Abstract Details

While auto-antibody markers for AIE have facilitated its identification, AIE must be clinically diagnosed in the significant subset of seronegative patients. Though seizures are a common feature of AIE, some patients progress to new onset refractory status epilepticus.

To report a complicated case of seronegative autoimmune encephalitis (AIE), in the context of potential primary immune deficiency, with the development of super-refractory status epilepticus requiring novel surgical intervention and complicated by posterior reversible encephalopathy syndrome (PRES).

A 21-year-old woman with a history of premature birth complicated by neonatal seizures, recurrent ear/sinus infections in childhood, thrombocytopenia, and atrioventricular nodal re-entrant tachycardia status post ablation presented with three days of worsening fever, lethargy, and headache. On admission, cerebrospinal fluid (CSF) studies were unremarkable for meningitis. Over next few days, she became anxious with restless legs before exhibiting confusion and developing seizures. She then went into status epilepticus that was refractory to escalating antiepileptic drug (AED) regimen, multiple immunotherapies, or ketogenic diet requiring prolonged induced coma with midazolam, ketamine, and phenobarbital. After weeks intubated, deep brain stimulation (DBS) was elected for seizure management. Shortly after reprogramming, she had her first notable decrease in seizure frequency.

Encephalitis and paraneoplastic auto-antibody panels were unrevealing. Repeat CSF studies were notable for pleocytosis and elevated CD-25 and IL-6. MRI was notable for bilateral temporal lobe changes and later PRES. An extensive infectious work-up showed no evidence of nervous system infections. Targeted sequencing revealed a heterozygous mutation in TNFSF13B, a gene encoding a tumor necrosis factor receptor expressed on B-cells, implicated in hypogammaglobulinemia and autoimmune disease.

This case of super-refractory status epilepticus secondary to AIE required a combination of AEDs and DBS to control, as well as continued immune modulation. It is especially complex as the presumed immune deficiency increases the likelihood of autoimmune disease and increases infection risk.