Cannabidiol as a Potential Treatment for Febrile Infection-Related Epilepsy Syndrome (FIRES) in the Acute and Chronic Phases

Abstract

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.

A systematic review of cannabidiol dosing in clinical populations

“…In the remaining 8 clinical trials of various study design, 7 studies reported CBD positively (average dosing 23 mg/kg/d) and 1 study was neutral (8 mg/kg/d) . Within the 12 case studies and case series, 9 described positive effects of CBD (average dosing 16 mg/kg/d), 2 were neutral (average dosing 21 mg/kg/d) and 1 study described mixed results (3 mg/kg/d)…”

“…Within the other 3 clinical trials of prospective open‐label design ( n = 203), CBD was administered at an average dosing of 42 mg/kg/d and significant improvements in quality of life and seizure frequency compared to baseline were observed . 3 case series and 1 case report (total n = 16) reported beneficial effects of CBD on seizure frequency, duration and severity with an average administered dose of 21 mg/kg/d …”

Early ictal and interictal patterns in FIRES: The sparks before the blaze

“…2,4,8 Although all our patients developed SRSE over a few days, the initial seizure burden was relatively low. Development of an early biomarker for identification of FIRES is needed, as patients present with relatively nonspecific symptoms.…”

“…The diagnosis is one of exclusion made after the infectious, metabolic, genetic, and autoimmune evaluation yields negative results. 2,8,9 Outcomes in children with FIRES are poor, with 10-30% of cases resulting in death, refractory epilepsy in 90% of survivors, and severe intellectual disability in a third. 2,[5][6][7] Most centers trial a combination of antiepileptic and immune-modulating therapies with disappointing results.…”

“…2,8,9 Outcomes in children with FIRES are poor, with 10-30% of cases resulting in death, refractory epilepsy in 90% of survivors, and severe intellectual disability in a third. 8,10,11 It is crucial to develop early diagnostic tools to aid in prompt diagnosis. 4 The lack of specific clinical criteria and/or confirmatory tests leads to a broad and expensive diagnostic evaluation for most patients.…”