Juvenile Myoclonic Epilepsy Patients Research Articles

Brain functional network changes in patients with juvenile myoclonic epilepsy: a study based on graph theory and Granger causality analysis.

Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown that the brain networks are disrupted in adolescent patients with juvenile myoclonic epilepsy (JME). However, previous studies have mainly focused on investigating brain connectivity disruptions from the perspective of static functional connections, overlooking the dynamic causal characteristics between brain network connections. In our study involving 37 JME patients and 35 Healthy Controls (HC), we utilized rs-fMRI to construct whole-brain functional connectivity network. By applying graph theory, we delved into the altered topological structures of the brain functional connectivity network in JME patients and identified abnormal regions as key regions of interest (ROIs). A novel aspect of our research was the application of a combined approach using the sliding window technique and Granger causality analysis (GCA). This method allowed us to delve into the dynamic causal relationships between these ROIs and uncover the intricate patterns of dynamic effective connectivity (DEC) that pervade various brain functional networks. Graph theory analysis revealed significant deviations in JME patients, characterized by abnormal increases or decreases in metrics such as nodal betweenness centrality, degree centrality, and efficiency. These findings underscore the presence of widespread disruptions in the topological features of the brain. Further, clustering analysis of the time series data from abnormal brain regions distinguished two distinct states indicative of DEC patterns: a state of strong connectivity at a lower frequency (State 1) and a state of weak connectivity at a higher frequency (State 2). Notably, both states were associated with connectivity abnormalities across different ROIs, suggesting the disruption of local properties within the brain functional connectivity network and the existence of widespread multi-functional brain functional networks damage in JME patients. Our findings elucidate significant disruptions in the local properties of whole-brain functional connectivity network in patients with JME, revealing causal impairments across multiple functional networks. These findings collectively suggest that JME is a generalized epilepsy with localized abnormalities. Such insights highlight the intricate network dysfunctions characteristic of JME, thereby enriching our understanding of its pathophysiological features.

Alterations in spatiotemporal characteristics of dynamic networks in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is characterized by altered patterns of brain functional connectivity (FC). However, the nature and extent of alterations in the spatiotemporal characteristics of dynamic FC in JME patients remain elusive. Dynamic networks effectively encapsulate temporal variations in brain imaging data, offering insights into brain network abnormalities and contributing to our understanding of the seizure mechanisms and origins. Resting-state functional magnetic resonance imaging (rs-fMRI) data were procured from 37 JME patients and 37 healthy counterparts. Forty-seven network nodes were identified by group-independent component analysis (ICA) to construct the dynamic network. Ultimately, patients' and controls' spatiotemporal characteristics, encompassing temporal clustering and variability, were contrasted at the whole-brain, large-scale network, and regional levels. Our findings reveal a marked reduction in temporal clustering and an elevation in temporal variability in JME patients at the whole-brain echelon. Perturbations were notably pronounced in the default mode network (DMN) and visual network (VN) at the large-scale level. Nodes exhibiting anomalous were predominantly situated within the DMN and VN. Additionally, there was a significant correlation between the severity of JME symptoms and the temporal clustering of the VN. Our findings suggest that excessive temporal changes in brain FC may affect the temporal structure of dynamic brain networks, leading to disturbances in brain function in patients with JME. The DMN and VN play an important role in the dynamics of brain networks in patients, and their abnormal spatiotemporal properties may underlie abnormal brain function in patients with JME in the early stages of the disease.

Transcranial brain parenchyma sonography in patients with juvenile myoclonic epilepsy.

There are rising evidences that subcortical structures, including the basal ganglia, are affected in patients with epilepsy. These structures are thought to influence the modulation and phenotypic expression of epileptic seizures. Our study aimed to evaluate the presence of structural abnormalities in subcortical structures in patients with juvenile myoclonic epilepsy (JME). This cross-sectional study included 51 patients who were diagnosed with JME and who were monitored on an outpatient basis at the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade from January 1985 to October 2017. All patients underwent transcranial parenchymal sonography (TCS) from October 2015 to October 2017. Relation of clinical parameters (seizure control andcognitive functioning,) with TCS results was assessed. Hyperechogenicity of the substantia nigra (SN) was detected in 37.2% of JME subjects and it was significantly more common in patients with JME than in the control group. The marked echogenicity of the red nucleus (RN) was detected in 17.6% of cases, while 11.8% of subjects had hyperechogenic RN. The presence of hyperechogenic RN (both right and left) was significantly more frequent in the group of patients with JME compared to the control group. The third ventricle diameter was larger in patients with JME than in controls. Structural changes of certain subcortical structures, primarily SN and RN, detected in JME patients indicate additional non-lesional abnormalities of the basal ganglia and midbrain structures in these patients.

A systematic review and meta-analysis of factors related to first line drugs refractoriness in patients with juvenile myoclonic epilepsy (JME).

Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients. The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis. A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity. In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.

A Comparative Study of Architecture and Quality of Sleep among Juvenile Myoclonic Epilepsy Patients and Healthy Individuals Attending Tertiary Care Hospital in Central India


 
 
 
 Background and Objective: Primary sleep disorders are common in patients with epilepsy. Seizures, epileptiform discharges, and antiepileptic drugs alter the sleep architecture of patients with juvenile myoclonic epilepsy (JME). We evaluated sleep architecture and its quality in these patients.
 Materials and Methods: Thirty patients with JME (11 men and 19 women with mean age of 21.10 ± 4.55 years) and 30 healthy controls underwent overnight polysomnography (PSG). Sleep quality and daytime sleepiness were assessed using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), respectively.
 Results: Myoclonus and generalized tonic-clonic seizures (GTCS) were present in all patients with JME, while absence seizures were in 13.3%. Sleep deprivation was the most frequent precipitating factor for seizures (56.6%) followed by fatigue, sound, and photic stimulation. Patients with JME reported a statistically significant drop in sleep efficiency (P<0.001) with prolonged sleep onset latency (P<0.001). There was prolongation in the N1 stage of non-rapid eye movement (NREM) sleep (P=0.002), and reduction in the N2 stage of NREM (P<0.001) and rapid eye movement (REM) sleep (P<0.001). The median PSQI score was higher in patients with JME, suggesting poor sleep quality (P<0.001), and the daytime sleepiness was not different as indicated by the similar median ESS score (P=0.033).
 Conclusion: Our results suggest a significant alteration in the sleep architecture of patients with JME with reduced sleep efficiency and poor sleep quality. The possible role of the disease itself is suggested for these alterations as a simi- lar trend was also observed in drug naïve patients.
 
 
 

Diffusion tensor imaging in photosensitive and nonphotosensitive juvenile myoclonic epilepsy

Introduction/backgroundJuvenile myoclonic epilepsy (JME) syndrome is known to cause alterations in brain structure and white matter integrity. The study aimed to determine structural white matter changes in patients with JME and to reveal the differences between the photosensitive (PS) and nonphotosensitive (NPS) subgroups by diffusion tensor imaging (DTI) using the tract-based spatial statistics (TBSS) method. MethodsThis study included data from 16 PS, 15 NPS patients with JME, and 41 healthy participants. The mean fractional anisotropy (FA) values of these groups were calculated, and comparisons were made via the TBSS method over FA values in the whole-brain and 81 regions of interest (ROI) obtained from the John Hopkins University White Matter Atlas. ResultsIn the whole-brain TBSS analysis, no significant differences in FA values were observed in pairwise comparisons of JME patient group and subgroups with healthy controls (HCs) and in comparison between JME subgroups. In ROI-based TBSS analysis, an increase in FA values of right anterior corona radiata and left corticospinal pathways was found in JME patient group compared with HC group. When comparing JME-PS patients with HCs, an FA increase was observed in the bilateral anterior corona radiata region, whereas when comparing JME-NPS patients with HCs, an FA increase was observed in bilateral corticospinal pathway. Moreover, in subgroup comparison, an increase in FA values was noted in corpus callosum genu region in JME-PS compared with JME-NPS. ConclusionsOur results support the disruption in thalamofrontal white matter integrity in JME, and subgroups and highlight the importance of using different analysis methods to show the underlying microstructural changes.

Recognition and Perception of Emotions in Juvenile Myoclonic Epilepsy.

Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments which might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional MRI (fMRI). Sixty-five patients with JME (median age 27 years, IQR 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age 24 years, IQR 21-31), matched for sex, age and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces", structured interview for psychiatric and personality disorders and comprehensive neuropsychological testing. JME patients versus healthy controls, demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures and treatment. This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutical interventions in the management of patients with JME.

MRI-Based Radiomics Approach for Differentiating Juvenile Myoclonic Epilepsy from Epilepsy with Generalized Tonic-Clonic Seizures Alone.

The clinical presentation of juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures alone (GTCA) is similar, and MRI scans are often perceptually normal in both conditions making them challenging to differentiate. To develop and validate an MRI-based radiomics model to accurately diagnose JME and GTCA, as well as to classify prognostic groups. Retrospective. 164 patients (127 with JME and 37 with GTCA) patients (age 24.0 ± 9.6; 50% male), divided into training (n = 114) and test (n = 50) sets in a 7:3 ratio with the same proportion of JME and GTCA patients kept in both sets. 3T; 3D T1-weighted spoiled gradient-echo. A total of 17 region-of-interest in the brain were identified as having clinical evidence of association with JME and GTCA, from where 1581 radiomics features were extracted for each subject. Forty-eight machine-learning combinations of oversampling, feature selection, and classification algorithms were explored to develop an optimal radiomics model. The performance of the best radiomics models for diagnosis and for classification of the favorable outcome group were evaluated in the test set. Model performance measured using area under the curve (AUC) of receiver operating characteristic (ROC) curve. Shapley additive explanations (SHAP) analysis to estimate the contribution of each radiomics feature. The AUC (95% confidence interval) of the best radiomics models for diagnosis and for classification of favorable outcome group were 0.767 (0.591-0.943) and 0.717 (0.563-0.871), respectively. SHAP analysis revealed that the first-order and textural features of the caudate, cerebral white matter, thalamus proper, and putamen had the highest importance in the best radiomics model. The proposed MRI-based radiomics model demonstrated the potential to diagnose JME and GTCA, as well as to classify prognostic groups. MRI regions associated with JME, such as the basal ganglia, thalamus, and cerebral white matter, appeared to be important for constructing radiomics models. 3 TECHNICAL EFFICACY: Stage 3.

A comparison of comorbid headache between patients with temporal lobe epilepsy and juvenile myoclonic epilepsy

Headache is one of the most common symptoms of epilepsy comorbidities. However, the relationship between the epilepsy and headache still needs clarification. Previous studies mostly investigated the overall incidence and clinical features of the headache in patients with the epilepsy. Temporal lobe epilepsy (TLE) and juvenile myoclonic epilepsy (JME) are the common types of focal epilepsy and generalized epilepsy, respectively. Nevertheless, there was no study comparing the clinical features of headache between TLE and JME. This study aimed to analyze the headache features of these two types of epilepsy. Patients with either TLE or JME diagnosed with headache and referred to the West China Hospital of Sichuan University were consecutively recruited from June 2021 to June 2022. The duration of epilepsy was longer than 6 months in these patients. Data on headache and epilepsy were obtained through face-to-face questionnaires. The headache was classified according to the International Classification Headache Disorders-3rd edition (ICHD-III) criteria. χ2-test, t-test, rank-sum test, logistic regression modeling and Mann Whitney test were used to compare the clinical differences of the headache in TLE and JME. A total of 151 TLE patients and 30 JME patients were enrolled in this study. There was no significant difference in the family history of headache, epilepsy durations, headache types, proportion receiving analgesic therapy, the frequency of inter-ictal headache (inter-IH), and the quality of life in epilepsy -10 inventory (QOLIE-10) between the TLE and JME patients. Patients in the TLE group were significantly older (p = 0.004), and a lower percentage of them had a family history of epilepsy (p = 0.007) compared with the JME patients. The proportion of cases with refractory epilepsy was higher in the TLE group than that in the JME group (p < 0.001). The types of seizures in the TLE group varied from those in the JME group (p < 0.001). The composition of the antiseizure medications (ASM) applied in the TLE group differed from that in the JME group (p = 0.047), and the usage of oxcarbazepine was more frequently in the TLE group than in the JME group (p = 0.003). There was no difference in the headache types among patients with TLE or JME. Specifically, 67 (44.37%), 12 (7.95%), and 118 (7.95%) patients were found with inter-IH, pre-ictal headache (Pre-IH) and post-ictal headache (Post-IH) in the TLE group; while 8 (26.67%), 4 (13.33%) and 26 (86.67%) patients had inter-IH, Pre-IH and Post-IH in the JME group. Thirty-nine patients in the TLE group and 4 patients in the JME group were identified with more than one type of headaches, respectively. Tension-type headache (TTH) were found in 38 patients (25.17%) in the TLE group and 3 patients (10.00%) in the JME group, respectively; migraines were found in 10 patients (6.62%) in the TLE group and in 2 patients (6.67%) in the JME group. Patients in the TLE group had a higher headache-attributed lost time-90 days (HLT-90) score than those in the JME group (p = 0.019). The proportion of patients with inter-IH accompanied by nausea in the TLE group was higher than that in the JME group (p = 0.029), while the proportion of patients with frontal headache was lower than that in the JME group (p < 0.05). There was no significant difference in headache severity, quality, headache nature, unilateral/bilateral, and headache duration either in inter-IH or peri-ictal headache (Peri-IH) between the two groups. The logistic regression analysis suggested that except for HLT-90 (AUC = 0.622, p = 0.027), other factors were not found to be correlated with refractory epilepsy. The clinical features of headache differed between TLE and JME patients. TLE patients had a higher ratio of refractory epilepsy, more headache time loss compared with JME patients. HLT-90 was associated with the occurrence of refractory epilepsy in TLE patients. Taken together, we suggested that the comorbid headache may essentially be different between TLE and JME patients.

Atypical juvenile myoclonic epilepsy with structural brain abnormalities and cognitive impairment: A case report

Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy affecting 5–10% of epilepsy patients. Its exact cause remains unknown, but recent studies indicate frontal region involvement. It responds well to anticonvulsants but is often misdiagnosed with focal-onset epilepsy. We present a 9-year-old girl with myoclonic, absence, and generalized tonic-clonic seizures happening over three months. EEG revealed slow spike and wave complexes with generalized polyspikes, while brain MRI identified encephalomalacia cysts with right frontotemporal lobe hemiatrophy. Valproic acid treatment led to seizure-free status for one month. In conclusion, timely EEG and neuroimaging are pivotal in identifying structural abnormalities in JME patients with pronounced cognitive impairment, enabling tailored treatment and better outcomes.

Neuropsychological Evaluation of Visual Spatial Functions in Juvenile Myoclonic Epilepsy Patients

Neuropsychological Evaluation of Visual Spatial Functions in Juvenile Myoclonic Epilepsy Patients

A Study On The Quality Of Life And Psychiatric Comorbidities In Patients Of Juvenile Myoclonic Epilepsy In A Tertiary Care Center In North India (P1-1.007)

<h3>Objective:</h3> To assess quality of life in patients with Juvenile Myoclonic Epilepsy with special emphasis on social, psychological, relationships and vocational aspects of life To screen and classify psychiatric co morbidities in patients with Juvenile Myoclonic Epilepsy <h3>Background:</h3> Juvenile myoclonic epilepsy (JME) is exemplary of a well-defined age-related genetic epilepsy syndrome representing 5–11 % of all epilepsy cases &amp; 3–11 % of all adolescent epilepsy cases. 74% of JME patients have at least one major marker of unfavorable social outcome. One of the contributing factors maybe the distinct personality profile such as unsteadiness, lack of discipline and an indifference to their disease. JME though usually well controlled, may adversely impact the Quality of Life. <h3>Design/Methods:</h3> This was an observational cross – sectional study carried out over a period of 18 months in a tertiary center at Delhi. Sample size was 50. Patients fulfilling the diagnostic criteria of Juvenile Myoclonic Epilepsy according to ILAE criteria 2001 were included in the study. They underwent a structured questionnaire to assess for the impact of JME on the Quality of Life. QOLIE-48 AD and QOLIE 31 P was used for adolescent and adult population respectively. Then they underwent M.I.N.I 7.0.2. Those testing positive for psychiatric disorders underwent DSM-5 categorization. <h3>Results:</h3> We found two important determinants of reduced Quality of Life in the adolescent patients – Physical Functioning [Mean score :57.36 ± 18.94] &amp; Health perception [Mean score: 57.36 ± 18.94] respectively. Quality of Life −31 P score [Mean score: 62.29 ± 25.02] was fair in (37.21 %) of adults. Academic underachievement was seen in 1(2%), 1(2%) public gatherings, 2 (4%) expressed fear of breaking marriage . Anxiety was found in (10%) and depression in (6%). <h3>Conclusions:</h3> Anxiety and depression were the comorbid psychiatric disorders in the study population The concurrent presence of these comorbid conditions must be addressed to improve the quality of life. <b>Disclosure:</b> Dr. Choudhury has nothing to disclose. Prof. CHAUDHRY has nothing to disclose. Dr. Laskar has nothing to disclose.

Juvenile Myoclonic Epilepsy: Seizure and Social Outcomes in Taiwan.

Patients with juvenile myoclonic epilepsy (JME) may not achieve seizure freedom despite optimal treatment with antiseizure medications (ASMs). The aim of this study was to investigate the clinical and social features of patients with JME, and to determine the factors associated with outcomes. We retrospectively identified 49 patients with JME (25 females, mean age 27.6 ± 8.9 years) who were assessed at the Epilepsy Centre of Linkou Chang Gung Memorial Hospital in Taiwan. The patients were divided into two groups, those who were seizure-free and those with ongoing seizures according to their seizure outcome at the last follow-up for one year. Clinical features and social status were compared between these two groups. Twenty-four (49%) of the JME patients were seizure-free for at least one year, while 51% continued to experience seizures despite being treated with multiple ASMs. The presence of epileptiform discharges in the last electroencephalogram and seizures during sleep were significantly associated with worse seizure outcomes (p < 0.05). The patients who were seizure-free had a higher employment rate compared to those who continued to experience seizures (75% vs. 32%, p = 0.004). Despite receiving ASM treatment, a considerable proportion of the patients with JME continued to have seizures. Moreover, poor seizure control was associated with a lower employment rate, which may lead to negative socioeconomic consequences related to JME.

Multilayer brain network modeling and dynamic analysis of juvenile myoclonic epilepsy.

Objective: It is indisputable that the functional connectivity of the brain network in juvenile myoclonic epilepsy (JME) patients is abnormal. As a mathematical extension of the traditional network model, the multilayer network can fully capture the fluctuations of brain imaging data with time, and capture subtle abnormal dynamic changes. This study assumed that the dynamic structure of JME patients is abnormal and used the multilayer network framework to analyze the change brain community structure in JME patients from the perspective of dynamic analysis. Methods: First, functional magnetic resonance imaging (fMRI) data were obtained from 35 JME patients and 34 healthy control subjects. In addition, the communities of the two groups were explored with the help of a multilayer network model and a multilayer community detection algorithm. Finally, differences were described by metrics that are specific to the multilayer network. Results: Compared with healthy controls, JME patients had a significantly lower modularity degree of the brain network. Furthermore, from the level of the functional network, the integration of the default mode network (DMN) and visual network (VN) in JME patients showed a significantly higher trend, and the flexibility of the attention network (AN) also increased significantly. At the node level, the integration of seven nodes of the DMN was significantly increased, the integration of five nodes of the VN was significantly increased, and the flexibility of three nodes of the AN was significantly increased. Moreover, through division of the core-peripheral system, we found that the left insula and left cuneus were core regions specific to the JME group, while most of the peripheral systems specific to the JME group were distributed in the prefrontal cortex and hippocampus. Finally, we found that the flexibility of the opercular part of the inferior frontal gyrus was significantly correlated with the severity of JME symptoms. Conclusion: Our findings indicate that the dynamic community structure of JME patients is indeed abnormal. These results provide a new perspective for the study of dynamic changes in communities in JME patients.

Dynamic flexibility and controllability of network communities in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is the most common syndrome within the idiopathic generalized epilepsy spectrum, manifested by myoclonic and generalized tonic-clonic seizures and spike-and-wave discharges (SWDs) on electroencephalography (EEG). Currently, the pathophysiological concepts addressing SWD generation in JME are still incomplete. In this work, we characterize the temporal and spatial organization of functional networks and their dynamic properties as derived from high-density EEG (hdEEG) recordings and MRI in 40 JME patients (25.4 ± 7.6 years, 25 females). The adopted approach allows for the construction of a precise dynamic model of ictal transformation in JME at the cortical and deep brain nuclei source levels. We implement Louvain algorithm to attribute brain regions with similar topological properties to modules during separate time windows before and during SWD generation. Afterwards, we quantify how modular assignments evolve and steer through different states towards the ictal state by measuring characteristics of flexibility and controllability. We find antagonistic dynamics of flexibility and controllability within network modules as they evolve towards and undergo ictal transformation. Prior to SWD generation, we observe concomitantly increasing flexibility (F(1,39) = 25.3, corrected p < 0.001) and decreasing controllability (F(1,39) = 55.3, p < 0.001) within the fronto-parietal module in γ-band. On a step further, during interictal SWDs as compared to preceding time windows, we notice decreasing flexibility (F(1,39) = 11.9, p < 0.001) and increasing controllability (F(1,39) = 10.1, p < 0.001) within the fronto-temporal module in γ-band. During ictal SWDs as compared to prior time windows, we demonstrate significantly decreasing flexibility (F(1,14) = 31.6; p < 0.001) and increasing controllability (F(1,14) = 44.7, p < 0.001) within the basal ganglia module. Furthermore, we show that flexibility and controllability within the fronto-temporal module of the interictal SWDs relate to seizure frequency and cognitive performance in JME patients. Our results demonstrate that detection of network modules and quantification of their dynamic properties is relevant to track the generation of SWDs. The observed flexibility and controllability dynamics reflect the reorganization of de−/synchronized connections and the ability of evolving network modules to reach a seizure-free state, respectively. These findings may advance the elaboration of network-based biomarkers and more targeted therapeutic neuromodulatory approaches in JME.

Clinical and electroencephalographic findings prior to the onset of juvenile myoclonic epilepsy: A case series.

The purpose of this study was to investigate the timing of generalized electroencephalographic abnormalities in patients with juvenile myoclonic epilepsy who were followed up long term before the onset of juvenile myoclonic epilepsy. We enrolled juvenile myoclonic epilepsy patients whose course of epilepsy had been observed for >5 years before the onset of juvenile myoclonic epilepsy, those who had undergone electroencephalogram recording more than twice before the onset of juvenile myoclonic epilepsy, and those who had terminated antiseizure medications for at least 2 years before the onset of juvenile myoclonic epilepsy. Patients who had transitioned from childhood absence epilepsy to juvenile myoclonic epilepsy were excluded. We retrospectively reviewed the medical records and neurophysiological data of the patients. Four patients met the inclusion criteria. One patient was diagnosed with febrile seizures during childhood, and the remaining three had transitioned to juvenile myoclonic epilepsy from other epileptic disorders, such as self-limited epilepsy with autonomic seizures, genetic epilepsy with febrile seizure plus, or nonspecific genetic generalized epilepsy. All patients exhibited generalized spike-wave discharges or photoparoxysmal responses for >2 years before the onset of juvenile myoclonic epilepsy. The four patients had transitioned to juvenile myoclonic epilepsy from other epileptological preconditions. Patients with juvenile myoclonic epilepsy may show generalized electroencephalographic abnormality many years prior to the onset of symptoms. Generalized spike-waves on the electroencephalogram during the course of any type of epilepsy or febrile seizure may be a risk factor for developing juvenile myoclonic epilepsy.

Paroxysmal Slow-Wave Events Are Uncommon in Parkinson's Disease.

Background: Parkinson’s disease (PD) is currently considered to be a multisystem neurodegenerative disease that involves cognitive alterations. EEG slowing has been associated with cognitive decline in various neurological diseases, such as PD, Alzheimer’s disease (AD), and epilepsy, indicating cortical involvement. A novel method revealed that this EEG slowing is composed of paroxysmal slow-wave events (PSWE) in AD and epilepsy, but in PD it has not been tested yet. Therefore, this study aimed to examine the presence of PSWE in PD as a biomarker for cortical involvement. Methods: 31 PD patients, 28 healthy controls, and 18 juvenile myoclonic epilepsy (JME) patients (served as positive control), underwent four minutes of resting-state EEG. Spectral analyses were performed to identify PSWEs in nine brain regions. Mixed-model analysis was used to compare between groups and brain regions. The correlation between PSWEs and PD duration was examined using Spearman’s test. Results: No significant differences in the number of PSWEs were observed between PD patients and controls (p > 0.478) in all brain regions. In contrast, JME patients showed a higher number of PSWEs than healthy controls in specific brain regions (p < 0.023). Specifically in the PD group, we found that a higher number of PSWEs correlated with longer disease duration. Conclusions: This study is the first to examine the temporal characteristics of EEG slowing in PD by measuring the occurrence of PSWEs. Our findings indicate that PD patients who are cognitively intact do not have electrographic manifestations of cortical involvement. However, the correlation between PSWEs and disease duration may support future studies of repeated EEG recordings along the disease course to detect early signs of cortical involvement in PD.

Abnormal gait and motor cortical processing in drug‐resistant juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is characterized by generalized seizures. Nearly 30% of JME patients are drug-resistant (DR-JME), indicating a widespread cortical dysfunction. Walking is an important function that necessitates orchestrated coordination of frontocentral cortical regions. However, gait alterations in JME have been scarcely investigated. Our aim was to assess changes in gait and motor-evoked responses in DR-JME patients. Twenty-nine subjects (11 JME drug-responder, 8 DR-JME, and 10 healthy controls) underwent a gait analyses during usual walking and dual-task walking. Later, subjects underwent 64-channel EEG recordings while performing a simple motor task. We calculated the motor-evoked current source densities (CSD) at a priori chosen cortical regions. Gait and CSD measures were compared between groups and tasks using mixed model analysis. DR-JME patients demonstrated an altered gait pattern that included slower gait speed (p=.018), reduced cadence (p=.003), and smaller arm-swing amplitude (p=.011). The DR-JME group showed higher motor-evoked CSD in the postcentral gyri compared to responders (p=.049) and both JME groups showed higher CSD in the superior frontal gyri compared to healthy controls (p<.011). Moreover, higher CSD in the superior frontal gyri correlated with worse performance in dual-task walking (r>|-0.494|, p<.008). These alterations in gait and motor-evoked responses in DRE-JME patients reflect a more severe dysfunction of motor-cognitive neural processing in frontocentral regions, leading to poorer gait performance. Further studies are needed to investigate the predictive value of altered gait and cortical motor processing as biomarkers for poor response to treatment in JME and other epilepsy syndromes.

Incidence and Associated Factors of Juvenile Myoclonic Epilepsy among Idiopathic Generalized Epilepsy

Juvenile myoclonic epilepsy (JME) is widely recognized presumed genetic, electroclinical idiopathic generalized epilepsy (IGE) syndrome. The prevalence of JME is about 18% of IGEs. However, there is a considerable variation in different settings.Aims: to determine the incidence and associated factors of JME among patients with IGEs.Patients and Methods: This retrospective study included a total of 52 patients with electro-clinical feature of IGE. All enrolled patients were undergone a three-hour video electroencephalography (EEG). JME was diagnosed on the basis of JME consensus definition clinical criteria class II. The demographic and clinical characteristics of the patients were abstracted from their records.Results: The most common epilepsy syndrome of IGE was generalized tonic-clonic seizure (GTCS) only affecting (32.7%) followed by juvenile absence epilepsy (JAE) (25%), JME and JME only (each 17.3%) and Generalized myoclonic epilepsy and generalized tonic-clonic (GMEGTC) (13.46%). All JME patients were females (100%) compared with 69.77% of the patients in other IGE syndromes with a highly significant difference. According to EEG results, 8 patients (88.89%) of JME patients had generalized polyspikes, and two patient (22.22%) showed generalized spikes and waves (3/second spike and wave complex). One patient (11.11%) two EEG findings (polyspike and generalized spike and waves)Conclusions: JME can affect adolescents and young adults and it can effect child age group. It is distinguished by the occurrence of myoclonic seizures, characteristic spike-and-wave EEG pattern at 4-6 Hz, and more common in females than males.

Altered Cerebro-Cerebellar Effective Connectivity in New-Onset Juvenile Myoclonic Epilepsy.

(1) Objective: Resting-state fMRI studies have indicated that juvenile myoclonic epilepsy (JME) could cause widespread functional connectivity disruptions between the cerebrum and cerebellum. However, the directed influences or effective connectivities (ECs) between these brain regions are poorly understood. In the current study, we aimed to evaluate the ECs between the cerebrum and cerebellum in patients with new-onset JME. (2) Methods: Thirty-four new-onset JME patients and thirty-four age-, sex-, and education-matched healthy controls (HCs) were included in this study. We compared the degree centrality (DC) between the two groups to identify intergroup differences in whole-brain functional connectivity. Then, we used a Granger causality analysis (GCA) to explore JME-caused changes in EC between cerebrum regions and cerebellum regions. Furthermore, we applied a correlation analysis to identify associations between aberrant EC and disease severity in patients with JME. (3) Results: Compared to HCs, patients with JME showed significantly increased DC in the left cerebellum posterior lobe (CePL.L), the right inferior temporal gyrus (ITG.R) and the right superior frontal gyrus (SFG.R), and decreased DC in the left inferior frontal gyrus (IFG.L) and the left superior temporal gyrus (STG.L). The patients also showed unidirectionally increased ECs from cerebellum regions to the cerebrum regions, including from the CePL.L to the right precuneus (PreCU.R), from the left cerebellum anterior lobe (CeAL.L) to the ITG.R, from the right cerebellum posterior lobe (CePL.R) to the IFG.L, and from the left inferior semi-lunar lobule of the cerebellum (CeISL.L) to the SFG.R. Additionally, the EC from the CeISL.L to the SFG.R was negatively correlated with the disease severity. (4) Conclusions: JME patients showed unidirectional EC disruptions from the cerebellum to the cerebrum, and the negative correlation between EC and disease severity provides a new perspective for understanding the cerebro-cerebellar neural circuit mechanisms in JME.