Background Wilson’s disease (WD) is an inherited disorder of copper metabolism. Agenesis of the corpus callosum is the complete or partial absence of the major united fiber bundles connecting the cerebral hemispheres. Intracranial lipoma is an adipose tissue tumor resulting from an abnormal embryonic development of the central nervous system. The simultaneous occurrence of these three disorders is rare and has not been reported. This report focuses on the pathogenesis and association between the three disorders and highlights the importance of recognizing and effectively managing their coexistence. Case presentation The purpose of this study was to present a patient with coexisting WD, intracranial lipoma, and corpus callosum dysplasia. We reviewed a female patient hospitalized in 2023 with clinical manifestations of elevated aminotransferases and decreased ceruloplasmin, as well as genetic testing for an initial diagnosis of Wilson’s disease. Subsequently, a cranial MRI showed corpus callosum dysplasia with short T1 signal changes in the cerebral falx, leading to a final diagnosis of Wilson’s disease combined with intracranial lipoma and corpus callosum dysplasia. The patient’s WD is currently stable after treatment with sodium dimercaptosulfonamide (DMPS) and penicillamine, and the patient’s abnormal copper metabolism may promote the growth of intracranial lipoma. Conclusion The pathogenesis of WD combined with intracranial lipoma and corpus callosum dysplasia is complex and clinically rare. The growth of intracranial lipomas may be associated with abnormal copper metabolism in WD. Abnormal copper metabolism affects lipid metabolism and triggers inflammatory responses. Therefore, early diagnosis and treatment are beneficial for improvement. Each new case of this rare co-morbidity is important as it allows for a better assessment and understanding of these cases’ more characteristic clinical manifestations, which can help estimate the course of the disease and possible therapeutic options.

Movement Disorders Clinical PracticeEarly View LETTERS: PUBLISHED ARTICLES Oculogyric Crisis in a Wilson's Disease Patient Ping Jin MD, Ping Jin MD orcid.org/0000-0001-6528-8330 Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorXiao-Ming Fu MD, Xiao-Ming Fu MD orcid.org/0000-0002-9127-081X Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorYu Wang MD, Yu Wang MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorXin-Feng Ma MD, Xin-Feng Ma MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorWen-Long Ai MD, Wen-Long Ai MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorYa-Yun Xu MD, Ya-Yun Xu MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorBo Li MD, Bo Li MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorQun-Rong Ye MD, Qun-Rong Ye MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorGong-Qiang Wang MD, Corresponding Author Gong-Qiang Wang MD [email protected] orcid.org/0009-0000-5317-4184 Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China Correspondence to: Dr. Gong-Qiang Wang, Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China. Institute of Neurology, Anhui University of Chinese Medicine. No. 357, Changjiang Middle Road, Hefei, China; E-mail: [email protected]Search for more papers by this author Ping Jin MD, Ping Jin MD orcid.org/0000-0001-6528-8330 Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorXiao-Ming Fu MD, Xiao-Ming Fu MD orcid.org/0000-0002-9127-081X Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorYu Wang MD, Yu Wang MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorXin-Feng Ma MD, Xin-Feng Ma MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorWen-Long Ai MD, Wen-Long Ai MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorYa-Yun Xu MD, Ya-Yun Xu MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorBo Li MD, Bo Li MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorQun-Rong Ye MD, Qun-Rong Ye MD Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, ChinaSearch for more papers by this authorGong-Qiang Wang MD, Corresponding Author Gong-Qiang Wang MD [email protected] orcid.org/0009-0000-5317-4184 Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China Correspondence to: Dr. Gong-Qiang Wang, Department of Neurology, The Affiliated Hospital of Institute of Neurology, Anhui University of Chinese Medicine, Hefei, China. Institute of Neurology, Anhui University of Chinese Medicine. No. 357, Changjiang Middle Road, Hefei, China; E-mail: [email protected]Search for more papers by this author First published: 10 December 2023 https://doi.org/10.1002/mdc3.13949 Funding: This study was supported by the Major Project of Clinical Research Fund of Anhui University of Traditional Chinese Medicine (2021sfylc04) and the Scientific Research Fund Project of Colleges and Universities in Anhui Province (2023AH050793). The funders had no role in conceptualization, and development or writing of the manuscript. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Kassavetis P, Kaski D, Anderson T, Hallett M. Eye Movement Disorders in Movement Disorders. Mov Disord Clin Pract 2022; 9(3): 284–295. https://doi.org/10.1002/mdc3.13413. 10.1002/mdc3.13413 PubMedWeb of Science®Google Scholar 2Leinweber B, Möller JC, Scherag A, et al. Evaluation of the unified Wilson's disease rating scale (UWDRS) in German patients with treated Wilson's disease. Mov Disord 2008; 23(1): 54–62. https://doi.org/10.1002/mds.21761. 10.1002/mds.21761 PubMedWeb of Science®Google Scholar 3Lee MS, Kim YD, Lyoo CH. Oculogyric crisis as an initial manifestation of Wilson's disease. Neurology 1999; 52(8): 1714–1715. https://doi.org/10.1212/wnl.52.8.1714. 10.1212/WNL.52.8.1714 CASPubMedWeb of Science®Google Scholar 4Barow E, Schneider SA, Bhatia KP, Ganos C. Oculogyric crises: etiology, pathophysiology and therapeutic approaches. Parkinsonism Relat Disord 2017; 36: 3–9. https://doi.org/10.1016/j.parkreldis.2016.11.012. 10.1016/j.parkreldis.2016.11.012 PubMedWeb of Science®Google Scholar 5Desai K, Agrawal S, Walzade P, Ravat SH, Agarwal PA. Atypical, early-onset dystonia-parkinsonism with oculogyric crises and anterior horn cell disorder due to a novel DJ-1 mutation. Mov Disord Clin Pract 2021; 8(Suppl 1): S16–S18. https://doi.org/10.1002/mdc3.13282. 10.1002/mdc3.13282 PubMedGoogle Scholar 6Lee JH, Lyoo CH, Lee JG, Lee MS. 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目的 分析肝豆状核变性(Wilson disease,WD)并发肌张力障碍持续状态(status dystonicus,SD)患者的临床特点.方法 回顾性分析15例WD并发SD患者的临床特征、重要辅助检查、治疗及转归.结果 患者均表现为严重的全身型肌张力障碍发作,其中强直型13例,相位型2例.14例伴吞咽障碍、呼吸功能障碍、疼痛和虚脱.WD患者发生SD的主要诱因是铜螯合剂和感染.患者血肌酸激酶(creatine kinase,CK)显著升高,脑MRI呈对称性豆状核,中脑、丘脑和桥脑异常信号伴脑萎缩.患者均在支持和对症治疗基础上,积极寻找和去除诱因,予适度镇静和麻醉,调整特异性抗肌张力障碍方案.随访有效4例,无效10例,死亡1例,总体预后不佳.结论 WD是导致SD的重要潜在病因之一.WD并发SD的临床特征是原有肌张力障碍异常运动和姿势的严重恶化,可伴多种内环境紊乱并发症.虽然及早治疗可终止发作,但本病复发率高,远期结局仍差.

Dysarthria is common in movement disorders, such as Wilson's disease (WD), Parkinson's disease, or Huntington's disease. Dysarthria severity assessment is often indispensable for the management of these diseases. However, such assessment is usually labor‐intensive, time‐consuming, and expensive. To seek efficient and cost‐effective solutions for dysarthria assessment, an artificial intelligence (AI)‐powered acoustic analysis system is proposed and its performance in a valuable sample of WD, an ideal disease model with mainly mixed dysarthria, is verified. A test‐retest reliability analysis yields excellent reproducibility in the acoustic measures (mean intraclass correlation coefficient [ICC] = 0.81). Then, a system for dysarthria assessment is trained with WD patients (n = 65) and sex‐matched healthy controls (n = 65) using a machine learning approach. The system achieves reasonable performance in evaluating dysarthria severity with either stepwise classification or regression (all areas under the curve >80%; mean absolute error = 6.25, r = 0.79, p < 0.0001). The diadochokinesis and sustained phonation tasks contribute the most to prediction, and the corresponding acoustic features can provide significant and independent contributions. The present study demonstrates the feasibility and good performance of the AI‐powered acoustic analysis framework, offering the potential to facilitate early screening and subsequent management of dysarthria.

Krabbe disease (KD), also known as globoid cell leukodystrophy, is a rare autosomal recessive condition caused by mutations in the galactocerebrosidase (GALC) gene. KD is more common in infants and young children than in adults. We reported the case of an adult-onset KD presenting with progressive myoclonic epilepsy (PME) and cortical lesions mimicking mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. The whole-exome sequencing (WES) identified a pathogenic homozygous missense mutation of the GALC gene. Parents of the patient were heterozygous for the mutation. The clinical, electrophysiological, and radiological data of the patient were retrospectively analyzed. The patient was a 24-year-old woman presenting with generalized seizures, progressive cognitive decline, psychiatric symptoms, gait ataxia, and action-induced myoclonus. The brain magnetic resonance imaging (MRI) revealed a right occipital cortical ribbon sign without any other damage. This single case expands the clinical phenotypes of adult-onset KD.

O'Sullivan-Mcleod syndrome is a very rare variant of MND with a good prognosis. Its clinical feature is distal lower motor neuron syndrome of both upper limbs, and there is no effective treatment at present. We reported a case of O'Sullivan-Mcleod syndrome in this paper.The patient exhibited with middle-aged progressive distal muscle weakness and atrophy of both upper limbs, without sensory, cognitive or behavioral impairment and without pyramidal tract sign. Laboratory examination, imaging and genetic tests showed no obvious abnormalities. EMG revealed neurogenic damage to the small muscles of both hands. Now we retrospectively analyzed the clinical features of a patient with O'Sullivan-McLeod syndrome, and data from 18 cases for comparative analysis, in order to improve its understanding by clinicians.

Objective To observe the changes of serum superoxide dismutase（SOD） activity in patients with hepatolenticular degeneration（HLD）, and to analyze the correlation of SOD activity with age, duration of disease, uric acid and 24 h urine copper.Method A retrospective analysis of 500 inpatients with HLD who were hospitalized.Referring to the HLD classification standard formulated by Yang Renmin et al in 2015, the gender, age, duration of disease, clinical classification, liver classification and clinical grade of the enrolled patients were counted.In addition, the serum SOD activity level, uric acid（UA） level and 24-hour urinary copper of the enrolled patients before copper complexation treatment, as well as the 24-hour urinary copper on the second day of the first course of treatment with sodium dimercaptopropanesulfonate.The differences in serum SOD activity levels of HLD patients with different gender, age, duration of disease, clinical classification, liver classification and clinical grade were analyzed and compared, and their correlation with serum SOD activity levels of patients was also analyzed.Results Among the 500 HLD patients, 25 had decreased serum SOD activity levels, and 136 had elevated serum SOD activity levels, with a total abnormal rate of 32.2%.There was no significant difference in serum SOD activity levels between males andfemales（P＞0.05）.There were significant differences in serum SOD activity levels among HLD patients with different age groups, duration of disease groups, clinical classification, liver classification and clinical grades（P＜0.05）.Among them, the serum SOD activity level of patients in the age group of 1-10 years was the highest, while that in the age group of 51-60 years was the lowest; the serum SOD activity level was the highest in patients with a course of 6-10 years, and the lowest in patients with a course of 21-30 years; the serum SOD activity levels were highest in patients with presymptomatic type, and lowest in patients with brain-visceral type; the level of serum SOD activity in patients with mild liver damage was the highest, and that in patients with liver nodule type was the lowest, and the serum SOD activity level of patients gradually decreased with the severity of liver damage; the serum SOD activity level of patients with clinical grade 0 was the highest, and that of patients with grade Ⅳ was the lowest, and the serum SOD activity level of patients gradually decreased with the increase of clinical grade.Spearman correlation analysis showed that: the serum SOD activity level of HLD patients was negatively correlated with age, disease course and 24 h urinary copper（P＜0.05）, and positively correlated with UA（P＜0.05）.Conclusion There were abnormal changes of SOD activity in HLD patients.The serum SOD activity of HLD patients was negatively correlated with age, duration of disease and 24-hour urinary copper, and positively correlated with UA.In addition, the level of serum SOD activity was affected by the degree of disease damage in HLD patients.With the aggravation of disease damage in HLD patients, the level of serum SOD activity decreased gradually.Observation of serum SOD activity in HLD patients has considerable clinical guidance value for the preliminary judgment of the severity of the disease in patients.

肌张力障碍持续状态是一种罕见的运动障碍疾病急症,其临床特征包括高热、自主神经功能紊乱、吞咽障碍和呼吸衰竭,多预后不良.需要紧急评估,并根据患者的临床特点和并发症进行干预.目前临床上对肌张力障碍持续状态的认识不足,文中针对肌张力障碍持续状态的诊治研究进行综述.

Objective To report a case of peripheral neuropathy secondary to copper deficiency (CD) by long‐term decoppering chelation in Wilson′s disease (WD) to enhance understanding of the disease, and to pay more attention to individualized treatment of WD. Methods A case of WD diagnosed 12 years ago confirmed by gene detection and since then treated with anti‐copper agent was diagnosed as CD based peripheral neuropathy and significant neutropenia and followed up for six months, and the clinical manifestations, laboratory examination, electrophysiology, imaging features were summarized. The related literatures were reviewed. Results A total of 16 cases of WD complicated with CD were reviewed and analyzed, including seven males and nine females aged 13-56 years. All of them were treated with zinc for 1-38 years, and nine cases with peripheral neuropathy. Hematological indicators can be significantly improved and neurological symptoms can be partially alleviated after stopping copper removal treatment. Conclusions Peripheral neuropathy in a WD with treatment‐related CD may occur in blind treatment, irregular treatment monitoring and without individualized treatment adjustment. It is necessary to monitor blood routine, copper and zinc metabolism regularly and advocate individualized treatment of WD.

本文报道1例感觉共济失调型慢性炎症性脱髓鞘性多发性神经病(CIDP),其是一种罕见的变异型CIDP,临床表现不典型,以感觉性共济失调和深感觉障碍为主要症状,极易误诊.但神经电生理和脑脊液检查可为诊断提供重要依据,糖皮质激素治疗效果较为肯定,预后较好.

Holmes震颤(Holmes tremble, HT)也称丘脑震颤、红核震颤,是一种少见的临床综合征,主要原因为脑血管病[1],通常在原发病后0.5～24个月发生. HT临床表现为以病灶对侧上肢为主的低频的静止性震颤、姿位性震颤和意向性震颤中 1 种或多种组合,亦可伴有脑损伤的其他症状[2].HT 文献报道较少,现报告我院 2018 年 1 月确诊的、经盐酸苯海索联合左乙拉西坦治疗后症状稍改善的 1 例 HT病例.

目的:探讨肝豆汤联合二巯基丙磺酸钠(DMPS)治疗对湿热内蕴型肝豆状核变性患者的认知功能障碍影响.方法:回顾性分析湿热内蕴型肝豆状核变性患者85例,其中治疗组45例,对照组40例,其中治疗组给予中药肝豆汤联合二巯基丙磺酸钠治疗,对照组为单独应用二巯基丙磺酸钠治疗的患者;治疗共进行4个疗程,每个疗程为8d,DMPS驱铜治疗6d后间歇休息2d,在治疗前后分别进行蒙特利尔认知评估量表(MoCA)评定,并检测认知功能相关指标血清超氧化物歧化酶(SOD),同型半胱胺酸(Hcy)水平的变化,观察24 h尿铜的改变,并检测肝功能、肾功能、白细胞、血小板等相关安全性指标.结果:两组患者在治疗后,MoCA评分总分较本组治疗前均明显改善,其中以治疗组改善最为明显;治疗后两组间子项目的评分比较,其中视空间与执行功能、注意力治疗组改善显著优于对照组(P＜0.05);两组血清学指标SOD水平组均改善明显,治疗组显著优于对照组(P＜0.05),治疗后Hcy水平治疗组明显改善(P＜0.05),对照组无明显变化;两组驱铜效果均较为显著(P＜0.01),两组组间对比,治疗组优于对照组(P＜0.05).结论:肝豆汤联合二巯基丙磺酸钠可显著改善Willson病认知功能,血清SOD,Hcy水平显著改善,驱铜效果明显,不良反应轻微,安全有效.

目的 观察电针联合吞咽功能训练对肝豆状核变性患者吞咽障碍的影响.方法 将63例患者随机分成电针综合治疗组(电针联合吞咽功能训练)和单纯吞咽功能训练组,15d为1个疗程,每组治疗2个疗程.应用洼田饮水试验和视频透视吞咽功能检查进行疗效评价.结果 两组患者治疗后洼田饮水试验评分显著降低(P＜0.05),视频透视吞咽功能评分显著升高(P＜0.05);电针综合治疗组视频透视吞咽功能评分升高值显著大于单纯吞咽功能训练组(P＜0.05).电针综合治疗组临床疗效明显优于单纯吞咽功能训练组(P＜0.05).结论 电针结合吞咽功能训练综合治疗能够有效改善肝豆状核变性患者吞咽功能.

目的 探讨中药肝豆汤对肝豆状核变性(WD)动物模型tx小鼠肝脏微量元素铜、锌、铁代谢及ATP7B蛋白表达水平的影响.方法 选择60只tx小鼠随机分为肝豆汤治疗组(n=25)和模型组(n=35),24只正常野生型DL小鼠为对照组.治疗组给予肝豆汤灌胃,模型组给予生理盐水灌胃,对照组仅常规饲养.检测各组小鼠不同月龄肝脏铜、锌、铁微量元素含量及肝组织ATP7B蛋白表达水平.微量元素检测采用原子吸收分光光度法;ATP7B蛋白表达水平分别采用免疫组化、Western blot法.结果 模型组和治疗组较同月龄对照组肝脏铜含量明显升高(P均＜0.01),但治疗组铜含量显著低于同月龄模型组(P均＜0.01),模型组和治疗组在5月龄内均表现出随月龄增加铜含量增加(P均＜ 0.01).模型组锌含量较同月龄对照组升高,但与治疗组差异无统计学意义,同时治疗组较模型组锌含量升高与铜含量降低表现出方向一致性,但并不呈现线性相关.模型组铁含量较对照组偏高,治疗组较同月龄模型组铁含量下降(P＜0.01,P＜0.05).ATP7B蛋白主要表达在细胞质.模型组ATP7B蛋白表达水平随月龄增加而上调,治疗组较同月龄模型组表达上调(P均＜0.05).结论 肝豆汤可以降低tx小鼠肝脏细胞内铜含量,同时升高锌含量,降低铁含量;肝豆汤可上调ATP7B蛋白的表达,从而促进过量铜离子从胆汁中排出,减少铜的蓄积.