Brain and Development Case Reports最新文献

Long-term use of efgartigimod alfa in treating a young adult with childhood-onset systemic lupus erythematosus and generalized myasthenia gravis 长期使用依加替莫德α治疗一名患有儿童期系统性红斑狼疮和全身性重症肌无力的年轻人

Brain and Development Case Reports

Pub Date : 2024-11-16 DOI: 10.1016/j.bdcasr.2024.100052

Koji Nagatani, Masatoshi Hayashi

Background

Patientis with myasthenia gravis (MG) are at increased risk of other autoimmune disorders, such as systemic lupus erythematosus (SLE). The neonatal Fc receptor (FcRn) antagonist, efgartigimod alfa (EFG-α), is effective in generalized MG (gMG) by a mechanism that decreases levels of IgG, including pathological autoantibodies. Although approved in Japan for gMG in 2022, its efficacy for other autoimmune disorders and the effects of long-term use of EFG-α for gMG in children and young adults remain to be elucidated.

Case

A 10-year-old girl diagnosed with SLE developed gMG 2 years later. Despite intensive therapy, she also had myasthenic crisis and two recurrences. Moreover, the anti-acetylcholine receptor (AChR) antibody titer remained high, making it difficult to reduce the prednisolone (PSL) dose to below 12.5 mg/day. Eight years later, she had a flare of SLE and was treated with pulse methylprednisolone followed by EFG-α to reduce the PSL dose. A total of six cycles of EFG-α (10 mg/kg) were administered, with four infusions per cycle (one infusion per week) over a period of one and a half years. Consequently, the quantitative MG (QMG) score, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and anti-double-stranded DNA (dsDNA) antibody titer remained low. Furthermore, the prolonged administration of EFG-α resulted in a reduction in the dosage of prednisolone, which led to improvement in the patient's obesity.

Conclusion

EFG-α may be effective not only for MG but also for SLE, maintaining low disease activity and antibody levels. Long-term use could reduce steroid requirement, and thus decrease adverse effects. Expanding the indication of EFG-α to other autoimmune diseases and considering its use in pediatric patients are recommended.

背景重症肌无力（MG）患者罹患系统性红斑狼疮（SLE）等其他自身免疫性疾病的风险增加。新生儿Fc受体（FcRn）拮抗剂依加替莫德α（EFG-α）通过降低IgG（包括病理性自身抗体）水平的机制对全身性肌无力（gMG）有效。虽然日本已于 2022 年批准 EFG-α 用于治疗全身性马格尼病，但它对其他自身免疫性疾病的疗效以及长期使用 EFG-α 治疗儿童和青少年全身性马格尼病的效果仍有待阐明。尽管接受了强化治疗，但她还是出现了肌无力危象，并两次复发。此外，抗乙酰胆碱受体（AChR）抗体滴度仍然很高，导致泼尼松龙（PSL）剂量难以降至每天12.5毫克以下。八年后，她的系统性红斑狼疮复发，在接受脉冲甲基强的松龙治疗后又接受了EFG-α治疗，以减少PSL的剂量。在一年半的时间里，她总共接受了六个周期的 EFG-α（10 毫克/千克）治疗，每个周期输注四次（每周输注一次）。结果，MG（QMG）定量评分、系统性红斑狼疮疾病活动指数（SLEDAI）和抗双链 DNA（dsDNA）抗体滴度仍然很低。结论EFG-α不仅对MG有效，对系统性红斑狼疮也同样有效，能维持较低的疾病活动度和抗体水平。长期使用可减少对类固醇的需求，从而减少不良反应。建议将EFG-α的适应症扩大到其他自身免疫性疾病，并考虑在儿童患者中使用。

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引用次数: 0

Successful coil embolization for treatment of systemic to pulmonary collateral arteries (SPCAs): A case report among series of six cases with KCNT1-epilepsy and literature reviews 成功的线圈栓塞治疗系统性肺侧动脉（SPCA）：六例 KCNT1 癫痫患者的病例报告和文献综述

Brain and Development Case Reports

Pub Date : 2024-11-11 DOI: 10.1016/j.bdcasr.2024.100049

Tanitnun Paprad , Wuttichart Kamolvisit , Chupong Ittiwut , Chureerat Phokaew , Sarin Lekchuensakul , Sirorat Suwannachote , Kamornwan Katanyuwong , Chanikhan Sattaporn , Apasri Lusawat , Tayard Deesudchit , Ponghatai Boonsimma , Kanya Suphapeetiporn , Vorasuk Shotelersuk

Background

KCNT1 pathogenic variants are associated with a broad range of neurological and non-neurological phenotypes. Neurologically, these variants are known to cause several epilepsy phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS) and autosomal dominant sleep-related hypermotor epilepsy (SHE). A potentially fatal cardiovascular phenotype, systemic to pulmonary collateral arteries (SPCAs), has also been suggested as part of the spectrum associated with KCNT1 mutations.

Case presentation

We describe a patient with KCNT1-associated epilepsy who was found to have SPCAs in a cohort of six Thai cases. The SPCAs were successfully treated with coil embolization.

Results

In this cohort, the prevalence of SPCAs in Thai patients with KCNT1-associated epilepsy is estimated to be 16.7 % (1 out of 6). Quinidine therapy was effective in 83 % (5 out of 6) of the reported cases.

Discussion

The presence of SPCAs as part of the KCNT1-associated disorder highlights the importance of recognizing cardiovascular phenotypes in these patients. Early identification and intervention, such as coil embolization, can be life-saving.

Conclusion

Awareness of SPCAs as a possible cardiac phenotype in KCNT1-associated epilepsy is crucial, as timely and effective treatment can significantly improve patient outcomes.

背景KCNT1致病变体与多种神经和非神经表型相关。在神经系统方面，已知这些变异可导致几种癫痫表型，包括婴儿癫痫伴移灶性发作（EIMFS）和常染色体显性睡眠相关运动性癫痫（SHE）。我们描述了一名 KCNT1 相关性癫痫患者，该患者在六例泰国病例中被发现患有 SPCA。结果在该队列中，泰国 KCNT1 相关性癫痫患者的 SPCA 患病率估计为 16.7%（6 例中有 1 例）。在报告的病例中，奎尼丁疗法对 83% 的病例（6 例中有 5 例）有效。讨论作为 KCNT1 相关性疾病的一部分，SPCA 的出现凸显了识别这些患者心血管表型的重要性。结论认识到 SPCAs 可能是 KCNT1 相关性癫痫的一种心脏表型至关重要，因为及时有效的治疗可以显著改善患者的预后。

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引用次数: 0

Reversible bilateral ptosis after levetiracetam administration in a 4-year-old girl: A case report 一名 4 岁女童服用左乙拉西坦后出现可逆性双侧眼睑下垂：病例报告

Brain and Development Case Reports

Pub Date : 2024-11-07 DOI: 10.1016/j.bdcasr.2024.100051

Takato Akiba , Taiki Shima , Shino Shimada , Mitsuru Ikeno , Shinpei Abe , Ken Takahashi

Background

Levetiracetam (LEV) is a frequently prescribed antiseizure medication for focal epilepsy in children because of its high efficacy and relatively mild side effects. We report a case of reversible bilateral ptosis following LEV administration.

Case presentation

A 4-year-old girl presented with unprovoked focal to bilateral tonic-clonic seizures, which had occurred at least twice since the age of 3 years and 10 months. The patient was initially diagnosed with focal epilepsy, and was treated with LEV at a dose of 20 mg/kg/day. After one week of treatment, the patient developed bilateral ptosis without diurnal fluctuation. After a month, LEV was discontinued and the patient's treatment was changed to perampanel. Various tests were performed to rule out myasthenia gravis; however, no significant findings were observed. The patient's ptosis gradually improved over the three months following the cessation of LEV.

Conclusion

Although an exact causal relationship is challenging, the clinical course suggests that LEV may induce ptosis in patients with focal epilepsy. Herein, we report detailed clinical information because ptosis is not a known side effect of LEV treatment; therefore, understanding this newfound side effect is important given the widespread use of LEV.

背景左乙拉西坦（LEV）是治疗儿童局灶性癫痫的常用抗癫痫药物，因为其疗效高且副作用相对较小。我们报告了一例服用左乙拉西坦后出现可逆性双侧眼睑下垂的病例。病例介绍一名 4 岁女孩因无诱因的局灶性至双侧强直阵挛发作而就诊，自 3 岁 10 个月起至少发作过两次。患者最初被诊断为局灶性癫痫，并接受了剂量为 20 毫克/千克/天的 LEV 治疗。治疗一周后，患者出现双侧上睑下垂，且无昼夜波动。一个月后，患者停用 LEV，改用 perampanel。为了排除肌无力症，医生对患者进行了各种检查，但没有发现明显异常。结论虽然确切的因果关系还很难确定，但临床表现表明 LEV 可能会诱发局灶性癫痫患者的上睑下垂。在此，我们报告了详细的临床信息，因为眼睑下垂并不是已知的 LEV 治疗副作用；因此，鉴于 LEV 的广泛使用，了解这种新发现的副作用非常重要。

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引用次数: 0

Transmantle heterotopia associated with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in an adolescent male patient 一名青少年男性患者的横纹肌异位症伴有急性脑病双相癫痫发作和晚期弥散功能减退（AESD）

Brain and Development Case Reports

Pub Date : 2024-11-05 DOI: 10.1016/j.bdcasr.2024.100047

Sachiho Saito , Toshiki Nakamura , Aki Kawakami , Sahoko Miyama , Mikako Enokizono , Tatsuo Kono , Hiroshi Hataya

Background

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common type of acute encephalopathy. It occurs frequently in infants but rarely in teenagers. More than half of patients with AESD have neurological sequelae, but there are few, evidence-based treatments. Transmantle heterotopia is a rare type of gray matter heterotopia. We report herein a case of transmantle heterotopia with suspected involvement in AESD.

Case report

A 10-year-old, male patient with developmental disabilities and a history of multiple febrile seizures was admitted for fever and convulsion. On day 2 of the fever, he experienced six, intermittent convulsions over three hours despite antiepileptic drug administration. On admission, he had impaired consciousness and was positive for influenza virus type B. Other examinations, including brain CT, found no abnormalities. After admission, targeted temperature management (TTM) and vitamin, antibiotic, and oseltamivir therapy was begun. The patient experienced a prolonged state of impaired consciousness, prompting MRI to be performed on hospital day 6. Brain MRI findings suggested AESD and transmantle heterotopia. His consciousness status gradually improved, and he was able to perform gross motor activities and engage in simple conversation. He was discharged after valproic acid administration was begun. Two months after discharge, the patient displayed heightened impulsivity.

Conclusion

The present case of transmantle heterotopia was strongly suspected of being involved in the development of febrile status epilepticus and AESD. Children with underlying neurological disorders can experience AESD development even if they are older than the usually affected aged group.

背景急性脑病伴双相癫痫发作和晚期弥散功能减退（AESD）是最常见的急性脑病类型。它经常发生在婴儿身上，但很少发生在青少年身上。一半以上的 AESD 患者会留下神经系统后遗症，但循证治疗方法却很少。横纹肌异位症是一种罕见的灰质异位症。我们在此报告一例疑似参与 AESD 的横贯性异位灶病例。病例报告一名 10 岁的男性患者因发热和抽搐入院，他有发育障碍和多次发热性癫痫发作史。发热第 2 天，尽管服用了抗癫痫药物，他仍在 3 小时内出现了 6 次间歇性抽搐。入院时，他意识障碍，乙型流感病毒检测呈阳性。其他检查，包括脑部 CT，均未发现异常。入院后，患者开始接受体温管理（TTM）、维生素、抗生素和奥司他韦治疗。患者出现了长时间的意识障碍，因此在住院第6天进行了核磁共振成像检查。脑部核磁共振成像结果表明，患者患有AESD和经颅异位症。他的意识状况逐渐好转，能够进行大运动量活动并进行简单对话。在开始服用丙戊酸后，他就出院了。出院后两个月，患者表现出更强的冲动性。患有潜在神经系统疾病的儿童即使年龄大于通常受影响的年龄组，也可能发生 AESD。

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引用次数: 0

Coagulopathy by vitamin K deficiency: Clinical pitfall in a case with cerebral palsy under long-term enteral nutrition 维生素 K 缺乏引起的凝血病：长期肠内营养脑瘫病例中的临床陷阱

Brain and Development Case Reports

Pub Date : 2024-11-05 DOI: 10.1016/j.bdcasr.2024.100050

Mariko Yada, Tomoyo Itonaga, Saori Oguri, Yuka Kimura, Kenji Ihara

Background

Vitamin K deficiency is common in patients with neurological impairment under long-term enteral nutrition; however, reports of vitamin K deficiency in pediatric patients under long-term enteral nutrition remain limited, and critical conditions potentially leading to coagulopathy have not been sufficiently acknowledged by healthcare professionals.

Case presentation

We report the case of a seven-year-old girl with severe cerebral palsy who had received enteral nutrition via a nasoduodenal tube due to recurrent acute pancreatitis that had persisted for six months, and who had received an elemental diet for seven weeks prior to her presentation. After two days of cefmetazole treatment for urinary tract infection, abnormal coagulation findings, including a prolonged prothrombin time, activated partial thromboplastin time, and elevated levels of protein induced by vitamin K absence or antagonist-II, were detected. The patient's hypoprothrombinemia improved after the intravenous administration of vitamin K and switching antibiotics. From a retrospective point of view, her intake of vitamin K over the past six months was below the recommended amount for her age.

Conclusions

Long-term enteral nutrition is associated with an increased risk of coagulopathy due to vitamin K deficiency, which can be precipitated by prolonged use of antibacterial agents. When long-term enteral nutrition is given to patients with severe motor or intellectual disabilities, caution should be exercised when using antibiotics with NMTT side chains.

背景在长期接受肠内营养的神经系统受损患者中，维生素 K 缺乏症很常见；然而，关于长期接受肠内营养的儿科患者维生素 K 缺乏症的报道仍然有限，可能导致凝血病的危急情况尚未得到医护人员的充分认识。病例介绍我们报告了一例患有重度脑瘫的七岁女孩的病例，她因反复发作的急性胰腺炎已持续六个月而通过鼻十二指肠插管接受肠内营养，并在就诊前接受了七周的元素饮食。因尿路感染接受头孢美唑治疗两天后，发现凝血功能异常，包括凝血酶原时间延长、活化部分凝血活酶时间延长以及维生素 K 缺乏或拮抗剂-II 引起的蛋白质水平升高。在静脉注射维生素 K 和更换抗生素后，患者的低凝血酶原血症得到了改善。结论长期肠内营养与维生素 K 缺乏导致的凝血病风险增加有关，而长期使用抗菌药可能会诱发凝血病。在为严重运动障碍或智力障碍患者提供长期肠内营养时，应谨慎使用具有 NMTT 侧链的抗生素。

{"title":"Coagulopathy by vitamin K deficiency: Clinical pitfall in a case with cerebral palsy under long-term enteral nutrition","authors":"Mariko Yada, Tomoyo Itonaga, Saori Oguri, Yuka Kimura, Kenji Ihara","doi":"10.1016/j.bdcasr.2024.100050","DOIUrl":"10.1016/j.bdcasr.2024.100050","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin K deficiency is common in patients with neurological impairment under long-term enteral nutrition; however, reports of vitamin K deficiency in pediatric patients under long-term enteral nutrition remain limited, and critical conditions potentially leading to coagulopathy have not been sufficiently acknowledged by healthcare professionals.</div></div><div><h3>Case presentation</h3><div>We report the case of a seven-year-old girl with severe cerebral palsy who had received enteral nutrition via a nasoduodenal tube due to recurrent acute pancreatitis that had persisted for six months, and who had received an elemental diet for seven weeks prior to her presentation. After two days of cefmetazole treatment for urinary tract infection, abnormal coagulation findings, including a prolonged prothrombin time, activated partial thromboplastin time, and elevated levels of protein induced by vitamin K absence or antagonist-II, were detected. The patient's hypoprothrombinemia improved after the intravenous administration of vitamin K and switching antibiotics. From a retrospective point of view, her intake of vitamin K over the past six months was below the recommended amount for her age.</div></div><div><h3>Conclusions</h3><div>Long-term enteral nutrition is associated with an increased risk of coagulopathy due to vitamin K deficiency, which can be precipitated by prolonged use of antibacterial agents. When long-term enteral nutrition is given to patients with severe motor or intellectual disabilities, caution should be exercised when using antibiotics with NMTT side chains.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"2 4","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Opportunistic infections associated with extremely low-dose adrenocorticotropic hormone therapy: Two cases of Legionella and Pneumocystis carinii pneumonia 与极低剂量肾上腺皮质激素治疗相关的机会性感染：两例军团菌和卡氏肺孢子菌肺炎病例

Brain and Development Case Reports

Pub Date : 2024-10-30 DOI: 10.1016/j.bdcasr.2024.100046

Azusa Ikeda , Megumi Tsuji , Hiroyuki Nagafuchi , Yukiko Kuroda , Kenji Kurosawa , Tomohide Goto

Background

Adrenocorticotropic hormone (ACTH) therapy, the first-line treatment for infantile spasms, is known to dose-dependently increase incidences of infectious diseases. Extremely low-dose ACTH therapy is considered safe, and there have been no reports of opportunistic or other serious infections associated with this therapy. Herein, we report two cases of Legionella and Pneumocystis carinii pneumonia associated with extremely low-dose ACTH therapy.

Case presentation

Patient 1 with PIGA variant was administered extremely low-dose ACTH therapy at 6 months, developing pneumonia 2 weeks after therapy initiation; Legionella pneumonia diagnosis was confirmed 14 days after onset. Although minocycline, ciprofloxacin, azithromycin, and rifampicin were administered, pneumonia progressed critically and required prolonged intensive care, resulting in chronic respiratory failure. Patient 2 with KLHL20 variant was administered extremely low-dose ACTH therapy for 4 weeks at the age of 3 months, developing Pneumocystis carinii pneumonia 1 week after completion of therapy, which recovered with trimethoprim-sulfamethoxazole therapy.

Conclusion

Extremely low-dose and short-term ACTH therapy can be associated with opportunistic infections, and early diagnosis and treatment are crucial, because delays in administering appropriate antibiotics can lead to severe complications.

背景促肾上腺皮质激素（ACTH）疗法是治疗婴儿痉挛症的一线疗法，众所周知，该疗法会按剂量增加感染性疾病的发病率。极低剂量的促肾上腺皮质激素疗法被认为是安全的，目前还没有与该疗法相关的机会性感染或其他严重感染的报道。在此，我们报告了两例与极低剂量促肾上腺皮质激素治疗相关的军团菌肺炎和卡氏肺孢子菌肺炎病例。病例 1 患有 PIGA 变异型，在接受极低剂量促肾上腺皮质激素治疗 6 个月后，于治疗开始 2 周后出现肺炎；军团菌肺炎在发病 14 天后确诊。虽然给予了米诺环素、环丙沙星、阿奇霉素和利福平治疗，但肺炎发展严重，需要长期重症监护，导致慢性呼吸衰竭。患者2患有KLHL20变异型，在3个月大时接受了为期4周的超低剂量ACTH治疗，治疗结束1周后出现卡氏肺孢子菌肺炎，经三甲双胍-磺胺甲噁唑治疗后痊愈。

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引用次数: 0

A case of CLCN4-related epilepsy presenting as epilepsy of infancy with migrating focal seizures 一例 CLCN4 相关性癫痫，表现为伴有迁移性局灶性癫痫发作的婴儿期癫痫

Brain and Development Case Reports

Pub Date : 2024-10-30 DOI: 10.1016/j.bdcasr.2024.100048

Kenta Suzuki , Yuichi Suzuki , Mika Yamada , Maki Nodera , Fuyuki Miya , Mitsuhiro Kato , Mitsuaki Hosoya

Background

CLCN4 pathogenic variants cause X-linked intellectual disability and epilepsy. CLCN4-related epilepsy presents with a variety of seizures including absence, tonic, and focal seizures, is refractory to treatments, and is complicated by severe global developmental delay. We herein report a case of epilepsy of infancy with migrating focal seizures (EIMFS) in a male infant with CLCN4 variant.

Case presentation

The patient was a 3-month-old male with no abnormal perinatal history or family history of epilepsy. Initially, the patient developed convulsive seizures in both upper limbs and the left face, which were refractory to focal epilepsy treatments. Subsequently, a diagnosis of EIMFS was made because the focal sites began to shift from the left hemisphere to the right hemisphere during seizures. The seizures could not be controlled with polytherapy using antiseizure medications, but finally responded to potassium bromide. Whole exome sequencing revealed a novel de novo CLCN4 variant, NM_001830.4:c.854A>G,p.(Tyr285Cys).

Discussion/conclusion

To date, there have been 24 reported cases of CLCN4-related epilepsy in the world, with only one case of EIMFS, excluding the present case. Additionally, to the best of our knowledge, there have been no previous reports that included a detailed clinical course of a case of CLCN4-related epilepsy showing EIMFS. Further studies with accumulation of clinical cases are needed to understand the pathophysiology of CLCN4-related epilepsy, as well as to establish treatment methods.

背景CLCN4致病变体可导致X连锁智力障碍和癫痫。CLCN4相关性癫痫表现为失神、强直和局灶性发作等多种发作，对治疗具有难治性，并伴有严重的全面发育迟缓。我们在此报告一例婴儿期癫痫伴迁移性局灶性发作（EIMFS）病例，患者为一名3个月大的男婴，围产期无异常病史，也无癫痫家族史。最初，患者的双上肢和左脸出现抽搐发作，局灶性癫痫治疗无效。随后，由于癫痫发作时病灶部位开始从左半球转移到右半球，患者被诊断为EIMFS。使用多种抗癫痫药物治疗也无法控制癫痫发作，但最后使用溴化钾治疗后有了反应。全外显子组测序发现了一个新的CLCN4基因变异，即NM_001830.4:c.854A>G,p.(Tyr285Cys)。讨论/结论迄今为止，世界上已有24例CLCN4相关癫痫的报道，除本例外，只有一例EIMFS。此外，据我们所知，以前还没有任何报道详细介绍过出现 EIMFS 的 CLCN4 相关癫痫病例的临床过程。要了解 CLCN4 相关癫痫的病理生理学，并确定治疗方法，还需要进一步的研究和临床病例的积累。

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引用次数: 0

Acute proximal weakness after cochlear implant: Riboflavin transporter deficiency onset in child 植入人工耳蜗后的急性近端乏力：儿童核黄素转运体缺乏症

Brain and Development Case Reports

Pub Date : 2024-10-26 DOI: 10.1016/j.bdcasr.2024.100045

Cristina Villar-Vera , Mika Aiko-Gesler , Lucía Monfort Belenguer , Ana Cuesta Peredo , Manuel de Entrambasaguas

Background

Riboflavin transporter deficiencies (RTDs) are treatable progressive neurodegenerative disorders that present with symptoms including weakness, ataxia and neurosensory hearing loss. Once converted to the flavin cofactor, riboflavin plays a pivotal role in redox metabolic reactions. Similarly to classical mitochondrial diseases, stress may act as a trigger for disease progression.

Case presentation

The subject is a 3-year-old girl with initially normal development who experienced language regression due to sensorineural deafness at 20 months old. One year later, the patient experienced an acute episode of asymmetric proximal weakness following cochlear implant surgery. All metabolic, immunological, and neuroimaging studies were normal. Serial electromyography studies revealed a rapidly progressive axonal sensory-motor neuropathy affecting the upper limbs. In search of treatable conditions, riboflavin was initiated, and later on, compound heterozygous pathogenic variants in SLC52A2 were identified.

Conclusion

This report describes the clinical and electromyography findings of this patient during the four years following diagnosis.

背景核黄素转运体缺乏症（RTD）是一种可治疗的进行性神经退行性疾病，其症状包括乏力、共济失调和神经听觉丧失。核黄素一旦转化为黄素辅助因子，就会在氧化还原代谢反应中发挥关键作用。与传统的线粒体疾病类似，压力也可能成为疾病进展的诱因。病例介绍患者是一名 3 岁女孩，最初发育正常，但在 20 个月大时因感音神经性耳聋而出现语言退化。一年后，患者在接受人工耳蜗植入手术后急性发作非对称性近端无力。所有代谢、免疫和神经影像学检查均正常。连续的肌电图检查显示，上肢轴索感觉运动神经病进展迅速。为了寻找可治疗的病症，患者开始服用核黄素，后来发现了 SLC52A2 的复合杂合致病变体。

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引用次数: 0

Sibling cases of DEPDC5-related developmental and epileptic encephalopathy successfully treated with lacosamide 拉科沙胺成功治疗DEPDC5相关发育性癫痫脑病的同胞病例

Brain and Development Case Reports

Pub Date : 2024-10-18 DOI: 10.1016/j.bdcasr.2024.100044

Chiho Tokorodani , Ritsuo Nishiuchi , Fuyuki Miya , Katsuhiro Kobayashi , Mitsuhiro Kato

Background

DEPDC5 is a causative gene for various familial focal epilepsies. We report the cases of two Japanese sisters with DEPDC5-related epilepsy presenting as developmental and epileptic encephalopathy (DEE) that were successfully treated with lacosamide as add-on therapy.

Patients

The elder sister had focal tonic seizures at 3 years 10 months old. Long-term video-electroencephalography (EEG) monitoring disclosed that she also had atypical absence seizures with asymmetric generalized slow spike-and-wave complexes, leading to a diagnosis of Lennox-Gastaut syndrome (LGS). Zonisamide, levetiracetam, and sodium valproate (VPA) failed to resolve her seizures, but subsequent lacosamide (LCM) treatment effectively stopped them. At 4 years and 6 months of age, her development was normal. Her younger sister had experienced epileptic spasms at 4 months of age. Her interictal EEG showed hypsarrhythmia, leading to a diagnosis of infantile epileptic spasms syndrome (IESS). VPA was partially effective at decreasing her epileptic spasms, and an add-on therapy of LCM finally suppressed her seizures with normalization of her EEG. At 1 year and 2 months of age, she had developed normally without seizures. The two sisters' brain MRI findings eventually became unremarkable. Trio-based whole-exome sequencing identified a heterozygous germline variant in the DEPDC5 gene (NM_001242896: exon37: c.3751delT: p.F1251fs) in both sisters and their asymptomatic mother, illustrating the variant's incomplete penetrance.

Conclusion

The DEPDC5 variant can be causative for LGS and IESS with no malformations of cortical development. LCM may be effective for drug-resistant DEPDC5-related DEE.

背景DEPDC5是多种家族性局灶性癫痫的致病基因。我们报告了两例日本姐妹的病例，她们均患有与 DEPDC5 相关的癫痫，表现为发育性癫痫性脑病（DEE），并使用拉科酰胺作为附加疗法获得成功。长期的视频脑电图（EEG）监测显示，她还伴有非典型失神发作和不对称的全身性慢速尖波综合征，因此被诊断为伦诺克斯-加斯托特综合征（LGS）。唑尼沙胺、左乙拉西坦和丙戊酸钠（VPA）未能缓解她的癫痫发作，但随后的拉科萨胺（LCM）治疗有效地阻止了癫痫发作。4 岁 6 个月时，她的发育正常。她的妹妹在 4 个月大时曾经历过癫痫痉挛。她的发作间期脑电图显示低节律，因此被诊断为婴儿癫痫痉挛综合征（IESS）。VPA 对减少她的癫痫痉挛有部分效果，LCM 的附加疗法最终抑制了她的癫痫发作，并使她的脑电图恢复正常。一岁零两个月时，她发育正常，没有癫痫发作。两姐妹的脑部核磁共振成像结果最终变得无异常。基于三重全外显子组测序在两姐妹及其无症状的母亲体内发现了 DEPDC5 基因的杂合子种系变异（NM_001242896: exon37: c.3751delT: p.F1251fs），说明该变异具有不完全渗透性。LCM可能对耐药的DEPDC5相关DEE有效。

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引用次数: 0

A new case of developmental and epileptic encephalopathy and macrocytic anemia with stretched-activated ion channel TMEM63B variant 一例发育性癫痫性脑病和巨幼红细胞性贫血的拉伸活化离子通道 TMEM63B 变异新病例

Brain and Development Case Reports

Pub Date : 2024-09-28 DOI: 10.1016/j.bdcasr.2024.100043

Kasumi Sasaki , Mitsuko Nakashima , Yuji Fujii , Shinji Itamura , Hirotomo Saitsu , Mitsuhiro Kato

Background

TMEM63B encodes a stretch-activated ion channel that mediates cation currents in response to osmotic and mechanical stresses. Heterozygous TMEM63B variants have recently been reported in patients with developmental and epileptic encephalopathies and progressive neurodegeneration. Here, we report a patient with a TMEM63B variant whose seizures were temporarily controlled using ketogenic diet (KD) therapy and perampanel (PER).

Case presentation

A 2-year-old female toddler showed early-onset seizures, severe global developmental delay, quadriparesis, nystagmus, central visual impairment, and macrocytic anemia. Brain magnetic resonance imaging revealed a thin corpus callosum, delayed myelination, and progressive cerebral and cerebellar atrophy. Exome sequencing identified a de novo heterozygous variant of TMEM63B (NM_018426.3: c.130G > A, p.(Val44Met)), which was classified as pathogenic.

Discussion/Conclusion

Although most patients with TMEM63B variants have drug-resistant seizures, our patient showed temporary seizure control after administering KD and PER. This combination treatment may be effective for treating seizures in patients with the TMEM63B variant.

背景TMEM63B编码一种拉伸激活的离子通道，它介导阳离子电流以应对渗透压和机械压力。最近有报道称，在患有发育性和癫痫性脑炎以及进行性神经变性的患者中存在杂合子 TMEM63B 变异。在此，我们报告了一名患有 TMEM63B 变异的患者，她的癫痫发作通过生酮饮食（KD）疗法和培南帕尼（PER）得到了暂时控制。病例介绍一名两岁的女性幼儿表现为早发性癫痫发作、严重的全身发育迟缓、四肢瘫痪、眼球震颤、中枢性视力障碍和巨幼红细胞性贫血。脑磁共振成像显示胼胝体变薄、髓鞘化延迟以及进行性大脑和小脑萎缩。外显子组测序发现了TMEM63B的一个新发杂合变异体（NM_018426.3：c.130G >A, p.(Val44Met)），该变异体被归类为致病性变异体。讨论/结论虽然大多数TMEM63B变异体患者的癫痫发作具有耐药性，但我们的患者在服用KD和PER后癫痫发作暂时得到控制。这种联合治疗可能对治疗 TMEM63B 变体患者的癫痫发作有效。

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