Brain and Development Case Reports最新文献_第2页

Temporal lobe-predominant cortical dysplasia with mild cortical thickening in FOXG1 syndrome FOXG1综合征伴轻度皮质增厚的颞叶显性皮质发育不良

Brain and Development Case Reports

Pub Date : 2025-12-01 DOI: 10.1016/j.bdcasr.2025.100119

Kei Yamada , Yu Kobayashi , Masaki Miura , Moemi Hojo , Ai Fukushima , Hiromi Nyuzuki , Naoya Saijo , Jun Takayama , Atsuo Kikuchi , Shigeo Kure , Jun Tohyama

Background

Forkhead box G1 (FOXG1) gene syndrome is a neurodevelopmental disorder characterized by severe developmental delays, microcephaly, autistic features, epilepsy, and complex hyperkinetic-dyskinetic movement disorders. We present the case of a Japanese patient with microcephaly, cortical dysplasia with irregular gyri and mild cortical thickening in the temporal and frontal lobes, and a de novo heterozygous missense variant in FOXG1.

Case presentation

The patient was an 11-year-old Japanese boy who presented with microcephaly at 3 months of age. At 2 years and 10 months of age, he presented with frequent tonic seizures of unknown onset. Physical examination revealed microcephaly and dysmorphic features. He exhibited severe developmental delays and generalized hypotonia. Brain magnetic resonance imaging (MRI) revealed anterior hypogenesis of the corpus callosum, decreased cerebral volume, mildly delayed myelination, and cortical dysplasia with irregular gyri and mild cortical thickening, particularly in the temporal lobes. His seizures resolved after administering carbamazepine. Trio-based whole-exome sequencing analysis of the patient and his parents revealed a de novo heterozygous missense variant, NM_005249.5:c.688C>T p.(Arg230Cys), located in the forkhead DNA-binding domain of FOXG1, a recurrent variant that was finally diagnosed as FOXG1 syndrome.

Conclusions

Cortical malformation in FOXG1 syndrome is often observed in the frontal lobe. The cortical dysplasia and mild cortical thickening observed in our patient was predominantly in the temporal cortex, suggesting distinctive findings. These results provide new insights into brain malformations associated with FOXG1 syndrome.

叉头盒G1 （FOXG1）基因综合征是一种以严重发育迟缓、小头畸形、自闭症特征、癫痫和复杂的多动-不动运动障碍为特征的神经发育障碍。我们报告了一例日本小头症患者，伴有不规则脑回和颞叶和额叶轻度皮质增厚的皮质发育不良，以及FOXG1的新杂合错义变异。患者是一名11岁的日本男孩，在3个月大时出现小头畸形。在2岁零10个月时，他出现了频繁的强直性癫痫发作，原因不明。体格检查显示小头畸形和畸形。他表现出严重的发育迟缓和全身性肌张力低下。脑磁共振成像（MRI）显示胼胝体前部发育不足，脑体积减小，轻度髓鞘形成延迟，皮质发育不良伴不规则脑回和轻度皮质增厚，尤其是颞叶。他的癫痫在服用卡马西平后消失了。对患者及其父母的三基全外显子组测序分析显示，在FOXG1叉头dna结合区域发现了一种新生杂合错义变异NM_005249.5:c.688C> tp .(Arg230Cys)，这是一种复发性变异，最终诊断为FOXG1综合征。结论FOXG1综合征皮层畸形多见于额叶。在我们的患者中观察到的皮质发育不良和轻度皮质增厚主要发生在颞叶皮层，这表明了不同的发现。这些结果为与FOXG1综合征相关的脑畸形提供了新的见解。

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引用次数: 0

Impact of high-dose vitamins on a patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome 高剂量维生素对高鸟氨酸血症-高氨血症-高尿酸血症综合征患者的影响

Brain and Development Case Reports

Pub Date : 2025-11-27 DOI: 10.1016/j.bdcasr.2025.100117

Hiroaki Ono , Jun Kido , Shiro Matsumoto

Background

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive metabolic disorder caused by a mutation of SLC25A15 encoding for the mitochondrial ornithine carrier. Recent study suggested that impaired mitochondrial function may play a major role in central nervous system impairment in HHH syndrome. We hypothesized that if the mitochondrial dysfunction was associated with neurological impairment in HHH syndrome, antioxidants might be effective to avoid aggravation of the brain injury. We presented the clinical outcome in a patient with HHH syndrome undergoing a high-dose vitamin treatment and discussed the effect of this treatment.

Case presentation

The male patient was definitively diagnosed by compound heterogeneous pathogenic variants in the SLC25A15 gene. He was started vitamin B1, C and E therapy at age of 3 years. The blood lactate (Lac) levels gradually decreased and serum β-hydroxybutyrate/acetoacetate (β-OHB/AcAc) ratio also decreased at age of 7 years. A verbal development score in Kyoto Scale of Psychological Development was 65 at age of 3 years. However, quotient of Verbal Comprehension Index in Wechsler Intelligence Scale for Children-Fourth Edition increased to 109 at age of 7 years during this vitamin therapy.

Discussion

The outcome in our patient suggested that high-dose vitamin therapy might contribute to preventing cognitive disability. Moreover, the decreased blood Lac level and serum β-OHB/AcAc ratio also suggested that the effect of this therapy might be due to improving the mitochondrial function such as citric acid cycle. This case report suggest that the high-dose vitamin therapy may enhance mitochondrial function in HHH syndrome.

背景：高鸟氨酸血症-高氨血症-高氮氨酸尿症（HHH）综合征是一种罕见的常染色体隐性代谢疾病，由编码线粒体鸟氨酸载体的SLC25A15基因突变引起。最近的研究表明，线粒体功能受损可能在HHH综合征中枢神经系统损伤中起主要作用。我们推测，如果线粒体功能障碍与HHH综合征的神经损伤有关，抗氧化剂可能有效避免脑损伤的加重。我们介绍了一位HHH综合征患者接受高剂量维生素治疗的临床结果，并讨论了这种治疗的效果。病例介绍：该男性患者经SLC25A15基因复合异质致病变异确诊。他3岁时开始服用维生素B1、C和E治疗。7岁时血乳酸（Lac）水平逐渐降低，血清β-羟基丁酸/乙酰乙酸（β-OHB/AcAc）比值也逐渐降低。三岁时京都心理发展量表语言发展得分为65分。然而，在维生素治疗期间，韦氏智力量表（第四版）中儿童的语言理解指数在7岁时增加到109。本例患者的结果提示，大剂量维生素治疗可能有助于预防认知障碍。此外，血Lac水平和血清β-OHB/AcAc比值的降低也提示该治疗的效果可能是由于改善了线粒体功能，如柠檬酸循环。本病例报告提示高剂量维生素治疗可增强HHH综合征的线粒体功能。

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引用次数: 0

Long-term outcomes of add-on risdiplam after nusinersen in pediatric spinal muscular atrophy: A three-year case report and literature review 小儿脊髓性肌萎缩症患者术后加用利斯普胺的长期疗效：三年病例报告及文献回顾

Brain and Development Case Reports

Pub Date : 2025-11-19 DOI: 10.1016/j.bdcasr.2025.100115

Qunyan Su , Jingjing Jin , Min Lin , Jian Hong , Yandan Yin , Yan Hong , Beibei Jiang , Guiying Ruan , Jin Chen

Background

Spinal muscular atrophy (SMA), caused by biallelic survival motor neuron 1 (SMN1) mutations, leads to progressive motor neuron degeneration. While nusinersen (intrathecal antisense oligonucleotide SMN2 splicing modifier) and risdiplam (oral SMN2 splicing modifier) have revolutionized SMA treatment, real-world evidence on add-on use remains limited.

Case presentation

Two pediatric SMA type II cases (Case 1: age 9 years 4 months; Case 2: age 5 years 2 months) underwent 3-year follow-up. Both received nusinersen monotherapy add-on risdiplam therapy. Case 1 (treatment initiated at age 6 years 1 month) achieved sustained motor improvements (Hammersmith Functional Motor Scale–Expanded [HFMSE]: 30 → 42), including independent ambulation (10 m), while Case 2 (treatment initiated at age 2 years 0 month) progressed from no head control to assisted standing (HFMSE: 3 → 28). Transient thrombocytopenia (Case 1) and alanine aminotransferase (ALT) elevation (Case 2) resolved without intervention. Pulmonary function showed no clinically significant decline (FVC >70 % predicted throughout), despite motor gains.

Conclusion

After risdiplam was added, both patients continued to gain motor function beyond the levels reached during nusinersen monotherapy. The safety profile aligned with prior trials, supporting its feasibility. Genetic modifiers (e.g., SMN2 microduplications) influenced therapeutic responses, highlighting personalized strategies. Future studies should optimize pharmacokinetic sequencing and validate biomarkers (e.g., neurofilament light chain) to guide multimodal regimens.

脊髓性肌萎缩症（SMA）是由双等位基因存活运动神经元1 （SMN1）突变引起的，可导致进行性运动神经元变性。虽然nusinersen（鞘内反义寡核苷酸SMN2剪接调节剂）和risdiplam（口服SMN2剪接调节剂）已经彻底改变了SMA的治疗，但实际使用的证据仍然有限。2例小儿II型SMA（病例1：年龄9岁4个月；病例2：年龄5岁2个月）进行了3年的随访。两名患者均接受了nusinersen单药治疗加利司哌仑治疗。病例1（6岁1个月开始治疗）实现了持续的运动改善（Hammersmith功能运动量表扩展[HFMSE]: 30→42），包括独立行走（10米），而病例2（2岁0个月开始治疗）从没有头部控制进展到辅助站立（HFMSE: 3→28）。短暂性血小板减少症（病例1）和丙氨酸转氨酶（ALT）升高（病例2）无需干预即可解决。尽管运动功能有所增强，但肺功能未出现临床显著下降（FVC >； 70%的预测）。结论加用利斯地普兰后，两例患者的运动功能均比诺西森单药治疗时的水平有所改善。安全性与先前的试验一致，支持其可行性。遗传修饰因子（如SMN2微重复）影响治疗反应，强调个性化策略。未来的研究应优化药代动力学测序和验证生物标志物（如神经丝轻链），以指导多模式方案。

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引用次数: 0

Japanese siblings with neuronal ceroid lipofuscinosis type 7 showing different initial symptoms due to biallelic MFSD8 variants: A case report 由于双等位基因MFSD8变异，日本7型神经性神经样脂褐变兄弟姐妹表现出不同的初始症状：1例报告

Brain and Development Case Reports

Pub Date : 2025-10-18 DOI: 10.1016/j.bdcasr.2025.100114

Yuka Nishizawa , Noriko Nishikura , Takao Morimune , Hiroki Sobajima , Yoshihiro Maruo , Mitsuko Nakashima , Hirotomo Saitsu , Naomichi Matsumoto , Mitsuhiro Kato

Background

Neuronal ceroid lipofuscinosis type 7 (CLN7) is caused by variants in the major facilitator superfamily domain-containing protein 8 (MFSD8) gene. Research on gene therapy for CLN7 is currently ongoing, highlighting the importance of early diagnosis. There are very few detailed case reports on the clinical course of this disease. This report presents the case of Japanese siblings with CLN7, whose definitive diagnosis was achieved through genetic testing.

Case presentation

Patient 1, a 20-year-old boy (elder brother), was diagnosed with psychomotor retardation and suspected autism spectrum disorder. He developed myoclonus and epilepsy, with brain magnetic resonance imaging (MRI) revealing cerebellar atrophy at 4.5 years of age. Seizures progressed refractorily. At age 9, he had difficulty walking, and became bedridden a year later. Patient 2, a 15-year-old boy (younger brother), began falling frequently at age 4, and developed epilepsy with visual acuity reduction at age 5. Brain MRI revealed cerebellar atrophy. The seizures progressed refractorily, and myoclonus was observed at the age of 8 years. He became bedridden shortly after. Exome sequencing identified compound heterozygous variants of MFSD8, NM_152778.2:c.599G>A, p.(Trp200*) and c.706C>A, p.(Arg236Ser) leading to the diagnosis of CLN7.

Conclusion

In this case, a definitive diagnosis was established through genetic testing, as enzyme activity assessment and skin biopsy results were inconclusive. The diversity of the initial symptoms and the low awareness due to the rarity of the disease contributed to diagnostic delays. The accumulation of case reports is necessary, and genetic testing is highly valuable for early diagnosis.

7型神经元类脂褐素病（CLN7）是由主要促进物超家族结构域蛋白8 （MFSD8）基因变异引起的。目前正在进行CLN7基因治疗的研究，强调了早期诊断的重要性。关于本病临床病程的详细病例报道很少。本报告介绍了一例患有CLN7的日本兄弟姐妹，其最终诊断是通过基因检测获得的。患者1,20岁男孩（哥哥），被诊断为精神运动迟缓，疑似自闭症谱系障碍。他在4.5岁时出现肌阵挛和癫痫，脑磁共振成像（MRI）显示小脑萎缩。癫痫发作难治性进展。9岁时，他行走困难，一年后卧床不起。患者2为15岁男童（弟弟），4岁时开始频繁摔倒，5岁时发展为癫痫伴视力下降。脑部MRI显示小脑萎缩。发作进展难治性，8岁时出现肌阵挛。不久之后，他卧床不起。外显子组测序鉴定出MFSD8， NM_152778.2的复合杂合变异体：c.599G>；A, p.（Trp200*）和c.706C>；A, p.(Arg236Ser)，导致CLN7的诊断。由于酶活性评估和皮肤活检结果不确定，因此通过基因检测建立了明确的诊断。最初症状的多样性以及由于该病罕见而引起的低认知度导致诊断延误。病例报告的积累是必要的，基因检测对早期诊断非常有价值。

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引用次数: 0

Fatal acute fulminant cerebral edema complicating Kawasaki disease in an infant: a case report 致命性急性暴发性脑水肿合并川崎病1例报告

Brain and Development Case Reports

Pub Date : 2025-10-14 DOI: 10.1016/j.bdcasr.2025.100113

Shunsuke Nukaga , Takeshi Ono , Michiko Fuse , Sho Horiguchi , Yukie Izumita , Ko Matsui , Fujito Numano , Akihiko Saitoh , Kei Nishiyama

Background: The neurological complications of Kawasaki disease (KD) are rare and typically benign. However, recent reports have described severe presentations including acute fulminant cerebral edema (AFCE), which may be associated with cerebral vasculitis.

Case presentation: A previously healthy 23-month-old girl was diagnosed with KD on day five of illness. Initial treatment with intravenous immunoglobulin (IVIG) and aspirin led to temporary resolution of fever. On day 14, symptoms recurred, and a second dose of IVIG was administered. On day 16, the patient developed generalized seizures refractory to midazolam that required fosphenytoin administration. Brain MRI performed 2 h after seizure onset revealed hyperintensity in the deep white matter on T2-weighted and fluid-attenuated inversion recovery imaging, isointensity on diffusion-weighted imaging (DWI), and high signal intensity on apparent diffusion coefficient (ADC) maps. The bilateral temporal lobes showed DWI hyperintensity and low ADC signals. Cerebrospinal fluid (CSF) analysis revealed markedly elevated protein levels (445 mg/dL) without pleocytosis or hypoglycorrhachia. The patient received intensive care with mechanical ventilation, continuous sedation, and supportive therapy. Approximately 12 h after seizure onset, the patient developed sudden bradycardia and bilateral fixed dilated pupils. Brain CT revealed extensive cerebral edema. Despite intensive care, she developed brain herniation and died two months after the onset of KD.

Conclusion: AFCE is a rare but life-threatening complication of KD. MRI findings suggesting vasogenic edema and markedly elevated CSF protein levels may serve as early warnings. Recognition of these findings may allow timely diagnosis and appropriate management of this devastating condition.

背景：川崎病（KD）的神经系统并发症罕见且典型为良性。然而，最近的报道已经描述了严重的表现，包括急性暴发性脑水肿（AFCE），这可能与脑血管炎有关。病例介绍：一名先前健康的23个月大的女孩在患病的第五天被诊断为KD。最初静脉注射免疫球蛋白（IVIG）和阿司匹林治疗导致发烧暂时消退。第14天，症状复发，并给予第二剂IVIG。第16天，患者出现对咪达唑仑难治的全局性癫痫发作，需要给予磷妥英。癫痫发作后2小时行脑MRI， t2加权和液体衰减反演恢复成像显示深部白质高信号，弥散加权成像（DWI）等信号，表观弥散系数（ADC）高信号。双侧颞叶DWI高，ADC信号低。脑脊液（CSF）分析显示蛋白水平明显升高（445 mg/dL），无细胞增多或低糖血症。患者接受了机械通气、持续镇静和支持治疗的重症监护。癫痫发作约12小时后，患者出现突发性心动过缓和双侧瞳孔固定放大。脑部CT显示大面积脑水肿。尽管经过重症监护，她还是出现了脑疝，并在KD发病两个月后死亡。结论：AFCE是一种罕见但危及生命的KD并发症。MRI结果提示血管源性水肿和脑脊液蛋白水平明显升高可作为早期预警。认识到这些发现可以及时诊断和适当的管理这种毁灭性的条件。

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引用次数: 0

Clinical characteristics for early diagnosis of PACS1 neurodevelopmental disorder: Two case reports 早期诊断PACS1神经发育障碍的临床特点：附2例报告

Brain and Development Case Reports

Pub Date : 2025-10-10 DOI: 10.1016/j.bdcasr.2025.100111

Ryo Takeguchi , Yoshio Makita , Shunsuke Haga , Ikue Fukuda , Akie Miyamoto , Hajime Tanaka , Taiga Aoki , Takaya Iida , Kumiko Yanagi , Tadashi Kaname , Satoru Takahashi

Background

PACS1 neurodevelopmental disorder (PACS1-NDD), also known as Schuurs-Hoeijmakers syndrome, is a rare autosomal dominant disorder predominantly caused by the recurrent de novo pathogenic PACS1 variant c.607C>T (p.Arg203Trp). The characteristic features include varying degrees of global developmental delay, autism spectrum disorder (ASD), behavioral problems, and distinct facial features. Although the number of reported cases has increased, PACS1-NDD remains underrecognized, suggesting that many cases remain undiagnosed.

Case presentation

We report two Japanese pediatric patients diagnosed with PACS1-NDD using whole-exome sequencing (WES) and filtering analysis to identify the recurrent pathogenic variant [NM_018026.4:c.607C>T,p.(Arg203Trp)]. Patient 1, a 4-year-old boy, demonstrated severe global developmental delay, ASD, behavioral problems, sleep disturbances, epilepsy, cryptorchidism, and chronic constipation. Patient 2, a 3-year-old girl, demonstrated profound global developmental delay, ASD, behavioral problems, sleep disturbances, mild cerebral atrophy, congenital heart defects, and chronic constipation. Both patients shared consistent facial features, including hypertelorism, downslanted palpebral fissures, a short nose with anteverted nares, a thin upper lip, and downturned mouth corners.

Discussion

This study provides critical diagnostic clues for PACS1-NDD to facilitate early recognition based on a combination of characteristic facial features, global developmental delays, ASD, and sleep disturbances. In addition, other systemic complications such as cryptorchidism, congenital heart defects, and chronic constipation have been frequently reported in PACS1-NDD. Recognizing these clinical features can strengthen the clinical indication for comprehensive genetic testing, such as WES. Early diagnosis enables tailored clinical management and genetic counseling for patients and their families.

PACS1神经发育障碍（PACS1- ndd），也称为Schuurs-Hoeijmakers综合征，是一种罕见的常染色体显性遗传病，主要由复发性新发致病性PACS1变异体c.607C>T （p.a g203trp）引起。这些特征包括不同程度的整体发育迟缓、自闭症谱系障碍（ASD）、行为问题和明显的面部特征。尽管报告的病例数量有所增加，但PACS1-NDD仍未得到充分认识，这表明许多病例仍未得到诊断。我们报告了两名日本儿科诊断为PACS1-NDD的患者，使用全外显性基因组测序（WES）和过滤分析来鉴定复发致病性变异[NM_018026.4:c.607C>；T,p.(Arg203Trp)]。患者1，一名4岁男孩，表现出严重的整体发育迟缓、ASD、行为问题、睡眠障碍、癫痫、隐睾和慢性便秘。患者2，一名3岁女孩，表现出严重的全面发育迟缓、ASD、行为问题、睡眠障碍、轻度脑萎缩、先天性心脏缺陷和慢性便秘。两例患者具有一致的面部特征，包括远视、睑裂下斜、鼻短鼻前倾、上唇薄、嘴角下翻。本研究为PACS1-NDD提供了关键的诊断线索，以促进基于特征面部特征、整体发育迟缓、ASD和睡眠障碍的早期识别。此外，其他系统性并发症如隐睾、先天性心脏缺陷和慢性便秘在PACS1-NDD中也经常被报道。认识到这些临床特征可以加强综合基因检测的临床指征，如WES。早期诊断可以为患者及其家属提供量身定制的临床管理和遗传咨询。

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引用次数: 0

Acute cerebellitis in a 10-year-old male: Diagnostic and management challenges in a resource-limited setting 10岁男性急性小脑炎：在资源有限的环境下诊断和管理的挑战

Brain and Development Case Reports

Pub Date : 2025-10-10 DOI: 10.1016/j.bdcasr.2025.100112

Erneus Ernest , Adam Chai

Introduction

Acute cerebellitis (AC) is an inflammatory disease of the cerebellum following viral, bacterial infections, or autoimmune-mediated processes. Diagnosis and management of its complications, such as hydrocephalus, are particularly challenging in resource-limited settings. This report highlights these challenges and the successful outcome achieved with conservative medical management, averting the need for surgical intervention for AC-associated obstructive hydrocephalus.

Case presentation

A 10-year-old male was referred to our facility with a complaint of persistent headache for 10 days associated with cerebellar signs (wide-based gait, dysarthria, and dysmetria) and projectile vomiting. Brain MRI showed features of AC with moderate hydrocephalus. The patient was managed conservatively with intravenous ceftriaxone, dexamethasone, and acetazolamide. This led to complete clinical recovery and averted the need for surgical intervention. A follow-up MRI one-month post-treatment confirmed complete radiological resolution of both the cerebellitis and hydrocephalus.

Conclusion

This case underscores the importance of a high index of suspicion for AC in resource-limited settings when a child presents with headache and neurological signs. It demonstrates that medical management with steroids and acetazolamide can successfully resolve AC-associated obstructive hydrocephalus in select patients. This approach offers a viable strategy to avoid neurosurgical intervention in environments where resources are constrained.

急性小脑炎（AC）是一种由病毒、细菌感染或自身免疫介导过程引起的小脑炎症性疾病。在资源有限的环境中，诊断和管理脑积水等并发症尤其具有挑战性。本报告强调了这些挑战，并通过保守的医疗管理取得了成功的结果，避免了ac相关的阻塞性脑积水手术干预的需要。病例介绍：一名10岁男性因持续头痛10天并伴有小脑症状（宽基步态、音感障碍和节律障碍）和呕吐而被转介至我院。脑MRI表现为AC伴中度脑积水。患者给予静脉注射头孢曲松、地塞米松和乙酰唑胺保守治疗。这导致了完全的临床恢复，避免了手术干预的需要。治疗后1个月的随访MRI证实小脑炎和脑积水的放射学完全消退。结论：本病例强调了在资源有限的环境中，当儿童出现头痛和神经系统症状时，高度怀疑AC的重要性。它表明，医疗管理与类固醇和乙酰唑胺可以成功地解决ac相关的梗阻性脑积水在选定的患者。这种方法提供了一种可行的策略，以避免在资源有限的环境中进行神经外科干预。

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引用次数: 0

Neuronal ceroid lipofuscinosis type 2 disease in a 4-year-old child with epilepsy and concerns for stuttering 2型神经性脑蜡样脂褐质病1例4岁癫痫患儿伴口吃

Brain and Development Case Reports

Pub Date : 2025-09-16 DOI: 10.1016/j.bdcasr.2025.100110

Lorena Galvan , Dorota Szczepaniak , Bri Dingmann , Emily Myers

Background

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative neuronal lysosomal storage disease associated with ataxia, seizures, vision loss, and clinical deterioration. Early diagnosis is of crucial importance to initiate early treatment with intraventricular enzyme replacement therapy. Though seizures are typically the first presenting symptom associated with CLN2, recent research suggests that language and speech delays may precede seizures.

Case presentation

Our case is a 4-year-old child with epilepsy who presented to our neurodevelopmental clinic with stuttering. Prior to his epilepsy diagnosis at approximately 41 months of age, the child demonstrated delayed early language milestones during infancy. Genetic and enzymatic testing confirmed the diagnosis of CLN2. We discuss his overall clinical presentation and current research regarding speech and language delays in CLN2.

Conclusion

There is emerging evidence that stuttering may be one of the early speech and language characterizations of children with CLN2. Our case supports this emerging evidence and may direct clinicians to recognize speech production differences as an early presentation of CLN2.

2型神经蜡样脂褐质病（CLN2）是一种罕见的神经退行性神经元溶酶体贮积病，与共济失调、癫痫发作、视力丧失和临床恶化相关。早期诊断对早期进行脑室内酶替代治疗至关重要。虽然癫痫发作通常是与CLN2相关的第一个症状，但最近的研究表明，语言和言语延迟可能先于癫痫发作。病例介绍我们的病例是一名患有癫痫的4岁儿童，他以口吃来到我们的神经发育诊所。在他大约41个月大时被诊断为癫痫之前，这个孩子在婴儿期表现出延迟的早期语言里程碑。基因和酶检测证实了CLN2的诊断。我们讨论了他的整体临床表现和目前关于CLN2的言语和语言延迟的研究。结论越来越多的证据表明，口吃可能是CLN2患儿早期言语和语言特征之一。我们的病例支持这一新兴证据，并可能指导临床医生将言语产生差异视为CLN2的早期表现。

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引用次数: 0

Delayed identification of MYBPC1-related myopathy in adolescence: Diagnostic value of resting tongue ultrasonography in myogenic tremor 青少年mybpc1相关肌病的延迟识别：静息舌超声对肌源性震颤的诊断价值

Brain and Development Case Reports

Pub Date : 2025-09-15 DOI: 10.1016/j.bdcasr.2025.100109

Megumi Tsuji , Yukiko Kuroda , Shotaro Morikawa , Yutaka Hatano , Azusa Ikeda , Tomohide Goto

Background

The MYBPC1 gene, which encodes the slow skeletal myosin binding protein-C, has recently been identified as the causative gene for a rare, mild myopathy associated with myogenic tremor

Case presentation

Our patient was a Japanese girl born full-term via normal delivery. No consanguinity or family history of neuromuscular disorders was reported. The patient's motor developmental milestones were slightly delayed. Independent walking was not achieved until 1 year and 7 months of age. Hand tremors had been observed since 2 years of age. The patient was not physically active and had been experiencing fatigue since 12 years of age. At her first visit to our hospital at 14 years of age, she presented with distal muscle weakness, a high-arched palate, decreased deep tendon reflexes, involuntary tongue movement resembling fasciculations, and mild scoliosis. However, the patient's nerve conduction velocity and electromyogram results were normal. Ultrasonographic examination of the tongue revealed rhythmic movement, consistent with tremors, which disappeared at rest. A heterozygous, missense pathogenic variant (c.[788T>G] (p.Leu263Arg)) in the MYBPC1 gene was identified using the TruSight One Sequencing Panel

Discussion

Muscle weakness is caused by the altered binding of the mutant MYBPC1 protein to myosin. However, the mechanism by which the dysfunction of the MYBPC1 protein, which is not expressed in the central or peripheral nervous system, leads to tremors remains unclear. The diagnosis can only be confirmed via genetic testing. However, tongue tremors may be mistaken for fasciculations. Electromyography and tongue ultrasonography may be useful in achieving an early diagnosis.

背景：MYBPC1基因编码慢速骨骼肌球蛋白结合蛋白c，最近被确定为与肌源性震颤相关的罕见轻度肌病的致病基因。病例介绍：我们的患者是一名日本女孩，通过正常分娩足月出生。无亲属或家族史的神经肌肉疾病的报道。患者的运动发育里程碑稍有延迟。直到1岁零7个月才实现独立行走。自2岁起就观察到手部震颤。患者从12岁开始就没有身体活动，一直感到疲劳。在她14岁第一次到我们医院就诊时，她表现为远端肌肉无力，上颚高弓，深肌腱反射减少，类似束状肌束的舌头不自主运动，以及轻度脊柱侧凸。然而，患者的神经传导速度和肌电图结果正常。舌的超声检查显示有节奏的运动，与震颤一致，静止时消失。使用TruSight One测序小组鉴定出MYBPC1基因的杂合子错义致病变体（c.[788T>G] (p.l u263arg)）。讨论肌肉无力是由突变的MYBPC1蛋白与肌球蛋白结合改变引起的。然而，在中枢或外周神经系统中不表达的MYBPC1蛋白的功能障碍导致震颤的机制尚不清楚。这种诊断只能通过基因检测来证实。然而，舌颤可能被误认为是震颤。肌电图和舌超音波可用于早期诊断。

{"title":"Delayed identification of MYBPC1-related myopathy in adolescence: Diagnostic value of resting tongue ultrasonography in myogenic tremor","authors":"Megumi Tsuji , Yukiko Kuroda , Shotaro Morikawa , Yutaka Hatano , Azusa Ikeda , Tomohide Goto","doi":"10.1016/j.bdcasr.2025.100109","DOIUrl":"10.1016/j.bdcasr.2025.100109","url":null,"abstract":"<div><h3>Background</h3><div>The <em>MYBPC1</em> gene, which encodes the slow skeletal myosin binding protein-C, has recently been identified as the causative gene for a rare, mild myopathy associated with myogenic tremor</div></div><div><h3>Case presentation</h3><div>Our patient was a Japanese girl born full-term via normal delivery. No consanguinity or family history of neuromuscular disorders was reported. The patient's motor developmental milestones were slightly delayed. Independent walking was not achieved until 1 year and 7 months of age. Hand tremors had been observed since 2 years of age. The patient was not physically active and had been experiencing fatigue since 12 years of age. At her first visit to our hospital at 14 years of age, she presented with distal muscle weakness, a high-arched palate, decreased deep tendon reflexes, involuntary tongue movement resembling fasciculations, and mild scoliosis. However, the patient's nerve conduction velocity and electromyogram results were normal. Ultrasonographic examination of the tongue revealed rhythmic movement, consistent with tremors, which disappeared at rest. A heterozygous, missense pathogenic variant (c.[788T>G] (p.Leu263Arg)) in the <em>MYBPC1</em> gene was identified using the TruSight One Sequencing Panel</div></div><div><h3>Discussion</h3><div>Muscle weakness is caused by the altered binding of the mutant MYBPC1 protein to myosin. However, the mechanism by which the dysfunction of the MYBPC1 protein, which is not expressed in the central or peripheral nervous system, leads to tremors remains unclear. The diagnosis can only be confirmed via genetic testing. However, tongue tremors may be mistaken for fasciculations. Electromyography and tongue ultrasonography may be useful in achieving an early diagnosis.</div></div>","PeriodicalId":100196,"journal":{"name":"Brain and Development Case Reports","volume":"3 4","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamics of the cytokine profiles in Rasmussen's encephalitis: A case report 细胞因子谱在拉斯穆森脑炎的动态：一个病例报告

Brain and Development Case Reports

Pub Date : 2025-08-29 DOI: 10.1016/j.bdcasr.2025.100107

Kotaro Watanabe, Kengo Moriyama, Shuya Kaneko, Asami Shimbo, Taisuke Yamauchi, Yumie Tamura, Hitoshi Irabu, Masaki Shimizu, Masatoshi Takagi, Tomoko Mizuno

Introduction

Although cytotoxic T cells (CTL) and activated microglia affect the pathophysiology of Rasmussen's encephalitis (RE), the correlation between these immune cells and cytokines has yet to be elucidated. We analyzed the dynamics of the cytokine profiles in a patient with RE.

Case presentation

A 6-year-old girl without any medical history developed right hemiconvulsions. EEG showed left parietal to temporal epileptiform discharges, and positron emission tomography revealed left parietal lobe hypoperfusion. At age 9 years, the patient developed epilepsia partialis continua, with subsequent MRI showing mild atrophy of the left hemisphere, based on which a diagnosis of RE was established. Monthly methylprednisolone pulse therapy was then initiated, with the patient's cytokine profiles being recorded at four time points. In the acute phase, C-X-C motif chemokine 9 (CXCL9) increased but later decreased in the cerebrospinal fluid (CSF). Meanwhile, interleukin-6 (IL-6) was negative in the acute phase but increased in the chronic phase.

Discussion

Elevated CXCL9 in the CSF during the acute phase indicates increased secretion of interferon γ due to the abnormal activation of CTL, which is characteristic of RE. Hence, measuring CXCL9 levels in the CSF during the acute phase may help diagnose RE. We observed elevated IL-6 levels in the CSF during the chronic phase, which possibly reflects long-lasting central nervous system inflammation.

Conclusion

We outline the cytokine profile dynamics in an RE patient in hopes of contributing to the early diagnosis of RE and selection of therapeutic approach.

虽然细胞毒性T细胞（CTL）和活化的小胶质细胞影响拉斯穆森脑炎（RE）的病理生理，但这些免疫细胞与细胞因子之间的关系尚未阐明。我们分析了一例re患者细胞因子谱的动态变化。病例介绍：一名无任何病史的6岁女孩发生右半脑瘫。脑电图显示左侧顶叶至颞叶癫痫样放电，正电子发射断层扫描显示左侧顶叶灌注不足。9岁时，患者出现持续部分性癫痫，随后的MRI显示左半球轻度萎缩，据此诊断为RE。然后开始每月进行甲基强的松龙脉冲治疗，并在四个时间点记录患者的细胞因子谱。在急性期，脑脊液中C-X-C基序趋化因子9 （CXCL9）升高，但随后降低。同时，白细胞介素-6 （IL-6）在急性期呈阴性，在慢性期呈升高。急性期脑脊液中CXCL9的升高表明由于CTL的异常激活导致干扰素γ分泌增加，这是RE的特征。因此，在急性期测量CSF中CXCL9的水平可能有助于RE的诊断。我们观察到在慢性期脑脊液中IL-6水平升高，这可能反映了长期的中枢神经系统炎症。结论我们概述了RE患者的细胞因子谱动态，希望对RE的早期诊断和治疗方法的选择有所帮助。

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引用次数: 0