Pediatric neurology最新文献

{"title":"Editorial Board and Masthead","authors":"","doi":"10.1016/S0887-8994(24)00241-8","DOIUrl":"10.1016/S0887-8994(24)00241-8","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"157 ","pages":"Pages A1-A2"},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141630386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copy Number Variation and Epilepsy: State of the Art in the Era of High-Throughput Sequencing—A Multicenter Cohort Study","authors":"Sarah Baer MD ,&nbsp;Audrey Schalk MD ,&nbsp;Marguerite Miguet MD ,&nbsp;Élise Schaefer MD, PhD ,&nbsp;Salima El Chehadeh MD, PhD ,&nbsp;Emmanuelle Ginglinger MD ,&nbsp;Anne de Saint Martin MD, PhD ,&nbsp;Marie-Thérèse Abi Wardé MD ,&nbsp;Vincent Laugel MD, PhD ,&nbsp;Yvan de Feraudy MD ,&nbsp;Lucas Gauer MD ,&nbsp;Edouard Hirsch MD, PhD ,&nbsp;Clotilde Boulay MD ,&nbsp;Claire Bansept MD ,&nbsp;Anamaria Bolocan MD ,&nbsp;Ismini Kitadinis MD ,&nbsp;Aurélie Gouronc MD ,&nbsp;Bénédicte Gérard pharmD, PhD ,&nbsp;Amélie Piton PhD ,&nbsp;Sophie Scheidecker MD, PhD","doi":"10.1016/j.pediatrneurol.2024.07.007","DOIUrl":"10.1016/j.pediatrneurol.2024.07.007","url":null,"abstract":"<div><h3>Background</h3><p>Genetic epilepsy diagnosis is increasing due to technological advancements. Although the use of molecular diagnosis is increasing, chromosomal microarray analysis (CMA) remains an important diagnostic tool for many patients. We aim to explore the role and indications of CMA in epilepsy, given the current genomic advances.</p></div><div><h3>Methods</h3><p>We obtained data from 378 epileptic described patients, who underwent CMA between 2015 and 2021. Different types of syndromic or nonsyndromic epilepsy were represented.</p></div><div><h3>Results</h3><p>After excluding patients who were undertreated or had missing data, we included 250 patients with treated epilepsy and relevant clinical information. These patients mostly had focal epilepsy or developmental and epileptic encephalopathy, with a median start age of 2 years. Ninety percent of the patients had intellectual disability, more than two thirds had normal head size, and 60% had an abnormal magnetic resonance imaging. We also included 10 patients with epilepsy without comorbidities. In our cohort, we identified 35 pathogenic copy number variations (CNVs) explaining epilepsy with nine recurrent CNVs enriched in patients with epilepsy, 12 CNVs related to neurodevelopmental disorder phenotype with possible epilepsy, five CNVs including a gene already known in epilepsy, and nine CNVs based on size combined with <em>de novo</em> occurrence. The diagnosis rate in our study reached 14% (35 of 250) with first-line CMA, as previously reported. Although targeted gene panel sequencing could potentially diagnose some of the reported epilepsy CNVs (34% [12 of 35]).</p></div><div><h3>Conclusions</h3><p>CMA remains a viable option as the first-line genetic test in cases where other genetic tests are not available and as a second-line diagnostic technique if gene panel or exome sequencing yields negative results.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 16-25"},"PeriodicalIF":3.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141691364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroencephalography Conductive Paste Made From Household Supplies: A Recipe for Resource-Limited Settings","authors":"Madeleine Hebert MD,&nbsp;Annah Adanene MD,&nbsp;Neal Sankhla MD,&nbsp;Sisay Tefera MD,&nbsp;Ayalew Moges MD,&nbsp;Behaylu Yibe MD,&nbsp;Endayen Deginet MD,&nbsp;Meskerem Abatkun MD,&nbsp;Anne Clarke","doi":"10.1016/j.pediatrneurol.2024.07.006","DOIUrl":"10.1016/j.pediatrneurol.2024.07.006","url":null,"abstract":"","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 30-31"},"PeriodicalIF":3.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Purkinje Cell Cytoplasmic Antibody Type 2-Associated Autoimmune Cerebellar Degeneration in Children: A Different Phenotype From Adults","authors":"Anna Zhou MD ,&nbsp;Haitao Ren MD ,&nbsp;Libing Fu MD ,&nbsp;Changhong Ren MD ,&nbsp;Ji Zhou MD ,&nbsp;Hongzhi Guan MD ,&nbsp;Xiaotun Ren MD ,&nbsp;Weihua Zhang MD","doi":"10.1016/j.pediatrneurol.2024.07.004","DOIUrl":"10.1016/j.pediatrneurol.2024.07.004","url":null,"abstract":"<div><h3>Background</h3><p>Anti-Purkinje cell cytoplasmic antibody type 2 (PCA-2) is associated with various neurological conditions in adults. However, related studies have not been conducted in children. The present study aimed to characterize the clinical features and outcomes of PCA-2-related autoimmune cerebellar degeneration in pediatric patients.</p></div><div><h3>Methods</h3><p>A total of 357 pediatric patients with acute or subacute cerebellar ataxia were recruited for the study from June 2015 to September 2022. Of these, PCA-2 was identified in four patients. Information on the clinical manifestations, patient response to treatment, and outcomes was collected and analyzed.</p></div><div><h3>Results</h3><p>The patient cohort in the present study included two boys and two girls, with the age of onset from six to 12 years. Axial ataxia was the most remarkable symptom observed in the entire patient cohort (four of four), followed by dysmetria in 75% (three of four), dysarthria in 50% (two of four), and nystagmus in 25% (one of four) of patients. Cognitive impairment was present in one patient. Peripheral neuropathy, which is an extracerebellar symptom, was found in two patients. One patient was diagnosed with a pelvic neuroblastoma before the onset of ataxia. The presence of oligoclonal bands was confirmed in the cerebrospinal fluid, and cerebellar atrophy was observed. Immunotherapy, including glucocorticoids and/or intravenous immunoglobulin, was administered to all four patients immediately following diagnosis, and mycophenolate mofetil was administered to three patients. Three patients responded to immunotherapy.</p></div><div><h3>Conclusions</h3><p>In children, PCA2-associated autoimmune cerebellar degeneration is rare, and they show comparatively fewer symptoms than adults. Timely and appropriate immunotherapy is beneficial.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 26-29"},"PeriodicalIF":3.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Clinical and Neuroimaging Markers to Predict the Onset of Posthemorrhagic Ventricular Dilatation in Preterm Neonates","authors":"Dr. Abdul Aziz Al-Garni MD (Clinical Fellow) ,&nbsp;Avneet Mazara BSc (Life Sciences) ,&nbsp;Nina Stein MD, MSc (Associate Professor) ,&nbsp;Lawrence Mbuagbaw MD, PhD (Associate Professor) ,&nbsp;Olufemi Ajani MD (Associate Professor) ,&nbsp;Ipsita Goswami MD, MSc (Assistant Professor)","doi":"10.1016/j.pediatrneurol.2024.07.005","DOIUrl":"10.1016/j.pediatrneurol.2024.07.005","url":null,"abstract":"<div><h3>Background</h3><p>Posthemorrhagic ventricular dilatation (PHVD) is a major complication of intraventricular hemorrhage (IVH); it is associated with high risks of cerebral palsy and cognitive deficits compared with infants without PHVD. This study aims to explore the early perinatal risk factors-associated with the risk of progressive PHVD.</p></div><div><h3>Methods</h3><p>Neonates ≤29 weeks gestational age (GA) with Grade II-III IVH and periventricular hemorrhagic infarct (PVHI) between 2015 and 2021 were retrospectively reviewed. All cranial ultrasounds done within 14 days postnatal age (PNA) were assessed for grade of IVH, anterior horn width (AHW), ventricular index (VI), and thalamo-occipital index (TOD). The outcome was defined as death of any cause or VI and/or AHW and/or TOD ≥ moderate-risk zone based on an ultrasound done beyond two weeks PNA.</p></div><div><h3>Results</h3><p>A total of 146 infants with a mean GA of 26 ± 1.8 weeks, birth weight 900 ± 234 g were included, 46% were females. The primary outcome occurred in 56 (39%) infants; among them 17 (30%) and 11 (20%) needed ventricular reservoir and shunt insertion, respectively. The risk factors present within 14 days PNA that significantly increased the odds of developing PHVD were hemodynamically significant patent ductus arteriosus (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9 to 22), culture-proven sepsis (OR 5.4, 95% CI 1.8 to 18), Grade III IVH (OR 4.6, 95% CI 1.1 to 22), PVHI (OR 3.0, 95% CI 0.9 to 10), and VI (OR 2.1, 95% CI 1.6 to 2.9).</p></div><div><h3>Conclusions</h3><p>Clinical predictors such as significant ductus arteriosus and bacterial septicemia, along with risk levels of AHW and VI measured with early cranial ultrasounds, are potential predictors of subsequent onset of PHVD.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 4-11"},"PeriodicalIF":3.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S088789942400256X/pdfft?md5=80934d85da97829a0969599155a943f0&pid=1-s2.0-S088789942400256X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141708645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"General Movements Assessment in Infants with High Birth Weight","authors":"S. Zeynep Kaşka MSc ,&nbsp;Gülsen Sırtbaş Işık PhD ,&nbsp;H. Tolga Çelik MD ,&nbsp;Akmer Mutlu PhD","doi":"10.1016/j.pediatrneurol.2024.07.003","DOIUrl":"10.1016/j.pediatrneurol.2024.07.003","url":null,"abstract":"<div><h3>Background</h3><p>High birth weight (HBW) describes fetal birth weight of more than 4000 g. Infants with HBW have a high risk of developing neurological and developmental problems. Until recently, there were no studies in the literature that investigated the quality of spontaneous movements and the integrity of the developing nervous system in infants with HBW. The aims of this study were (1) to describe age-specific detailed early spontaneous movements in infants with HBW and (2) to compare the detailed early spontaneous movements of infants with HBW and normal birth weight (NBW).</p></div><div><h3>Methods</h3><p>Twenty-two infants with HBW (median birth weight = 4190 g) and 22 infants with NBW (median birth weight = 3255 g) were included at 10 to 19 weeks post-term age (median = 13 weeks). All infants were assessed according to General Movement Assessment using three- to five-minute video recordings. Video recordings of each infant were evaluated using Motor Optimality Score for three- to five-month-old infants-Revised score sheet.</p></div><div><h3>Results</h3><p>Motor Optimality Score-Revised (MOS-R) (<em>P</em> &lt; 0.001), observed postural patterns (<em>P</em> &lt; 0.001), and age-adequate movement repertoire (<em>P</em> = 0.005) were significantly lower in the infants with HBW. Infants with HBW had more aberrant (abnormal or absent) fidgety movements (18%) than those with NBW (0%).</p></div><div><h3>Conclusions</h3><p>The results of this study demonstrated that the motor repertoire of infants with HBW tended to decrease more than that of those with NBW. To enable the follow-up of progression as a result of these assessments infants in need should be referred to age-adequate early intervention programs.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 26-32"},"PeriodicalIF":3.2,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141695083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Imaging in New-Onset Seizure of Children Living With Human Immunodeficiency Virus in Zambia","authors":"Sarah Mohajeri MD, MPH ,&nbsp;Michael Potchen MD ,&nbsp;Izukanji Sikazwe MD ,&nbsp;Samuel Kampondeni MD ,&nbsp;Colleen Hoffman ARRT ,&nbsp;David Bearden MD ,&nbsp;Lisa Kalungwana MSc ,&nbsp;Namwiya Musonda MS ,&nbsp;Manoj Mathews MD ,&nbsp;Musaku Mwenechanya MD ,&nbsp;Ifunanya Dallah MPH ,&nbsp;Brent Johnson PhD ,&nbsp;Christopher Bositis MD ,&nbsp;Jessie Huang BSc ,&nbsp;Gretchen L. Birbeck MD, MPH","doi":"10.1016/j.pediatrneurol.2024.07.002","DOIUrl":"10.1016/j.pediatrneurol.2024.07.002","url":null,"abstract":"<div><h3>Background</h3><p>There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure.</p></div><div><h3>Methods</h3><p>In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered.</p></div><div><h3>Results</h3><p>Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9).</p></div><div><h3>Conclusions</h3><p>Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 41-47"},"PeriodicalIF":3.2,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887899424002534/pdfft?md5=7c954a9d958771bb5198164d5d9ebe55&pid=1-s2.0-S0887899424002534-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141693494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Side Effects of Topiramate in Treatment of Children With Pseudotumor Cerebri Syndrome","authors":"Jacqueline Jeon-Chapman BS ,&nbsp;Tais Estrela MD ,&nbsp;Gena Heidary MD, PhD ,&nbsp;Ryan Gise MD","doi":"10.1016/j.pediatrneurol.2024.06.015","DOIUrl":"10.1016/j.pediatrneurol.2024.06.015","url":null,"abstract":"<div><h3>Background</h3><p>Topiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children.</p></div><div><h3>Methods</h3><p>Retrospective study of patients aged &lt;21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded.</p></div><div><h3>Results</h3><p>A total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss.</p></div><div><h3>Conclusions</h3><p>Topiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 32-37"},"PeriodicalIF":3.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generative Pre-trained Transformer for Pediatric Stroke Research: A Pilot Study","authors":"Anna K. Fiedler BS ,&nbsp;Kai Zhang PhD ,&nbsp;Tia S. Lal BS ,&nbsp;Xiaoqian Jiang PhD ,&nbsp;Stuart M. Fraser MD","doi":"10.1016/j.pediatrneurol.2024.07.001","DOIUrl":"10.1016/j.pediatrneurol.2024.07.001","url":null,"abstract":"<div><h3>Background</h3><p>Pediatric stroke is an important cause of morbidity in children. Although research can be challenging, large amounts of data have been captured through collaborative efforts in the International Pediatric Stroke Study (IPSS). This study explores the use of an advanced artificial intelligence program, the Generative Pre-trained Transformer (GPT), to enter pediatric stroke data into the IPSS.</p></div><div><h3>Methods</h3><p>The most recent 50 clinical notes of patients with ischemic stroke or cerebral venous sinus thrombosis at the UTHealth Pediatric Stroke Clinic were deidentified. Domain-specific prompts were engineered for an offline artificial intelligence program (GPT) to answer IPSS questions. Responses from GPT were compared with the human rater. Percent agreement was assessed across 50 patients for each of the 114 queries developed from the IPSS database outcome questionnaire.</p></div><div><h3>Results</h3><p>GPT demonstrated strong performance on several questions but showed variability overall. In its early iterations it was able to match human judgment occasionally with an accuracy score of 1.00 (n = 20, 17.5%), but it scored as low as 0.26 in some patients. Prompts were adjusted in four subsequent iterations to increase accuracy. In its fourth iteration, agreement was 93.6%, with a maximum agreement of 100% and minimum of 62%. Of 2400 individual items assessed, our model entered 2247 (93.6%) correctly and 153 (6.4%) incorrectly.</p></div><div><h3>Conclusions</h3><p>Although our tailored generative model with domain-specific prompt engineering and ontological guidance shows promise for research applications, further refinement is needed to enhance its accuracy. It cannot enter data entirely independently, but it can be employed in tandem with human oversight contributing to a collaborative approach that reduces overall effort.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"160 ","pages":"Pages 54-59"},"PeriodicalIF":3.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141716701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-Resistant Epilepsy in Tuberous Sclerosis Complex Is Associated With TSC2 Genotype: More Findings From the Preventing Epilepsy Using Vigatrin (PREVeNT) Trial","authors":"Laura S. Farach MD ,&nbsp;Melissa A. Richard PhD ,&nbsp;Aynara C. Wulsin MD, PhD ,&nbsp;Elizabeth M. Bebin MD ,&nbsp;Darcy A. Krueger MD, PhD ,&nbsp;Mustafa Sahin MD, PhD ,&nbsp;Brenda E. Porter MD, PhD ,&nbsp;Tarrant O. McPherson PhD ,&nbsp;Jurriaan M. Peters MD, PhD ,&nbsp;Sarah O'Kelley PhD ,&nbsp;Katherine S. Taub MD ,&nbsp;Rajsekar Rajaraman MD ,&nbsp;Stephanie C. Randle MD ,&nbsp;William M. McClintock MD ,&nbsp;Mary Kay Koenig MD ,&nbsp;Michael D. Frost MD ,&nbsp;Klaus Werner MD, PhD ,&nbsp;Danielle A. Nolan MD ,&nbsp;Michael Wong MD, PhD ,&nbsp;Gary Cutter PhD ,&nbsp;Elida Salazar","doi":"10.1016/j.pediatrneurol.2024.06.012","DOIUrl":"10.1016/j.pediatrneurol.2024.06.012","url":null,"abstract":"<div><h3>Background</h3><p>Children with tuberous sclerosis complex (TSC) are at high risk for drug-resistant epilepsy (DRE). The ability to stratify those at highest risk for DRE is important for counseling and prompt, aggressive management, necessary to optimize neurocognitive outcomes. Using the extensively phenotyped PREVeNT cohort, we aimed to characterize whether the TSC genotype was associated with DRE.</p></div><div><h3>Methods</h3><p>The study group (N = 70) comprised participants with TSC enrolled at age less than or equal to six months with detailed epilepsy and other phenotypic and genotypic data, prospectively collected as part of the PREVeNT trial. Genotype-phenotype correlations of DRE, time to first abnormal electroencephalography, and time to epilepsy onset were compared using Fisher exact test and regression models.</p></div><div><h3>Results</h3><p>Presence of a <em>TSC2</em> pathogenic variant was significantly associated with DRE, compared with <em>TSC1</em> and participants with no pathogenic mutation identified. In fact, all participants with DRE had a <em>TSC2</em> pathogenic variant. Furthermore, <em>TSC2</em> variants expected to result in no protein product were associated with higher risk for DRE. Finally, <em>TSC1</em> pathogenic variants were associated with later-onset epilepsy, on average 21.2 months later than those with other genotypes.</p></div><div><h3>Conclusions</h3><p>Using a comprehensively phenotyped cohort followed from infancy, this study is the first to delineate genotype-phenotype correlations for epilepsy severity and onset in children with TSC. Patients with <em>TSC2</em> pathogenic variants, especially <em>TSC2</em> pathogenic variants predicted to result in lack of TSC2 protein, are at highest risk for DRE, and are likely to have earlier epilepsy onset than those with <em>TSC1</em>. Clinically, these insights can inform counseling, surveillance, and management.</p></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"159 ","pages":"Pages 62-71"},"PeriodicalIF":3.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}