Juvenile Myoclonic Epilepsy Research Articles

Neuropsychological profile and drug treatment response in Idiopathic Generalized Epilepsy

PurposeThe endophenotype of Idiopathic Generalized Epilepsies (IGE) comprises distinct neuropsychological deficits compared to normal controls. It is unknown if the severity of features of the endophenotype correlates with resistance to anti-seizure medication. Therefore, we here studied the association of neuropsychological profiles with treatment response. MethodsWe evaluated 106 Danish patients aged ≥18 and diagnosed with IGE using a neuropsychological test battery comprising tests for executive dysfunction, visual attention, episodic memory, and verbal comprehension. Tests were complemented by the Purdue Pegboard test. Patients with suspected ongoing psychogenic non-epileptic seizures were excluded. ResultsAt testing, 72 patients were seizure free, and 34 patients had recent seizures despite anti-seizure medication. As compared to age corrected Danish normative values, IGE patients showed significant impairments in semantic fluency and performed significantly worse in the Purdue Pegboard test. The vocabulary subtest of the WAIS-IV suggested lower verbal comprehension in IGE patients. We found no signs of memory impairment. Comparisons between results of the test battery, drug resistance, and the different IGE subsyndromes revealed consistent null-associations in various predefined and exploratory univariate and multivariate analyses. ConclusionWe here found and confirmed the distinct neuropsychological profile comprising impaired executive functions, reduced psychomotor speed, and normal memory previously described in juvenile myoclonic epilepsy. This profile was, however, not restricted to juvenile myoclonic epilepsy but equally affected all IGE patients. The neuropsychological deficits were not significantly associated with drug treatment outcome.

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.

Long-term Remission in Juvenile Myoclonic Epilepsy (S44.009)

Long-term Remission in Juvenile Myoclonic Epilepsy (S44.009)

Prevalence, nature, and severity of the psychiatric comorbidities and their impact on quality of life in adolescents with Juvenile myoclonic epilepsy

IntroductionAdults with Juvenile myoclonic epilepsy (JME) are at increased risk for psychiatric comorbidities, personality traits, and abnormality in executive function. But studies on adolescents and their impact on quality of life are scarce in the literature. Materials and MethodsThis cross-sectional study was performed between August 2019 and October 2022 to compare the prevalence of psychiatric comorbidities in adolescents with JME and age and gender-matched healthy controls. After completing DSM-5 Structured Clinical Interview (SCID-5) initially in all patients, we measured the severity of individual psychiatric problems like anxiety, depression, and somatic symptoms by using an appropriate psychometric scale. We also measured both groups' intelligence quotient (IQ), executive function, and quality of life. ResultsOne hundred patients with JME (14.3 ± 2.5 years, 48 boys) and 100 controls were enrolled. Psychiatric disorders were observed in 46% of JME and 6% of controls (p < 0.01). Psychiatric comorbidities noted in the patients with JME were: somatic symptom and related disorders(n = 14), anxiety (n = 13), adjustment disorders (n = 12), depression (n = 11), oppositional defiant disorder (n = 6), conduct disorder (n = 5), anorexia nervosa (n = 3), narcissistic (n = 3), histrionic (n = 1), substance-related disorder (n = 1), borderline (n = 2) and antisocial personality disorder (n = 2). The prevalence of depressive disorders, anxiety disorders, adjustment disorders, somatic symptoms, related disorders, and any personality disorder was significantly more in the JME group (p < 0.01 for all). Female gender, higher Epilepsy Stigma Scale score, and lower Epilepsy Outcome Expectancy Scale were significantly associated with depressive disorders (p = 0.04, 0.03, 0.03 respectively). Similarly, for anxiety, only female gender and lower Epilepsy Outcome Expectancy Scale were significant associated factors (p = 0.03, 0.02 respectively). ConclusionsPsychiatric disorders like anxiety, depression, and personality disorders are more frequent in adolescents with JME than in controls.

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.

Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy.

Gene sub-region encoded protein domain is the basic unit for protein structure and function. The DMD gene is the largest coding gene in humans, with its phenotype relevant to idiopathic generalized epilepsy. We hypothesized variants clustered in sub-regions of idiopathic generalized epilepsy genes and investigated the relationship between the DMD gene and idiopathic generalized epilepsy. Whole exome sequencing was performed in 106 idiopathic generalized epilepsy individuals. DMD variants were filtered with variant type, allele frequency, in silico prediction, hemizygous or homozygous status in the population, inheritance mode, and domain location. Variants located at the sub-regions were selected by the subRVIS software. The pathogenicity of variants was evaluated by the American College of Medical Genetics and Genomics criteria. Articles on functional studies related to epilepsy for variants clustered protein domains were reviewed. In sub-regions of the DMD gene, two variants were identified in two unrelated cases with juvenile absence epilepsy or juvenile myoclonic epilepsy. The pathogenicity of both variants was uncertain significance. Allele frequency of both variants in probands with idiopathic generalized epilepsy reached statistical significance compared with the population (Fisher's test, p = 2.02 × 10-6, adjusted α = 4.52 × 10-6). The variants clustered in the spectrin domain of dystrophin, which binds to glycoprotein complexes and indirectly affects ion channels contributing to epileptogenesis. Gene sub-region analysis suggests a weak association between the DMD gene and idiopathic generalized epilepsy. Functional analysis of gene sub-region helps infer the pathogenesis of idiopathic generalized epilepsy.

Electroencephalographic findings in asymptomatic relatives of patients with juvenile myoclonic epilepsy: relationship with the degree of kinship.

A prevalence of 1 to 71% of electroencephalogram (EEG) abnormalities has been reported in asymptomatic relatives of patients with juvenile myoclonic epilepsy (JME). To determine the frequency of EEG abnormalities in asymptomatic relatives of patients with JME according to the degree of kinship. Prospective, analytical study. First-, second, and third-degree relatives of patients with JME who agreed to participate and signed informed consent were included. The analysis was descriptive, bivariate. 209 asymptomatic relatives were included, out of which 115 (55%) were females and 94 (45%) were males, with a mean age of 35.9 ± 16.9 (range between 6 and 73 years). Forty-four (21.1%) relatives had abnormal EEGs. First-degree relatives (12%) had abnormalities more frequently in comparison with second- and third-degree relatives (p = 0.007). EEG abnormalities were observed in one third of asymptomatic relatives. It is important to highlight that there were more alterations among first-degree relatives. In the future, these findings might enable for the risk of clinically developing the disease to be estimated and for genetic counseling to be provided.

Clinical Characteristics and Prognosis of Juvenile Myoclonic Epilepsy: Single-Center Retrospective Study

AbstractJuvenile myoclonic epilepsy (JME) is one of the most common idiopathic (genetic) generalized epilepsy syndromes. It occurs in healthy adolescents and is characterized by the triad of myoclonic jerks, generalized tonic-clonic seizures (GTCs), and absence seizures. The study's primary aim was to determine the demographic and clinical characteristics, family history of seizure, electroencephalogram findings, treatments, and short-term prognosis of patients diagnosed with JME. Patients diagnosed with JME at the Pediatric Neurology Department of Sağlık Bilimleri University Adana Numune Training and Research Hospitals were enrolled. Thirteen (30%) of 44 patients were male, whereas 31 (70%) were female, with a mean age at diagnosis of 14 ± 1.3 years. In total, 21 patients (48%) had a family history of epilepsy, and 14 patients (32%) had JME in their families. Those having a family history of JME seizures were identified at a younger age. Thirty (68%) patients presented with GTCs, while 14 (32%) presented with myoclonic seizures at the time of diagnosis. In the history, 98% of patients had myoclonus and one patient had an absence seizure. Patients with the first seizure type GTCs were diagnosed later, while patients with myoclonus were diagnosed earlier (p &lt; 0,05). The most precipitating factors for seizures were sleep deprivation and stress. Thirty-eight (86%) of the EEGs recorded during the initial admission was abnormal. Valproic acid was administered to 32 patients (73%), while levetiracetam was administered to 12 patients (27%) as the initial treatment. Forty-one (93%) of the patients exhibited a complete response to the initial medication therapy, while forty (91%) of the patients received monotherapy, and only four (9%) received polytherapy. JME may be well-controlled epilepsy with early diagnosis and appropriate treatment. A family history of JME is also common among patients with JME. Patients with the myoclonus as a first seizure type are diagnosed earlier than GTCs because of family awareness. A family history of JME may facilitate the diagnosis of new cases in the family.

New Epilepsy Syndrome Classification of International League Against Epilepsy: Idiopathic Generalized Epilepsy Syndromes

The idiopathic generalized epilepsies (IGEs) have historically included the syndromes of childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and epilepsy with generalized tonic-clonic seizures alone. The goal of this paper is to provide updated diagnostic criteria for the four syndromes of IGEs determined by the expert consensus opinion of the International League Against Epilepsy’s Task Force on Nosology and Definitions (2017–2021). The IGEs have polygenic inheritance, with or without environmental factors. Development is typically normal. Seizure types include one or a combination of the following: absence, myoclonic, tonic-clonic, and myoclonic-tonic-clonic seizures. Electroencephalography shows generalized 2.5 to 5.5-Hz spike-waves, which may be activated by hyperventilation or photic stimulation. Key words: Seizures; Childhood absence epilepsy; Juvenile absence epilepsy; Juvenile myoclonic epilepsy; generalized tonic-clonic seizures alone.

Altered Cerebellar Volumes and Intrinsic Cerebellar Network in Juvenile Myoclonic Epilepsy

Objectives. This study is aimed at investigating the alterations in cerebellar volumes and intrinsic cerebellar network in patients with juvenile myoclonic epilepsy (JME) in comparison with healthy controls. Methods. Patients newly diagnosed with JME and healthy controls were enrolled. Three-dimensional T1-weighted imaging was conducted, and no structural lesions were found on brain magnetic resonance imaging. Cerebellar volumes were obtained using the ACAPULCO program, while the intrinsic cerebellar network was evaluated by applying graph theory using the BRAPH program. The nodes were defined as individual cerebellar volumes and edges as partial correlations, controlling for the effects of age and sex. Cerebellar volumes and intrinsic cerebellar networks were compared between the two groups. Results. Forty-five patients with JME and 45 healthy controls were enrolled. Compared with the healthy controls, the patients with JME had significantly lower volumes of the right and left cerebellar white matter (3.33 vs. 3.48%, p = 0.009 ; 3.35 vs. 3.49%, p = 0.009 ), corpus medullare (0.99 vs. 1.03%, p = 0.04 ), and left lobule V (0.19 vs. 0.22%, p = 0.002 ). The intrinsic cerebellar networks also showed significant differences between the two groups. The small-worldness index in the patients with JME was significantly lower than that in the healthy controls (0.771 vs. 0.919, p = 0.04 ). Conclusion. The cerebellar volumes and intrinsic cerebellar network demonstrated alterations in the patients with JME when compared with those of the healthy controls. Our study results provide evidence that the cerebellum may play a role in the pathogenesis of JME.

The role of additive and diffusive coupling on the dynamics of neural populations

Dynamical models consisting of networks of neural masses commonly assume that the interactions between neural populations are via additive or diffusive coupling. When using the additive coupling, a population’s activity is affected by the sum of the activities of neighbouring populations. In contrast, when using the diffusive coupling a neural population is affected by the sum of the differences between its activity and the activity of its neighbours. These two coupling functions have been used interchangeably for similar applications. In this study, we show that the choice of coupling can lead to strikingly different brain network dynamics. We focus on a phenomenological model of seizure transitions that has been used both with additive and diffusive coupling in the literature. We consider small networks with two and three nodes, as well as large random and scale-free networks with 64 nodes. We further assess resting-state functional networks inferred from magnetoencephalography (MEG) from people with juvenile myoclonic epilepsy (JME) and healthy controls. To characterize the seizure dynamics on these networks, we use the escape time, the brain network ictogenicity (BNI) and the node ictogenicity (NI), which are measures of the network’s global and local ability to generate seizure activity. Our main result is that the level of ictogenicity of a network is strongly dependent on the coupling function. Overall, we show that networks with additive coupling have a higher propensity to generate seizures than those with diffusive coupling. We find that people with JME have higher additive BNI than controls, which is the hypothesized BNI deviation between groups, while the diffusive BNI provides opposite results. Moreover, we find that the nodes that are more likely to drive seizures in the additive coupling case are more likely to prevent seizures in the diffusive coupling case, and that these features correlate to the node’s number of connections. Consequently, previous results in the literature involving such models to interrogate functional or structural brain networks could be highly dependent on the choice of coupling. Our results on the MEG functional networks and evidence from the literature suggest that the additive coupling may be a better modeling choice than the diffusive coupling, at least for BNI and NI studies. Thus, we highlight the need to motivate and validate the choice of coupling in future studies involving network models of brain activity.

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.

Idiopathic generalized epilepsies: Analysis of 101 patients

Idiopathic generalized epilepsies (IGI) are an electroclinical syndrome that includes four subsyndromes according to the ILAE 2017 classification. The long-term prognosis of these syndromes is uncertain due to the scarcity and heterogeneity of the studies. The objective of this study is to analyze the long-term prognosis of these syndromes, pharmacological treatment and the seizure recurrence. Observational and retrospective study of a serie of patients diagnosed with EGI. Epidemiological variables, pharmacological treatment, freedom of seizures and recurrence after withdrawal of treatment were collected. We included 101 patients, the majority women (56.4%), with a median evolution of epilepsy of 17 years (interquartile range: 7-31). The most frequent syndrome was juvenile myoclonic epilepsy (46.5%), followed by epilepsy with generalized tonic-clonic seizures alone (25.7%), juvenile absence epilepsy (13.9%) and childhood absence epilepsy (13.9%). The 71.29% were on monotherapy and 20.79% on polytherapy, with significant differences between the different syndromes (P=.001). The most widely used drug was valproic acid. 39.6% presented seizure remission at 5 years, but we did not observe significant differences between the different syndromes (P=.982). The recurrence rate was 71.4% after withdrawal of treatment. Juvenile myoclonic epilepsy was the most frequent subtype of IGE. We observed significant differences in terms of polytherapy in the different syndromes, although not in the rates of remission of seizures at one year and at five years. The majority of patients with treatment withdrawal relapsed.

Relationship between Juvenile Myoclonic Epilepsy and Melatonin

Amaç: Melatoninin sirkadiyen ritmi düzenleyerek antikonvülsan ve nöroprotektif özelliklere sahip olduğu bulunmuştur. Bu etkisinden yola çıkarak Juvenil myoklonik epilepsili (JME) hastalar ve sağlıklı bireylerde melatonin serum düzeylerinin belirlenmesi amaçlanmıştır. JME’li hastalar ile sağlıklı bireylerdeki serum melatonin seviyelerini karşılaştıran ilk çalışma olma özelliğini de taşımaktadır. Hastalar ve Yöntem: Bu çapraz-kesitsel çalışmaya JME’li 30 hasta ve benzer cinsiyet ve yaş dağılımına sahip 30 sağlıklı kontrol dahil edildi. JME’li hastalar ve sağlıklı bireylerden, gece meydana gelen serum melatonin pik düzeyini ve sabahki en düşük serum melatonin düzeyini belirlemek üzere venöz kan örnekleri alınarak ELISA yöntemiyle çalışıldı. Bulgular: Sağlıklı kontrollere kıyasla JME'li hastaların serum MELn (p = 0,002) ve MELm (p = 0,001) düzeyi daha düşük tespit edildi. Ayrıca JME’li hastalar ve kontrol grubu arasında MELn/MELm oranı ve MELn-MELm farkı açısından istatistiksel olarak anlamlı farklılıklar vardı (sırasıyla p = 0,005 ve 0,014). Sonuç: Elde edilen sonuçlar JME’li hastalar ve kontrol grubunda melatoninin sirkadien ritminin korunduğunu fakat hastalarda serum melatonin düzeylerinin kontrollere göre düşük seyrettiğini göstermektedir. Bundan dolayı JME’li hastalarda melatonin düzeyinin tespiti hem hastalık etyolojisinin belirlenmesine hem de gerektiğinde melatonin takviyesi yapılması ile gereksiz ve yüksek doz antiepileptik ilaç kullanımının engellenmesine katkı sağlayabilir.

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.

Differential diagnosis of familial adult myoclonic epilepsy.

Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses. Thedifferential diagnoses and frequent presentations leading to misdiagnosisofFAMEwereinvestigatedfromtheavailableliteratureandreportedbasedonanexpertopinionsurvey. The phenotypic features of FAME, including generalized tonic-clonic and myoclonic seizures, are also seen in other epilepsy syndromes, such as juvenile myoclonic epilepsy, with a resultant risk of misdiagnosis and lack of identification of the underlying cause. Cortical myoclonus may mimic essential tremor or drug-induced tremor. In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht-Lundborg disease, whereas, in adulthood, late-onset variants of PMEs, such as sialidoses, myoclonus epilepsy, and ataxia due to potassium channel pathogenic variants should be considered. PMEs may also be suggested by cognitive impairment, cerebellar signs, or psychiatric disorders. Electroencephalography (EEG) may show similarities to other idiopathic generalized epilepsies or PMEs, with generalized spike-wave activity. Signs of cortical hyperexcitability may be seen, such as an increased amplitude of somatosensory evoked potentials or enhanced cortical reflex to sensory stimuli, together with the neurophysiological pattern of the movement disorder. Recognition of FAME will inform prognostic and genetic counseling and diagnosis of the insidious progression, which may occur in older individuals who show mild cognitive deterioration. Distinguishing FAME from other disorders in individuals or families with this constellation of symptoms is essential to allow the identification of underlying etiology.

Idiopathic generalized epilepsies: Analysis of 101 patients

PurposeIdiopathic generalized epilepsies (IGI) are an electroclinical syndrome that include four subsyndromes according to the ILAE 2017 classification. The long-term prognosis of these syndromes is uncertain due to the scarcity and heterogeneity of the studies. The objective of this study is to analyze the long-term prognosis of these syndromes, pharmacological treatment and the seizure recurrence. MethodObservational and retrospective study of a serie of patients diagnosed with EGI. Epidemiological variables, pharmacological treatment, freedom of seizures and recurrence after withdrawal of treatment were collected. ResultsWe included 101 patients, the majority women (56.4%), with a median evolution of epilepsy of 17 years (interquartile range: 7–31). The most frequent syndrome was juvenile myoclonic epilepsy (46.5%), followed by epilepsy with generalized tonic-clonic seizures alone (25.7%), juvenile absence epilepsy (13.9%) and childhood absence epilepsy (13.9%). 71.29% were on monotherapy and 20.79% on polytherapy, with significant differences between the different syndromes (p=0.001). The most widely used drug was valproic acid. 39.6% presented seizure remission at 5 years, but we did not observe significant differences between the different syndromes (p=0.982). The recurrence rate was 71.4% after withdrawal of treatment. ConclusionJuvenile myoclonic epilepsy was the most frequent subtype of IGE. We observed significant differences in terms of polytherapy in the different syndromes, although not in the rates of remission of seizures at one year and at five years. The majority of patients with treatment withdrawal relapsed.

A cross-sectional investigation of cognition and epileptiform discharges in juvenile absence epilepsy.

Despite the prevalence of cognitive symptoms in the idiopathic generalized epilepsies (IGEs), cognitive dysfunction in juvenile absence epilepsy (JAE), a common yet understudied IGE subtype, remains poorly understood. This descriptive study provides a novel, comprehensive characterization of cognitive functioning in a JAE sample and examines the relationship between cognition and 24-h epileptiform discharge load. Forty-four individuals diagnosed with JAE underwent cognitive assessment using Woodcock Johnson III Test of Cognitive Abilities with concurrent 24-h ambulatory EEG monitoring. Generalized epileptiform discharges of any length, and prolonged generalized discharges ≥3s were quantified across wakefulness and sleep. The relationship between standardized cognitive scores and epileptiform discharges was assessed through regression models. Cognitive performances in overall intellectual ability, acquired comprehension-knowledge, processing speed, long-term memory storage and retrieval, and executive processes were 0.63-1.07 standard deviation (SD) units lower in the JAE group compared to the population reference mean, adjusted for educational attainment. Prolonged discharges (≥3s) were recorded in 20 patients (47.6%) from 42 available electroencephalography (EEG) studies and were largely unreported. Duration and number of prolonged discharges were associated with reduced processing speed and long-term memory storage and retrieval. Cognitive dysfunction is seen in patients with JAE across various cognitive abilities, including those representing more stable processes like general intellect. During 24-h EEG, prolonged epileptiform discharges are common yet underreported in JAE despite treatment, and they show moderate effects on cognitive abilities. If epileptiform burden is a modifiable predictor of cognitive dysfunction, therapeutic interventions should consider quantitative 24-h EEG with routine neuropsychological screening. The growing recognition of the spectrum of neuropsychological comorbidities of IGE highlights the value of multidisciplinary approaches to explore the causes and consequences of cognitive deficits in epilepsy.

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.