Increased Thalamic Connectivity in Juvenile Myoclonic Epilepsy Based on Electroencephalography Source-Level Analysis.

Background: This study investigated alterations in the intrinsic thalamic network of patients with juvenile myoclonic epilepsy (JME) based on an electroencephalography (EEG) source-level analysis. Materials and Methods: We enrolled patients newly diagnosed with JME as well as healthy controls. The assessments were conducted in the resting state. We computed sources based on the scalp electrical potentials using a minimum-norm imaging method and a standardized, low-resolution, brain electromagnetic tomography approach. To create a functional connectivity matrix, we used the Talairach atlas to define thalamic nodes and applied the coherence method to measure brain synchronization as edges. We then calculated the intrinsic thalamic network using graph theory. We compared the intrinsic thalamic network of patients with JME with those of healthy controls. Results: This study included 67 patients with JME and 66 healthy controls. EEG source-level analysis revealed significant differences in the intrinsic thalamic networks between patients with JME and healthy controls. The measures of functional connectivity (radius, diameter, and characteristic path length) were significantly lower in patients with JME than in healthy controls (radius: 2.769 vs. 3.544, p = 0.015; diameter: 4.464 vs. 5.443, p = 0.024; and characteristic path length: 2.248 vs. 2.616, p = 0.046). Conclusions: We demonstrated alterations in the intrinsic thalamic network in patients with JME compared with those in healthy controls based on the EEG source-level analysis. These findings indicated increased thalamic connectivity in the JME group. These intrinsic thalamic network changes may be related to the pathophysiology of JME.

Sex-specific disease modifiers in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.

Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures.

BACKGROUND: The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). OBJECTIVE: We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. METHODS: Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). RESULTS: Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. CONCLUSIONS: The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence.

Prolonged epileptic discharges predict seizure recurrence in JME: Insights from prolonged ambulatory EEG.

OBJECTIVE: Markers of seizure recurrence are needed to personalize antiseizure medication (ASM) therapy. In the clinical practice, EEG features are considered to be related to the risk of seizure recurrence for genetic generalized epilepsies (GGE). However, to our knowledge, there are no studies analyzing systematically specific EEG features as indices of ASM efficacy in GGE. In this study, we aimed at identifying EEG indicators of ASM responsiveness in Juvenile Myoclonic Epilepsy (JME), which, among GGE, is characterized by specific electroclinical features. METHODS: We compared the features of prolonged ambulatory EEG (paEEG, 22 h of recording) of JME patients experiencing seizure recurrence within a year ("cases") after EEG recording, with those of patients with sustained seizure freedom for at least 1 year after EEG ("controls"). We included only EEG recordings of patients who had maintained the same ASM regimen (dosage and type) throughout the whole time period from the EEG recording up to the outcome events (which was seizure recurrence for the "cases", or 1-year seizure freedom for "controls"). As predictors, we evaluated the total number, frequency, mean and maximum duration of epileptiform discharges (EDs) and spike density (i.e. total EDs duration/artifact-free EEG duration) recorded during the paEEG. The same indexes were assessed also in standard EEG (stEEG), including activation methods. RESULTS: Both the maximum length and the mean duration of EDs recorded during paEEG significantly differed between cases and controls; when combined in a binary logistic regression model, the maximum length of EDs emerged as the only valid predictor. A cut-off of EDs duration of 2.68 seconds discriminated between cases and controls with a 100% specificity and a 93% sensitivity. The same indexes collected during stEEG lacked both specificity and sensitivity. SIGNIFICANCE: The occurrence of prolonged EDs in EEG recording might represent an indicator of antiepileptic drug failure in JME patients.

Juvenile myoclonic epilepsy: Long-term prognosis and risk factors.

OBJECTIVE: Our goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases. METHODS: We retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution. We collected clinical, neurophysiological and neuroimaging data from patients who met defined inclusion and exclusion criteria. RESULTS: Study involved 61 patients (65.5% female) with mean age at study of 37.6 years, and mean age at its outset of 14.8 years. Median follow-up was 31.0 years (mean 28.9, range 15-53). They presented more frequently with a combination of myoclonic and generalized tonic-clonic seizures (GTCS) (65.6%). Sixty-five percent of patients (n = 40) had a 5-year terminal remission with a mean age at last seizure of 27.4 years. Thirty-two percent of seizure-free patients (n = 13) withdrew ASMs: 6 out of 13 had a recurrence of the seizures while 7 remained seizure-free (mean age at ASMs withdrawal 21.0 versus 35.7 years, p < 0.05). In the multivariate model, a high GTCS frequency at onset (p = 0.026) was a prognostic factor of drug resistance. CONCLUSION: JME is often regarded as a benign epileptic syndrome, although a quarter of the individuals have refractory epilepsy. The possibility of withdrawing ASMs in patients who have been free of seizures over an extended time seems feasible.

A computational biomarker of juvenile myoclonic epilepsy from resting-state MEG.

OBJECTIVE: For people with idiopathic generalized epilepsy, functional networks derived from their resting-state scalp electrophysiological recordings have shown an inherent higher propensity to generate seizures than those from healthy controls when assessed using the concept of brain network ictogenicity (BNI). Herein we tested whether the BNI framework is applicable to resting-state magnetoencephalography (MEG) from people with juvenile myoclonic epilepsy (JME). METHODS: The BNI framework consists in deriving a functional network from apparently normal brain activity, placing a mathematical model of ictogenicity into the network and then computing how often such network generates seizures in silico. We considered data from 26 people with JME and 26 healthy controls. RESULTS: We found that resting-state MEG functional networks from people with JME are characterized by a higher propensity to generate seizures (i.e., higher BNI) than those from healthy controls. We found a classification accuracy of 73%. CONCLUSIONS: The BNI framework is applicable to MEG and was capable of differentiating people with epilepsy from healthy controls. SIGNIFICANCE: The BNI framework may be applied to resting-state MEG to aid in epilepsy diagnosis.

Potential role of brivaracetam in pediatric epilepsy.

Brivaracetam (BRV) is a new antiseizure medication (ASM) that is currently approved for adjunctive treatment in patients with focal onset seizures. Similarly to levetiracetam (LEV), BRV works by binding SV2A vesicles with a high affinity and a linear pharmacokinetic profile. Retrospective studies and randomized clinical trials have already proven the efficacy of BRV, even in patients who failed treatment with LEV. Most studies about the efficacy and tolerability conducted so far were performed in adult cohorts, whereas few studies have been performed in children; however, BRV was proven to be a useful ASM for pediatric focal epilepsies, with fewer studies and conflicting results among patients with generalized epilepsies and epileptic syndromes. Retention rates were high in the cohorts analyzed, and no serious treatment-emergent adverse events were reported in the majority of patients, with somnolence, drowsiness, irritability, aggression, and decreased appetite being the most frequently reported side effects. Although there are few original papers published on the subject so far, the analysis of the literature data demonstrated the efficacy and safety of BRV in pediatric patients, with more evidence for children aged 4-16 years with an onset of focal seizures. However, a positive response was also achieved in patients affected by encephalopathic epilepsies (eg, Jeavons' epilepsy, Dravet syndrome, Lennox-Gastaut syndrome, and juvenile myoclonic epilepsy), and ongoing studies are now testing BRV in order to widen its application to other forms of epilepsy and to test its effectiveness when used in monotherapy. This review aims to provide a comprehensive analysis of the literature surrounding the efficacy and tolerability of BRV for pediatric patients.

Surround inhibition in patients with juvenile myoclonic epilepsy.

OBJECTIVE: In healthy subjects, there is a reduction in the amplitudes of somatosensory-evoked potentials (SEPs) after the simultaneous stimulation of two nerves compared to the sum of separate stimulations. This reduction is due to the inhibition of one area in the cortex after stimulation of the neighboring area, which results from the surround inhibition (SI) phenomenon. In this study, we aimed to investigate whether there was a decrease in SI of SEP in patients with juvenile myoclonic epilepsy (JME). METHODS: We included 17 patients with JME and 18 healthy subjects. Groups were similar in terms of age and gender. We recorded SEPs after stimulating (i) median nerve (mSEP), (ii) ulnar nerve (uSEP), (iii) median and ulnar nerves simultaneously (muSEP) at wrist. The arithmetic sum (aSEP) of amplitudes of mSEP and uSEP was compared with the amplitudes of muSEP. We also calculated SI%. RESULTS: The amplitudes of SEPs were significantly higher in the JME group than in the healthy subjects (mSEP, p = 0.005; uSEP, p = 0.032; muSEP, p = 0.014). In healthy subjects and the JME group, the amplitude of muSEP was significantly lower than the aSEP (p = 0.014; p = 0.001, respectively). However, SI% was significantly higher in the JME group (p = 0.010). SIGNIFICANCE: Although the SI is maintained in JME patients, the higher SI% indicates an impairment relative to healthy subjects.

Persistent treatment resistance in genetic generalized epilepsy: A long-term outcome study in a tertiary epilepsy center.

OBJECTIVE: To assess prognostic patterns and investigate clinical and electroencephalography (EEG) variables associated with persistent treatment resistance in a population of genetic generalized epilepsy (GGE) patients with a long-term follow-up. METHODS: Data from GGE patients followed from 1975 to 2019 were reviewed retrospectively. Subjects with a follow-up >10 years, starting from epilepsy diagnosis, were included. Persistent treatment resistance was defined as the absence of any period of remission ≥1 year despite treatment with two appropriate and adequate antiepileptic drugs (AEDs). RESULTS: One hundred ninety-nine patients were included. The median age was 39.5 years (interquartile range [IQR] 30-49) and the median follow-up was 27 years (IQR 18-35). The most common syndrome was juvenile myoclonic epilepsy (JME), diagnosed in 44.2% of patients. During follow-up, 163 subjects (81.9%) experienced 3-year remission from any seizure type, whereas 5- and 10-year remission occurred in 141 (70.8%) and 92 (46.2%) cases, respectively. The most common prognostic pattern was a relapsing-remitting course, observed in 80 patients (40.2%), whereas 29 (14.6%) displayed persistent treatment resistance. According to multivariable logistic regression analysis, febrile seizures (FS), specific EEG patterns (namely generalized paroxysmal fast activity, GPFA) and valproate (VPA) resistance were the only variables significantly associated with persistent treatment resistance. JME was the only epilepsy syndrome statistically associated with persistent treatment resistance in univariable logistic regression analysis. SIGNIFICANCE: Persistent treatment resistance was observed in almost 15% of GGE patients followed in a tertiary epilepsy center. A worse outcome was associated with specific clinical variables (JME, FS) and EEG patterns (GPFA).

Interrater agreement of classification of photoparoxysmal electroencephalographic response.

Our goal was to assess the interrater agreement (IRA) of photoparoxysmal response (PPR) using the classification proposed by a task force of the International League Against Epilepsy (ILAE), and a simplified classification system proposed by our group. In addition, we evaluated IRA of epileptiform discharges (EDs) and the diagnostic significance of the electroencephalographic (EEG) abnormalities. We used EEG recordings from the European Reference Network (EpiCARE) and Standardized Computer-based Organized Reporting of EEG (SCORE). Six raters independently scored EEG recordings from 30 patients. We calculated the agreement coefficient (AC) for each feature. IRA of PPR using the classification proposed by the ILAE task force was only fair (AC = 0.38). This improved to a moderate agreement by using the simplified classification (AC = 0.56; P = .004). IRA of EDs was almost perfect (AC = 0.98), and IRA of scoring the diagnostic significance was moderate (AC = 0.51). Our results suggest that the simplified classification of the PPR is suitable for implementation in clinical practice.

How to diagnose and classify idiopathic (genetic) generalized epilepsies.

Idiopathic or genetic generalized epilepsies (IGE) constitute an electroclinically well-defined group that accounts for almost one third of all people with epilepsy. They consist of four well-established syndromes and some other rarer phenotypes. The main four IGEs are juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilepsy and IGE with generalized tonic-clonic seizures alone. There are three main seizure types in IGE, namely generalized tonic-clonic seizures, typical absences and myoclonic seizures, occurring either alone or in any combination. Diagnosing IGEs requires a multidimensional approach. The diagnostic process begins with a thorough medical history with a specific focus on seizure types, age at onset, timing and triggers. Comorbidities and family history should be questioned comprehensively. The EEG can provide valuable information for the diagnosis, including specific IGE syndromes, and therefore contribute to their optimal pharmacological treatment and management.

Can we predict drug response by functional connectivity in patients with juvenile myoclonic epilepsy?

OBJECTIVES: We investigated functional connectivity based on EEG using graph theoretical analysis in patients with newly diagnosed juvenile myoclonic epilepsy (JME), and whether it could play a role as a biomarker predicting antiepileptic drug (AED) response. METHODS: We consecutively enrolled 38 patients with JME and 40 normal controls. The initial EEG was undertaken at the time of diagnosis of JME in a drug-naïve state. The second EEG was done after at least 12 months from the time of the initial EEG. We classified the patients with JME into two groups according to AED response at the time of taking the second EEG. We investigated functional connectivity based on graph theoretical analysis using connectivity measures of the coherence and phase locking value. RESULTS: In the analysis of functional connectivity using coherence as a connectivity measure, the global efficiency and local efficiency in the AED poor responders (N = 4) decreased, whereas the small-worldness index increased. In the analysis of functional connectivity using phase locking value as a connectivity measure, the global efficiency and local efficiency in the AED poor responders decreased. However, in the AED good responders (N = 34), none of the network measures were different from those in healthy controls. CONCLUSIONS: We newly found that there were significant differences of functional connectivity based on initial EEG according to AED response in the patients with JME. This suggests that brain connectivity could play a role as a new biomarker predicting AED response in patients with JME.

Do interictal EEG findings reflect cognitive function in juvenile myoclonic epilepsy?

PURPOSE: This study investigated the relationship between frontal lobe cognitive function and frontal focal electroencephalography (EEG) findings in patients with juvenile myoclonic epilepsy (JME). METHODS: The study enrolled 60 patients diagnosed with JME and followed at the Epilepsy Outpatient Clinic of the University of Health Sciences, Bakirkoy Psychiatric Hospital, and 30 healthy volunteers. Demographic and clinical features were recorded. Frontal lobe cognitive functions were tested in both groups. Video-EEG recordings of patients with JME were evaluated. The presence and duration of generalized discharges, the presence and lateralization of focal findings, and the presence of generalized discharges during hyperventilation and photic stimulation were recorded during EEG. Cognitive function test results were compared between the two groups, and the relationship between the EEG findings and cognitive function was investigated. RESULTS: The study included 35 (58.3%) female and 25 (41.6%) male patients and 17 (56.7%) female and 13 (43.3%) male healthy controls. The mean ages of the group with JME and controls were 28.3 ±â€¯8.6 (16-50) and 31.3 ±â€¯7.9 (17-45) years, respectively. Patients with JME performed more poorly on the frontal lobe cognitive tests than controls (p < 0.05). Patients whose generalized discharges were longer than 1 s performed more poorly on tests evaluating attention and made more perseverative errors (p < 0.05). There was no significant correlation between the presence of focal EEG findings and the scores on frontal lobe cognitive functions tests in the group with JME (p > 0.05). CONCLUSION: Frontal lobe cognitive functions are affected in patients with JME. The cognitive effects were more pronounced in patients with prolonged generalized discharges on EEG.

Motor hyperactivation during cognitive tasks: An endophenotype of juvenile myoclonic epilepsy.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME. METHODS: This prospective cross-sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks. RESULTS: During both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure-free patients. Receiver-operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient-sibling group against controls, respectively; P < .005). SIGNIFICANCE: Motor system hyperactivation represents a cognitive, domain-independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.

Thalamic and cortical hyperexcitability in juvenile myoclonic epilepsy.

OBJECTIVES: Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy marked by cortical hyperexcitability. Recent neuroimaging data suggested also a thalamic role in sustaining epileptic propensity in JME. However, thalamic hyperexcitability was not demonstrated so far. Low-frequency (LF-SEPs) and high-frequency somatosensory evoked potentials (HF-SEPs) are very sensitive to thalamic (early HF-SEPs burst, eHFO) and cortical (late HF-SEPs burst, lHFO) excitability. The aim of our experiment was to explore and discern the role of thalamic and cortical excitability in epileptic susceptibility of JME through a LF-SEPs and HF-SEPs study. METHODS: Twenty-three subjects with JME (11 females, 30.2 ± 9.8-year-old) and 23 healthy control subjects (12 females, age: 34.7 ± 7.7-year-old) underwent right median LF-SEPs scalp recordings. Cp3'-Fz traces were filtered (400-800 Hz) to reveal HF-SEPs. All JME patients were on drug treatment and seizure free, except for sporadic myoclonus. RESULTS: N20 LF-SEPs amplitude (p < 0.009), areas of totHFO, eHFO and lHFO (all p < 0.005) and totHFO duration (p = 0.013) were increased in JME respect to healthy subjects. totHFO area was negatively correlated with the number of antiepileptic drugs (rho = -0.505, sig.: 0.027), while eHFO area was positively correlated with the myoclonus frequency (rho = 0.555, sig = 0.014). CONCLUSIONS: We demonstrated that in JME the thalamic hyperexcitability assists the cortical one in sustaining epileptic susceptibility. SIGNIFICANCE: Our results support the concept of JME as a network and genetic disorder.

Juvenile myoclonic epilepsy shows increased posterior theta, and reduced sensorimotor beta resting connectivity.

BACKGROUND: Widespread structural and functional brain network changes have been shown in Juvenile Myoclonic Epilepsy (JME) despite normal clinical neuroimaging. We sought to better define these changes using magnetoencephalography (MEG) and source space connectivity analysis for optimal neurophysiological and anatomical localisation. METHODS: We consecutively recruited 26 patients with JME who underwent resting state MEG recording, along with 26 age-and-sex matched controls. Whole brain connectivity was determined through correlation of Automated Anatomical Labelling (AAL) atlas source space MEG timeseries in conventional frequency bands of interest delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (40-60 Hz). We used a Linearly Constrained Minimum Variance (LCMV) beamformer to extract voxel wise time series of 'virtual sensors' for the desired frequency bands, followed by connectivity analysis using correlation between frequency- and node-specific power fluctuations, for the voxel maxima in each AAL atlas label, correcting for noise, potentially spurious connections and multiple comparisons. RESULTS: We found increased connectivity in the theta band in posterior brain regions, surviving statistical correction for multiple comparisons (corrected p < 0.05), and decreased connectivity in the beta band in sensorimotor cortex, between right pre- and post- central gyrus (p < 0.05) in JME compared to controls. CONCLUSIONS: Altered resting-state MEG connectivity in JME comprised increased connectivity in posterior theta - the frequency band associated with long range connections affecting attention and arousal - and decreased beta-band sensorimotor connectivity. These findings likely relate to altered regulation of the sensorimotor network and seizure prone states in JME.

Meta-analysis of response inhibition in juvenile myoclonic epilepsy.

BACKGROUND: Patients with juvenile myoclonic epilepsy (JME) show evidence of cognitive impulsivity that may be linked to later adverse psychosocial outcomes. Here, we quantify the strength of association and estimate effect size (ES) of response inhibition by pooling available evidence in a meta-analysis. METHODS: We conducted a systematic review of the literature using Ovid MEDLINE and Ovid EMBASE databases (covering 2001-2019) with a search strategy using combinations of the specific Medical Subject Headings (MeSH) terms 'juvenile myoclonic epilepsy, cognitive impulsivity, response inhibition, Stroop, cognition, personality, traits' using the 'explode' feature where possible. We also searched within references of retrieved articles. We included studies reporting ESs describing established measures of response inhibition in teenage and adult patients with JME. RESULTS: Using the ESs pooled from 16 studies comprising 1047 patients and controls, we found ESs for response inhibition to be homogeneous with a significant moderate mean ES of d = 0.50 (95% confidence interval [CI]: 0.37-0.63). CONCLUSIONS: We confirm that reduced response inhibition is a consistently observed homogeneous trait in patients with JME.

Subcortical gray matter changes in pediatric patients with new-onset juvenile myoclonic epilepsy.

OBJECTIVE: The objective of the study was to identify the relationship between subcortical gray matter (GM) volumes and juvenile myoclonic epilepsy (JME). METHODS: We analyzed the brain magnetic resonance imaging (MRI) scans that were performed during the time of the diagnosis of epilepsy by using voxel-based morphometry (VBM) method. The volumetric three-dimensional sequence was used for structural investigation. The volumes of the thalamus, caudate nucleus, pallidum, and putamen were measured in both hemispheres of patients with JME, patients with generalized tonic-clonic seizures alone (GTCS) (as a disease control group) and healthy controls (HCs). All patients were drug-naïve, and treatment had been started after evaluating MRI results. RESULTS: Fifteen patients with JME (9 females, mean age = 16.1 ±â€¯3.2), 18 patients with GTCS (10 females, mean age = 15.5 ±â€¯2.9), and 43 HCs (24 females, mean age = 15.9 ±â€¯2.8) were included in the analysis. No significant difference was found for relative globus pallidus, caudate, and putamen volumes among the groups with JME, GTCS, and the HC group. The relative left and right thalamic volumes were significantly different between groups (Kruskal-Wallis rank test, p = 0.007, p = 0.001). In pairwise comparisons, both right and left relative thalamic volumes were lower in patients with JME than in HCs (right thalamus: means: 0.521 ±â€¯0.066 vs. 0.597 ±â€¯0.058, p < 0.001; left thalamus: means: 0.526 ±â€¯0.088 vs. 0.605 ±â€¯0.057, p < 0.001, Bonferroni post hoc corrections) and in patients with JME than in patients with GTCS (right thalamus: means: 0.521 ±â€¯0.066 vs. 0.578 ±â€¯0.066, p = 0.03; left thalamus: means: 0.526 ±â€¯0.088 vs. 0.592 ±â€¯0.068, p = 0.01, Bonferroni post hoc corrections), whereas there was no significant difference between the HCs and patients with GTCS (right thalamus: means: 0.597 ±â€¯0.058 vs. 0.578 ±â€¯0.066, p = 0.8; left thalamus: means: 0.605 ±â€¯0.057 vs. 0.592 ±â€¯0.068, p = 0.999, Bonferroni post hoc corrections). CONCLUSION: This study allowed us to know that microstructural abnormalities exist from the disease onset, and the thalamus might play a critical role in the pathogenesis of JME.

Recovery function of somatosensory evoked potentials in juvenile myoclonic epilepsy.

Objective: We analysed the recovery function of somatosensory evoked potentials (SEPs) in juvenile myoclonic epilepsy (JME) patients. We hypothesized that there may be disinhibition in the recovery of SEPs at 20-100 ms intervals in JME patients. Methods: We recorded SEPs and SEP recovery in 19 consecutive patients with JME admitted for a routine follow-up examination, and in a control group composed of 13 healthy subjects who were similar to the patient group regarding age and sex. The recovery function of SEPs was examined using paired stimuli at 30, 40, 60, and 100 ms intervals. Results: The amplitudes of N20-P25 and P25-N33 components were higher in patients with JME. Ten patients had high-amplitude SEPs. By paired stimulation, there was inhibition of SEPs in both groups. The mean recovery percentages of N20-P25 and P25-N33 components at 30, 40, 60, and 100 ms were not different between healthy subjects and patients with JME. Conclusions: The recovery function of SEP is normal in JME even in the presence of high-amplitude SEPs.