L. Matthew Frank

Lamictal (Lamotrigine) Monotherapy for Typical Absence Seizures in Children

Summary: Purpose: To investigate whether lamotrigine (LTG) monotherapy is effective and safe for newly diagnosed typical absence seizures in children and adolescents (aged 3–15 years, n = 45).

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:u2002 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).

Design and phenomenology of the FEBSTAT study.

Purpose:u2002 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.

Autosomal recessive congenital cerebellar hypoplasia.

We report three sibling pairs with congenital cerebellar hypoplasia. All six children presented in the first years of life with delays in motor and language development. All patients showed cerebellar and/or vermal dysfunction and, on formal psychometric testing, cognitive abilities ranged from normal to moderately retarded. Abnormalities on CT scan ranged from prominent valleculla to an enlarged cisterna magna with hypoplasia of the cerebellar hemispheres and vermis. The pedigrees are consistent with autosomal recessive inheritance.

Lamotrigine monotherapy for newly diagnosed typical absence seizures in children

Summary Purpose To evaluate the efficacy, tolerability, and effects on behavior and psychosocial functioning of lamotrigine monotherapy in children with newly diagnosed typical absence seizures. Patients and methods Children meeting enrollment criteria (n = 54) received a confirmatory 24-h ambulatory electroencephalogram (EEG) and then entered a Escalation Phase of up to 20-weeks during which lamotrigine was titrated until seizures were controlled or maximum dose (10.2 mg/kg) was reached. Seizure freedom was assessed by diary review and clinic hyperventilation (clinic HV) and then confirmed by EEG with hyperventilation (HV/EEG). Patients who maintained seizure freedom for two consecutive weekly visits were entered into the Maintenance Phase (n = 30). Diary, clinic HV, and HV/EEG data were supplemented with 24-h ambulatory EEG at baseline and the ends of the Escalation and Maintenance Phases. Health outcome assessments were completed at screening and at the end of the Maintenance Phase. Results By the end of the Escalation Phase, seizure-free rates (responders) were 59% by seizure diary (n = 51), 56% by HV/EEG (n = 54) (primary endpoint), and 49% by 24-h ambulatory EEG (n = 49). During the Maintenance Phase, 89% (week 24) and 86% (week 32) remained seizure free by diary (n = 28), 78% by clinic HV (n = 27), and 81% by 24-h ambulatory EEG (n = 26). Seizure freedom was first observed beginning at the fifth week of the Escalation Phase. The most frequent adverse events were headache and cough. Health outcome scores were either improved or unchanged at the end of the Maintenance Phase. Conclusions Lamotrigine monotherapy results in complete seizure freedom in a substantial number of children with typical absence seizures. Lamotrigine was well tolerated in this study.

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.