Ruth C. Shinnar

MRI abnormalities following febrile status epilepticus in children The FEBSTAT study

Objective: The FEBSTAT study is a prospective study that seeks to determine the acute and long-term consequences of febrile status epilepticus (FSE) in childhood. Methods: From 2003 to 2010, 199 children age 1 month to 5 years presenting with FSE (>30 minutes) were enrolled in FEBSTAT within 72 hours of the FSE episode. Of these, 191 had imaging with emphasis on the hippocampus. All MRIs were reviewed by 2 neuroradiologists blinded to clinical details. A group of 96 children with first simple FS who were imaged using a similar protocol served as controls. Results: A total of 22 (11.5%) children had definitely abnormal (n = 17) or equivocal (n = 5) increased T2 signal in the hippocampus following FSE compared with none in the control group (p < 0.0001). Developmental abnormalities of the hippocampus were more common in the FSE group (n = 20, 10.5%) than in controls (n = 2, 2.1%) (p = 0.0097) with hippocampal malrotation being the most common (15 cases and 2 controls). Extrahippocampal imaging abnormalities were present in 15.7% of the FSE group and 15.6% of the controls. However, extrahippocampal imaging abnormalities of the temporal lobe were more common in the FSE group (7.9%) than in controls (1.0%) (p = 0.015). Conclusions: This prospective study demonstrates that children with FSE are at risk for acute hippocampal injury and that a substantial number also have abnormalities in hippocampal development. Follow-up studies are in progress to determine the long-term outcomes in these children.

Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study

Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine whether FSE produces acute hippocampal injury that evolves to HS.

Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study.

Purpose:  In a prospective study, Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT), we determined the frequency of human herpesvirus (HHV)‐6 and HHV‐7 infection as a cause of febrile status epilepticus (FSE).

Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy

Objective: To determine the neurocognitive deficits associated with newly diagnosed untreated childhood absence epilepsy (CAE), develop a model describing the factorial structure of items measuring academic achievement and 3 neuropsychological constructs, and determine short-term differential neuropsychological effects on attention among ethosuximide, valproic acid, and lamotrigine. Methods: Subjects with newly diagnosed CAE entering a double-blind, randomized controlled clinical trial had neuropsychological testing including assessments of general intellectual functioning, attention, memory, executive function, and achievement. Attention was reassessed at the week 16–20 visit. Results: At study entry, 36% of the cohort exhibited attention deficits despite otherwise intact neurocognitive functioning. Structural equation modeling of baseline neuropsychological data revealed a direct sequential effect among attention, memory, executive function, and academic achievement. At the week 16–20 visit, attention deficits persisted even if seizure freedom was attained. More subjects receiving valproic acid (49%) had attention deficits than subjects receiving ethosuximide (32%) or lamotrigine (24%) (p = 0.0006). Parental assessment did not reliably detect attention deficits before or after treatment (p < 0.0001). Conclusions: Children with CAE have a high rate of pretreatment attentional deficits that persist despite seizure freedom. Rates are disproportionately higher for valproic acid treatment compared with ethosuximide or lamotrigine. Parents do not recognize these attentional deficits. These deficits present a threat to academic achievement. Vigilant cognitive and behavioral assessment of these children is warranted. Classification of evidence: This study provides Class I evidence that valproic acid is associated with more significant attentional dysfunction than ethosuximide or lamotrigine in children with newly diagnosed CAE.

Design and phenomenology of the FEBSTAT study.

Purpose:  Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hippocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology.

Acute EEG findings in children with febrile status epilepticus: Results of the FEBSTAT study

ABSTRACT Objective: The FEBSTAT (Consequences of Prolonged Febrile Seizures) study is prospectively addressing the relationships among serial EEG, MRI, and clinical follow-up in a cohort of children followed from the time of presentation with febrile status epilepticus (FSE). Methods: We recruited 199 children with FSE within 72 hours of presentation. Children underwent a detailed history, physical examination, MRI, and EEG within 72 hours. All EEGs were read by 2 teams and then conferenced. Associations with abnormal EEG were determined using logistic regression. Interrater reliability was assessed using the κ statistic. Results: Of the 199 EEGs, 90 (45.2%) were abnormal with the most common abnormality being focal slowing (n = 47) or attenuation (n = 25); these were maximal over the temporal areas in almost all cases. Epileptiform abnormalities were present in 13 EEGs (6.5%). In adjusted analysis, the odds of focal slowing were significantly increased by focal FSE (odds ratio [OR] = 5.08) and hippocampal T2 signal abnormality (OR = 3.50) and significantly decreased with high peak temperature (OR = 0.18). Focal EEG attenuation was also associated with hippocampal T2 signal abnormality (OR = 3.3). Conclusions: Focal EEG slowing or attenuation are present in EEGs obtained within 72 hours of FSE in a substantial proportion of children and are highly associated with MRI evidence of acute hippocampal injury. These findings may be a sensitive and readily obtainable marker of acute injury associated with FSE.

A consensus-based approach to patient safety in epilepsy monitoring units: Recommendations for preferred practices

Patients in an epilepsy monitoring unit (EMU) with video-EEG telemetry have a risk for seizure emergencies, injuries and adverse events, which emphasizes the need for strategies to prevent avoidable harm. An expert consensus process was used to establish recommendations for patient safety in EMUs. Workgroups analyzed literature and expert opinion regarding seizure observation, seizure provocation, acute seizures, and activity/environment. A Delphi methodology was used to establish consensus for items submitted by these workgroups. Fifty-three items reached consensus and were organized into 30 recommendations. High levels of agreement were noted for items pertaining to orientation, training, communication, seizure precautions, individualized plans, and patient/family education. It was agreed that seizure observation should include direct observation or use of closed-circuit camera. The use of continuous observation was strongest in patients with invasive electrodes, at high risk for injury, or undergoing AED withdrawal. This process provides a first step in establishing EMU safety practices.

Emergency Management of Febrile Status Epilepticus: Results of the FEBSTAT Study.

Treatment of seizures varies by region, with no standard emergency treatment protocol. Febrile status epilepticus (FSE) is often a childs first seizure; therefore, families are rarely educated about emergency treatment.

Cerebrospinal fluid findings in children with fever-associated status epilepticus: results of the consequences of prolonged febrile seizures (FEBSTAT) study.

This prospective multicenter study of 200 patients with fever-associated status epilepticus (FSE), of whom 136 underwent a nontraumatic lumbar puncture, confirms that FSE rarely causes cerebrospinal fluid (CSF) pleocytosis. CSF glucose and protein levels were unremarkable. Temperature, age, seizure focality, and seizure duration did not affect results. CSF pleocytosis should not be attributed to FSE.

Risk factors for febrile status epilepticus: A case-control study

OBJECTIVE To identify risk factors for developing a first febrile status epilepticus (FSE) among children with a first febrile seizure (FS). STUDY DESIGN Cases were children with a first FS that was FSE drawn from the Consequences of Prolonged Febrile Seizures in Childhood and Columbia cohorts. Controls were children with a first simple FS and separately, children with a first complex FS that was not FSE. Identical questionnaires were administered to family members of the 3 cohorts. Magnetic resonance imaging protocol and readings were consistent across cohorts, and seizure phenomenology was assessed by the same physicians. Risk factors were analyzed using logistic regression. RESULTS Compared with children with simple FS, FSE was associated with younger age, lower temperature, longer duration (1-24 hours) of recognized temperature before FS, female sex, structural temporal lobe abnormalities, and first-degree family history of FS. Compared with children with other complex FS, FSE was associated with low temperature and longer duration (1-24 hours) of temperature recognition before FS. Risk factors for complex FS that was not FSE were similar in magnitude to those for FSE but only younger age was significant. CONCLUSIONS Among children with a first FS, FSE appears to be due to a combination of lower seizure threshold (younger age and lower temperatures) and impaired regulation of seizure duration. Clinicians evaluating FS should be aware of these factors as many episodes of FSE go unnoticed. Further work is needed to develop strategies to prevent FSE.