Michael Yoong

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.

Management of convulsive status epilepticus in children

Convulsive status epilepticus (CSE), with an incidence of 17–23 episodes per 100 000 children per year,1 is the most common medical neurological emergency in children. Since there is significant associated morbidity and mortality, which in part may be related to seizure length,2 it is essential that acute paediatric and paediatric emergency staff are comfortable and familiar with its management. To maximise the probability of seizure termination, protocols for early appropriate treatment need to be developed. This review aims to examine the justification for early treatment and evidence supporting certain therapeutic interventions and to identify similarities and differences in protocols worldwide to identify and promote best practice. CSE is often defined as either two or more convulsions without complete recovery of consciousness between seizures (intermittent CSE) or a single prolonged seizure lasting at least 30 min (continuous CSE) with a motor component. The motor component usually consists of tonic stiffening followed by clonic movements of all limbs, although purely tonic or clonic as well as myoclonic status epilepticus can occur.3 There has been a move towards an operational definition of CSE for treatment purposes as any seizure lasting longer than 5 min, which will be discussed later.4 The diagnosis of overt tonic-clonic seizures is usually straightforward. The main differential diagnoses are non-epileptic events (previously known as pseudoseizures) and other causes of abnormal movements such as acute dystonia, paroxysmal dyskinesia or involuntary movements associated with cerebral palsy. While uncommon, children with non-epileptic events can appear to be in CSE, but such children usually have a background of coexisting epilepsy (which may or may not have been recognised) or a family history of epilepsy.5 6 Therefore, in the acute situation it will usually be preferable to treat for CSE unless background information is available, although it is equally important …

Application of diffusion tensor imaging and tractography of the optic radiation in anterior temporal lobe resection for epilepsy: a systematic review.

BACKGROUND Approximately 50-100% of patients with temporal lobe epilepsy undergoing anterior temporal lobe resection (ATLR) will suffer a postoperative visual field defect (VFD) due to disruption of the optic radiation (OpR). OBJECTIVE We conducted a systematic review of the literature to examine the role of DTI and tractography in ATLR and its potential in reducing the incidence of postoperative VFD. METHODS We conducted an electronic literature search using PubMed, Embase, Web of Science and BMJ case report databases. Eligibility for study inclusion was determined on abstract screening using the following criteria: the study must have been (1) an original investigation or case report in humans; (2) investigating the OpR with DTI in cases of ATLR in temporal lobe epilepsy; (3) investigating postoperative VFD. All forms of ATLR and ways of assessing VFD were included to reflect clinical practice. RESULTS 13 studies (four case reports, eight prospective observational studies, one prospective comparative trial) were included in the review, 179 (mean±SD, 13.8±12.6; range, 1-48) subjects were investigated using DTI. The time of postoperative VFD measurement differed between the detected studies, ranging from two weeks to nine years following ATLR. A modest number of studies and insufficient statistical homogeneity precluded meta-analysis. However, DTI methods were consistently accurate at quantifying and predicting postoperative damage to the OpR. These methods revealed a correlation between the extent of OpR damage and the severity of postoperative VFD. The first and only trial with 15 subjects compared to 23 controls reported that using intraoperative tractography in ATLR significantly reduces the occurrence of postoperative VFD on comparison to conventional surgical planning. CONCLUSIONS DTI shows potential to be an effective method used in planning ATLR. Findings from a single modest sized study suggest that tractography may be employed as part of intraoperative navigation techniques in order to avoid injury to the OpR. Further research needs to be conducted to ensure the applicability and effectiveness of this technology before implementation in routine clinical practice.

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.

Quantifying the deficit—imaging neurobehavioural impairment in childhood epilepsy

BACKGROUND Neurobehavioral impairments such as learning difficulty, autism, attention deficit hyperactivity disorder (ADHD) and mood or behavioural problems are known to be increased in children with epilepsy; however, they remain under-recognised and often cause considerable morbidity. Quantitative neuroimaging techniques offer a potential avenue to improving our understanding of the underlying pathological basis for these disorders, aiding with diagnosis and risk stratification. METHODS A systematic review was undertaken for original research articles involving magnetic resonance imaging in children with epilepsy and one or more neurobehavioural impairments. Studies were reviewed with respect to patient population, methodology and magnetic resonance imaging (MRI) findings. RESULTS A total of 25 studies were identified and included in this review. The majority of studies looked at single impairments, commonly cognitive impairment or ADHD, with few studies reporting on other impairments. Reductions in cortical grey matter and disruptions of functional and structural brain networks were associated with poorer cognitive performance and disruptions of grey and white matter within a fronto-striatal-cerebellar network associated with ADHD. Insufficient studies were available to report on other impairments. CONCLUSIONS Relatively few studies exist in this field and those that do are methodologically diverse. Further investigation is required to determine if the changes reported to date are epilepsy syndrome specific or have broader applicability.

Estimating intracranial volume using intracranial area in healthy children and those with childhood status epilepticus

Correcting volumetric measurements of brain structures for intracranial volume (ICV) is important in comparing volumes across subjects with different ICV. The aim of this study was to investigate whether intracranial area (ICA) reliably predicts actual ICV in a healthy pediatric cohort and in children with convulsive status epilepticus (CSE).

Analysis of EEG networks and their correlation with cognitive impairment in preschool children with epilepsy

Objective: Cognitive impairment (CI) is common in children with epilepsy and can have devastating effects on their quality of life and that of their family. Early identification of CI is a priority to improve outcomes, but the current gold standard of detection with psychometric assessment is resource intensive and not always available. This paper proposes a novel technique of network analysis using routine clinical electroencephalography (EEG) to help identify CI in children with early-onset epilepsy (CWEOE) (0-5 y.o.). Methods: We analyzed functional networks from routinely acquired EEGs of 51 newly diagnosed CWEOE from a prospective population-based study. Combinations of connectivity metrics (e.g. phase-slope index (PSI)) with sub-network analysis (e.g. cluster-span threshold (CST)) identified significant correlations between network properties and cognition scores via rank correlation analysis with Kendall’s τ. Predictive properties were investigated using a 5-fold cross-validated K-Nearest Neighbor classification model with normal cognition, mild/moderate CI and severe CI classes. Results: Phase-dependent connectivity metrics had higher sensitivity to cognition scores, with sub-networks identifying significant functional network changes over a broad range of spectral frequencies. Approximately 70.5% of all children were appropriately classified as normal cognition, mild/moderate CI or severe CI using CST network features. CST classification predicted CI classes 55% better than chance, and reduced misclassification penalties by half. Conclusions: CI in CWEOE can be detected with sensitivity at 85% (with respect to identifying either mild/moderate or severe CI) and specificity of 84%, by EEG network analysis. Significance: This study outlines a data-driven methodology for identifying candidate biomarkers of CI in CWEOE from network features. Following additional replication, the proposed method and its use of routinely acquired EEG forms an attractive proposition for supporting clinical assessment of CI.

Cognitive impairment in early onset epilepsy is associated with reduced left thalamic volume

OBJECTIVE The objective of this study was to investigate whether reduction of thalamic volumes in children with early onset epilepsy (CWEOE) is associated with cognitive impairment. METHODS This is a nested case-control study including a prospectively recruited cohort of 76 children with newly-diagnosed early onset epilepsy (onset <5years age) and 14 healthy controls presenting to hospitals within NHS Lothian and Fife. Quantitative volumetric analysis of subcortical structures was performed using volumetric T1-weighted magnetic resonance imaging (MRI) and correlated with the results of formal neurocognitive and clinical assessment. False discovery rate was used to correct for multiple comparisons as appropriate with q<0.05 used to define statistical significance. RESULTS Age, gender, and intracranial volume (ICV)-adjusted left thalamic volumes were significantly reduced in CWEOE with cognitive impairment compared to CWEOE without impairment (5295mm3 vs 6418mm3, q=0.008) or healthy controls (5295mm3 vs 6410mm3, q<0.001). The differences in left thalamic volume remained if gray matter or cortical/cerebellar volumes were used as covariates rather than ICV (q<0.05). The degree of volume reduction correlated with the severity of cognitive impairment (q=0.048). SIGNIFICANCE Reduced left thalamic volume may be a biomarker for cognitive impairment in CWEOE and could help inform the need for further formal cognitive evaluations and interventions.