Long‐term follow‐up of febrile infection–related epilepsy syndrome

Abstract

SUMMARYPurpose: Febrile infection-related epilepsy syndrome (FIRES) is an increasingly recognized epileptic syndrome that presents with multifocal refractory status epilepticus in previously normal children and evolves into a chronic, refractory, focal epilepsy with associated cognitive and behavioral difficulties. Herein we describe the features of the chronic epilepsy and critically review evidence for the etiology of this syndrome. Methods: Seven patients with FIRES were studied. The duration of follow-up in six survivors was 5-17 years. Clinical, electroencephalography (EEG), neuroimaging, and other investigative findings during the acute and chronic phases were reviewed. Key Findings: These previously normal children presented with a febrile illness and status epilepticus that was refractory to antiepileptic medications in all children, to immunotherapies (including immunoglobulin, corticosteroids, plasma exchange, and rituximab) in four, and to acute vagus nerve stimulation in one. Markers of cerebral inflammation were few and response to antiepileptic and immunomodulatory therapies was poor. Evolution to chronic epilepsy occurred without a silent period. Seizure characteristics in the chronic phase were strikingly stereotyped and similar to the acute phase, with head and eye version, unilateral facial jerking, asymmetric tonic posturing, and unilateral limb jerking in all patients. Electrographic ictal onset was lateralized in all recorded seizures, unilateral in one patient, and independent bilateral in three. Seizures were refractory to multiple antiepileptic medications in all patients and partly responsive to chronic vagus nerve stimulation in two patients. Moderate to severe intellectual impairment was noted in four patients, and borderline intellectual abilities were noted in two. Magnetic resonance imaging (MRI) in the chronic phase was normal in three patients and showed mild diffuse cortical atrophy and/or mild hippocampal atrophy or sclerosis in three. Significance: The similar perirolandic and perisylvian features of acute and chronic seizures, the lack of a silent period, the absence of evidence of cerebral inflammation, and the poor response to immunotherapies suggest FIRES is best conceptualized as a chronic epilepsy with explosive onset, not a remote-symptomatic epilepsy with an acute inflammatory antecedent.

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

“…Devastating outcomes are common in FIRES with ongoing seizures, severe cognitive impairment and mortality rates near 20%. 2 The limited data on outcomes in FIRES patients reveal that only 18% of children surviving the acute illness retained normal cognition long-term and 93% develop refractory epilepsy. 1,10 Thus the need for new, alternative therapeutic options is tremendous.…”

“…9 Seizure semiology in acute and chronic phases often include oral automatisms, head deviation and autonomic features such as apnea and salivation. 2 Another clinical feature of FIRES is fever 1-6 days (mean 4 days) prior to seizure onset, though some children are still febrile when seizures occur. 9 Mean age of onset is 6.5 years.…”

“…6 The persistence of seizures after the acute phase of illness has led some to postulate that mesial temporal damage causes the intractable epilepsy, 4 while others suggest that FIRES is a type of chronic epilepsy syndrome which presents acutely because of its explosive onset. 2 It is important to consider other epilepsy syndromes, such as Dravet, when making the diagnosis of FIRES, though the explosive onset and lack of genetic markers distinguish it from other epilepsy syndromes.…”

“…FIRES is an epileptic encephalopathy affecting previously normal school aged children which is characterized by an explosive and catastrophic onset of status epilepticus 1 followed by a chronic, refractory focal epilepsy with significant cognitive impairment. 2 First described in 1986, 3 the syndrome has been referred to as ''devastating epileptic encephalopathy in school age children, '' 4 ''acute encephalitis with refractory repetitive partial seizures,'' 5 and the currently used name, ''fever-induced refractory epileptic encephalopathy in school age children'' (FIRES). 6 Regardless of the name given to this syndrome, it is appears to be a distinct entity in which with no infectious, metabolic, or genetic basis has been found.…”

DRESS following FIRES: A Clinical Conundrum

“…Then within one month, mild-moderate cerebral atrophy and hippocampal sclerosis were noted and by one year severe cerebral and cerebellar atrophy was noted. Sequelae of FIRES are commonly drug-resistant epilepsy and neurologic and potentially psychologic impairments occurring without relief [7].…”