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OBJECTIVE: To investigate the repercussions of the war in Ukraine on people with epilepsy (PWE), focusing on access to health care, seizure control, quality of life (QoL), psychological distress, anxiety, and depression; and to identify the key factors influencing these measures. METHODS: Consecutive PWE, ≥18 years of age, presenting to one of seven health centers across Ukraine were invited to complete a self-administered survey in 2023. The survey gathered information on clinical and demographic aspects, geographic displacement, and access to care and medications. It also contained five valid questionnaires exploring psychological distress (Kessler-10), QoL with the EuroQOL-5D-5L (EQ-5D-5L), depression with the Neurological Disorders in Epilepsy scale (NDDIE), anxiety with the Hospital Anxiety and Depression Scalae-Anxiety (HADS-A), and epilepsy severity with the Global Assessment of the Severity of Epilepsy scale (GASE). Multivariate linear regression models assessed the relationship between measures of mental health and QoL and their potential predictors. Ethical approval was obtained from the Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine, Ukraine. RESULTS: Among 305 participants (mean age 38 years), 40% were female and 44% had to change residence because of the war. Seizures worsened during the war in 52% of those with active epilepsy and 42% of those with well-controlled epilepsy. Difficulties accessing health care and anti-seizure medications occurred in 25% and 34% of PWE, respectively, and was worse among those who were displaced. According to the mental health instruments, 46% suffered psychological distress, 62% experienced anxiety, 50% were depressed, and 59% rated their epilepsy as somewhat severe or worse. Statistically significant predictors of psychological distress, anxiety, and depression included female gender, more severe epilepsy, increased seizures during the war, and requiring mental health support. SIGNIFICANCE: The war significantly disrupted access to health care and availability of medication in PWE, who suffer from significant anxiety, depression, and psychological distress. We identify high-risk factors that can guide resource allocation for prevention and treatment.
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PURPOSE: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. METHODS: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. RESULTS: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. CONCLUSION: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants.
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Transtorno do Espectro Autista , Encefalopatias , Epilepsia , Transtorno do Espectro Autista/genética , Encefalopatias/genética , Epilepsia/genética , Feminino , Genes Ligados ao Cromossomo X/genética , Humanos , Masculino , Proteínas do Tecido Nervoso , Convulsões/genéticaRESUMO
Two patients with insular and striatal postnatal scar had epileptic spasms (ES) that were asymmetrical and the only seizure type, whereas none of the usual ictal symptoms of insular seizures occurred. Ictal electroencephalography (EEG) showed the high-amplitude slow-wave characteristic of ES. Vigabatrin remained efficient for over 4 years for one patient and right into the third decade for the other one. Such ES are distinct from infantile and late onset spasms. Furthermore, these observations suggest that in ES insular epilepsy triggers paroxysmal activation of the striatum, and that vigabatrin inhibits the striatal startle motor program, thus interrupting the corticostriatal loop.
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Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Epilepsia/fisiopatologia , Adulto , Anticonvulsivantes/administração & dosagem , Criança , Eletroencefalografia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Vigabatrina/administração & dosagem , Adulto JovemRESUMO
CHD2-related epilepsy is characterized by early-onset photosensitive myoclonic epilepsy with developmental delay and a high rate of pharmacoresistance. We sought to evaluate the efficacy of acetazolamide (ACZ) in CHD2-related epilepsy, due to ACZ's unexpected efficacy in our first patient harboring a pathogenic CHD2 variant. We collected patients from different Eastern European countries with drug-resistant CHD2-related epilepsy who were then treated with ACZ. Patients underwent video EEG before and during ACZ treatment. In a zebrafish model of CHD2-related epilepsy, ictal-like events were recorded 5 days post-fertilization after overnight ACZ exposure. Developmental delay preceded the onset of seizures in 10 of the 12 patients. Four had ataxia, and 6 exhibited autistic features. Seizures, primarily myoclonic, began at an average age of 3.4 years and were photosensitive in all 12 patients. Add-on ACZ treatment controlled photosensitive seizures in all patients: 6 became seizure-free, and in the remaining 6, seizure frequency decreased by over 75%. Four patients transitioned to ACZ monotherapy. The median follow-up was 13 months. In the zebrafish model, ACZ exposure reduced ictal-like events by 72%. ACZ, a well-tolerated and cost-effective medication, could be a good option for CHD2-related epilepsy, predominantly manifesting with myoclonic seizures and photosensitivity. PLAIN LANGUAGE SUMMARY: Epilepsy associated with CHD2 mutations is often pharmacoresistant and associated with developmental delay and eventually ataxia. There are several generalized seizure types, including generalized tonic-clonic seizures, but the most characteristic are jerks triggered by light stimulation. We collected 12 patients who received acetazolamide, a drug usually given as a diuretic and registered as a mild antiseizure medication. All jerks triggered by light disappeared while the frequency of spontaneous seizures decreased by over 75%. Further studies are needed to confirm this promising finding and identify the mechanism by which an old compound seems to have such a specific antiseizure effect.
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This study introduces a framework for the information-theoretic analysis of brain functional connectivity performed at the level of electroencephalogram (EEG) sources. The framework combines the use of common spatial patterns to select the EEG components which maximize the variance between two experimental conditions, simultaneous implementation of vector autoregressive modeling (VAR) with independent component analysis to describe the joint source dynamics and their projection to the scalp, and computation of information dynamics measures (information storage, information transfer, statistically significant network links) from the source VAR parameters. The proposed framework was tested on simulated EEGs obtained mixing source signals generated under different coupling conditions, showing its ability to retrieve source information dynamics from the scalp signals. Then, it was applied to investigate scalp and source brain connectivity in a group of children manifesting episodes of focal and generalized epilepsy; the analysis was performed on EEG signals lasting 5 s, collected in two consecutive windows preceding and one window following each ictal episode. Our results show that generalized seizures are associated with a significant decrease from pre-ictal to post-ictal periods of the information stored in the signals and of the information transferred among them, reflecting reduced self-predictability and causal connectivity at the level of both scalp and source brain dynamics. On the contrary, in the case of focal seizures the scalp EEG activity was not discriminated across conditions by any information measure, while source analysis revealed a tendency of the measures of information transfer to increase just before seizures and to decrease just after seizures. These results suggest that focal epileptic seizures are associated with a reorganization of the topology of EEG brain networks which is only visible analyzing connectivity among the brain sources. Our findings emphasize the importance of EEG modeling approaches able to deal with the adverse effects of volume conduction on brain connectivity analysis, and their potential relevance to the development of strategies for prediction and clinical treatment of epilepsy.
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OBJECTIVE: In this work we explore the potential of combining standard time and frequency domain indexes with novel information measures, to characterize pre- and post-ictal heart rate variability (HRV) in epileptic children, with the aim of differentiating focal and generalized epilepsy regarding the autonomic control mechanisms. APPROACH: We analyze short-term HRV in 37 children suffering from generalized or focal epilepsy, monitored 10 s, 300 s, 600 s and 1800 s both before and after seizure episodes. Nine indexes are computed in time (mean, standard deviation of normal-to-normal intervals, root mean square of the successive differences (RMSSD)), frequency (low-to-high frequency power ratio LF/HF, normalized LF and HF power) and information (entropy, conditional entropy and self-entropy) domains. Focal and generalized epilepsy are compared through statistical analysis of the indexes and using linear discriminant analysis (LDA). MAIN RESULTS: In children with focal epilepsy, early post-ictal phase is characterized by significant tachycardia, depressed HRV, increased LF power and LF/HF, and decreased complexity, progressively recovered across time windows after the episodes. Children with generalized seizures instead show significant tachycardia, lower RMSSD, higher LF power and LF/HF ratio before the seizure. These different behaviors are exploited by LDA analysis to separate focal and generalized epilepsy up to an accuracy of 75%. Results suggest a shift of the sympatho-vagal balance towards sympathetic dominance and vagal withdrawal, noticeable just after the termination of seizure episodes and then reverted in focal epilepsy, and persistent during inter-ictal and pre-ictal periods in generalized epilepsy. SIGNIFICANCE: Our analysis helps in elucidating the pathophysiology of inter-ictal HRV autonomic control and the differential diagnosis of generalized and focal epilepsy. These findings may have clinical relevance since altered sympatho-vagal control can be related to a higher danger of morbidity and mortality, may reduce thresholds for life-threatening arrhythmias, and could be a biomarker of risk for sudden unexpected death in epilepsy.