Pediatric neurology最新文献

英文中文

Febrile Seizures, Ongoing Epileptiform Activity, and the Resulting Long-Term Consequences: Lessons From Animal Models 热性惊厥、持续的癫痫样活动以及由此产生的长期后果：动物模型的启示

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-28 DOI: 10.1016/j.pediatrneurol.2024.09.026

Sydney A. Harris MSc , Emily E. Gordon BSc , Karlene T. Barrett PhD , Morris H. Scantlebury MBBS, MD , G. Campbell Teskey PhD

Febrile seizures affect 2% to 14% of children. Prospective studies indicate that following a relatively prolonged febrile seizure there are long-term consequences. Although controlled experiments in children have ethical limitations, nonhuman animal models give us the ability to discover new phenomena, determine their mechanisms, and test treatments that can potentially translate to the human clinical population. Rat models of febrile seizures show two temporally distinct phases: (1); behavioral seizures and (2); ongoing epileptiform activity associated with hyperoxia. The behavioral seizures mimic those displayed by children including tonic-clonic convulsions and loss of postural control. Recordings show classic spiking discharges from cortical regions during the behavioral seizures. Following behavioral seizure termination electrical recordings in rodent models reveal that there is ongoing epileptiform activity that lasts longer than the duration of the behavioral seizures themselves. This ongoing epileptiform activity is also associated with hyperoxia—levels of brain tissue oxygen well above the normoxic zone (typical oxygen levels)—and can last more than an hour. When this hyperoxia, but not the epileptiform activity, is prevented in febrile rat pups the long-term learning impairments are also prevented. This leaves important questions unanswered, “Do children also have ongoing and long-lasting epileptiform activity and associated hyperoxia following termination of their febrile behavioral seizures and does this second phase have long-term consequences”? Here we discuss appropriate animal models of febrile seizures that replicate much of the human condition with special attention to the long-term effects of occult epileptiform activity following termination of a behavioral febrile seizure.

2%到14%的儿童会出现发热性惊厥。前瞻性研究表明，相对较长时间的发热性癫痫发作会造成长期后果。尽管在儿童中进行受控实验存在伦理限制，但非人类动物模型使我们有能力发现新现象、确定其机制并测试有可能应用于人类临床人群的治疗方法。发热性癫痫发作的大鼠模型表现出两个时间上截然不同的阶段：（1）行为性癫痫发作；（2）与高氧相关的持续性癫痫样活动。行为性癫痫发作与儿童表现出的行为性癫痫发作相似，包括强直阵挛性抽搐和失去姿势控制。记录显示，在行为发作期间，大脑皮层区域会出现典型的尖峰放电。啮齿类动物模型在行为发作终止后进行的电记录显示，癫痫样活动仍在持续，持续时间比行为发作本身的持续时间更长。这种持续的癫痫样活动还与高氧有关--脑组织氧含量远高于常氧区（典型的氧含量）--可持续一个多小时。当发热大鼠幼崽的高氧（而非癫痫样活动）被阻止时，长期学习障碍也会被阻止。这就留下了一个重要的问题："在发热行为发作终止后，儿童是否还会有持续和持久的痫样活动及相关的高氧症？在此，我们将讨论热性惊厥的适当动物模型，这些模型复制了人类的大部分情况，并特别关注行为性热性惊厥终止后隐性癫痫样活动的长期影响。

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引用次数: 0

Response to Hamid et al., “Equitable Access of Delandistrogene Moxeparvovec for Patients With Duchenne Muscular Dystrophy” 对 Hamid 等人 "杜氏肌肉萎缩症患者公平使用 Delandistrogene Moxeparvovec "的回应。

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-27 DOI: 10.1016/j.pediatrneurol.2024.09.019

David K. Urion MD, Juan Francisco Cabello MD, Rodrigo Salinas MD

引用次数: 0

Do Vaccines Cause Postural Orthostatic Tachycardia Syndrome (POTS)? Review of Cases in the National Vaccine Injury Compensation Program 疫苗会导致体位性正位性心动过速综合征吗？国家疫苗伤害赔偿计划案例回顾》。

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-27 DOI: 10.1016/j.pediatrneurol.2024.09.025

Waqar Waheed MD, Gregory L. Holmes MD

Purpose

The National Childhood Vaccine Injury Act of 1986 created the National Vaccine Injury Compensation Program (VICP), a no-fault alternative to the traditional tort system. Since 1988, the total compensation paid exceeds $6 billion. While postural orthostatic tachycardia syndrome (POTS) is a frequent reason for filing a claim, there has been no review of the process and validity of the legal outcomes given current medical information. The purpose of this study was to review vaccine-related POTS and assess the rationale behind decisions made by the court.

Methods

We identified 102 unique cases with POTS. All published reports were reviewed for petitioner’s theories supporting vaccine-induced POTS, respondent’s counterarguments, the final decision regarding compensation and the rationale underlying these decisions. The primary goal was to determine which factors went into decisions regarding whether vaccines cause POTS.

Results

In deciding the cases the Special Masters hearing the cases places a high reliance on expert witnesses for both the petitioners and respondents. Petitioners’ experts frequently implicated vaccines, primarily human papillomavirus vaccine (HPV) as causing POTS through autoimmunity induced by molecular mimicry. However, in none of the 102 cases was POTS considered to be directly caused by a vaccine.

Conclusion

Despite the lack of epidemiological or mechanistic evidence indicating that childhood vaccines covered by the VICP result in POTS, these cases continue to be adjudicated, at considerable cost to the government. Unless there is emerging scientific support for implicating vaccines in POTS it is time that the VICP stop considering these cases.

背景：1986 年《全国儿童疫苗伤害法案》创立了全国疫苗伤害赔偿计划 (VICP)，这是传统侵权制度的一种无过失替代方案。自 1988 年以来，支付的赔偿总额已超过 60 亿美元。尽管体位性正位性心动过速综合症（POTS）是一个经常被提起索赔的原因，但鉴于目前的医疗信息，还没有对法律结果的过程和有效性进行审查。本研究的目的是审查与疫苗相关的 POTS，并评估法院做出裁决的理由：我们确定了 102 例 POTS 病例。我们对所有已发表的报告进行了审查，以了解申请人支持疫苗诱发 POTS 的理论、答辩人的反驳、关于赔偿的最终裁决以及这些裁决背后的基本原理。主要目的是确定哪些因素会影响有关疫苗是否会导致 POTS 的决定：在裁决案件时，审理案件的特别法官高度依赖申请人和被申请人的专家证人。请愿人的专家经常暗示疫苗（主要是人类乳头瘤病毒疫苗）会通过分子模仿引起自身免疫而导致 POTS。然而，在 102 例病例中，没有一例 POTS 被认为是由疫苗直接引起的：结论：尽管缺乏流行病学或机理方面的证据表明 VICP 涵盖的儿童疫苗会导致 POTS，但这些病例仍在继续审理，政府为此付出了巨大的代价。除非有新的科学证据证明疫苗与 POTS 有关，否则现在是时候让 VICP 停止审理这些案件了。

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引用次数: 0

Dengue-Associated Acute Necrotizing Encephalopathy Is an Acute Necrotizing Encephalopathy Variant Rather than a Mimic: Evidence From a Systematic Review 登革热相关急性坏死性脑病是急性坏死性脑病的变异型而非模仿型：来自系统综述的证据。

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-27 DOI: 10.1016/j.pediatrneurol.2024.09.021

Sophie Barron MD , Velda X. Han MD, PhD , Juhi Gupta MD , Lokesh Lingappa MD , Naveen Sankhyan MD , Terrence Thomas MD

Background

Bilateral hemorrhagic thalamic lesions in dengue encephalitis resemble lesions seen in acute necrotizing encephalopathy (ANE). We investigate whether dengue-associated ANE (DANE) should be considered an ANE variant or a mimic.

Methods

Systematic review of dengue encephalitis literature from PubMed and SCOPUS (inception to December 31, 2022). Diagnostic criteria for ANE, acute encephalitis (AE), acute disseminated encephalomyelitis (ADEM), and infection-triggered encephalopathy syndromes were applied.

Results

Data on 162 patients (median age 20 [0.4 to 79] years; 69 [42.3%] female; 72 [44.4%] aged ≤18 years) from 103 articles were analyzed. DANE (62, 38.3%) was the commonest, followed by AE (56, 34.6%) and ADEM (27, 16.7%). The main clinical features were fever (100%), thrombocytopenia (79.0%), headache (57.8%), and seizures (43.7%). Patients with DANE had earlier neurological deterioration (3.5 [1 to 8] vs 5 [1 to 14] days in other encephalitis syndromes, P = 0.0127), seizures (54.2% vs 37.4%, P = 0.0471), higher cerebrospinal fluid (CSF) protein (0.92 [0.18 to 4.8] vs 0.73 [1 to 16] g/L, P = 0.0469), thalamic (100% vs 8.0%) and hemorrhagic brain lesions (73.3% vs 7.5%, P < 0.0001). CSF pleocytosis and positive CSF dengue IgM/viral polymerase chain reaction were reported in 66.7% and 78.6% with DANE. Mortality was 16.1% in DANE, and 40.6% of survivors had disability. High-risk ANE severity scores predicted poor outcomes (positive predictive value 64.3% [95% confidence interval 38.8% to 83.7%]).

Conclusion

DANE differs from other dengue encephalitis syndromes and is clinicoradiologically indistinguishable from sporadic ANE with sufficient evidence to be considered an ANE variant.

背景：登革热脑炎的双侧丘脑出血性病变与急性坏死性脑病（ANE）的病变相似。我们研究了登革热相关ANE（DANE）是否应被视为ANE的变异体或模仿体：方法：对 PubMed 和 SCOPUS 上的登革热脑炎文献进行系统回顾（从开始到 2022 年 12 月 31 日）。采用ANE、急性脑炎（AE）、急性播散性脑脊髓炎（ADEM）和感染诱发脑病综合征的诊断标准：分析了 103 篇文章中 162 名患者（中位年龄 20 [0.4 至 79] 岁；69 [42.3%] 名女性；72 [44.4%] 名患者年龄小于 18 岁）的数据。DANE（62 例，38.3%）最常见，其次是AE（56 例，34.6%）和ADEM（27 例，16.7%）。主要临床特征为发热（100%）、血小板减少（79.0%）、头痛（57.8%）和癫痫发作（43.7%）。DANE 患者的神经系统恶化时间（3.5 [1 至 8] 天 vs 其他脑炎综合征的 5 [1 至 14] 天，P = 0.0127）、癫痫发作（54.2% vs 37.4%，P = 0.0471）、较高的脑脊液（CSF）蛋白（0.92 [0.18 至 4.8] vs 0.73 [1 至 16] g/L，P = 0.0469）、丘脑（100% vs 8.0%）和出血性脑损伤（73.3% vs 7.5%，P < 0.0001）。66.7%和78.6%的DANE患者出现脑脊液多细胞和脑脊液登革热IgM/病毒聚合酶链反应阳性。DANE患者的死亡率为16.1%，40.6%的幸存者致残。高风险 ANE 严重程度评分预示着不良后果（阳性预测值为 64.3% [95% 置信区间为 38.8% 至 83.7%]）：结论：DANE不同于其他登革热脑炎综合征，在临床放射学上与散发性ANE无异，有足够证据将其视为ANE变异型。

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引用次数: 0

Cenobamate's Efficacy for Seizure Treatment in Tuberous Sclerosis Complex 塞诺巴马特治疗结节性硬化症复合体癫痫发作的疗效。

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-26 DOI: 10.1016/j.pediatrneurol.2024.09.023

Gewalin Aungaroon MD , Alexander Cooke BS , David Ritter MD, PhD , Darcy Krueger MD, PhD , Paul Horn PhD , David N. Franz MD

Background

Epilepsy is prevalent, and seizure control is challenging in patients with tuberous sclerosis complex (TSC). Cenobamate (CBM) has proven efficacy in several studies; however, its benefit in the TSC population is not known.

Methods

We performed a retrospective review of patients with TSC who received adjunctive CBM for seizure treatments. We assessed treatment efficacy by comparing seizure frequencies three months before CBM (baseline) and those at 3-, 6-, 12-, and 18- month follow-ups.

Results

We identified 70 patients with TSC receiving CBM and excluded 16 with insufficient data. Fifty-four patients aged 2 to 39 years, with an average baseline seizure of 66.1 ± 88.9 per month, were analyzed. Treatment retention rates at 3, 6, 12, and 18 months were 94.4%, 79.6%, 66.7%, 44.4%, and responder rates (proportions of patients who remained on treatment and had ≥50% seizure reduction) were 38.1%, 51.7%, 53.1%, and 59.1%, respectively. Seizure-free rates at these respective follow-ups were 7.1%, 13.8%, 6.3%, and 9.1%. For patients experiencing reduced seizures, the mean percentage of change ranged from 61.5% to 74.6%. Side effects were common (64.8%), particularly sedation (42.6%), behavioral disturbance (24.1%), and gastrointestinal disturbance (22.2%).

Conclusions

Most patients in this study showed seizure reduction; however, the overall responder and seizure-free rates were lower than the literature, likely due to the unique underlying epileptogenesis in TSC and the challenges of tolerating CBM. The lower treatment retention rates signal areas for improvement in concurrent medication adjustment practices.

背景：在结节性硬化症复合体（TSC）患者中，癫痫是一种常见病，而癫痫发作控制是一项挑战。几项研究已证明塞诺巴马特（CBM）具有疗效，但其对 TSC 患者的益处尚不清楚：我们对接受CBM辅助治疗的TSC患者进行了回顾性研究。我们通过比较CBM治疗前三个月（基线）和随访3个月、6个月、12个月和18个月时的癫痫发作频率来评估治疗效果：我们确定了70名接受CBM治疗的TSC患者，并排除了16名数据不足的患者。对54名年龄在2至39岁之间的患者进行了分析，他们的平均基线发作率为每月66.1±88.9次。3、6、12和18个月的治疗保持率分别为94.4%、79.6%、66.7%和44.4%，应答率（保持治疗且发作减少≥50%的患者比例）分别为38.1%、51.7%、53.1%和59.1%。在这些随访中，无癫痫发作率分别为 7.1%、13.8%、6.3% 和 9.1%。对于发作次数减少的患者，平均变化百分比从61.5%到74.6%不等。副作用很常见（64.8%），尤其是镇静（42.6%）、行为紊乱（24.1%）和胃肠道紊乱（22.2%）：本研究中的大多数患者癫痫发作有所减少，但总体应答率和无发作率低于文献报道，这可能是由于TSC独特的潜在癫痫发生机制以及CBM的耐受性所带来的挑战。较低的治疗保持率预示着同时用药调整实践中需要改进的地方。

{"title":"Cenobamate's Efficacy for Seizure Treatment in Tuberous Sclerosis Complex","authors":"Gewalin Aungaroon MD , Alexander Cooke BS , David Ritter MD, PhD , Darcy Krueger MD, PhD , Paul Horn PhD , David N. Franz MD","doi":"10.1016/j.pediatrneurol.2024.09.023","DOIUrl":"10.1016/j.pediatrneurol.2024.09.023","url":null,"abstract":"<div><h3>Background</h3><div>Epilepsy is prevalent, and seizure control is challenging in patients with tuberous sclerosis complex (TSC). Cenobamate (CBM) has proven efficacy in several studies; however, its benefit in the TSC population is not known.</div></div><div><h3>Methods</h3><div>We performed a retrospective review of patients with TSC who received adjunctive CBM for seizure treatments. We assessed treatment efficacy by comparing seizure frequencies three months before CBM (baseline) and those at 3-, 6-, 12-, and 18- month follow-ups.</div></div><div><h3>Results</h3><div>We identified 70 patients with TSC receiving CBM and excluded 16 with insufficient data. Fifty-four patients aged 2 to 39 years, with an average baseline seizure of 66.1 ± 88.9 per month, were analyzed. Treatment retention rates at 3, 6, 12, and 18 months were 94.4%, 79.6%, 66.7%, 44.4%, and responder rates (proportions of patients who remained on treatment and had ≥50% seizure reduction) were 38.1%, 51.7%, 53.1%, and 59.1%, respectively. Seizure-free rates at these respective follow-ups were 7.1%, 13.8%, 6.3%, and 9.1%. For patients experiencing reduced seizures, the mean percentage of change ranged from 61.5% to 74.6%. Side effects were common (64.8%), particularly sedation (42.6%), behavioral disturbance (24.1%), and gastrointestinal disturbance (22.2%).</div></div><div><h3>Conclusions</h3><div>Most patients in this study showed seizure reduction; however, the overall responder and seizure-free rates were lower than the literature, likely due to the unique underlying epileptogenesis in TSC and the challenges of tolerating CBM. The lower treatment retention rates signal areas for improvement in concurrent medication adjustment practices.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 201-207"},"PeriodicalIF":3.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472238","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}

引用次数: 0

Beyond Numbers: A Call to Action for Accurate Estimation of Spinal Muscular Atrophy in the Middle East and North Africa Region 超越数字：呼吁采取行动，准确估计中东和北非地区脊髓性肌肉萎缩症的发病率

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-25 DOI: 10.1016/j.pediatrneurol.2024.09.024

Maryam Bemanalizadeh MD , Vahid Mansouri MD

引用次数: 0

Cerebrovascular Injury From Early-Onset Neonatal Escherichia coli Meningitis: Expanding the Clinical-Radiologic Phenotype 早发型新生儿大肠埃希氏菌脑膜炎引起的脑血管损伤：扩展临床放射学表型。

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-24 DOI: 10.1016/j.pediatrneurol.2024.09.020

Francesca G. García MD , Yi Li MD , Rachel Vassar MD , Cheryl Hawkins MD , Mark Petersen MD , Dawn Gano MD, MAS

引用次数: 0

Exploring the Genetic Landscape of Epilepsy With Eyelid Myoclonia: A Comprehensive Review on Clinical Features and Diagnostic Challenges 探索眼睑肌张力障碍性癫痫的遗传规律：临床特征和诊断难题的全面回顾。

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-23 DOI: 10.1016/j.pediatrneurol.2024.09.018

Samia Aziz Sulaiman MD , Ihda Bani Khalaf MD , Ahmad E. Saeed MD , Waseem Hoshan MD , Ahmed W. Hageen MBBCh , Jatin Motwani MBBS , Aman Goyal MBBS

Jeavons syndrome (JS), also known as epilepsy with eyelid myoclonia (EEM), is an idiopathic epileptic syndrome that primarily affects children. JS constitutes a significant portion of idiopathic generalized epilepsies and overall epileptic conditions and is characterized by frequent eyelid myoclonia. JS is often triggered by factors such as eyelid closure and exposure to light, leading to absence seizures with photoparoxysmal responses. Although previous studies indicate that some genes have demonstrated an association with the syndrome, no definitive causative gene has yet been identified. The current review therefore aims to shed emphasis on the potential value genetic testing holds in the context of EEM, as well as the need to investigate potential early diagnosis and management strategies in future research.

杰文斯综合征（JS），又称眼睑肌阵挛癫痫（EEM），是一种主要影响儿童的特发性癫痫综合征。JS 在特发性全身癫痫和整体癫痫中占很大比例，其特征是频繁出现眼睑肌张力障碍。JS 常常由眼睑闭合和光线照射等因素诱发，导致失神发作和光敏反应。尽管以往的研究表明，一些基因与该综合征有关联，但尚未发现明确的致病基因。因此，本综述旨在强调基因检测在 EEM 方面的潜在价值，以及在未来研究中调查潜在早期诊断和管理策略的必要性。

引用次数: 0

Severe Epilepsy in an Individual With a TSC2 R905Q Variant Prompting Late Diagnosis in Affected Family Members 一名 TSC2 R905Q 变异患者的严重癫痫导致受影响家庭成员的晚期诊断。

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-21 DOI: 10.1016/j.pediatrneurol.2024.09.014

Alice Man BSc , Matteo Di Scipio BSc , Breanne Dale MSc, CGC , Paula Teixeira Marques MD , Cynthia Sloan Birbeck BScN, RN, MN , Puneet Jain MBBS, MD, DM , Elisabetta Trinari MD, MSc , Resham Ejaz MD , Robyn Whitney MD

Background

Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes TSC1 and TSC2. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in TSC2 are typically associated with a more severe phenotype compared with TSC1; the TSC2 R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected.

Methods

We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant.

Results

Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3–diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4–diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis.

Conclusions

This study expands the possible phenotypic spectrum of TSC2 R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur.

背景：结节性硬化症综合征（TSC）是一种多系统疾病，由 mTOR 通路抑制基因 TSC1 和 TSC2 的失活变异引起。TSC患者易患多器官良性肿瘤以及TSC相关神经精神障碍（TAND）和癫痫。与TSC1相比，TSC2的致病变异通常与更严重的表型相关；TSC2 R905Q变异已被证明是一个例外，有报道称患者表现出异常轻微的TSC特征，而这些特征可能未被检测到：方法：我们研究了一名13岁患者和三名家族成员的TSC2 c.2714G>A（R905Q）致病变异的TSC表型：患者 1 患有严重的药物难治性癫痫，无小管或蝶鞍下结节，在虚拟检查中仅发现轻微的 TSC 皮肤特征。她的母亲和姨妈（患者 2 和 3，50 岁后确诊）表现为轻度表型，有皮肤特征和 TAND。她的舅舅（患者4，47岁确诊）的表型最为严重，表现为智力障碍、药物难治性癫痫、强迫症、创伤后应激障碍和精神病：本研究扩展了TSC2 R905Q变异型的可能表型谱，表明该变异型与严重癫痫有关，但没有相关的神经放射学标志。该研究强调了TSC隐匿性局灶性皮质发育不良的可能性，并强调了对严重癫痫患者进行基因检测的重要性。此外，该患者的其他家族成员随后也被确诊为晚期成人患者，因此可以对该患者进行适当的TSC监测。

{"title":"Severe Epilepsy in an Individual With a TSC2 R905Q Variant Prompting Late Diagnosis in Affected Family Members","authors":"Alice Man BSc , Matteo Di Scipio BSc , Breanne Dale MSc, CGC , Paula Teixeira Marques MD , Cynthia Sloan Birbeck BScN, RN, MN , Puneet Jain MBBS, MD, DM , Elisabetta Trinari MD, MSc , Resham Ejaz MD , Robyn Whitney MD","doi":"10.1016/j.pediatrneurol.2024.09.014","DOIUrl":"10.1016/j.pediatrneurol.2024.09.014","url":null,"abstract":"<div><h3>Background</h3><div>Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes <em>TSC1</em> and <em>TSC2</em>. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in <em>TSC2</em> are typically associated with a more severe phenotype compared with <em>TSC1</em>; the <em>TSC2</em> R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected.</div></div><div><h3>Methods</h3><div>We studied the TSC phenotype of a 13-year-old individual and three family members with a <em>TSC2</em> c.2714G>A (R905Q) pathogenic variant.</div></div><div><h3>Results</h3><div>Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3–diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4–diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis.</div></div><div><h3>Conclusions</h3><div>This study expands the possible phenotypic spectrum of <em>TSC2</em> R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 158-161"},"PeriodicalIF":3.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392413","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}

引用次数: 0

Rare CCND2 (p.Thr280Ile) Variant Associated With Infantile Spasms in a Patient With Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 罕见的 CCND2（p.Thr280Ile）变异与巨脑畸形-多发性畸形-多指畸形-脑积水综合征患者的婴儿痉挛有关

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY

Pediatric neurology

Pub Date : 2024-09-21 DOI: 10.1016/j.pediatrneurol.2024.09.016

Kent M. Mok MD , Jessica L. Carpenter MD , Pamela Herrada MS, CGC , Carol Greene MD , Sandrine Yazbek MD , Gozde Erdemir MD

Background

This report describes a pediatric case of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, a rare neurodevelopmental disorder caused by pathogenic variants in the AKT3, CCND2, or PIK3R2 genes. We present a patient with a rare CCND2 variant (c.839C>T, p.Thr280Ile), associated with infantile spasms, ventriculomegaly, polymicrogyria, and intraventricular hemorrhage (IVH).

Methods

A retrospective chart review and literature search were performed using PubMed.

Results

Our patient was found to have ventriculomegaly, grade 3 IVH, bilateral polymicrogyria, and restricted diffusion in the caudate nuclei prenatally. No polydactyly was observed. The patient developed infantile spasms at age 5 months. While high-dose prednisone treatment failed to control the spasms, they resolved with topiramate. By age 2 years, the patient continued to have significant developmental delays, including having poor tone and being nonverbal.

Conclusion

MPPH syndrome remains a rare and challenging diagnosis, with fewer than 100 cases reported. This case highlights the importance of early genetic testing and neuroimaging in the diagnosis and management of MPPH. The unique presentation of IVH and restricted diffusion warrants further investigation into the syndrome’s variable phenotypic spectrum. Early intervention and targeted therapy may help manage seizure activity and improve outcomes.

背景本报告描述了一例巨脑-多小脑-多乳-脑积水（MPPH）综合征的儿科病例，这是一种由 AKT3、CCND2 或 PIK3R2 基因致病变体引起的罕见神经发育障碍。我们报告了一名患有罕见CCND2变异（c.839C>T, p.Thr280Ile）的患者，该患者伴有婴儿痉挛、脑室肥大、多发性畸形和脑室内出血（IVH）。结果我们发现患者有脑室肥大、3级IVH、双侧多发性畸形和出生前尾状核弥散受限。未发现多指畸形。患者在 5 个月大时出现婴儿痉挛症。虽然大剂量强的松治疗未能控制痉挛，但使用托吡酯后痉挛得到缓解。到 2 岁时，患者仍有明显的发育迟缓，包括音调不佳和不善言语。本病例强调了早期基因检测和神经影像学检查在 MPPH 诊断和治疗中的重要性。IVH和弥散受限的独特表现值得进一步研究该综合征的多变表型谱。早期干预和针对性治疗有助于控制癫痫发作活动和改善预后。

{"title":"Rare CCND2 (p.Thr280Ile) Variant Associated With Infantile Spasms in a Patient With Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome","authors":"Kent M. Mok MD , Jessica L. Carpenter MD , Pamela Herrada MS, CGC , Carol Greene MD , Sandrine Yazbek MD , Gozde Erdemir MD","doi":"10.1016/j.pediatrneurol.2024.09.016","DOIUrl":"10.1016/j.pediatrneurol.2024.09.016","url":null,"abstract":"<div><h3>Background</h3><div>This report describes a pediatric case of megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, a rare neurodevelopmental disorder caused by pathogenic variants in the <em>AKT3</em>, <em>CCND2</em>, or <em>PIK3R2</em> genes. We present a patient with a rare <em>CCND2</em> variant (c.839C>T, p.Thr280Ile), associated with infantile spasms, ventriculomegaly, polymicrogyria, and intraventricular hemorrhage (IVH).</div></div><div><h3>Methods</h3><div>A retrospective chart review and literature search were performed using PubMed.</div></div><div><h3>Results</h3><div>Our patient was found to have ventriculomegaly, grade 3 IVH, bilateral polymicrogyria, and restricted diffusion in the caudate nuclei prenatally. No polydactyly was observed. The patient developed infantile spasms at age 5 months. While high-dose prednisone treatment failed to control the spasms, they resolved with topiramate. By age 2 years, the patient continued to have significant developmental delays, including having poor tone and being nonverbal.</div></div><div><h3>Conclusion</h3><div>MPPH syndrome remains a rare and challenging diagnosis, with fewer than 100 cases reported. This case highlights the importance of early genetic testing and neuroimaging in the diagnosis and management of MPPH. The unique presentation of IVH and restricted diffusion warrants further investigation into the syndrome’s variable phenotypic spectrum. Early intervention and targeted therapy may help manage seizure activity and improve outcomes.</div></div>","PeriodicalId":19956,"journal":{"name":"Pediatric neurology","volume":"161 ","pages":"Pages 185-187"},"PeriodicalIF":3.2,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426925","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}

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