ResearchPad - full‐length-original-research https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Visual seizure annotation and automated seizure detection using behind‐the‐ear electroencephalographic channels]]> https://www.researchpad.co/article/elastic_article_7022 Seizure diaries kept by patients are unreliable. Automated electroencephalography (EEG)‐based seizure detection systems are a useful support tool to objectively detect and register seizures during long‐term video‐EEG recording. However, this standard full scalp‐EEG recording setup is of limited use outside the hospital, and a discreet, wearable device is needed for capturing seizures in the home setting. We are developing a wearable device that records EEG with behind‐the‐ear electrodes. In this study, we determined whether the recognition of ictal patterns using only behind‐the‐ear EEG channels is possible. Second, an automated seizure detection algorithm was developed using only those behind‐the‐ear EEG channels.MethodsFifty‐four patients with a total of 182 seizures, mostly temporal lobe epilepsy (TLE), and 5284 hours of data, were recorded with a standard video‐EEG at University Hospital Leuven. In addition, extra behind‐the‐ear EEG channels were recorded. First, a neurologist was asked to annotate behind‐the‐ear EEG segments containing selected seizure and nonseizure fragments. Second, a data‐driven algorithm was developed using only behind‐the‐ear EEG. This algorithm was trained using data from other patients (patient‐independent model) or from the same patient (patient‐specific model).ResultsThe visual recognition study resulted in 65.7% sensitivity and 94.4% specificity. By using those seizure annotations, the automated algorithm obtained 64.1% sensitivity and 2.8 false‐positive detections (FPs)/24 hours with the patient‐independent model. The patient‐specific model achieved 69.1% sensitivity and 0.49 FPs/24 hours.SignificanceVisual recognition of ictal EEG patterns using only behind‐the‐ear EEG is possible in a significant number of patients with TLE. A patient‐specific seizure detection algorithm using only behind‐the‐ear EEG was able to detect more seizures automatically than what patients typically report, with 0.49 FPs/24 hours. We conclude that a large number of refractory TLE patients can benefit from using this device. ]]> <![CDATA[Understanding the challenge of comparative effectiveness research in focal epilepsy: A review of network meta‐analyses and real‐world evidence on antiepileptic drugs]]> https://www.researchpad.co/article/elastic_article_6899 Head‐to‐head randomized controlled trials (RCTs) are the gold standard for assessing comparative treatment effects. In the absence of direct comparisons between all possible antiepileptic drugs (AEDs), however, clinical decision‐making in focal (partial onset) epilepsy relies on alternative evidence borne from indirect comparisons including network meta‐analyses (NMAs) and from real‐world evidence (RWE) studies. We review NMAs and observational RWE studies comparing AEDs in the adjunctive setting to compare the robustness of these methods and to formulate recommendations for future evidence development.MethodsA literature review identified NMAs and RWE studies comparing AEDs for the adjunctive treatment of focal seizures published between January 2008 and October 2018. NMAs were evaluated for robustness using a framework based on guidelines from the National Institute for Health and Care Excellence Decision Support Unit and the International Society for Pharmacoeconomics and Outcomes Research. RWE studies were evaluated using the GRACE checklist.ResultsFrom a total of 1993 records, 11 NMAs and six RWE studies were eligible. Key limitations identified in the NMAs include nonsystematic selection of RCTs, unexplored heterogeneity between included RCTs in terms of study and patient characteristics, and selection of AEDs and AED doses or dosing strategies that are not reflective of clinical practice. The main limitations of RWE studies concern sample size, design, and analysis methods. Approximately 90% of comparisons between individual AEDs were nonsignificant in the NMAs. None of the RWE studies adjusted for baseline differences between comparator groups; therefore, they lack the validity to make comparative conclusions.SignificanceCurrent NMAs and RWE studies provide only nominal comparative evidence for AED treatments in focal epilepsy, and should be used with caution for decision‐making due to their methodological limitations. To overcome these hurdles, adherence to methodological guidelines and concerted efforts to collect relevant outcome data in the real world are needed. ]]> <![CDATA[A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects]]> https://www.researchpad.co/article/N990a4937-bf9e-488d-8e8b-809b74fcff65

Abstract

Objective

The pharmacokinetics (PK) and safety of single oral 750‐mg doses of a plant‐derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the USA and Epidyolex in Europe; 100‐mg/mL oral solution) were assessed in healthy adults following a high‐fat/calorie meal (n = 15), a low‐fat/calorie meal (n = 14), whole milk (n = 15), or alcohol (n = 14), relative to the fasted state (n = 29).

Methods

Blood samples were collected until 96 hours postdose in each period and evaluated by liquid chromatography and tandem mass spectrometry. PK parameters (maximum observed plasma concentration [Cmax], area under the plasma concentration‐time curve from time zero to the last observed quantifiable concentration, area under the concentration‐time curve from time zero to infinity [AUC0‐∞], and time to maximum plasma concentration [tmax]) of CBD and its major metabolites were derived using noncompartmental analysis.

Results

CBD exposure increased by 3.8‐fold for AUC0‐∞ and 5.2‐fold for Cmax when CBD was administered with a high‐fat/calorie meal versus fasted. To a lesser extent, a low‐fat/calorie meal enhanced CBD exposure versus fasted with a 2.7‐fold increase in AUC0‐∞ and a 3.8‐fold increase in Cmax. Similarly, when dosed with whole milk, CBD exposure increased versus fasted by 2.4‐fold for AUC0‐∞ and 3.1‐fold for Cmax. Modest elevations in CBD exposure occurred when it was dosed with alcohol: 1.6‐fold for AUC0‐∞ and 1.9‐fold for Cmax. No clinically relevant effect of any test condition on CBD tmax or t½ versus the fasted state was apparent. The same trend was seen for the CBD metabolites, except that 7‐carboxy‐cannabidiol tmax was considerably longer when CBD was administered with alcohol (14 vs 4 hours fasted). Inter‐ and intrasubject variability in PK parameters was moderate to high during the trial.

Significance

CBD and metabolite exposures were most affected by a high‐fat/calorie meal. CBD exposures also increased with a low‐fat/calorie meal, whole milk, or alcohol, but to a lesser extent. CBD was tolerated, and there were no severe or serious adverse events during the trial.

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<![CDATA[Early detection rate changes from a brain‐responsive neurostimulation system predict efficacy of newly added antiseizure drugs]]> https://www.researchpad.co/article/N6501b2ae-81e2-4dc1-aa4c-e0a11255b304

Abstract

Objective

Brain‐responsive neurostimulation (RNS System, NeuroPace) is used to treat medically refractory focal epilepsy and also provides long‐term ambulatory neurophysiologic data. We sought to determine whether these data could predict the clinical response to antiseizure drugs (ASDs).

Methods

First, newly added medications were identified in RNS System patients followed at a single epilepsy center. Daily detection rates including “episode starts” (predominantly interictal activity) and “long episodes” (often electrographic seizures) were compared before and after ASD initiation. Efficacy was determined from documentation of clinical improvement and medication retention. Next, the analysis was repeated on an independent sample of patients from a multicenter long‐term treatment trial, using an efficacy measure of ≥50% reduction in diary‐recorded seizure frequency after 3 months.

Results

In the single center cohort, long episodes, but not episode starts, had a significantly greater reduction in the first week for clinically efficacious compared to inefficacious medications. In this cohort, having no long episodes in the first week was highly predictive of ASD efficacy. In the multicenter cohort, both long episodes and episode starts had a significantly greater reduction for effective medications starting in the first 1‐2 weeks. In this larger dataset, a ≥50% decrease in episode starts was 90% specific for efficacy with a positive predictive value (PPV) of 67%, and a ≥84% decrease in long episodes was 80% specific with a PPV of 48%. Conversely, a <25% decrease in long episodes (including any increase) or a <20% decrease in episode starts had a predictive value for inefficacy of >80%.

Significance

In RNS System patients with stable detection settings, when new ASDs are started, detection rates within the first 1‐2 weeks may provide an early, objective indication of efficacy. These data could be used to identify responses to medication trials early to allow more rapid medication adjustments than conventionally possible.

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<![CDATA[Long‐term safety and efficacy of lacosamide and controlled‐release carbamazepine monotherapy in patients with newly diagnosed epilepsy]]> https://www.researchpad.co/article/Nd510e437-be6d-4087-802e-8f72c3ff91c6

Abstract

Objective

A large‐scale, double‐blind trial (SP0993; NCT01243177) demonstrated that lacosamide was noninferior to controlled‐release carbamazepine (carbamazepine‐CR) in terms of efficacy, and well tolerated as first‐line monotherapy in patients (≥16 years of age) with newly diagnosed epilepsy. We report primary safety outcomes from the double‐blind extension of the noninferiority trial (SP0994; NCT01465997) and post hoc analyses of pooled long‐term safety and efficacy data from both trials.

Methods

Patients were randomized 1:1 to lacosamide or carbamazepine‐CR. Doses were escalated (lacosamide: 200/400/600 mg/d; carbamazepine‐CR: 400/800/1200 mg/d) based on seizure control. Eligible patients continued randomized treatment in the extension. Primary outcomes of the extension were treatment‐emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Post hoc analyses of data from combined trials included 12‐ and 24‐month seizure freedom and TEAEs by number of comorbid conditions.

Results

A total of 886 patients were treated in the initial trial and 548 in the extension; 211 of 279 patients (75.6%) on lacosamide and 180/269 (66.9%) on carbamazepine‐CR completed the extension. In the extension, 181 patients (64.9%) on lacosamide and 182 (67.7%) on carbamazepine‐CR reported TEAEs; in both groups, nasopharyngitis, headache, and dizziness were most common. Serious TEAEs were reported by 32 patients (11.5%) on lacosamide and 22 (8.2%) on carbamazepine‐CR; 12 (4.3%) and 21 (7.8%) discontinued due to TEAEs. In the combined trials (median exposure: lacosamide 630 days; carbamazepine‐CR 589 days), Kaplan‐Meier estimated proportions of patients with 12‐ and 24‐month seizure freedom from first dose were 50.8% (95% confidence interval 46.2%‐55.4%) and 47.0% (42.2%‐51.7%) on lacosamide, and 54.9% (50.3%‐59.6%) and 50.9% (46.0%‐55.7%) on carbamazepine‐CR. Incidences of drug‐related TEAEs and discontinuations due to TEAEs increased by number of comorbid conditions and were lower in patients on lacosamide.

Significance

Long‐term (median ~2 years) lacosamide monotherapy was efficacious and generally well tolerated in adults with newly diagnosed epilepsy. Seizure freedom rates were similar with lacosamide and carbamazepine‐CR.

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<![CDATA[Estimating the period prevalence of non‐convulsive status epilepticus among comatose adults at the University Teaching Hospital in Lusaka, Zambia]]> https://www.researchpad.co/article/Nd934dc5c-7fc0-4168-a1db-f90be64684a2

Abstract

Objective

In Western settings, non‐convulsive status epilepticus (NCSE) and non‐convulsive seizures (NCSz) are associated with high mortality. In comatose patients, interictal epileptiform discharges (IEDs) identified on routine electroencephalogram (EEG) are predictive of NCSE/NCS. Little is known regarding the prevalence, causes, or outcomes of NCSE/NCSz in sub‐Saharan Africa (SSA). We sought to investigate the prevalence of IEDs and NCSE/NCSz at a single teaching institution in SSA.

Methods

From October 3, 2017, to May 21, 2018, adult inpatients on the internal medicine service at Zambia's University Teaching Hospital (UTH) with a Glasgow Coma Score (GCS) of ≤10 were identified, excluding patients with mechanical ventilation or open head wounds. Signed consent by a proxy was required for enrollment and 30‐minute EEG. Chart abstractions provided coma duration, presence/absence of clinical seizures during/prior to admission, history of epilepsy, and presumed coma etiology. A structured neurological examination was completed. Patients were followed to discharge or death. Risk factors for IEDs were evaluated.

Results

Of 392 eligible patients, 250 had EEGs. EEGs were not completed on eligible patients due to death (74), improved GCS (37), transfer within UTH (25), or lack of proxy (6). NCSE occurred in 22 of 250 (8.8%), NCSz in 3 of 250 (1.2%), and IEDs in 46 of 250 (18.4%) patients. Of the 250, 197 (78.8%) died. No specific risk factors for IEDs were identified.

Significance

If the association between IEDs and NCSE among monitored populations in developed settings holds true for SSA, a projected 17%‐21% of comatose African adults have NCSE. No clinical characteristics identified those at risk.

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<![CDATA[Regional hippocampal diffusion abnormalities associated with subfield‐specific pathology in temporal lobe epilepsy]]> https://www.researchpad.co/article/N742c94b9-6993-4633-8f50-0d827ac20937

Abstract

Objective

Hippocampal sclerosis (HS) is the most common pathology and best predictor of surgical outcome for medically refractory patients with temporal lobe epilepsy (TLE). Current clinical MRI methods can detect HS, but subfield pathology is poorly characterized, limiting accurate prediction of seizure‐free outcomes after surgery. Diffusion tensor imaging (DTI) can probe regional microstructural changes associated with focal hippocampal pathology, but is typically limited by low‐resolution whole‐brain acquisitions.

Methods

High‐resolution (1 × 1 × 1 mm3) DTI, T1, and quantitative T2 of the hippocampus was acquired in 18 preoperative TLE patients and 19 healthy controls. Diffusion images were qualitatively assessed for loss of internal architecture, and whole‐hippocampus diffusion, volume, and quantitative T2 were compared across groups. Regional hippocampal diffusion abnormalities were examined in all subjects and compared to histology in four subjects who underwent anterior temporal lobectomy.

Results

High‐resolution mean diffusion‐weighted images enabled visualization of internal hippocampal architecture, used to visually identify HS with 86% specificity and 93% sensitivity. Mean diffusivity (MD) elevations were regionally heterogenous within the hippocampus and varied across TLE patients. The spatial location of diffusion abnormalities corresponded with the location of focal subfield neuron loss, gliosis, and reduced myelin staining abnormalities identified with postsurgical histology in four subjects who underwent anterior temporal lobectomy. Whole‐hippocampus MD and T2 relaxation times were higher, and fractional anisotropy (FA) and volumes were lower in TLE patients relative to controls. Left hippocampus MD correlated with verbal memory in the TLE group.

Significance

Visualization of internal architecture and focal diffusion abnormalities on high‐resolution diffusion imaging suggests potential clinical utility of diffusion imaging in TLE and may have significant implications for surgical planning and prediction of seizure‐free outcomes in individual patients.

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<![CDATA[Genomic and clinical predictors of lacosamide response in refractory epilepsies]]> https://www.researchpad.co/article/N7fc73c40-bce5-4352-9864-dc8e56d936fe

Abstract

Objective

Clinical and genetic predictors of response to antiepileptic drugs (AEDs) are largely unknown. We examined predictors of lacosamide response in a real‐world clinical setting.

Methods

We tested the association of clinical predictors with treatment response using regression modeling in a cohort of people with refractory epilepsy. Genetic assessment for lacosamide response was conducted via genome‐wide association studies and exome studies, comprising 281 candidate genes.

Results

Most patients (479/483) were treated with LCM in addition to other AEDs. Our results corroborate previous findings that patients with refractory genetic generalized epilepsy (GGE) may respond to treatment with LCM. No clear clinical predictors were identified. We then compared 73 lacosamide responders, defined as those experiencing greater than 75% seizure reduction or seizure freedom, to 495 nonresponders (<25% seizure reduction). No variants reached the genome‐wide significance threshold in our case‐control analysis.

Significance

No genetic predictor of lacosamide response was identified. Patients with refractory GGE might benefit from treatment with lacosamide.

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<![CDATA[Epilepsy, impaired functioning, and quality of life in patients with tuberous sclerosis complex]]> https://www.researchpad.co/article/Naca37543-de8c-4523-844d-b756ed98f7dd

Abstract

Objective

To estimate health‐related quality of life (HRQoL) in patients with tuberous sclerosis complex (TSC) and associated manifestations and to identify potential factors associated with HRQoL in this population of patients.

Methods

We performed a retrospective chart review of adults with TSC who attended the outpatient clinic of the University Medical Center Utrecht in the Netherlands from 1990 to 2015 (N = 363; on average 33.6 years of follow‐up). HRQoL data were assessed in 2012 using the Health Utility Index version 3 (HUI‐3) questionnaire completed by patients or caregivers (N = 214 with HUI score and ≥1 TSC manifestation, including renal angiomyolipomas [rAMLs], subependymal giant cell astrocytoma [SEGA], or epilepsy).

Results

Of 214 patients in the study sample, 171 had TSC‐associated epilepsy (with or without rAML/SEGA), 37 had TSC and rAML (without epilepsy or SEGA), and 6 had other combinations of manifestations. The median HUI score for the 214 patients with ≥1 TSC manifestation was 0.51 (−0.371 to 1 scale, 1 = perfect health, 0 = death, <0 = worse than death). Among all components used to build the overall HUI score, the cognition component had the lowest score (mean = 0.47; 0‐1 scale). Patients with TSC‐epilepsy had significantly lower overall HUI than patients with TSC and rAML only (median HUI = 0.31 vs 0.95, P < .05), especially those who were in refractory state for prolonged periods of time (median HUI = −0.11 among patients with seizures during the entire duration of their follow‐up time). In multivariate analyses, severe impairment of daily functioning was the strongest predictor of HRQoL decrement (adjusted HUI difference between patients with severe vs. no impairment = −0.55, P < .05).

Significance

This study showed that TSC‐related epilepsy is associated with lower HUI, especially for patients who have refractory seizures for prolonged periods of time. Early and effective interventions to control or reduce seizures and preserve patients’ cognitive functions may help to improve patients’ quality of life.

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<![CDATA[Acute metabolic effects of tonic‐clonic seizures]]> https://www.researchpad.co/article/N051e77a3-e07a-44f5-886d-c1b6d947f4a5

Abstract

Objective

Tonic‐clonic seizures (TCS) lead to metabolic stress and changes in related blood markers. Such markers may indicate harmful conditions but can also help to identify TCS as a cause of transient loss of consciousness. In this study, we hypothesized that the alterations of circulating markers of metabolic stress depend on the clinical features of TCS.

Methods

Ninety‐one adults undergoing video‐EEG monitoring participated in this prospective study. Electrolytes, renal parameters, creatine kinase (CK), prolactin (PRL), lactate, ammonia, glucose, and other parameters were measured at inclusion and different time points after TCS.

Results

A total of 39 TCS were recorded in 32 patients (six generalized onset tonic‐clonic seizures in 6 and 33 focal to bilateral tonic‐clonic seizures in 26 patients). Shortly after TCS, mean lactate, ammonia, and PRL levels were significantly increased 8.7‐fold, 2.6‐fold, and 5.1‐fold, respectively, with levels of more than twofold above the upper limits of the normal (ULN) in 90%, 71%, and 70% of the TCS and returned to baseline levels within 2 hours. Only postictal lactate levels were significantly correlated with the total duration of the tonic‐clonic phase. In contrast, CK elevations above the ULN were found in three TCS (~10%) only with a peak after 48 hours. Immediately after the TCS, hyperphosphatemia occurred in one third of the patients, whereas hypophosphatemia was observed in one third 2 hours later. TCS led to subtle but significant alterations of other electrolytes, creatinine, and uric acid, whereas glucose levels were moderately increased.

Significance

Lactate is a robust metabolic marker of TCS with elevations found in ~90% of cases within 30 minutes after seizure termination, whereas ammonia rises in ~ 70%, similarly to PRL. Phosphate levels show an early increase and a decrease 2 hours after TCS in a third of patients. CK elevations are rare after video‐EEG‐documented TCS, challenging its value as a diagnostic marker.

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<![CDATA[Headache in epilepsy: A prospective observational study]]> https://www.researchpad.co/article/N29b5e1e9-7bf3-496e-9731-ad8c0867b2aa

Abstract

Objective

To assess the frequency and characteristics of interictal and postictal headaches (using International Classification of Headache Disorders, 3rd edition criteria) in a population of patients with epilepsy admitted to the Mayo Clinic Rochester epilepsy monitoring unit and assess their localizing value.

Methods

This was a cross‐sectional study. Participants were voluntarily recruited upon admission to the epilepsy monitoring unit. Two separate questionnaires were then administered. The first was to assess the presence and character of headaches experienced in the past 12 months. The second was to assess characteristics of postictal headaches experienced during their admission including localization.

Results

One‐hundred and twenty subjects (77%) met inclusion criteria and completed the initial questionnaire. Mean age was 38.1 years (range 18‐82), and 67 (55.8%) were female. Interictal headaches were reported in 97 of 120 (81%) subjects, and these met ICHD3 criteria for migraine in 48 (50%). Postictal headaches were reported by 75 of 120 (63%) subjects on the initial admission questionnaire, representing migraine in 38 (51%). Thirty‐nine (32%) subjects completed the secondary questionnaire related to postictal headaches experienced during admission, of which nine (23%) met criteria for migraine. There was no seizure lateralizing or localizing value noted based on postictal headache localization.

Significance

Migraine was frequent in this cohort and appears to be the dominant interictal and postictal headache type in patients with epilepsy. In this study, the first to assess incident postictal headache in the setting of an ictal EEG, headache localization was of no seizure localizing value. Few patients were being actively treated; suggesting headache management is often overlooked in the epilepsy population.

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<![CDATA[Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models]]> https://www.researchpad.co/article/5c8bf8b0d5eed0c484b1fdce

Summary

Objective

Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in a battery of acute seizure models. Additionally, we defined the disease‐modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus–spontaneous recurrent seizures (RISESRS) model of temporal lobe epilepsy (TLE).

Methods

We evaluated the acute antiseizure effect of CBD in the maximal electroshock seizure, 6‐Hz psychomotor seizure, and pentylenetetrazol acute seizure tests, as well as the corneal kindling model of chronic seizures in mice following intraperitoneal administration. Median effective or behavioral toxic dose was determined in both mice and rats. Next, we tested an intravenous preparation of CBD (10 mg/kg single dose) in a rat model of pilocarpine‐induced status epilepticus. We defined the effect of chronic CBD administration (200 mg/kg orally) on spontaneous seizures, motor control, gait, and memory function in the rat RISESRS model of TLE.

Results

CBD was effective in a battery of acute seizure models in both mice and rats following intraperitoneal administration. In the pilocarpine‐induced status epilepticus rat model, CBD attenuated maximum seizure severity following intravenous administration, further demonstrating CBD's acute antiseizure efficacy in this rat model. We established that oral CBD attenuated the time‐dependent increase in seizure burden and improved TLE‐associated motor comorbidities of epileptic rats in the RISESRS model without affecting gait. Chronic administration of CBD after the onset of SRS ameliorated reference memory and working memory errors of epileptic animals in a spatial learning and memory task.

Significance

The present study illustrates that CBD is a well‐tolerated and effective antiseizure agent and illustrates a potential disease‐modifying effect of CBD on reducing both seizure burden and associated comorbidities well after the onset of symptomatic seizures in a model of TLE.

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<![CDATA[Seven tesla MRI improves detection of focal cortical dysplasia in patients with refractory focal epilepsy]]> https://www.researchpad.co/article/5bfb2f4fd5eed0c48495e597

Summary

Objective

The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery.

Methods

In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient‐quality lower‐field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR‐visible mesiotemporal sclerosis—dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower‐field MRI scans.

Results

In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower‐field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development.

Significance

Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.

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<![CDATA[A study on spike focus dependence of high‐frequency activity in idiopathic focal epilepsy in childhood]]> https://www.researchpad.co/article/5bfb2f3bd5eed0c48495e0f6

Summary

Objective

Spike foci in benign epilepsy with centrotemporal spikes (BECTS) are related to seizure semiologies, but this relationship is inconspicuous in Panayiotopoulos syndrome (PS). We analyzed spike‐associated high‐frequency activity (HFA) and its relationship to spike foci in the electroencephalograms (EEGs) of patients with BECTS and PS in order to elucidate the pathophysiology of these epileptic syndromes.

Methods

In 35 patients with BECTS and 29 with PS, focal spikes in scalp sleep EEGs were first classified by clustering according to their characteristics, including shape and distribution. For each patient, three or fewer spike clusters were investigated by time‐frequency spectral analysis and single‐dipole analysis using a realistic three‐dimensional head model to explore the relationships between the presence or absence of spike‐associated HFA and the distribution of estimated spike sources.

Results

A total of 159 spike clusters were analyzed (96 in BECTS and 63 in PS). HFA was detected in 73 spike clusters (76.0%) in BECTS and 37 (58.7%) in PS, with a significant difference in the proportion of spike clusters with HFA (p = 0.024 by Fisher's exact test). In BECTS, spikes had relatively uniform distributions, but the proportion of spikes with associated HFA was significantly higher in the spike group with dipoles in the perirolandic areas (42 of 49) than in that with dipoles outside of the perirolandic areas (23 of 36; p = 0.037). In PS, The proportion of spikes with associated HFA was significantly higher in the spike group with dipoles in the occipital lobes (20 of 26) than in that with dipoles outside of the occipital lobes (13 of 33; p = 0.020).

Significance

The proportion of spike‐associated HFA was higher in BECTS than in PS. Particular pathophysiological meaning was indicated in spikes with dipoles in the perirolandic areas in BECTS and in spikes with dipoles in the occipital lobes in PS owing to the high proportions of spike‐associated HFA in these areas.

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<![CDATA[Cathodal transcranial direct‐current stimulation for treatment of drug‐resistant temporal lobe epilepsy: A pilot randomized controlled trial]]> https://www.researchpad.co/article/5bfb2f37d5eed0c48495e062

Summary

Objective

To investigate the effect of cathodal transcranial direct‐current stimulation (c‐tDCS) on seizure frequency in patients with drug‐resistant temporal lobe epilepsy (TLE).

Method

Twenty‐nine patients with drug‐resistant TLE participated in this study. They were randomized to experimental or sham group. Twenty participants (experimental group) received within‐session repeated c‐tDCS intervention over the affected temporal lobe, and nine (sham group) received sham tDCS. Paired‐pulse transcranial magnetic stimulation was used to assess short interval intracortical inhibition (SICI) in primary motor cortex ipsilateral to the affected temporal lobe. SICI was measured from motor evoked potentials recorded from the contralateral first dorsal interosseous muscle. Adverse effects were monitored during and after each intervention in both groups. A seizure diary was given to each participant to complete for 4 weeks following the tDCS intervention. The mean response ratio was calculated from their seizure rates before and after the tDCS intervention.

Results

The experimental group showed a significant increase in SICI compared to the sham group (F = 10.3, p = 0.005). None of the participants reported side effects of moderate or severe degree. The mean response ratio in seizure frequency was −42.14% (standard deviation [SD] 35.93) for the experimental group and −16.98% (SD 52.41) for the sham group.

Significance

Results from this pilot study suggest that tDCS may be a safe and efficacious nonpharmacologic intervention for patients with drug‐resistant TLE. Further evaluation in larger double‐blind randomized controlled trials is warranted.

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<![CDATA[Understanding the burden of focal epilepsy as a function of seizure frequency in the United States, Europe, and Brazil]]> https://www.researchpad.co/article/5bfb2f53d5eed0c48495e622

Summary

Objective

To understand the current burden of focal epilepsy (FE) as a function of seizure frequency.

Methods

Patients were identified from the United States (2011, 2012, and 2013), five European countries (EU; France, Germany, Italy, Spain, United Kingdom) (2011 and 2013), and Brazil (2011 and 2012) National Health and Wellness Survey (NHWS), a nationally representative, Internet‐based survey of adults (18+ years). The NHWS collected data on respondents’ quality of life (QoL), health utilities, productivity loss, and healthcare resource utilization. Indirect and direct costs were calculated from the literature. Altogether, 345 of 176,093 (U.S.A.), 73 of 30,000 (United Kingdom), 53 of 30,001 (Germany), 53 of 30,000 (France), 41 of 12,011 (Spain), 37 of 17,500 (Italy), and 71 of 24,000 (Brazil) respondents self‐reported a diagnosis of FE.

Results

Many respondents (U.S.A.: 56.2%; 5EU: 41.6%; Brazil + 5EU: 40.5%) reported persistent seizures (≥1 per year). Over 60% to just over 71% of respondents with FE were treated with antiepileptic drugs (AEDs). In the United States, seizure frequency was associated with hospitalizations, indirect costs (ages 18–60), and total direct costs. For the 5EU and Brazil + 5EU, seizure frequency was associated with physical QoL, health utilities, activity impairment, and emergency room (ER) visits. Additional associations were observed for the 5EU on hospitalizations, indirect costs (ages 18–60), ER visit costs, and total direct costs and for Brazil + 5EU on absenteeism, overall work impairment, and provider visits. Costing was not performed for Brazil + 5EU.

Significance

Around half of the patients had persistent seizures despite most taking an AED in this 2011–2013 dataset. The results support the hypothesis that reducing seizures can improve productivity and reduce resource utilization and associated costs. Regional differences may reflect differences in healthcare systems and selected patient populations. Overall, the results suggest that additional treatment options are needed to improve seizure control and reduce related costs.

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<![CDATA[Single‐item measure for assessing quality of life in children with drug‐resistant epilepsy]]> https://www.researchpad.co/article/5bfb3005d5eed0c484960b4e

Summary

Objective

The current study investigated the psychometric properties of a single‐item quality of life (QOL) measure, the Global Quality of Life in Childhood Epilepsy question (G‐QOLCE), in children with drug‐resistant epilepsy.

Method

Data came from the Impact of Pediatric Epilepsy Surgery on Health‐Related Quality of Life Study (PESQOL), a multicenter prospective cohort study (n = 118) with observations collected at baseline and at 6 months of follow‐up on children aged 4–18 years. QOL was measured with the QOLCE‐76 and KIDSCREEN‐27. The G‐QOLCE was an overall QOL question derived from the QOLCE‐76. Construct validity and reliability were assessed with Spearman's correlation and intraclass correlation coefficient (ICC). Responsiveness was examined through distribution‐based and anchor‐based methods.

Results

The G‐QOLCE showed moderate (r ≥ 0.30) to strong (r ≥ 0.50) correlations with composite scores, and most subscales of the QOLCE‐76 and KIDSCREEN‐27 at baseline and 6‐month follow‐up. The G‐QOLCE had moderate test‐retest reliability (ICC range: 0.49–0.72) and was able to detect clinically important change in patients' QOL (standardized response mean: 0.38; probability of change: 0.65; Guyatt's responsiveness statistics: 0.62 and 0.78). Caregiver anxiety and family functioning contributed most strongly to G‐QOLCE scores over time.

Significance

Results offer promising preliminary evidence regarding the validity, reliability, and responsiveness of the proposed single‐item QOL measure. The G‐QOLCE is a potentially useful tool that can be feasibly administered in a busy clinical setting to evaluate clinical status and impact of treatment outcomes in pediatric epilepsy.

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<![CDATA[Adverse perinatal events, treatment gap, and positive family history linked to the high burden of active convulsive epilepsy in Uganda: A population‐based study]]> https://www.researchpad.co/article/5bfb2f58d5eed0c48495e71f

Summary

Objective

To determine the prevalence of active convulsive epilepsy (ACE) and describe the clinical characteristics and associated factors among a rural Ugandan population.

Methods

The entire population in Iganga/Mayuge Health Demographic Surveillance Site (IMHDSS) was screened using two questions about seizures during a door‐to‐door census exercise. Those who screened positive were assessed by a clinician to confirm diagnosis of epilepsy. A case control study with the patients diagnosed with ACE as the cases and age/sex‐matched controls in a ratio of 1:1 was conducted.

Results

A total of 64,172 (92.8%) IMHDSS residents, with a median age of 15.0 years (interquartile range [IQR]: 8.0–29.0), were screened for epilepsy. There were 152 confirmed ACE cases, with a prevalence of 10.3/1,000 (95% confidence interval [CI]: 9.5–11.1) adjusted for nonresponse and screening sensitivity. Prevalence declined with age, with the highest prevalence in the 0–5 years age group. In an analysis of n = 241 that included cases not identified in the survey, nearly 70% were unaware of their diagnosis. Seizures were mostly of focal onset in 193 (80%), with poor electroencephalogram (EEG) agreement with seizure semiology. Antiepileptic drug use was rare, noted in 21.2% (95% CI: 16.5–25.8), and 119 (49.3%) reported using traditional medicines. History of an abnormal antenatal period (adjusted odds ratio [aOR] 10.28; 95%CI 1.26–83.45; p = 0.029) and difficulties in feeding, crying, breathing in the perinatal period (aOR 10.07; 95%CI 1.24–81.97; p = 0.031) were associated with ACE in children. In adults a family history of epilepsy (aOR 4.38 95%CI 1.77–10.81; p = 0.001) was the only factor associated with ACE.

Significance

There is a considerable burden of epilepsy, low awareness, and a large treatment gap in this population of rural sub‐Saharan Africa. The identification of adverse perinatal events as a risk factor for developing epilepsy in children suggests that epilepsy burden may be decreased by improving obstetric and postnatal care.

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<![CDATA[Copy number variation in a hospital‐based cohort of children with epilepsy]]> https://www.researchpad.co/article/5bfb2f5ad5eed0c48495e769

Summary

Objective

To evaluate the diagnostic yield of microarray analysis in a hospital‐based cohort of children with seizures and to identify novel candidate genes and susceptibility loci for epilepsy.

Methods

Of all children who presented with their first seizure in the University Medical Center Groningen (January 2000 through May 2013) (n = 1,368), we included 226 (17%) children who underwent microarray analysis before June 2014. All 226 children had a definite diagnosis of epilepsy. All their copy number variants (CNVs) on chromosomes 1–22 and X that contain protein‐coding genes and have a prevalence of <1% in healthy controls were evaluated for their pathogenicity.

Results

Children selected for microarray analysis more often had developmental problems (82% vs. 25%, p < 0.001), facial dysmorphisms (49% vs. 8%, p < 0.001), or behavioral problems (41% vs. 13%, p < 0.001) than children who were not selected. We found known clinically relevant CNVs for epilepsy in 24 of the 226 children (11%). Seventeen of these 24 children had been diagnosed with symptomatic focal epilepsy not otherwise specified (71%) and five with West syndrome (21%). Of these 24 children, many had developmental problems (100%), behavioral problems (54%) or facial dysmorphisms (46%). We further identified five novel CNVs comprising four potential candidate genes for epilepsy: MYT1L, UNC5D, SCN4B, and NRXN3.

Significance

The 11% yield in our hospital‐based cohort underscores the importance of microarray analysis in diagnostic evaluation of children with epilepsy.

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<![CDATA[Risk of convulsive epilepsy following acute seizures in Kenyan children]]> https://www.researchpad.co/article/5bfb2f41d5eed0c48495e275

Summary

Objective

The prevalence of epilepsy is high in Africa, and people with epilepsy often have a history of acute seizures. We determined whether acute seizures are associated with risk for epilepsy in rural Africa, where both conditions are common and may have shared risk factors.

Methods

A total of 16,438 children (2,991 with acute seizures and 13,447 without seizures) admitted to Kilifi County Hospital from 2002 to 2008 were followed up with epidemiological surveys conducted in 2003 and 2008 to assess the prevalence of epilepsy and the associated risk factors. Cox proportional hazards regression models were used to identify the risk factors. Prevalence ratios were computed using log binomial regression models.

Results

The prevalence of epilepsy was higher in admissions with acute seizures (5.0% [95% confidence interval (CI), 4.3–5.9%]) than in those without seizures (0.7% [95% CI, 0.5–0.8%]), p < 0.0001). Acute seizures were associated with epilepsy after accounting for potential confounders in a Cox regression model (hazard ratio [HR] = 1.53 [95% CI, 1.10–2.14]). Prevalence was greater in complex acute seizures (5.9%; prevalence ratio [PR] = 1.58 [95% CI, 1.13–2.20]) or status epilepticus (7.5%; PR = 1.96 [95% CI, 1.32–2.91]) than in simple acute seizures (3.7%). Factors independently associated with epilepsy following acute seizures in Cox regression models were perinatal complications (HR = 3.60 [95% CI, 1.89–6.87]), cerebral palsy (HR = 1491.51 [95% CI, 144.30–15,416.21]), duration of follow‐up (HR = 1.21 [95% CI, 1.09–1.35]), and malnutrition (relative risk [RR] = 0.24 [95% CI, 0.08–0.69]).

Significance

Acute seizures in children are associated with subsequent risk for epilepsy that is greater than in the general population. The burden of epilepsy may be reduced by control of causes of acute seizures.

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