•Reliability of the photic stimulation procedure is heavily influenced by methodological aspects such as the type of stimulator/lamp used.•Normative data has traditionally been collected using a ...family of xenon lamp photic stimulator produced by Grass instruments which are no longer available.•This is the first study to compare the efficacy of LED vs Xenon-lamp stimulators in detecting photoparoxysmal responses photosensitive patients.•Two of the most widely available LED stimulators (Lifeline and FSA10) have equivalent efficacy to the Grass PS 33 stimulator.•This is important for clinical studies that use the standardised photosensitivity range as proxy measure of efficacy of antiepileptic drugs.
The assessment of the effect of photic stimulation is an integral component of an EEG exam and is especially important in patients referred for ascertained or suspected photosensitivity with or without a diagnosis of epilepsy. A positive test result relies on eliciting a specific abnormality defined as the “photoparoxysmal response”. Reliability of this assessment is strongly influenced by technical and procedural variables, a critical one represented by the physical properties of the stimulators used. Established clinical norms are based on data acquired with the “gold-standard” Grass PS stimulators. These are no longer commercially available and have been replaced by stimulators using light emitting diode (LED) technology. To our knowledge no comparative study on their efficacy has been conducted. To address this gap, we recruited 39 patients aged 5–54 years, referred to two specialized centers with confirmed of suspected diagnosis of photosensitive epilepsy or generalized epilepsy with photosensitivity in a prospective randomized single-blind cross-over study to compare two commercially available LED-bases stimulation systems (FSA 10® and Lifeline® stimulators) against the Grass PS 33 xenon lamp device. Our findings indicate that the LED systems tested are equivalent to the Grass stimulator both in identifying the PPR in affected individuals.
Eyelid myoclonia (EM) with absences (EMA) is a generalized epilepsy syndrome with a prognosis and clinical characteristics that are still partially undefined. We investigated electroclinical ...endophenotypes and long-term seizure outcome in a large cohort of patients with EMA.
In this multicenter retrospective study, patients with EMA with ≥5 years of follow-up were included. We investigated prognostic patterns and sustained terminal remission (STR), along with their prognostic factors. Moreover, a 2-step cluster analysis was used to investigate the presence of distinct EMA endophenotypes.
We included 172 patients with a median age at onset of 7 years (interquartile range IQR 5-10 years) and a median follow-up duration of 14 years (IQR 8.25-23.75 years). Sixty-six patients (38.4%) displayed a nonremission pattern, whereas remission and relapse patterns were encountered in 56 (32.6%) and 50 (29.1%) participants. Early epilepsy onset, history of febrile seizures (FS), and EM status epilepticus significantly predicted a nonremission pattern according to multinomial logistic regression analysis. STR was achieved by 68 (39.5%) patients with a mean latency of 14.05 years (SD ±12.47 years). Early epilepsy onset, psychiatric comorbid conditions, and a history of FS and generalized tonic-clonic seizures were associated with a lower probability of achieving STR according to a Cox regression proportional hazards model. Antiseizure medication (ASM) withdrawal was attempted in 62 of 172 patients, and seizures recurred in 74.2%. Cluster analysis revealed 2 distinct clusters with 86 patients each. Cluster 2, which we defined as EMA-plus, was characterized by an earlier age at epilepsy onset, higher rate of intellectual disability, EM status epilepticus, generalized paroxysmal fast activity, self-induced seizures, FS, and poor ASM response, whereas cluster 1, the EMA-only cluster, was characterized by a higher rate of seizure remission and more favorable neuropsychiatric outcome.
Early epilepsy onset was the most relevant prognostic factor for poor treatment response. A long latency between epilepsy onset and ASM response was observed, suggesting the effect of age-related brain changes in EMA remission. Last, our cluster analysis showed a clear-cut distinction of patients with EMA into an EMA-plus insidious subphenotype and an EMA-only benign cluster that strongly differed in terms of remission rates and cognitive outcomes.
Purpose: This study was designed to assess whether sleep disturbance is more frequent among patients with partial seizures and what impact on quality of life (QoL) sleep disturbance may have on ...patients with partial seizures.
Methods: Questionnaire booklets were mailed to 1,183 patients from four Dutch clinics. Each patient was asked to find two age‐ and gender‐matched controls to complete the same set of questionnaires Sleep Diagnosis List (SDL), Medical Outcomes Study (MOS)‐Sleep Scale, Groningen Sleep Questionnaire, Epworth Sleepiness Scale, and the SF‐36 Health Survey. The prevalence of sleep disturbance, based on the SDL, was compared between those with partial epilepsy and controls. Mean scores on sleep and the SF‐36 Physical (PCS) and Mental (MCS) Component Summary scales were compared.
Results: Responses from 486 patients and 492 controls were analyzed. Respondents with partial epilepsy had a highly significant, twofold higher prevalence of sleep disturbance compared with controls (38.6 vs. 18.0%; p < 0.0001). Most sleep‐disorder subscales showed significant abnormalities in respondents with epilepsy, compared with controls. Mean SF‐36 MCS and PCS scores were significantly lower in respondents with epilepsy compared with controls in both the strata with sleep disturbance and without (all p values <0.05). The presence of a sleep disturbance in respondents with epilepsy was associated with the greatest impairment in QoL.
Conclusions: Sleep disturbance is more than twice as prevalent in persons with partial epilepsy compared with controls, and most domains of sleep are significantly disturbed. Persons with partial epilepsy have significant QoL impairment, and sleep disturbance further compounds this.
Summary
We report the history of a 14‐year‐old girl with atypical childhood occipital epilepsy “Gastaut type” whose first generalized tonic–clonic seizure was preceded by migraine without aura and ...followed by a status migrainosus. This status lasted for 3 days despite standard analgesic therapy. An EEG recording revealed an occipital status epilepticus during her migraine complaints. Seven minutes after intravenous administration of 10 mg diazepam under continuous EEG recording, a suppression of the epileptiform discharges over the right occipital was seen, while the headache subsided 3 min later. After precise questioning about the circumstances that possibly could have led to these events, it appeared that she had played for hours with a play station on the new color TV and she had visited an exhibition of Matisse and Bonnard with bright colors and contrast‐rich text. Standardized extensive intermittent photic stimulation (IPS), 2 days after the status migrainosus, evoked besides asymmetrical right‐sided driving, green spots in her left visual field, while in the EEG sharp waves were recorded over the right parietotemporal region. After further IPS with 20 Hz (eye closure), she started complaining of a light pulsating headache right occipitally and in the EEG right parietotemporal sharp‐waves were seen. This lasted for about 10 min. Later, an interictal routine EEG was normal except for some theta over the right temporooccipital area. The most likely diagnosis is an atypical form of occipital epilepsy “Gastaut type.” We would therefore advocate recording EEGs with photic stimulation in patients with atypical migraneous features.
Epilepsy with eyelid myoclonia (EEM) is a generalized epilepsy syndrome with childhood-onset and 2:1 female predominance that consists of: 1. eyelid myoclonia with or without absence seizures, 2. eye ...closure induced seizures or EEG paroxysms, 3. clinical or EEG photosensitivity. While eyelid myoclonia is the disease hallmark, other seizure types, including absence seizures and generalized tonic-clonic seizures, may be present. It is thought to have a genetic etiology, and around one-third of patients may have a positive family history of epilepsy. Recently, specific genetic mutations have been recognized in a minority patients, including in SYNGAP1, NEXMIF, RORB, and CHD2 genes. There are no randomized controlled trials in EEM, and the management literature is largely restricted to small retrospective studies. Broad-spectrum antiseizure medications such as valproate, levetiracetam, lamotrigine, and benzodiazepines are typically used. Seizures typically persist into adulthood, and drug-resistant epilepsy is reported in over 50%.
•Epilepsy with eyelid myoclonia is an under-recognized generalized epilepsy syndrome.•Eyelid myoclonia are frequent and may occur multiple times a day.•Specific genetic mutations have been found in some patients.•There is limited data about treatment, and drug-resistant epilepsy is common.
Although headache and epilepsy have often been associated, the precise electroclinical and pathophysiological interaction between these disorders and in particular its relations with photosensitivity ...is as yet to be fully understood in adults or children. The association between headache and epilepsy commonly occurs in all types of epilepsy and not only in occipital epilepsy. Generally, peri-ictal headache is often neglected, regardless of its severity, because patients are more concerned about their seizures. Altered cerebral cortex excitability may be the link between these two conditions and photosensitivity shows this. The physician should bear this association in mind when dealing with epileptic and migraine patients so as to be able to offer such patients an accurate diagnosis and appropriate treatment; this should be borne in mind when declaring epileptic patients ‘seizure free’. To date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may, on occasion, be the sole ictal epileptic manifestation. Lastly, studies designed to investigate the triggering role of photosensitivity in both headache and epilepsy are warranted.
Highlights • The clinical use is of benzodiazepines (BZDs) is limited due to adverse effects • Partial or subtype selective agonists at the BZD receptor may have advantages • One of these compounds, ...abecarnil, exerts anxiolytic activity in patients • Here, we compared abecarnil and flumazenil in patients with photosensitive epilepsy • Abecarnil was antiepileptic and significantly differed from both placebo and flumazenil
Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to ...investigate the burden of rare genetic variants in genetic generalised epilepsy.
For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes.
Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio OR 2·40 95% CI 1·41–4·10; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 95% CI 1·05–2·03; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABAA receptor genes in cases compared with controls (OR 1·46 95% CI 1·02–2·08; pNonsyn=0·013, adjusted pNonsyn=0·027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors.
Functionally relevant variants in genes encoding GABAA receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy.
EuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund).
Photoparoxysmal response (PPR) is an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. It is an epilepsy-related electroencephalographic trait with high ...prevalence in idiopathic epilepsies, especially in common idiopathic generalized epilepsies (IGEs), such as childhood absence epilepsy and juvenile myoclonic epilepsy. This degree of co-morbidity suggests that PPR may be involved in the predisposition to IGE. The identification of genes for PPR would, therefore, aid the dissection of the genetic basis of IGE. Sixteen PPR-multiplex families were collected to conduct a genome-wide linkage scan using broad (all PPR types) and narrow (exclusion of PPR types I and II and the occipital epilepsy cases) models of affectedness for PPR. We found an empirical genome-wide significance for parametric (HLOD) and non-parametric (NPL) linkage (Pgw(HLOD)=0.004 and Pgw(NPL)=0.01) for two respective chromosomal regions, 7q32 at D7S1804 (HLOD=3.47 with α=1, PNPL=3.39×10−5) and 16p13 at D16S3395 (HLOD=2.44 with α=1, PNPL=7.91×10−5). These two genomic regions contain genes that are important for the neuromodulation of cortical dynamics and may represent good targets for candidate-gene studies. Our study identified two susceptibility loci for PPR, which may be related to the underlying myoclonic epilepsy phenotype present in the families studied.
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