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Frontiers in Neuroscience 2024A third of patients with epilepsy continue to have seizures despite receiving adequate antiseizure medication. Transcranial direct current stimulation (tDCS) might be a...
OBJECTIVE
A third of patients with epilepsy continue to have seizures despite receiving adequate antiseizure medication. Transcranial direct current stimulation (tDCS) might be a viable adjunct treatment option, having been shown to reduce epileptic seizures in patients with focal epilepsy. Evidence for the use of tDCS in genetic generalized epilepsy (GGE) is scarce. We aimed to establish the feasibility of applying tDCS during fMRI in patients with GGE to study the acute neuromodulatory effects of tDCS, particularly on sensorimotor network activity.
METHODS
Seven healthy controls and three patients with GGE received tDCS with simultaneous fMRI acquisition while watching a movie. Three tDCS conditions were applied: anodal, cathodal and sham. Periods of 60 s without stimulation were applied between each stimulation condition. Changes in sensorimotor cortex connectivity were evaluated by calculating the mean degree centrality across eight nodes of the sensorimotor cortex defined by the Automated Anatomical Labeling atlas (primary motor cortex (precentral left and right), supplementary motor area (left and right), mid-cingulum (left and right), postcentral gyrus (left and right)), across each of the conditions, for each participant.
RESULTS
Simultaneous tDCS-fMRI was well tolerated in both healthy controls and patients without adverse effects. Anodal and cathodal stimulation reduced mean degree centrality of the sensorimotor network (Friedman's ANOVA with Dunn's multiple comparisons test; adjusted = 0.02 and = 0.03 respectively). Mean degree connectivity of the sensorimotor network during the sham condition was not different to the rest condition (adjusted = 0.94).
CONCLUSION
Applying tDCS during fMRI was shown to be feasible and safe in a small group of patients with GGE. Anodal and cathodal stimulation caused a significant reduction in network connectivity of the sensorimotor cortex across participants. This initial research supports the feasibility of using fMRI to guide and understand network modulation by tDCS that might facilitate its clinical application in GGE in the future.
PubMed: 38572149
DOI: 10.3389/fnins.2024.1354523 -
Heliyon Apr 2024Paroxysmal kinesigenic dyskinesia (PKD) represents the most prevalent form of paroxysmal dyskinesia, characterized by recurrent and transient attacks of involuntary...
Paroxysmal kinesigenic dyskinesia (PKD) represents the most prevalent form of paroxysmal dyskinesia, characterized by recurrent and transient attacks of involuntary movements triggered by a sudden voluntary action. In this study, whole-exome sequencing was conducted on a cohort of Chinese patients to identify causal mutations. In one young female case, a de novo variant (NM_000718.3:exon3:c.479C > T:p.S160F) was identified as the causative lesion. This finding may broaden the phenotypic spectrum of mutations and provide a prospective cause of primary PKD. Additionally, a novel start-loss variant (NM_000682.7:c.3G > A) within further denied its association with benign adult familial myoclonic epilepsy, and a E515D variant that was reported as a genetic susceptibility factor for seizures had no damaging effect in this family. In sum, this study established a correlation between and primary PKD, and found valid evidence that further negates the pathogenic role of in benign adult familial myoclonic epilepsy.
PubMed: 38571653
DOI: 10.1016/j.heliyon.2024.e28674 -
The Journal of Small Animal Practice Jun 2024Myoclonic seizures are considered a type of generalised seizure characterised by brief, jerking movements of the body. The aim of this study is to describe cases of...
OBJECTIVES
Myoclonic seizures are considered a type of generalised seizure characterised by brief, jerking movements of the body. The aim of this study is to describe cases of suspected canine myoclonic seizure of idiopathic aetiology and to discuss the successful use of the anticonvulsant levetiracetam as treatment in each of these cases.
MATERIALS AND METHODS
Dogs with epileptic myoclonus suspected to be idiopathic in aetiology were considered for inclusion. Medical records were reviewed for physical and neurologic examination findings, clinicopathologic results, and diagnostic imaging results. All included dogs were treated with levetiracetam, and their response was reported.
RESULTS
Five dogs were included, all of which had suspected myoclonic seizures either observed in-person or on video recording by a board-certified veterinary neurologist. The duration of myoclonic seizures preceding treatment ranged from one day to one year. One dog also experienced a generalised tonic-clonic seizure. All dogs were treated with levetiracetam. Two dogs experienced long-term myoclonic seizure freedom (duration seizure-free of at least 1 year), and two dogs experienced marked decreased myoclonic seizure frequency. One dog experienced immediate abatement of myoclonic seizures, although levetiracetam was only utilised for 1 month following onset of myoclonic seizures in this patient.
CLINICAL SIGNIFICANCE
Myoclonic seizures can be idiopathic in aetiology. Levetiracetam can be used effectively to rapidly stop myoclonic seizures and to decrease the frequency of myoclonic seizures.
Topics: Dogs; Levetiracetam; Animals; Anticonvulsants; Dog Diseases; Female; Male; Epilepsies, Myoclonic; Treatment Outcome
PubMed: 38566458
DOI: 10.1111/jsap.13719 -
EMBO Molecular Medicine May 2024In this Correspondence, B. Minassian and colleagues report that GHF201, an autophagy activator shown to diminish abnormal glycogen aggregates in a mouse model of Adult...
In this Correspondence, B. Minassian and colleagues report that GHF201, an autophagy activator shown to diminish abnormal glycogen aggregates in a mouse model of Adult Polyglucosan Body Disease, fails to reduce such accumulations in a mouse model of Lafora disease. [Image: see text]
Topics: Lafora Disease; Autophagy; Humans; Glycogen; Animals; Epilepsy; Mice
PubMed: 38565807
DOI: 10.1038/s44321-024-00063-9 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Apr 2024To retrospectively analyze the clinical phenotype and pathogenic variants in patients with Progressive myoclonus epilepsy (PME).
OBJECTIVE
To retrospectively analyze the clinical phenotype and pathogenic variants in patients with Progressive myoclonus epilepsy (PME).
METHODS
Clinical data and results of genetic testing for 11 patients diagnosed with PME at the Department of Neurology, the First Affiliated Hospital of Zhejiang University School of Medicine from June 2017 to December 2022 were collected and analyzed.
RESULTS
All of the patients, including 4 males and 7 females, had predominant action myoclonus. Three patients had myoclonus as the initial manifestation, whilst eight were diagnosed through genetic testing, including three cases with NEU1 gene variants, two with EPM2A gene variants (1 was novel), one with MT-TK gene variant, one with ATN1 gene variant, and one with CSTB gene variant. No pathogenic variant was identified in the remaining three cases. Among the eight patients with a genetic diagnosis, three were diagnosed with sialidosis, two with Lafora disease, one with Dentatorubral-pallidoluysian atrophy (DRPLA), one with Unverricht-Lundborg disease (ULD), and one with Myoclonic epilepsy with ragging red fibers (MERRF).
CONCLUSION
Compared with pediatric patients, adult patients with PME represent a distinct subtype with slower progression and milder cognitive impairment.
Topics: Male; Adult; Female; Humans; Child; Unverricht-Lundborg Syndrome; Retrospective Studies; Myoclonic Epilepsies, Progressive; Epilepsies, Myoclonic; Genetic Testing
PubMed: 38565508
DOI: 10.3760/cma.j.cn511374-20230214-00073 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Apr 2024To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE).
OBJECTIVE
To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE).
METHODS
Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children's Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed.
RESULTS
Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c.677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group (P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures.
CONCLUSION
The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.
Topics: Child; Humans; Female; Child, Preschool; NAV1.1 Voltage-Gated Sodium Channel; Epilepsies, Myoclonic; Phenotype; Genotype; Genetic Testing; Seizures; Mutation
PubMed: 38565507
DOI: 10.3760/cma.j.cn511374-20230421-00227 -
Epilepsy & Behavior : E&B May 2024Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC)-associated epilepsy are rare conditions associated with severe childhood-onset...
A quantitative cross-sectional study of the burden of caring for patients with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex-associated epilepsy in Japan.
INTRODUCTION
Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC)-associated epilepsy are rare conditions associated with severe childhood-onset epilepsy. Caregivers play a critical role in the patients' care and may experience significant psychosocial and socioeconomic burden. This cross-sectional study determined the burden of caring for patients with these rare epilepsy conditions in Japan.
METHODS
A quantitative online survey was used to assess patients' and caregivers' characteristics and the caregivers' emotional state, among others. Several validated questionnaires were used: the Hospital Anxiety and Depression Scale (HADS; 0-21 score) assessed the caregivers' emotional wellbeing, the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM; 0-100 score) assessed the health-related quality of life (HRQoL) of the caregivers and their families, and the Work Productivity and Activity Impairment General Health (WPAI:GH; 0-100 % score) questionnaire assessed work productivity.
RESULTS
A total of 36 caregivers responded (median [interquartile range (IQR)] age 43.5 [39.5, 48.3] years; 33/36 [92 %] female; 13/36 [36 %] working part-time and 13/36 [36 %] not working). Participants cared for 7/36 (19 %), 19/36 (53 %), and 10/36 (28 %) patients with LGS, DS, and TSC, respectively (median [IQR] age, 11.0 [6.8, 16.3] years; age at first seizure, 0 [0, 0] years). Patients received a median (IQR) of 4 (3, 5) treatment drug types. Patients experienced median (IQR) 3.0 (0, 21.0) epileptic seizures in the previous week; 28/36 (78 %) had severe intellectual disabilities, and 34/36 (94 %) had developmental delays. Caregivers reported stress (17/36 [47 %]), sleep problems (13/36 [36 %]), and anxiety (12/36 [33 %]). They spent a median (IQR) of 50.0 (17.5, 70.0) hours caregiving in the previous week, with 3.0 (1.0, 11.0) hours of seizure-specific care. Caregivers reported that their lives would be easier with a median (IQR) of 1.5 (0, 5.0) hours fewer per week caring for patients during/following seizures. Median HADS scores were 9.5 ('suspected anxiety diagnosis') and 7.5 ('no depression') for caregivers, and PedsQL FIM Total median score was 60.1, indicating HRQoL impairment for the caregiver and their family. WPAI:GH scores for paid workers indicated important work impairment. Higher caregiving hours (≥ 21 h vs. < 21 h in the previous week) resulted in higher caregiver burden as indicated by the HADS Total score (p = 0.0062) and PedsQL FIM Total score (p = 0.0007).
CONCLUSIONS
Caregivers of patients with LGS, DS, or TSC in Japan experience a significant time burden, reduced HRQoL, and high level of work/activity impairment. Caregivers provide round-the-clock care to patients and rely on family and specialized caring services to help manage the increased caregiving time, which tends to be associated with greater emotional burden and HRQoL impact.
Topics: Humans; Female; Male; Cross-Sectional Studies; Tuberous Sclerosis; Japan; Adult; Caregivers; Middle Aged; Quality of Life; Lennox Gastaut Syndrome; Epilepsies, Myoclonic; Child; Adolescent; Surveys and Questionnaires; Epilepsy; Cost of Illness; Young Adult; Child, Preschool
PubMed: 38555725
DOI: 10.1016/j.yebeh.2024.109741 -
Clinical Genetics Aug 2024We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by...
We summarize the copy number variations (CNVs) and phenotype spectrum of infantile epileptic spasms syndrome (IESS) in a Chinese cohort. The CNVs were identified by genomic copy number variation sequencing. The CNVs and clinical data were analyzed. 74 IESS children with CNVs were enrolled. 35 kinds of CNVs were identified. There were 11 deletions and 5 duplications not reported previously in IESS, including 2 CNVs not reported in epilepsy. 87.8% were de novo, 9.5% were inherited from mother and 2.7% from father. Mosaicism occurred in one patient with Xq21.31q25 duplication. 16.2% (12/74) were 1p36 deletion, and 20.3% (15/74) were 15q11-q13 duplication. The age of seizure onset ranged from 17 days to 24 months. Seizure types included epileptic spasms, focal seizures, tonic seizures, and myoclonic seizures. All patients displayed developmental delay. Additional features included craniofacial anomaly, microcephaly, congenital heart defects, and hemangioma. 29.7% of patients were seizure-free for more than 12 months, and 70.3% still had seizures after trying 2 or more anti-seizure medications. In conclusion, CNVs is a prominent etiology of IESS. 1p36 deletion and 15q duplication occurred most frequently. CNV detection should be performed in patients with IESS of unknown causes, especially in children with craniofacial anomalies and microcephaly.
Topics: Humans; DNA Copy Number Variations; Spasms, Infantile; Female; Male; Infant; Phenotype; Chromosome Duplication; Chromosomes, Human, Pair 15; Child, Preschool; Infant, Newborn; Chromosome Deletion; Mosaicism; Chromosome Aberrations; Intellectual Disability
PubMed: 38544467
DOI: 10.1111/cge.14520 -
Epilepsia Open Jun 2024Myotonia is a clinical sign typical of a group of skeletal muscle channelopathies, the non-dystrophic myotonias. These disorders are electrophysiologically characterized...
OBJECTIVES
Myotonia is a clinical sign typical of a group of skeletal muscle channelopathies, the non-dystrophic myotonias. These disorders are electrophysiologically characterized by altered membrane excitability, due to specific genetic variants in known causative genes (CLCN1 and SCN4A). Juvenile Myoclonic Epilepsy (JME) is an epileptic syndrome identified as idiopathic generalized epilepsy, its genetics is complex and still unclarified. The co-occurrence of these two phenotypes is rare and the causes likely have a genetic background. In this study, we have genetically investigated an Italian family in which co-segregates myotonia, JME, or abnormal EEG without seizures was observed.
METHODS
All six individuals of the family, 4 affected and 2 unaffected, were clinically evaluated; EMG and EEG examinations were performed. For genetic testing, Exome Sequencing was performed for the six family members and Sanger sequencing was used to confirm the candidate variant.
RESULTS
Four family members, the mother and three siblings, were affected by myotonia. Moreover, EEG recordings revealed interictal generalized sharp-wave discharges in all affected individuals, and two siblings were affected by JME. All four affected members share the same identified variant, c.644 T > C, p.Ile215Thr, in SCN4A gene. Variants that could account for the epileptic phenotype alone, separately from the myotonic one, were not identified.
SIGNIFICANCE
These results provide supporting evidence that both myotonic and epileptic phenotypes could share a common genetic background, due to variants in SCN4A gene. SCN4A pathogenic variants, already known to be causative of myotonia, likely increase the susceptibility to epilepsy in our family.
PLAIN LANGUAGE SUMMARY
This study analyzed all members of an Italian family, in which the mother and three siblings had myotonia and epilepsy. Genetic analysis allowed to identify a variant in the SCN4A gene, which appears to be the cause of both clinical signs in this family.
Topics: Adolescent; Adult; Female; Humans; Male; Middle Aged; Electroencephalography; Epilepsy, Generalized; Italy; Myotonia; NAV1.4 Voltage-Gated Sodium Channel; Pedigree; Phenotype
PubMed: 38544349
DOI: 10.1002/epi4.12920 -
Epileptic Disorders : International... Jun 2024Myoclonic-tonic (MT) and spasm-tonic (ST) seizures represent distinctive features in late infantile epileptic encephalopathy (LIEE). This commentary aims to delineate...
Myoclonic-tonic (MT) and spasm-tonic (ST) seizures represent distinctive features in late infantile epileptic encephalopathy (LIEE). This commentary aims to delineate the electroclinical characteristics of MT and ST seizures, setting them apart from other seizure types. Our analysis encompasses 211 ST and MT seizures observed in 31 patients diagnosed with LIEE, providing a comprehensive overview of video-EEG features and polygraphic signatures. In MT seizures, EEG findings reveal a high-voltage diffuse spike/polyspike and wave discharge, often succeeded by diffuse electrodecrements. The amplitude-integrated EEG (aEEG) signature is described as a "reversed checkmark." Conversely, ST seizures exhibit EEG findings such as a vertex positive deflection after a slow-wave and relative electrodecrement, with intermixed epileptiform discharges. In comparison to MT seizures, polygraphic characteristics in ST seizures appear more distinct, featuring a brief rhomboid shape corresponding to the spasm, followed by a lengthier rectangular shape indicative of the tonic phase of the ST seizure. While the pathophysiology of ST and MT seizures remains inadequately understood, their concurrent occurrence and association with other seizure types (tonic, epileptic spasm, myoclonic) within the temporal context of LIEE and other epileptic encephalopathies prompt us to anticipate advancements in our understanding through future research. We hope that this study serves as a foundation for unraveling these complexities in the times to come.
Topics: Humans; Electroencephalography; Epilepsies, Myoclonic; Seizures; Infant; Child, Preschool; Child; Spasms, Infantile; Male; Female
PubMed: 38536013
DOI: 10.1002/epd2.20213