Abstracts

Rationale: PCDH-19 is an X-linked, female predominant, early infantile epileptic encephalopathy syndrome, which presents with multiple seizure semiologies and associated with varying degrees of intellectual disability. Patients initially present with difficult to control seizures often triggered by the onset of a fever. While clusters of seizures are frequently reported, initial presentation as new-onset refractory status epilepticus (NORSE) in infancy has not yet been reported. We present a challenging case of PCDH-19 epilepsy presenting as NORSE. Role of cytokine storm in pathogenesis of NORSE and successful treatment using Anakinra is highlighted.

Methods: A 7-month-old girl with no previous medical history presented to the hospital for frequent clusters of seizures for one day. Episodes of behavioral arrest and cyanosis, generalized jerks, or generalized stiffening were reported. One day prior, she received pneumococcal vaccine and second influenza booster but did not develop fever. She evolved into refractory status epilepticus after failing multiple anti-seizure medications (ASM) and was placed in a pentobarbital coma for burst suppression. Extensive work up for infectious, metabolic, and structural causes of NORSE was negative. A rapid epilepsy gene panel reported a pathogenic PCDH19 mutation, (c.1211 C >T, p.T404I). Serial serum and CSF cytokine panels were used to guide therapy with Anakinra.

Results: Patient required two rounds of pentobarbital-induced burst suppression to abate persistent seizures, with persistence of seizure despite midazolam and ketamine infusions. Patient was also started on intravenous immunoglobulin and ketogenic diet. Initial cytokine panels revealed elevated IL-2, IL-4, IL-10, IL-13, IL-17, IL-1 IL-1β, and IL-8. Work up for secondary Hemophagocytic Lymphohistiocytosis was negative. Anakinra was started with dose escalation (5-20mg/kg/day) and slowly weaned guided by repeat cytokine panels. Patient was successfully weaned from pentobarbital with subsequent cytokine panels showing improvement. Patient was discharged home on three ASMs and ketogenic diet.

Conclusions: To the best of our knowledge, this is a novel case of PCDH-19 in an infant presenting as super refractory status epilepticus after routine vaccinations. This case further underscores the interplay of genetic cause of epilepsy and activation of the neuroinflammatory response in status epilepticus with important therapeutic opportunities guided by the cytokine panels.

Funding: Please list any funding that was received in support of this abstract.: none.