Brain and Development Case Reports最新文献

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

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

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。

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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

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

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

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

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

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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引用次数: 0

A female patient with paramyotonia congenita. Part 2: Contribution of SCN4A to the developing brain 一名患有先天性副肌张力障碍的女性患者。第二部分：SCN4A 对大脑发育的贡献

Brain and Development Case Reports

Pub Date : 2024-09-28 DOI: 10.1016/j.bdcasr.2024.100042

Background

SCN4A encodes the α-subunit of the voltage-gated sodium channel Na_V1.4, which is responsible for the generation of action potentials and excitation of skeletal muscle fibers. Paramyotonia congenita (PMC) is a congenital disorder characterized by non-dystrophic myotonia due to variants of SCN4A. SCN4A has been considered to be exclusively expressed in muscles, and the brain phenotype has not been reported until recently, including descriptions of essential tremor and epilepsy.

Patient

The patient is a 20-year-old woman with PMC by detecting a c.3917G>A, p.(Gly1306Glu) variant in SCN4A. The patient also showed neurological symptoms, such as epilepsy, from 1 year old and intellectual disability (intelligence quotient 48).

Mouse brain

We confirmed the Na_V 1.4 expression in the brain of developing mice, 10 days after birth, immunohistochemically, in the entire cerebral cortex, the olfactory bulb and the midbrain but not in the hippocampus or cerebellum. However, the Na_V 1.4 expression was not detected in adult mouse cortex.

Discussion

Na_V1.4 was shown to be expressed in the cerebral cortex of young mice but not in adults. Since our patient had shown intellectual disability and epilepsy from infancy, Na_V1.4 was considered to be involved in the developing brain and cause central nervous system symptom in some situations.

背景SCN4A编码电压门控钠通道NaV1.4的α亚基，它负责产生动作电位和兴奋骨骼肌纤维。先天性副肌张力障碍（PMC）是一种先天性疾病，其特征是由于 SCN4A 的变异而导致的非萎缩性肌张力障碍。一直以来，SCN4A 被认为只在肌肉中表达，而大脑表型直到最近才有报道，包括对本质性震颤和癫痫的描述。患者是一名 20 岁女性，通过检测 SCN4A 中的 c.3917G>A，p.(Gly1306Glu) 变体，发现患有先天性副肌张力障碍。小鼠大脑我们用免疫组化方法证实了出生后 10 天的发育中小鼠大脑中 NaV 1.4 的表达，在整个大脑皮层、嗅球和中脑中均有表达，但在海马和小脑中没有表达。讨论NaV1.4在幼鼠大脑皮层有表达，但在成年小鼠中没有表达。由于我们的患者在婴儿期就表现出智力障碍和癫痫，因此认为 NaV1.4 参与了大脑的发育，并在某些情况下导致中枢神经系统症状。

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引用次数: 0

Hemorrhagic shock and encephalopathy syndrome occurring in the setting of dual pathogenesis of cerebral cavernous malformation 1 and Houge-Janssens syndrome 2 脑海绵畸形1和侯格-扬森综合征2双重发病机制下的出血性休克和脑病综合征

Brain and Development Case Reports

Pub Date : 2024-09-23 DOI: 10.1016/j.bdcasr.2024.100038

Background

Hemorrhagic shock and encephalopathy syndrome is a lethal form of acute childhood encephalopathy that occurs in the setting of various neurodevelopmental conditions. In undiagnosed patients, exome sequencing identifies dual genetic diagnoses in 5% of affected individuals.

Clinical Report

A male infant with a family history of cavernous malformation syndrome with profound developmental delay and hypotonia was brought to our clinic. A trio-based exome analysis identified dual genetic diagnoses: cerebral cavernous malformation 1 (OMIM#116860) due to a maternally inherited heterozygous frameshift mutation in KRIT1 and Houge-Janssens syndrome 2 (OMIM#616362) due to a de novo heterozygous mutation in PPP2R1A. At the age of two years, the child developed hemorrhagic shock and encephalopathy syndrome and died.

Discussion

The dual genetic diagnoses well explained the patient's overall clinical and neuroradiographic phenotype. The differential risk of recurrence of two independent disorders was informative from a genetic counseling standpoint. Known underlying neurological comorbidities in cases developing hemorrhagic shock and encephalopathy syndrome do not appear to have a shared molecular mechanism, but perhaps have perturbations in the basal neuronal activity, predisposing to acute lethal encephalopathy.

Conclusion

A thorough genetic investigation to search for multiple genetic causes to fully explain a patient's overall phenotype is critical. Multiplicity of the underlying genetic conditions may increase the risk of development of acute childhood encephalopathy.

背景失血性休克和脑病综合征是一种致命的儿童急性脑病，可在各种神经发育疾病的背景下发生。在未确诊的患者中，5% 的患者通过外显子组测序确定了双重基因诊断。临床报告一名男婴被送到我们诊所就诊，他有海绵畸形综合征家族史，伴有严重的发育迟缓和肌张力低下。基于三组外显子组的分析确定了双重基因诊断：因 KRIT1 基因的母系遗传性杂合框移位突变导致的脑海绵状畸形 1（OMIM#116860）和因 PPP2R1A 基因的新生杂合突变导致的 Houge-Janssens 综合征 2（OMIM#616362）。讨论双重基因诊断很好地解释了患者的整体临床和神经放射表型。从遗传咨询的角度来看，两种独立疾病复发风险的不同具有参考价值。在发生失血性休克和脑病综合征的病例中，已知的潜在神经系统合并症似乎没有共同的分子机制，但可能存在基底神经元活动紊乱，容易导致急性致死性脑病。多重潜在遗传病可能会增加儿童急性脑病的发病风险。

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引用次数: 0

A female patient with paramyotonia congenita. Part 1: Combination therapy of lacosamide and topiramate 一名患有先天性副肌张力障碍的女性患者。第一部分：拉科萨胺和托吡酯的联合疗法

Brain and Development Case Reports

Pub Date : 2024-09-23 DOI: 10.1016/j.bdcasr.2024.100041

Background

Paramyotonia congenita (PMC) is a congenital disorder characterized by non-dystrophic myotonia due to variants of SCN4A. SCN4A encodes the α-subunit of the voltage-gated sodium channel Na_V1.4, which is responsible for the generation of action potentials and excitation of skeletal muscle fibers. Despite some reduction of myotonia by sodium channel blockers, a more effective treatment is still being sought. We herein report a patient whose myotonia was ameliorated by combination therapy with topiramate, mexiletine and lacosamide.

Patient

The patient was a 20-year-old woman. A few days after birth, laryngospasm and cyanosis had appeared repeatedly on crying, gradually followed by local myotonia in various parts of the body. Exposure to both hot and cold, exercise, and mental stress induced myotonia in her fingers, orbicularis oculi, neck, trunk, and limbs, lasting for several minutes to hours, several times a day. We diagnosed her with PMC by detecting a c.3917G > A, p.(Gly1306Glu) variant in SCN4A. She also had epilepsy with tonic-clonic seizure since 1 year old. Combination therapy of topiramate and lacosamide in addition to mexiletine reduced the myotonia markedly.

Discussion

A sodium channel blocker, the combination of fast inactivation by topiramate and mexiletine, and slow inactivation by lacosamide may be effective in reducing myotonia in PMC. The further accumulation of data concerning this treatment is required.

背景先天性肌张力障碍（Paramyotonia congenita，PMC）是一种先天性疾病，其特征是由于 SCN4A 的变异而导致的非萎缩性肌张力障碍。SCN4A编码电压门控钠通道NaV1.4的α亚基，负责产生动作电位和兴奋骨骼肌纤维。尽管钠通道阻滞剂可减轻肌张力，但人们仍在寻找更有效的治疗方法。我们在此报告了一名患者，她的肌张力症在托吡酯、甲昔列汀和拉科沙胺的联合治疗下得到了改善。出生几天后，反复哭闹时出现喉痉挛和发绀，随后逐渐出现身体各部位的局部肌张力障碍。暴露于冷热环境、运动和精神压力会诱发她的手指、眼轮匝肌、颈部、躯干和四肢出现肌张力障碍，持续数分钟至数小时，每天数次。通过检测 SCN4A 中的 c.3917G > A, p.(Gly1306Glu) 变异，我们诊断她患有 PMC。她从一岁起就患有强直阵挛性癫痫。讨论钠通道阻滞剂、托吡酯和甲昔列汀的快速灭活与拉科萨胺的慢速灭活相结合，可能会有效减轻 PMC 患者的肌张力障碍。有关这种治疗方法的数据还需要进一步积累。

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