Epileptic Disorders最新文献

{"title":"Autoimmune-associated seizure disorders","authors":"Kelsey M. Smith,&nbsp;Adrian Budhram,&nbsp;Christian Geis,&nbsp;Andrew McKeon,&nbsp;Claude Steriade,&nbsp;Coral M. Stredny,&nbsp;Maarten J. Titulaer,&nbsp;Jeffrey W. Britton","doi":"10.1002/epd2.20231","DOIUrl":"10.1002/epd2.20231","url":null,"abstract":"<p>With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA-receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T-cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune-associated seizure disorders.</p>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epd2.20231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outpatient management of prolonged seizures and seizure clusters to prevent progression to a higher-level emergency: Consensus recommendations of an expert working group","authors":"Jesus Eric Pina-Garza,&nbsp;Michael Chez,&nbsp;James Cloyd,&nbsp;Lawrence J. Hirsch,&nbsp;Reetta Kälviäinen,&nbsp;Pavel Klein,&nbsp;Lieven Lagae,&nbsp;Raman Sankar,&nbsp;Nicola Specchio,&nbsp;Adam Strzelczyk,&nbsp;Manuel Toledo,&nbsp;Eugen Trinka","doi":"10.1002/epd2.20243","DOIUrl":"10.1002/epd2.20243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The management of prolonged seizures (PS) and seizure clusters (SC) is impeded by the lack of international, evidence-based guidance. We aimed to develop expert recommendations regarding consensus definitions of PS, SC, and treatment goals to prevent progression to higher-level emergencies such as status epilepticus (SE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An expert working group, comprising 12 epileptologists, neurologists, and pharmacologists from Europe and North America, used a modified Delphi consensus methodology to develop and anonymously vote on statements. Consensus was defined as ≥75% voting “Agree”/”Strongly agree.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All group members strongly agreed that termination of an ongoing seizure in as short a time as possible is the primary goal of rapid and early seizure termination (REST) and that an ideal medication for REST would start to act within 2 min of administration to terminate ongoing seizure activity. Consensus was reached on the terminology defining PS (with proposed thresholds of 5 min for prolonged focal seizures and 2 min for prolonged absence seizures and the convulsive phase of bilateral tonic-clonic seizures) and SC (an abnormal increase in seizure frequency compared with the individual patient's usual seizure pattern). All group members strongly agreed or agreed that patients who have experienced a PS should be offered a REST medication, and all patients who have experienced a SC should be offered an acute cluster treatment (ACT). Further, when prescribing a REST medication or ACT, a seizure action plan should be agreed upon in consultation with the patient and caregiver.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>The expert working group had a high level of agreement on the recommendations for defining and managing PS and SC. These recommendations will complement the existing guidance for the management of acute seizures, with the possibility of treating them earlier to potentially avoid progression to more severe seizures, including SE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epd2.20243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perampanel and Postictal Agitation","authors":"Michael Kolesnik,&nbsp;Naveed Chaudhry,&nbsp;Randi Libbon,&nbsp;Mark Spitz","doi":"10.1002/epd2.20249","DOIUrl":"10.1002/epd2.20249","url":null,"abstract":"","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disconjugate paroxysmal oculomotor movements in psychogenic nonepileptic seizures: A video-EEG study of three patients","authors":"Jeanne Benoit,&nbsp;Florence Martin,&nbsp;Pierre Thomas","doi":"10.1002/epd2.20232","DOIUrl":"10.1002/epd2.20232","url":null,"abstract":"<p>Content available: Video</p>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: A case series","authors":"Esteban Jaramillo-Jiménez,&nbsp;Juliana Sandoval-Barrios,&nbsp;Fergus John Walsh,&nbsp;María Clara Jaramillo-Jiménez,&nbsp;Juan David Echeverri-Sánchez,&nbsp;Iader Alfonso Rodríguez-Márquez,&nbsp;Hernán Darío Barrientos-Montoya,&nbsp;José Luis Ascencio-Lancheros,&nbsp;John Freddy Giraldo-Palacio,&nbsp;Iván Manuel Sierra-Arrieta,&nbsp;David Ignacio Gómez-Duque,&nbsp;Simón Pérez-López,&nbsp;Mariana Torres Bustamante","doi":"10.1002/epd2.20246","DOIUrl":"10.1002/epd2.20246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24–26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extremely long RNS implantation effect: The extended impact of RNS electrodes on clinical and ECoG findings without the confounding effect of RNS stimulation","authors":"Matthew T. Rumschlag,&nbsp;Kalina A. Misiolek,&nbsp;Prachi Parikh,&nbsp;Ifrah Zawar","doi":"10.1002/epd2.20233","DOIUrl":"10.1002/epd2.20233","url":null,"abstract":"<p>Implantation effect is the phenomenon of a transient decrease in clinical seizure frequency following the placement of intracranial electrodes or neuromodulatory devices.<span>¹</span> This effect has been demonstrated in different procedures such as stereo-EEG, deep brain stimulation, and subdural strips or grids.<span>^2-4</span> This effect is typically thought to last for no longer than a few months.<span>^{5, 6}</span> Recently, Responsive Neurostimulation (RNS) system (NeuroPace, Inc.) electrode placement has also demonstrated similar transient improvement in clinical seizure frequency.<span>³</span> Electrocorticographic (ECoG) spectral power changes and reduction in spike rates have also been described for up to 5 months of chronic ECoG in RNS patients.<span>⁷</span> However, RNS stimulation is routinely turned on within a few weeks of implantation.<span>^{3, 7}</span> Therefore, the degree to which RNS implantation versus stimulation leads to long-term clinical and electrophysiologic changes beyond the initial post-implant period is unclear.</p><p>To our knowledge, no previous studies have investigated the impact of RNS implantation on long episodes and electrographic seizures in patients not receiving RNS stimulation. Long episodes refer to any pattern that meets the RNS detection threshold but without evolution, whereas electrographic seizures constitute a pattern with distinct evolution. Here, we describe a patient who underwent bilateral RNS implantation and remained free of clinical seizures for at least 2 years and 1 month and free of long episodes and electrographic seizures for 14 months with no RNS stimulation during the initial 8-month period. Informed consent was obtained.</p><p>A 19-year-old woman with a longstanding history of drug-resistant focal epilepsy with focal seizures with impaired awareness, with and without secondary generalization underwent presurgical evaluation. At baseline, she had five to nine seizures per month. The longest seizure-free period prior to RNS was a few months. Stereo-EEG confirmed independent seizures arising from (Figure 1) bilateral hippocampi (Table 1). She underwent RNS implantation with bilateral hippocampal leads, after which she remained seizure-free. Given her lack of clinical and electrographic seizures, long episodes, or other epileptiform activity on ECoG, RNS stimulation was not turned on for 8 months post-implantation. At 8 months, RNS stimulation was ultimately turned on at the suggestion of the NeuroPace team despite the continued lack of clinical or electrographic events. After self-weaning anti-seizure medications (ASMs), she started to have rare long episodes and electrographic seizures at 14 months. These resolved after increasing her ASMs back to their original doses. She continues to remain completely free of clinical seizures at 2 years and 1 month post-implantation.</p><p>Our case demonstrates the extended impac","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epd2.20233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrical stimulation mapping guides individualized surgical approach in an epilepsy-associated tumor within language representing cortex","authors":"Susana Palao-Duarte,&nbsp;Dirk-Matthias Altenmüller,&nbsp;Christian Scheiwe,&nbsp;Anika Schinkel,&nbsp;Hansjörg Mast,&nbsp;Horst Urbach,&nbsp;Theo Demerath,&nbsp;Marius Schwabenland,&nbsp;Andreas Schulze-Bonhage,&nbsp;Kathrin Wagner,&nbsp;Marcel Heers","doi":"10.1002/epd2.20245","DOIUrl":"10.1002/epd2.20245","url":null,"abstract":"<p>In epilepsy patients with tumors involving the cortex with language representations, a comprehensive interdisciplinary workup is required to protect language function during surgical resection.<span>¹</span></p><p>We report the presurgical evaluation of a patient with focal epilepsy due to a progressive tumor in the language area of the left temporal lobe. After non-invasive presurgical diagnostics, we performed an invasive subdural electroencephalogram (iEEG) with extraoperative electrical stimulation mapping (ESM) prior to tumor surgery.<span>²</span></p><p>A 22-year-old female university student with left-sided temporal lobe epilepsy was referred for invasive video-EEG monitoring and language mapping to guide resective tumor surgery. Her epilepsy began at the age of 20 years, and it was characterized by focal aware seizures with speech arrest, occasionally followed by focal impaired awareness seizures. Under monotherapy with Levetiracetam up to 4 g/day, she had two to three focal aware seizures/day, despite which she was able to finish her university studies. High-resolution 3T structural magnetic resonance imaging (s-MRI) showed a slowly progressive, partially contrast-enhancing low-grade neuroglial tumor located at the left posterior superior temporal gyrus (Figure 1, Panels A and B) and the basal insula. A functional language MRI (l-fMRI) confirmed left-hemispheric language dominance with activations directly adjacent to the tumor (Figure 1, Panel C). Presurgical neuropsychological assessment (NPS) revealed discrete word-finding difficulties, partly reduced verbal fluency and impaired verbal short-term and working memory performance. The right-handed patient had a normal physical examination. Written informed consent was obtained for the scientific publication of the patient's clinical data.</p><p>Invasive video-EEG monitoring for 4 days with a 32-contact subdural grid implanted over the left temporal lobe was performed (Figure 1, Panel D). The ESM language cortical mapping with 50 Hz (biphasic pulses, duration 250 μs, bipolar stimulation up to 15 mA, referential stimulation up to 18 mA) comprised six different language tasks as described in detail before.<span>³</span> Language representations were identified in contacts B2-3, B6, C5-C8, and D7 (Figure 1, Panel D). The language representation around contacts A3-4 and B4-5 could not be assessed due to unavoidable afterdischarges despite the additional use of lorazepam. In summary, the ESM showed a clear overlap of language representation and tumor in the left superior temporal gyrus. The irritative zone and the seizure onset zone overlapped with language representations (Figure 1, Panel D).</p><p>Due to the tumor's location, only the contrast-enhancing solid component and the cyst membrane could be resected via a transsylvian approach to minimize the risk of postoperative language deficits. No need for awake surgery with additional intraoperative language","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epd2.20245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seizure and movement disorder in CACNA1E developmental and epileptic encephalopathy: Two sides of the same coin or same side of two different coins?","authors":"Valentina Di Micco,&nbsp;Leonardo Affronte,&nbsp;Marianne Søndergaard Khinchi,&nbsp;Gitte Rønde,&nbsp;Maria Jose Miranda,&nbsp;Trine Bjørg Hammer,&nbsp;Nicola Specchio,&nbsp;Sándor Beniczky,&nbsp;Kern Olofsson,&nbsp;Rikke S. Møller,&nbsp;Elena Gardella","doi":"10.1002/epd2.20242","DOIUrl":"10.1002/epd2.20242","url":null,"abstract":"<p>Pathogenic variants in <i>CACNA1E</i> are associated with early-onset epileptic and developmental encephalopathy (DEE). Severe to profound global developmental delay, early-onset refractory seizures, severe hypotonia, and macrocephaly are the main clinical features. Patients harboring the recurrent <i>CACNA1E</i> variant p.(Gly352Arg) typically present with the combination of early-onset DEE, dystonia/dyskinesia, and contractures. We describe a 2-year-and-11-month-old girl carrying the p.(Gly352Arg) <i>CACNA1E</i> variant. She has a severe DEE with very frequent drug-resistant seizures, profound hypotonia, and episodes of dystonia and dyskinesia. Long-term video-EEG-monitoring documented subsequent tonic asymmetric seizures during wakefulness and mild paroxysmal dyskinesias of the trunk out of sleep which were thought to be a movement disorder and instead turned out to be focal hyperkinetic seizures. This is the first documented description of the EEG findings in this disorder. Our report highlights a possible overlap between cortical and subcortical phenomena in <i>CACNA1E</i>-DEE. We also underline how a careful electro-clinical evaluation might be necessary for a correct discernment between the two disorders, playing a fundamental role in the clinical assessment and proper management of children with <i>CACNA1E</i>-DEE.</p>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epd2.20242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy","authors":"Anni Saarela,&nbsp;Oskari Timonen,&nbsp;Jarkko Kirjavainen,&nbsp;Yawu Liu,&nbsp;Katri Silvennoinen,&nbsp;Esa Mervaala,&nbsp;Reetta Kälviäinen","doi":"10.1002/epd2.20244","DOIUrl":"10.1002/epd2.20244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Recessive <i>LAMC3</i> mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed <i>LAMC3</i> variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re-evaluating our database regarding the patients with developmental and/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among our study population of 323 DEE patients we recognized three patients with similar homozygous <i>LAMC3</i> c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic <i>LAMC3</i> c.4231-12C&gt;G variant on another allele. All these patients have severe epilepsy and either bilateral agyria-pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox–Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. <i>LAMC3</i> c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Only a few patients with epilepsy caused by <i>LAMC3</i> homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/epd2.20244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEPDC5 plays a vital role in epilepsy: Genotypic and phenotypic features in cohort and literature","authors":"Chunyu Gu,&nbsp;Xinping Wei,&nbsp;Dandan Yan,&nbsp;Yingzi Cai,&nbsp;Dong Li,&nbsp;Jianbo Shu,&nbsp;Chunquan Cai","doi":"10.1002/epd2.20223","DOIUrl":"10.1002/epd2.20223","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p><i>DEPDC5</i> emerges to play a vital role in focal epilepsy. However, genotype–phenotype correlation in <i>DEPDC5</i>-related focal epilepsies is challenging and controversial. In this study, we aim to investigate the genotypic and phenotypic features in <i>DEPDC5</i>-affected patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic testing combined with criteria published by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), was used to identify pathogenic/likely pathogenic variants in <i>DEPDC5</i> among the cohort of 479 patients with focal epilepsy. Besides, the literature review was performed to explore the genotype–phenotype correlation and the penetrance in <i>DEPDC5</i>-related focal epilepsies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight unrelated probands were revealed to carry different pathogenic/likely pathogenic variants in <i>DEPDC5</i> and the total prevalence of <i>DEPDC5</i>-related focal epilepsy was 1.67% in the cohort. Sixty-five variants from 28 studies were included in our review. Combined with the cases reported, null variants accounted for a larger proportion than missense variants and were related to unfavorable prognosis (drug resistance or even sudden unexpected death in epilepsy; <i>χ</i>^<i>2</i> = 5.429, <i>p</i> = .020). And, the prognosis of probands with developmental delay/intellectual disability or focal cortical dysplasia was worse than that of probands with simple epilepsy (<i>χ</i>^<i>2</i> = −, <i>p</i> = .006). Besides, the overall penetrance of variants in <i>DEPDC5</i> was 68.96% (231/335).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>The study expands the variant spectrum of <i>DEPDC5</i> and proves that the <i>DEPDC5</i> variant plays a significant role in focal epilepsy. Due to the characteristics of phenotypic heterogeneity and incomplete penetrance, genetic testing is necessary despite no specific family history. And we propose to adopt the ACMG/AMP criteria refined by ClinGen Sequence Variant Interpretation Working Group, for consistency in usage and transparency in classification rationale. Moreover, we reveal an important message to clinicians that the prognosis of <i>DEPDC5</i>-affected patients is related to the variant type and complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50508,"journal":{"name":"Epileptic Disorders","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}