further studies were performed on CSF samples and included a viral panel including herpes simplex virus (HSV) PCR, culture, 16 S RNA, Tuberculosis PCR, toxoplasma PCR, Brucella culture, EBV PCR, West Nile virus PCR, anti-NMDA antibodies, anti-potassium channel antibodies, anti GABA antibodies, ammonia, lactate, amino acids, neurotransmitters and oligoclonal bands. CSF cytology was not done. Serum autoimmune workup included anti-GAD antibodies. The method of processing was through ELISARSR  by Laboratoires Cerba  for quantitative determination of autoantibodies to glutamic acid decarboxylase (GAD65) in serum. The value of CSF anti-GAD antibodies could not be obtained as the test is not available at our institution. Serum COVID19-PCR was tested twice and was negative. Despite negative pan-cultures and a repeated CSF HSV PCR, broad spectrum antibiotics and acyclovir, (that was later switched to foscarnet to cover for the possibility of acyclovir-resistant HSV), were continued for a total of 21 days.
The patient was intubated a few hours after admission due to refractory status epilepticus and was started on Midazolam drip in addition to the ASM. Long term EEG monitoring showed frequent electrographic multifocal seizures mainly from right and left temporal areas. ASMs were adjusted with the addition of clobazam, topiramate and perampanel. Attempt to initiate ketogenic diet was unsuccessful due to an elevated lipase level, that reached a maximum of 195 U/L.
In addition, due to a high suspicion for autoimmune encephalitis, she was started on intravenous immunoglobulin at a dose of 1 gram per kg on two consecutive days, followed by a 3-day course of high dose methylprednisolone (30 mg per kg per dose). Unfortunately, her seizures remained refractory despite high-dose of midazolam (MDZ) infusion, therefore propofol IV drip was added as a continuous infusion and induced a burst-suppression pattern on EEG. An attempt to wean propofol after 72 h was unsuccessful, therefore it was replaced with an IV ketamine drip. Phenobarbital was also started, targeting a serum trough level in the high 40 s (mg/l) with a partial seizure reduction. She also received 5 sessions of plasma exchange two days after high-dose corticosteroids administration.
Ten days after admission, the ketogenic diet was initiated after normalization of lipase level. Due to inadequate response to the immunomodulatory therapies, tocilizumab was administered at a dose of 8 mg/kg/day divided in two doses one week apart. The patient became seizure-free 24 h following the first dose of tocilizumab and three days following the initiation of ketogenic diet. Ketamine and MDZ infusions were weaned and discontinued. The patient was successfully extubated a few days later.
At this time, the results of infectious and autoimmune workup turned out to be unrevealing except for a positive serum anti-GAD antibody level of 303.1 U/ml (reference range <5 U/ml). The diagnosis of anti-GAD encephalitis was confirmed. Further investigations for a paraneoplastic process including a chest x-ray and a CT scan of abdomen and pelvis were unremarkable. The patient showed rapid and significant clinical improvement and was discharged home with normal cognition and a minor ataxia that is improving. A timeline describing the frequency of seizures and the various immunomodulatory therapies is illustrated in Fig. 1 (Appendix).
Upon follow up 1 month later, our patient was symptom-free except for occasional breakthrough seizures, on three AEDs (phenobarbital, levetiracetam, perampanel) and on a monthly tocilizumab infusion schedule of 8 mg per kg. Her exam remained with no evidence of focal weakness and normal cognition. Serum anti-GAD antibody titer repeated three weeks later declined to 30 U/ml. A follow-up brain MRI showed mild parenchymal brain atrophy.