Sudden unexplained death in childhood: A comparison of cases with and without a febrile seizure history
We considered whether a subset of children with sudden unexplained death in childhood (SUDC) and a history of febrile seizures (FS) may parallel those in sudden unexpected death in epilepsy (SUDEP). The prevalence of a history of FS was examined, and factors that may distinguish SUDC cases with and without FS were described.Methods
Characteristics were assessed in 123 consecutive children with SUDC reported to the SUDC program (4/1/11-3/31/14) by their parents. Parental interview covered the decedent's medical history, circumstances of death, environmental factors, cause of death, and family medical history. Features of SUDC cases were compared by FS history.Results
Overall, 31.7% of SUDC cases had a history of FS, among which 74.4% had simple FS. Compared to those without a history of FS, a history of FS was associated with a greater median age at death (p = 0.03) and death during the weekdays (p = 0.02). Terminal fever was similar in those with and without FS. The median time from FS to death was 6.0 months (interquartile range [IQR] 3.0–10.0). In all SUDC cases, prone position at death, death during sleep, and unwitnessed deaths predominated.Significance
There are parallels among SUDC, sudden infant deaths, and sudden unexpected death in epilepsy (SUDEP) with regard to prone position, unwitnessed deaths mostly during sleep, and male predominance. In children with SUDC and a history of FS, terminal fever may increase the risk for an unwitnessed terminal seizure. The greater than expected prevalence of a FS history and the proportion with terminal fever or illness in this cohort suggests that some SUDC deaths may be seizure related and therefore have potential commonalities with SUDEP.
Epilepsy and hippocampal neurodegeneration induced by glutamate decarboxylase inhibitors in awake rats
Fycompa (perampanel) receives European MA for PGTC seizures in patients with idiopathic generalised epilepsy
Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug–drug interaction, which we evaluate in this article.Methods
Thirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N-desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored.Results
We report elevated CLB and nCLB levels in these subjects. The mean (± standard deviation [SD]) increase in CLB levels was 60 ± 80% (95% confidence interval (CI) [−2–91%] at 4 weeks); the mean increase in nCLB levels was 500 ± 300% (95% CI [+90–610%] at 4 weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction.Significance
Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.
ASSESSING LONG-TERM EFFECTS OF ESLICARBAZEPINE ACETATE ON LIPID METABOLISM PROFILE, SODIUM VALUES AND LIVER FUNCTION TESTS
Functional MRI of Neuronal Activation in Epilepsy Patients with Malformations of Cortical Development
Seizure Semiology in Males with Psychogenic Nonepileptic Seizures is Associated with Somatic Complaints
X-linked focal epilepsy with reflex bathing seizures: Characterization of a distinct epileptic syndrome
We recently reported a Q555X mutation of synapsin 1 (SYN1) on chromosome Xp11-q21 in a family segregating partial epilepsy and autistic spectrum disorder. Herein, we provide a detailed description of the epileptic syndrome in the original family.Methods
A total of 34 members from a large French-Canadian family were evaluated. Family members with seizures or epilepsy underwent (when possible) clinical, neuropsychological, electrophysiologic, and neuroimaging assessments.Results
Epilepsy was diagnosed in 10 family members (4 deceased, 6 living). In addition to occasional spontaneous complex partial seizures, seven family members clearly had reflex seizures triggered by bathing or showering. Hippocampal atrophy was found in two of five epileptic family members family members who underwent magnetic resonance (MR) imaging. Video–electroencephalography (EEG) recordings of three triggered seizures in two affected members showed rhythmic theta activity over temporal head regions. Ictal single-photon emission computed tomography (SPECT) showed temporoinsular perfusion changes. Detailed neuropsychological assessments revealed that SYN1 Q555X male mutation carriers showed specific language impairment and mild autistic spectrum disorder. Female carriers also exhibited reading impairments and febrile seizures but no chronic epilepsy.Significance
Available evidence suggests that impaired SYN1 function is associated with hyperexcitability of the temporoinsular network and disturbance of high mental functions such as language and social interaction. The presence of reflex bathing seizures, a most peculiar clinical feature, could be helpful in identifying other patients with this syndrome.
Temporal and extratemporal white matter abnormalities have been identified frequently in patients with refractory mesial temporal lobe epilepsy (rMTLE). However, the identification of potential water diffusion abnormalities in patients with drug-responsive, benign MTLE (bMTLE) is still missing. The aim of this study was to identify markers of refractoriness in MTLE.Methods
The study group included 48 patients with bMTLE (mean age 42.8 + 13.5 years), 38 with rMTLE (mean age 41.7 + 14.1 years) and 54 healthy volunteers. Diffusion tensor imaging (DTI) was performed to measure mean diffusivity (MD) and fractional anisotropy (FA) in a regions-of-interest analysis comprising hippocampi and temporal lobe gray and white matter regions. The presence of hippocampal sclerosis (Hs) was assessed using automated magnetic resonance imaging (MRI) evaluation. For statistics we used chi-square test; two-tailed, two-sample t-test; and stratified linear regression.Results
The significant demographic differences between the two patient groups were sex (p = 0.003), duration of epilepsy (p = 0.003) and complex febrile convulsions (p = 0.0001). In rMTLE, temporal white matter MD was higher and FA lower, as compared to bMTLE. The analysis of diagnostic accuracy (area under the receiver operator characteristic [ROC] curve [AUC]) showed that FA had an AUC for discriminating patients affected from those unaffected by refractory MTLE of 74.0% (p < 0.001), a value that was higher than that of temporal MD (64.0%), hippocampus volume (65.0%), and Hs (66.0%).Significance
We performed DTI measurements in MTLE and found a significant reduction of FA along the white matter of the temporal lobes in rMTLE, suggesting it as a valuable measure of refractoriness in MTLE.
Response to “Association of IDH1/2 mutation with preoperative seizure in low-grade gliomas: how strong is the evidence?”
Alterations in γ-aminobutyric acid (GABA)-ergic cortical neurons have been reported in focal cortical dysplasia (FCD)Ia/IIIa, a malformation of cortical development associated with drug-resistant epilepsy. We compared numbers of neurons containing calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR) and densities of respective fibers in lateral temporal lobe surgical specimens of 17 patients with FCD with 19 patients who underwent anterior temporal lobe resection due to nonlesional temporal lobe epilepsy (non-FCD) as well as with 7 postmortem controls.Methods
PV-, CB-, and CR-immunoreactive (IR) neurons were quantitatively investigated with use of two-dimensional cell counting and densitometry (reflecting mainly IR fibers) in cortical layers II, IV, and V.Results
Numbers of PV-IR neurons, ratios of PV-containing to Nissl-stained neurons (correcting for eventual cell loss), and densities of PV-IR were higher in layer II of the cortex of FCD compared to non-FCD patients. Similarly, densities of CB-IR and CR-IR were also higher in layers II and V, respectively, of FCD than of non-FCD patients. Comparison with postmortem controls revealed significant higher cell numbers and fiber labeling for all three calcium-binding proteins in FCD cortex, whereas numbers of Nissl-stained neurons did not vary between FCD, non-FCD, and postmortem controls. In non-FCD versus postmortem controls, ratios of calcium-binding protein-IR cells to Nissl-stained neurons were unchanged in most instances except for increased CB/Nissl ratios and CB-IR densities in all cortical layers.Significance
Increased numbers of PV neurons and fiber labeling in FCD compared to nondysplastic epileptic temporal neocortex and postmortem controls may be related to cortical malformation, whereas an increased number of CB-IR neurons and fiber labeling both in FCD and non-FCD specimens compared with postmortem controls may be associated with ongoing seizure activity. The observed changes may represent increased expression of calcium-binding proteins and thus compensatory mechanisms for seizures and neuronal loss in drug-resistant epilepsy.