European Journal of Paediatric Neurology最新文献_第5页

Mortality in Tuberous sclerosis Complex: Current understandings 结节性硬化症复合体的死亡率：目前的认识

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-08-11 DOI: 10.1016/j.ejpn.2025.08.002

Rowan Pentz , Lauren Sham , Maria Zak , Katherine Muir , Elisabetta Trinari , Elizabeth J. Donner , Maryam N. Nouri , Robyn Whitney

Background

Tuberous Sclerosis Complex (TSC) is a multisystemic neurocutaneous disorder caused by pathogenic loss of function variants in the tumour suppressor genes TSC1 and TSC2. The resultant hamartomas confer significant medical risks by disruption of local tissues. Risk of mortality in TSC is known to be elevated, but only recently have multiple studies assessed specific causes of mortality in TSC.

Methods

A critical literature review of all available studies examining mortality in TSC was conducted using the terms “TSC”, “Tuberous Sclerosis Complex”, “mortality”, “death”, and “life expectancy”, in PubMed and Google Scholar, until December 15, 2024.

Results

We identified 13 studies that reported a total of 411 deaths from 6735 TSC individuals. Data were typically incomplete and causes of death in many cases were obtained from death certificates. Crude mortality per 100 individuals ranged from 1.4 to 13.8 over average intervals of 11–45 years. Standardized Mortality Ratios or hazard ratios (versus control group) ranged from 3.0 to 4.9 (mean 4.3). Mean life expectancy was 66.2 years compared to an average of 81.8 in the general population. In the seven studies that reported specific causes of mortality in the general TSC population, 6/7 studies (85 %) had renal or central nervous system disease as the most common cause of mortality. Lymphangioleiomyomatosis was also found to confer significant risk of mortality in adult women and cardiac rhabdomyomas were the dominant cause of neonatal mortality. TSC-associated neuropsychiatric disorders-related mortality and morbidity may be underestimated.

Conclusion

Mortality in TSC is elevated compared to the general population, with central nervous system and renal disease most frequently culpable. Further cohort studies will be required to establish and characterize the risk of mortality in TSC in the age of disease-modifying therapies.

结节性硬化症（TSC）是一种多系统神经皮肤疾病，由肿瘤抑制基因TSC1和TSC2功能变异的致病性丧失引起。由此产生的错构瘤由于局部组织的破坏而带来重大的医疗风险。已知TSC的死亡风险升高，但直到最近才有多项研究评估了TSC死亡的具体原因。方法对截至2024年12月15日，PubMed和谷歌Scholar上所有可用的关于TSC死亡率的研究进行批判性文献综述，检索词为“TSC”、“结节性硬化症”、“死亡率”、“死亡”和“预期寿命”。结果：我们确定了13项研究，报告了6735例TSC患者的411例死亡。数据通常是不完整的，在许多情况下，死亡原因是从死亡证明获得的。在11-45年的平均时间间隔内，每100个人的粗死亡率为1.4至13.8。标准化死亡率或危险比（相对于对照组）范围为3.0至4.9（平均4.3）。平均预期寿命为66.2岁，而普通人群的平均预期寿命为81.8岁。在报告一般TSC人群具体死亡原因的7项研究中，6/7（85%）的研究将肾脏或中枢神经系统疾病作为最常见的死亡原因。淋巴管平滑肌瘤病也被发现在成年女性中具有显著的死亡风险，心脏横纹肌瘤是新生儿死亡的主要原因。tsc相关的神经精神疾病相关的死亡率和发病率可能被低估。结论与一般人群相比，TSC的死亡率升高，中枢神经系统和肾脏疾病是最常见的罪魁祸首。需要进一步的队列研究来确定和描述TSC在疾病改善疗法时代的死亡风险。

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引用次数: 0

Rethinking the Brighton Criteria for pediatric Guillain-Barré syndrome: Toward clinical flexibility and global relevance 重新思考儿童格林-巴- <s:1>综合征的布莱顿标准：走向临床灵活性和全球相关性

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-08-06 DOI: 10.1016/j.ejpn.2025.08.001

Bassel Alrabadi, Natalie Bandak

引用次数: 0

Can inter-stride variability capture signs of mixed tone in individuals with cerebral palsy? An exploratory study 跨步幅变异性是否能捕捉脑瘫患者混合音调的迹象？探索性研究

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-08-05 DOI: 10.1016/j.ejpn.2025.07.014

Gilad Sorek , Marije Goudriaan , Itai Schurr , Simon-Henri Schless

Introduction

The identification of dystonia in addition to spasticity (mixed-tone) for individuals with cerebral-palsy (CP) is important, as it can alter clinical management. This study aims to examine if the inter-stride variability of conventionally used gait features can be used for recognizing mixed-tone during gait in individuals with CP.

Methods

Retrospective treadmill-based 3D gait-analysis data for 20 individuals (mean ± SD age 10.4 ± 3.3 years) with mixed-tone CP were extracted (mixed-tone-group). A control group of individuals diagnosed with spastic-CP and no dystonia during gait were individually matched (spastic-group). Gait-kinematics were evaluated using Spatiotemporal characteristics and the Gait-Profile-Score (GPS). Selective-motor-control was assessed by the dynamic-motor-control-index (walk-DMC). Inter-stride variability was calculated per-individual using the coefficient-of-variation (CV; (SD/mean)∗100).

Results

The mixed-tone-group presented with significantly smaller step-length and higher CV only in spatiotemporal parameters (p < 0.050). After controlling for walking-speed, only the CV for cadence remained significant (p < 0.001); a cut-off of 11.5 % CV in cadence could identify individuals with mixed-tone CP with 65 % sensitivity and 85 % specificity.

Interpretation

Larger inter-stride variability was identified for spatiotemporal characteristics in individuals with mixed-tone CP, compared to individuals with spastic CP. Capturing the highly variable movements may be a biomarker of dystonia during gait. Further prospective studies with larger sample size are needed.

脑瘫（CP）患者除痉挛（混合性）外，肌张力障碍的识别很重要，因为它可以改变临床管理。本研究旨在探讨常规步态特征的跨步变异性是否可以用于识别CP患者步态中的混合音调。方法提取20例混合音调CP患者（平均±SD年龄10.4±3.3岁）的回顾性跑步机三维步态分析数据（混合音调组）。诊断为痉挛性脑瘫且步态中无肌张力障碍的对照组被单独匹配（痉挛组）。利用时空特征和步态轮廓评分（GPS）对步态运动学进行评价。采用动态电机控制指数（walk-DMC）评价电机控制的选择性。跨步变异性计算采用变异系数(CV；(SD /意味着)∗100)。结果混合音调组仅在时空参数上表现出较低的步长和较高的CV (p <；0.050)。在控制步行速度后，只有节奏的CV仍然显著(p <；0.001);以11.5%的CV为截断值，以65%的敏感性和85%的特异性识别混合性CP患者。解释：与痉挛性脑瘫患者相比，混合性脑瘫患者在时空特征上的跨步变异性更大。捕捉高度可变的运动可能是步态肌张力障碍的生物标志物。需要进一步的更大样本量的前瞻性研究。

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引用次数: 0

CSF IL-6 in children with neuroinflammatory conditions 脑脊液IL-6与儿童神经炎症的关系

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-07-30 DOI: 10.1016/j.ejpn.2025.07.013

Valeria Pozzilli , Manori Prasadani Thambiliyagodage , Kshitij Mankad , Austen Worth , Paul Brogan , Sara Ghorashian , Alasdair Bamford , Cheryl Hemingway , Marios Kaliakatsos , Kimberly Gilmour , Yael Hacohen

Introduction

Cerebrospinal fluid (CSF) cytokines may contribute to immune-mediated processes affecting the central nervous system (CNS). We evaluated CSF cytokine profiles in children with suspected neuroinflammatory conditions to explore their clinical relevance.

Methods

Between 2019 and 2024, CSF from children <18 years were analyzed using BD Biosciences cytokine bead array for interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-alpha (IFN-α), and tumour necrosis-factor-alpha (TNF-α). Clinical phenotyping was conducted. Serum cytokine levels were measured in cases with abnormal CSF, when available.

Results

112 patients were included (median age 6 years [IQR 3.6–11.2]; 54 % male). CSF IL-6 was raised in 35/112 (31 %; median 107 pg/ml, IQR 24–329). No other cytokine was raised without concurrent IL-6. Raised CSF IL-6 occurred in 16/50 acquired neuroimmune conditions (including myelin oligodendrocyte glycoprotein antibody-associated disease, seronegative demyelination, seronegative autoimmune encephalitis, and febrile-infection-related epilepsy syndrome), 5/9 CNS infections; 9/17 monogenic autoinflammatory syndromes, and 5/7 cancer treatment-related neurotoxicities.

Of the 35 patients with raised CSF IL-6, 21 had serum cytokines tested; 13 (62 %) showed elevated serum IL-6. In demyelinating cases, higher IL-6 was associated with increased CSF protein (p = 0.007). Follow-up CSF samples (n = 16, median 34 days) showed persistent elevation in 7 and normalisation in 9. IL-6 inhibitors (tocilizumab and/or siltuximab) were used in 10 patients with variable outcomes, depending on the underlying etiology.

Conclusions

CSF IL-6 was the most frequently elevated cytokine in our cohort, observed across a range of primary and secondary neuroinflammatory disorders. While not diagnostic of a specific condition, its elevation may help guide treatment decisions.

脑脊液（CSF）细胞因子可能有助于影响中枢神经系统（CNS）的免疫介导过程。我们评估了疑似神经炎症的儿童脑脊液细胞因子谱，以探讨其临床相关性。方法采用BD Biosciences细胞因子头阵列分析2019年至2024年间来自18岁儿童的脑脊液中白细胞介素-2 （IL-2）、IL-4、IL-6、IL-10、干扰素-α (IFN-α)和肿瘤坏死因子-α (TNF-α)的含量。进行临床表型分析。在脑脊液异常的情况下，测定血清细胞因子水平。结果纳入112例患者(中位年龄6岁[IQR 3.6-11.2]；54%男性)。CSF IL-6升高35/112 (31%；中位数107 pg/ml， IQR 24-329)。没有IL-6的同时，其他细胞因子均未升高。CSF IL-6升高发生在16/50的获得性神经免疫疾病（包括髓鞘少突胶质细胞糖蛋白抗体相关疾病、血清阴性脱髓鞘、血清阴性自身免疫性脑炎和发热感染相关性癫痫综合征）和5/9的中枢神经系统感染中；9/17是单基因自身炎症综合征，5/7是癌症治疗相关的神经毒性。在35例CSF IL-6升高的患者中，21例进行了血清细胞因子检测；13例（62%）血清IL-6升高。在脱髓鞘病例中，高IL-6与CSF蛋白升高相关（p = 0.007）。随访的脑脊液样本（n = 16，中位34天）显示7例持续升高，9例恢复正常。IL-6抑制剂（tocilizumab和/或siltuximab）用于10例患者，根据潜在病因，结果不同。结论：在我们的队列中，在一系列原发性和继发性神经炎性疾病中观察到，scsf IL-6是最常升高的细胞因子。虽然不能诊断出特定的疾病，但它的升高可能有助于指导治疗决策。

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引用次数: 0

Neurological manifestations in children with SARS-CoV-2 infection: a French multicentric cohort SARS-CoV-2感染儿童的神经系统表现：法国多中心队列研究

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-07-23 DOI: 10.1016/j.ejpn.2025.07.010

J. Roux , F. Angoulvant , M. Aubart , S. Auvin , C. Brehin , E. Cheuret , M.-A. Dommergues , F. Girard , D. Graber , V. Hoeusler , E. Lametery , C. Le Stradic , A. Lepine , S. Nguyen , S. Peudenier , C. Pons , A.-L. Poulat , S. Rivera , B. Robert , M. Shum , K. Deiva

Objectives

This study aimed to assess neurological manifestations in French children hospitalized with SARS-CoV-2 infection. Secondary objectives were to evaluate the severity of these presentations and estimate the frequency of long-term neurological sequelae.

Methods

A multicenter observational study was conducted, including 71 children hospitalized for neurological manifestations of SARS-CoV-2 infection from January 2020 to March 2022.

Results

The median age was 8.7 years (range 4.2–13), with 49 % being girls. The most common neurological manifestations were encephalitis and meningoencephalitis (32 %). Brain imaging was abnormal in 68 % of cases. Half of the children required admission in intensive care unit (ICU). Nearly one-third of the children had neurological symptoms at the end of the follow-up, with cognitive difficulties being the most reported complaints. No significant associations were made between sex, age, neurological comorbidities, and the severity nor presence of sequelae. However, abnormal brain imaging was significantly associated with a higher risk of ICU stay (OR = 8.01 [95 % CI 2.37–27.1], p < 0.01) and with the presence of sequelae at discharge (OR = 4.65 [1.45–14.9], p = 0.011) and last follow-up (OR = 5.14 [1.40–18.9], p = 0.015).

Conclusion

Although rare, neurological manifestations in children with SARS-CoV-2 infection can be severe, with encephalitis as the most common clinical presentation. Abnormal brain imaging is a strong prognostic marker of acute severity and long-term neurological and cognitive sequelae. Objective assessment tools and longer follow-up are necessary to evaluate the long-term outcomes in these children.

目的评价法国住院儿童SARS-CoV-2感染的神经学表现。次要目的是评估这些症状的严重程度和估计长期神经系统后遗症的频率。方法对2020年1月至2022年3月因SARS-CoV-2感染神经系统症状住院的71例患儿进行多中心观察性研究。结果中位年龄为8.7岁（4.2 ~ 13岁），女孩占49%。最常见的神经学表现为脑炎和脑膜脑炎（32%）。68%的病例脑成像异常。半数儿童需要入住重症监护病房（ICU）。在随访结束时，近三分之一的儿童出现了神经系统症状，其中认知困难是报告最多的症状。性别、年龄、神经合并症和严重程度及是否存在后遗症之间没有明显的关联。然而，脑成像异常与ICU住院风险升高显著相关(OR = 8.01 [95% CI 2.37-27.1], p <；出院时存在后遗症（OR = 4.65 [1.45-14.9], p = 0.011）和末次随访时（OR = 5.14 [1.40-18.9], p = 0.015）。结论SARS-CoV-2感染患儿的神经系统表现虽然少见，但可能很严重，以脑炎为最常见的临床表现。异常脑成像是急性严重程度和长期神经和认知后遗症的预后标志。客观的评估工具和更长的随访是评估这些儿童长期预后的必要条件。

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引用次数: 0

Impact of lesion metrics and neurological functions on long-term cognitive outcome in childhood stroke 损伤指标和神经功能对儿童中风长期认知结果的影响

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-07-23 DOI: 10.1016/j.ejpn.2025.07.012

Saskia Salzmann , Leonie Steiner , Tatia Aprasidze , Andrea Klein , Gabriela Oesch , Hakim Arsany , Maja Steinlin , Regula Everts

The prevalence of cognitive impairment after childhood stroke is high and various risk factors influence long-term cognitive outcome. Whether and how risk factors are associated with cognitive outcome is still incompletely understood. This study investigated how lesion volume, lesion location and neurological functions at discharge, 6 months and 2 years after childhood stroke contribute to long-term cognitive outcome.

This observational study included patients after childhood arterial ischemic stroke. Long-term cognitive outcome (intelligence, processing speed, working memory) was assessed at least one year after stroke (Md = 3.52, IQR = 5.57). Neurological functions were measured using the pediatric stroke outcome measure at discharge, at 6-month and 2-year follow-up. Magnetic resonance imaging at stroke manifestation was applied to analyze acute to subacute lesion metrics (volume & location).

43 patients aged 6–23 years (Md = 6.17, IQR = 7.58) were enrolled in the study. Cognitive functions significantly correlated with lesion volume (processing speed: r = −.423, p = .005; working memory: r = −.478, p = .002). Working memory was worse if the left caudate nucleus was involved (U = 284.5, p < .001, d = 1.43). Long-term cognitive outcome correlated with neurological functions at discharge, 6-month and 2-year follow-up, although effects varied depending on the cognitive domain measured (discharge: r = .449, p = .003; 6-month; r = .509 to .538, p <.001; 2-year follow-up: r = .588 to .744, p <.001).

Long-term cognitive outcome was associated with lesion volume, lesion location and neurological functions. Our study adds to the determination of risk factors for long-term cognitive rehabilitation and highlights the need for the combined evaluation of neurological and cognitive outcome.

儿童中风后认知功能障碍的患病率很高，各种危险因素影响长期认知预后。风险因素是否以及如何与认知结果相关联仍不完全清楚。本研究调查了儿童中风后出院时、6个月和2年的病变体积、病变位置和神经功能对长期认知预后的影响。这项观察性研究包括儿童动脉缺血性卒中后的患者。卒中后至少一年评估长期认知结果（智力、处理速度、工作记忆）（Md = 3.52, IQR = 5.57）。在出院时、6个月和2年随访时使用小儿卒中结局测量法测量神经功能。应用脑卒中表现时的磁共振成像分析急性到亚急性病变指标(体积&；位置)。43例6 ~ 23岁患者（Md = 6.17, IQR = 7.58）入组研究。认知功能与病变体积（处理速度：r =−）显著相关。423, p = 0.005；工作记忆：r =−。478, p = .002)。当左尾状核受累时，工作记忆较差(U = 284.5, p <；.001, d = 1.43)。长期认知结果与出院、6个月和2年随访时的神经功能相关，尽管影响因所测量的认知领域而异(出院：r = .449, p = .003；6个月;R = .509 ~ .538, p <；2年随访：r = .588 ~ .744, p <.001)。长期认知结果与病变体积、病变位置和神经功能有关。我们的研究增加了长期认知康复的危险因素的确定，并强调了对神经和认知结果进行综合评估的必要性。

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引用次数: 0

Atypical neuroaxonal dystrophy in childhood related to PLA2G6: a French cohort 与PLA2G6相关的儿童非典型神经轴突营养不良：一项法国队列研究

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-07-23 DOI: 10.1016/j.ejpn.2025.07.011

Lorenzo Menicucci , Moussa Mane , Agathe Roubertie , Odile Boespflug-Tanguy , Lena Damaj , Aline Delignieres , Laurine Perrin , Diana Rodriguez , Imen Dorboz , Michel Koenig , Lydie Burglen , Nelly Durand , Catherine Sarret

Atypical neuroaxonal dystrophy (ANAD) is a rare form of neurodegeneration linked to the PLA2G6 gene. Unlike classical infantile neuroaxonal dystrophy (INAD), it occurs later in childhood and seems less progressive. It appears phenotypically different from juvenile form of Parkinson disease linked to PLA2G6 (PARK14). A genotype-phenotype correlation has been suggested.

We describe a large genetically confirmed cohort of pediatric patients with ANAD, describe their clinical symptomatology, brain imaging, other complementary explorations, symptomatic medication and compare to patients reported in the literature.

Fourteen patients were identified with early childhood onset and slowly progressive cerebello-spastic syndrome with variable dystonia and parkinsonism. Complementary investigations were inconsistently abnormal compared to INAD, with variable iron deposits on brain imaging, infrequent rapid rhythms on EEG and absence of neuronal spheroids on skin biopsy leading to diagnosis difficulties in absence of large molecular analysis. Nine of the seventeen reported variants were novel variants and a relative genotype-phenotype correlation was confirmed.

This study reports a large cohort of ANAD, providing new insights into this paediatric phenotype; which is less frequently described in the literature compared to INAD or PARK14.

非典型神经轴突营养不良（ANAD）是一种罕见的与PLA2G6基因相关的神经退行性疾病。与典型的婴儿神经轴突营养不良（INAD）不同，它发生在儿童期较晚，似乎进展较慢。它在表型上不同于与PLA2G6 （PARK14）相关的少年型帕金森病。基因型与表型之间存在相关性。我们描述了一个大的遗传证实的儿童ANAD患者队列，描述了他们的临床症状，脑成像，其他补充探索，对症用药，并与文献报道的患者进行比较。14例患者被确定为儿童早期发病和缓慢进行性小脑痉挛综合征伴可变张力障碍和帕金森病。与INAD相比，补充检查不一致异常，脑成像上有不同的铁沉积，脑电图上有罕见的快速节律，皮肤活检上没有神经元球体，导致缺乏大分子分析的诊断困难。17个报告的变异中有9个是新变异，并且证实了相对的基因型-表型相关性。本研究报告了大量的ANAD队列，为这种儿科表型提供了新的见解；与INAD或PARK14相比，这在文献中较少被描述。

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引用次数: 0

Demographic, clinical, and genetic characteristics of patients with Limb-Girdle Muscular Dystrophies (LGMD): A single tertiary-center experience 肢体带状肌营养不良症（LGMD）患者的人口统计学、临床和遗传特征：单一三中心经验

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-07-22 DOI: 10.1016/j.ejpn.2025.07.009

Murat Yildirim Kale , Huseyin Anil Korkmaz , Berk Ozyilmaz , Aysel Çoban Taşkın , Ebru Boluk

Objective

Given that pathogenic variants related to limb-girdle muscular dystrophies (LGMD) are rarely found in Turkish populations, we aim to characterize pathogenic genetic variants of LGMD associated with age of disease onset, family characteristics, final clinical status, and muscle biopsy findings.

Materials and methods

We retrospectively evaluated adult patients with LGMD whose diagnoses were confirmed by genetic and/or muscle biopsy and who were being followed up in the Muscle Diseases Center of Izmir Tepecik Training and Research Hospital. We tested for LGMD genes on the DNA sample obtained from peripheral blood using the next-generation sequencing method on the MiSeq Platform (Illimunia, USA). A minor allele frequency of <0.01 in the GnomAD or ExAC database was used to filter for significant variants. Sanger sequencing was then conducted to validate the findings. Function prediction by SIFT, PolyPhen-2, and PROVEAN or CADD was carried out in missense pathogenic genes.

Results

A total of 13 LGMD subtypes were identified in 69 patients. Twenty-eight of the patients were male, and 41 were female. The mean age at disease onset was 14.98 years (minimum 1 year, maximum 30 years). Consanguinity was found in 51 (71.6 %) of the 69 patients. Our study included 23 patients with type R1 (calpainopathy), 16 with type R2 (dysferlinopathy), eight with type R3 (alpha sarcoglycanopathy), two with type R4 (beta sarcoglycanopathy), seven with type R5 (gamma sarcoglycanopathy), five with type R7 (telethoninopathy), one with type R8 (TRIM32), one with type R9 (dystroglycanopathy), one with type R10 (titinopathy), one with type R11 (POMT1), two with type R12 (anoctamin 5), one with type R14 (POMT2), and one with formerly type R18 (desminopathy).

Conclusion

The importance of genetic diagnosis for LGMD is increasing, especially because treatment methods are being developed in this field that hold promise for truly treating the disease. This study adds to the emerging pattern of LGMD epidemiology demonstrating that the proportion of LGMD explained by known pathogenic genes is higher than that previously reported.

鉴于在土耳其人群中很少发现与肢体带状肌营养不良症（LGMD）相关的致病变异，我们的目标是表征与发病年龄、家族特征、最终临床状态和肌肉活检结果相关的LGMD致病遗传变异。材料和方法我们回顾性评估了通过遗传和/或肌肉活检确诊的成年LGMD患者，这些患者在Izmir Tepecik培训和研究医院肌肉疾病中心接受了随访。我们在MiSeq平台（illinois， USA）上使用新一代测序方法对从外周血中获得的DNA样本进行LGMD基因检测。在GnomAD或ExAC数据库中使用<；0.01的小等位基因频率来过滤重要的变异。然后进行桑格测序来验证这些发现。用SIFT、polyphen2、provan或CADD对错义致病基因进行功能预测。结果69例患者共检出13种LGMD亚型。其中男性28例，女性41例。平均发病年龄为14.98岁（最小1岁，最大30岁）。69例患者中有51例（71.6%）有血缘关系。我们的研究包括23个患者类型R1 (calpainopathy), 16型R2 (dysferlinopathy),八个R3型(αsarcoglycanopathy),两个R4型(βsarcoglycanopathy)、7型R5(γsarcoglycanopathy)、五型R7 (telethoninopathy),一个R8型(TRIM32),一个型R9机型(dystroglycanopathy),一个R10型(titinopathy),一个R11 (POMT1)型两型R12 (anoctamin 5),一个R14型(POMT2),另一人原为R18型（神经病变）。结论遗传诊断对LGMD的重要性日益增加，特别是由于该领域的治疗方法正在开发，有望真正治疗该病。这项研究增加了LGMD流行病学的新模式，表明由已知致病基因解释的LGMD比例高于先前报道的比例。

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引用次数: 0

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-07-19 DOI: 10.1016/j.ejpn.2025.07.007

Laia Nou-Fontanet , Uliana Musokhranova , Alia Ramírez Camacho , Verónica Delgadillo Chilavert , Víctor Soto Insuga , Luisa Arrabal Fernández , Itziar Alonso-Colmenero , Alexis Arzimanoglou , Ángeles García Cazorla , Alfonso Oyarzabal , Carmen Fons

AFG2A-related encephalopathy (AFG2A-RE) is a neurodevelopmental disorder that may present with drug-resistant epilepsy (DRE). Our aims were: to evaluate the clinical response to a ketogenic diet (KD) in a series of patients with AFG2A-RE and DRE, and to describe the mitochondrial effects in patient's fibroblasts cultured in a KD mimicking medium (KD-MM). This was a collaborative, descriptive, and experimental study involving a total of five patients. The primary outcomes assessed following ketogenic diet (KD) treatment were the percentage of seizure reduction and the parents' global impression of change. Additionally, patient-derived fibroblasts (n = 3) were cultured in a KD-MM to evaluate effects on mitochondrial dynamics and metabolism. The mean age of the patients was 7.9 years, and four were males. All patients presented with developmental and epileptic encephalopathy with DRE, motor impairment, severe intellectual disability, deafness, and microcephaly. In all but one case, the initial epilepsy presentation was infantile epileptic spasms syndrome (IESS), with a mean age at onset of 13.6 months. Four patients received KD treatment for DRE, with seizure reduction rates of 0 %, 30 %, 70 % and 100 %, respectively. Improvement in social interaction improvement was observed in one patient, while improvements in attentional and motor function were noted in two. In vitro studies demonstrated that AFG2A-deficient fibroblasts exhibited altered mitochondrial morphology and dynamics, as well as reduced ATP production and ROS levels. These abnormalities were significantly reversed when the fibroblasts were cultured in KD-MM. In conclusion, this small series of patients with AFG2A-RE showed beneficial effects from KD treatment. Greater seizure control was achieved when the ketogenic diet was initiated during early childhood. These findings are preliminary and validation in multicenter prospective study is required.

afg2a相关脑病（AFG2A-RE）是一种神经发育障碍，可能伴有耐药癫痫（DRE）。我们的目的是：评估一系列AFG2A-RE和DRE患者对生酮饮食（KD）的临床反应，并描述在KD模拟培养基（KD- mm）中培养的患者成纤维细胞对线粒体的影响。这是一项协作性、描述性和实验性研究，共涉及5名患者。生酮饮食（KD）治疗后评估的主要结果是癫痫发作减少的百分比和父母对变化的总体印象。此外，患者来源的成纤维细胞（n = 3）在KD-MM中培养，以评估对线粒体动力学和代谢的影响。患者平均年龄7.9岁，男性4例。所有患者均表现为发育性和癫痫性脑病，并伴有DRE、运动障碍、严重智力残疾、耳聋和小头畸形。除一例外，所有患儿的初始癫痫表现均为婴儿癫痫性痉挛综合征（IESS），平均发病年龄为13.6个月。4例患者接受KD治疗，癫痫发作减少率分别为0%、30%、70%和100%。其中一名患者的社交能力有所改善，两名患者的注意力和运动功能有所改善。体外研究表明，缺乏afg2a的成纤维细胞表现出线粒体形态和动力学的改变，以及ATP产生和ROS水平的降低。当成纤维细胞在KD-MM中培养时，这些异常明显逆转。总之，这一小部分AFG2A-RE患者显示出KD治疗的有益效果。当在儿童早期开始生酮饮食时，癫痫发作的控制效果更好。这些发现是初步的，需要在多中心前瞻性研究中进行验证。

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引用次数: 0

Assessment of psychosocial adjustment and reduced initiative in children with myotonic dystrophy type 1: a pilot study on the reliability and clinical utility of a short parent-report questionnaire 评估1型肌强直性营养不良儿童的心理社会适应和主动性降低：一项关于简短父母报告问卷的可靠性和临床应用的初步研究

IF 2.3 3区医学 Q3 CLINICAL NEUROLOGY

European Journal of Paediatric Neurology

Pub Date : 2025-07-19 DOI: 10.1016/j.ejpn.2025.07.008

Dirk J.J. Sweere , Sylvia Klinkenberg , R. Jeroen Vermeulen , Hilde M.H. Braakman , Jos G.M. Hendriksen

We describe the reliability and clinical utility of the personal adjustment and role skills scale III (PARS-III) for screening of psychosocial adjustment in children with myotonic dystrophy type 1 (DM1). Data of 36 pediatric DM1 patients were included from the Dutch MYODRAFT patient registry. Reliability was assessed using Cronbach's alpha. Associations between PARS-III scores and estimates of brain-related comorbidity and parent-reported physical disease burden were explored as possible factors affecting psychosocial adjustment. PARS-III data of children with DM1 in this study were compared to PARS-III data from children with Duchenne muscular dystrophy in order to describe specificity to the pediatric DM1 population. The PARS-III showed adequate internal consistency. PARS-III total scores correlated with parent-reported symptoms of autism spectrum disorder and attention deficit/hyperactivity disorder and parent-reported physical disease burden. No statistically significant associations were found with intelligence. Parents reported most problems in reduced social activity and reduced initiative. Reduced initiative was not associated with attention deficit/hyperactivity disorder, autism spectrum disorder or reported physical disease burden. Parents of children with DM1 reported more problems in initiative compared to parents of children with Duchenne muscular dystrophy. We conclude that the PARS-III is a reliable instrument for screening psychosocial adjustment in general and deficits in initiative in particular. More research is needed on this clinically relevant symptom as a possible brain-related comorbidity of children with DM1.

我们描述了个人适应和角色技能量表III （PARS-III）筛选1型肌强直性营养不良症（DM1）儿童的社会心理适应的可靠性和临床应用。36名儿童DM1患者的数据来自荷兰MYODRAFT患者登记处。采用Cronbach’s alpha评估信度。PARS-III评分与脑相关合并症和父母报告的身体疾病负担之间的关联被探讨为影响心理社会适应的可能因素。本研究将DM1患儿的PARS-III数据与Duchenne肌营养不良患儿的PARS-III数据进行比较，以描述儿童DM1人群的特异性。PARS-III显示出足够的内部一致性。PARS-III总分与父母报告的自闭症谱系障碍、注意缺陷/多动障碍症状和父母报告的身体疾病负担相关。没有发现与智力有统计学意义的关联。父母报告的主要问题是社交活动减少和主动性降低。主动性降低与注意缺陷/多动障碍、自闭症谱系障碍或报告的身体疾病负担无关。与杜氏肌营养不良儿童的父母相比，DM1儿童的父母报告了更多的主动性问题。我们的结论是，PARS-III是一种可靠的工具，用于筛查一般的社会心理适应，特别是主动性缺陷。这一临床相关症状作为DM1患儿可能的脑相关合并症还需要更多的研究。

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引用次数: 0