Marina M. Martinos

Early developmental outcomes in children following convulsive status epilepticus: a longitudinal study.

Convulsive status epilepticus (CSE) is the most common pediatric neurologic emergency and is often associated with unfavorable neurodevelopmental outcomes. The early developmental trajectory of children following CSE has not been previously investigated, leaving a gap in our understanding of how these adverse long‐term outcomes emerge.

Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures

Childhood convulsive status epilepticus (CSE), in particular prolonged febrile seizures (PFS), has been linked with mesial temporal sclerosis (MTS). Previous studies have shown that hippocampal injury occurs in the acute phase immediately following CSE, but little is known about the longer term evolution of such injury. This study aimed to investigate the longer term outcome of childhood CSE with sequential magnetic resonance imaging (MRI) looking for progressive hippocampal injury during the first year post‐CSE.

The role of magnetic resonance imaging in the follow-up of children with convulsive status epilepticus

Aim  The aim of this study was to determine the yield of magnetic resonance imaging (MRI) after an episode of childhood convulsive status epilepticus (CSE) and to identify the clinical predictors of an abnormal brain scan.

Prolonged febrile seizures cause reversible reductions in white matter integrity

Prolonged febrile seizures (PFS) are the commonest cause of childhood status epilepticus and are believed to carry a risk of neuronal damage, in particular to the mesial temporal lobe. This study was designed to determine: i) the effect of prolonged febrile seizures on white matter and ii) the temporal evolution of any changes seen. 33 children were recruited 1 month following PFS and underwent diffusion tensor imaging (DTI) with repeat imaging at 6 and 12 months after the original episode of PFS. 18 age-matched healthy control subjects underwent similar investigations at a single time point. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) between patients and controls on a voxel-wise basis within the white matter skeleton. Widespread reductions in FA along multiple white matter tracts were found at 1 and 6 months post-PFS, but these had resolved at 12 months. At one month post-PFS the main changes seen were reductions in AD but at 6 months these had predominantly changed to increases in RD. These widespread white matter changes have not previously been noted following PFS. There are many possible explanations, but one plausible hypothesis is that this represents a temporary halting of normal white matter development caused by the seizure, that then resumes and normalises in the majority of children.

Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study

BACKGROUND The prognosis of convulsive status epilepticus (CSE), a common childhood medical neurological emergency, is not well characterised. We aimed to investigate the long-term outcomes in a cohort of participants who previously had CSE. METHODS In this prospective study, we followed up a population-based childhood CSE cohort from north London, UK (the north London convulsive status epilepticus surveillance study cohort; NLSTEPSS). We collected data from structured clinical neurological assessment, neurocognitive assessment (Wechsler Abbreviated Scale of Intelligence), brain MRI, medical records, and structured interviews with participants and their parents to determine neurological outcomes, with adverse outcome defined as presence of one or more of epilepsy (active or in remission), motor disability, intellectual disability, or statement of special educational needs. We applied multiple imputation to address missing data and performed binary logistic regression analyses on complete-case and imputed datasets to investigate sociodemographic and CSE factors associated with adverse outcomes. FINDINGS Of 203 survivors (90% of inception cohort), 134 (66%) were assessed at a median follow-up of 8·9 years (IQR 8·2-9·5). The cumulative incidence of epilepsy was 24·7% (95% CI 16·2-35·6), with most (89%) emerging within 18 months after CSE. The cumulative incidence of epilepsy was lower in patients with prolonged febrile seizures (14·3%, 6·3-29·4) and survivors of acute symptomatic CSE (13·3%, 3·7-37·9) than in those of remote symptomatic CSE (45·5%, 21·3-72·0) and unclassified CSE (50·0%, 25·4-74·6). One participant (2·9%, 0·5-14·5) in the prolonged febrile seizures group developed temporal lobe epilepsy with mesial temporal sclerosis. The absence of fever at CSE was the only predictor of incident epilepsy (odds ratio [OR] 7·5, 95% CI 2·25-25·1). Motor and intellectual disability was seen predominantly in participants who had idiopathic and cryptogenic CSE (seven [36·8%, 95% CI 19·1-59·0] and 16 [84·2%, 62·4-94·5] of 19, respectively) and remote symptomatic CSE (33 [62·3%, 48·8-74·1] and 40 [75·5%, 62·4-85·1] of 53), and most of these participants had pre-existing disabilities. Pre-existing epilepsy was the only predictor of intellectual disability (OR 8·0, 95% CI 1·1-59·6). 51·5% (95% CI 43·1-59·8) of those followed up had a statement of special educational needs. INTERPRETATION Childhood CSE is associated with substantial long-term neurological morbidity, but primarily in those who have epilepsy, neurological abnormalities, or both before the episode of CSE. Survivors without neurological abnormalities before CSE have favourable outcomes. FUNDING BUPA Foundation, The Academy of Medical Sciences, Wellcome Trust, National Institute for Health Research, and Young Epilepsy.

Long-term behavioural outcomes after paediatric convulsive status epilepticus: a population-based cohort study

To describe behavioural and psychiatric outcomes of children within 10 years of convulsive status epilepticus (CSE).

Long-term white matter tract reorganization following prolonged febrile seizures

Diffusion magnetic resonance imaging (MRI) studies have demonstrated acute white matter changes following prolonged febrile seizures (PFS), but their longer‐term evolution is unknown. We investigated a population‐based cohort to determine white matter diffusion properties 8 years after PFS.

Hippocampal sclerosis and other forms of status epilepticus

Hippocampal Sclerosis and Other Forms of Status Epilepticus Michael Yoong, MRCPCH, PhD, Marina M. Martinos, PhD, Suresh Pujar, MRCPCH PhD, Rodney C. Scott, MRCPCH PhD, and Richard F. Chin, PhD We note with interest the FEBSTAT 1-year follow-up study, in which they found significantly decreased right hippocampal volumes in children with febrile status epilepticus (FSE) compared to children with simple febrile seizures on initial and follow-up magnetic resonance imaging. However, in a longitudinal study [Status Epilepticus Imaging and Neurocognitive study (STEPIN)] of British children with all forms of convulsive status epilepticus (CSE; 26 with FSE), we found that 19% (95% confidence interval [CI] 5 4–35%) of children with FSE and 30% (95% CI 5 15–45%) of the non-FSE group showed significant hippocampal volume loss over the year following CSE. Thus, hippocampal injury is not only an FSE phenomenon, but occurs in all forms of CSE. Further follow-up is needed to determine how persistent this impact is and what the longer-term implications might be. Although we found no child who developed hippocampal sclerosis (HS) following FSE, our findings are consistent with the FEBSTAT findings of 7%, because the 95% CIs overlap (95% CI 5 0–13% and 4–13%, respectively). Taken together, however, a small proportion of children will develop HS within 1 year following FSE. In STEPIN, hippocampal volume loss was associated with a history of previous febrile seizures and recurrent CSE. It would be interesting to see whether similar findings emerge in FEBSTAT.