Annals of Clinical and Translational Neurology最新文献

{"title":"Neuromuscular transmission deficits in patients with CMT and ClC-1 inhibition in CMT animal models","authors":"Thomas Skjærlund Grønnebæk,&nbsp;Helga Haahr-Lillevang,&nbsp;Martin Skov,&nbsp;Kristina Kelly,&nbsp;Nathan R. Kerr,&nbsp;Jose A. Viteri,&nbsp;Andrea Jaworek,&nbsp;Amy Bartlett,&nbsp;Jane Bold,&nbsp;John Hutchison,&nbsp;Jorge Quiroz,&nbsp;Hatice Tankisi,&nbsp;Thomas Holm Pedersen,&nbsp;Henning Andersen,&nbsp;William David Arnold","doi":"10.1002/acn3.52252","DOIUrl":"10.1002/acn3.52252","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Charcot–Marie Tooth (CMT) is a hereditary neuropathy characterized by muscle weakness and fatigue with no approved therapies. Preclinical studies implicate neuromuscular junction (NMJ) transmission deficits in muscle dysfunction in CMT. This study aimed to evaluate NMJ function in patients with CMT types 1 and 2, and to determine whether enhancing NMJ transmission can improve muscle function in preclinical CMT models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, an observational study involving single fiber electromyography (SFEMG) and clinical testing in patients with CMT 1 and 2 and healthy controls (HC) was conducted. Next, preclinical studies examined muscle function, specifically nerve-stimulated muscle force after partially inhibiting ClC-1 chloride channels with the novel small molecule NMD670.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-one CMT patients (46.4 ± 14.4 years) and 10 HC (43.3 ± 12.7 years) were enrolled. SFEMG jitter (NMJ variability) was higher [median (range)] in the CMT patients [56 μs (35; 197 μs)] vs. HC [29 μs (19; 36 μs)], (<i>p</i> &lt; 0.05). Blocking (NMJ failure) was higher in the CMT patients (13.4% (0.0; 90.9%)) vs. HC (0.0% (0.0; 4.5%)), (<i>p</i> &lt; 0.05). In CMT, jitter and blocking correlated inversely with muscle strength, mobility, balance, and endurance. In CMT 1A and 2D mice, NMD670 increased both peak force and contractile endurance in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our study suggests that NMJ dysfunction contributes to muscle dysfunction in patients with CMT 1 and 2. Furthermore, our preclinical data provide proof-of-mechanism for recovery of muscle function with ClC-1 inhibition in CMT mouse models. Collectively, these findings suggest that targeting NMJ dysfunction with ClC-1 inhibitors could enhance muscle function in CMT patients, warranting further clinical trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"320-331"},"PeriodicalIF":4.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis","authors":"Eva A. Krijnen,&nbsp;Hansol Lee,&nbsp;Samantha Noteboom,&nbsp;Florence L. Chiang,&nbsp;Martijn D. Steenwijk,&nbsp;Menno M. Schoonheim,&nbsp;Eric C. Klawiter,&nbsp;Susie Y. Huang","doi":"10.1002/acn3.52237","DOIUrl":"10.1002/acn3.52237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To quantify alterations in soma and neurite density imaging measures within and surrounding cortical lesions in people with multiple sclerosis using in vivo high-gradient diffusion MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this cross-sectional study, 41 people with multiple sclerosis and 34 age- and sex-matched healthy controls underwent 3 T high-gradient diffusion MRI. Cortical lesions were segmented on artificial intelligence-enabled double inversion recovery images. “Inner” and “outer” perilesional layers were segmented as two expanding shells of 2 mm surrounding a cortical lesion. Intracellular, intra-neurite, and extracellular signal fractions and apparent soma radius were estimated in (peri)lesional and normal-appearing cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cortical lesions were present in all people with multiple sclerosis with a median count of 8 [IQR 5–18] and total volume of 0.16 [0.09–0.46 mL]. People with multiple sclerosis (mean 0.27 ± 0.03) showed lower normalized cortical volumes compared to healthy controls (0.30 ± 0.02). Compared to healthy controls (mean 0.58 ± 0.028), normal-appearing cortex in multiple sclerosis (0.57 ± 0.034) showed lower intra-cellular signal fraction. Cortical lesions (0.49 ± 0.089) exhibited lower intra-cellular signal fractions compared to perilesional (“inner”: 0.55 ± 0.049, “outer”: 0.55 ± 0.039) and normal-appearing cortex, demonstrating a gradation of change. The soma radius varied significantly across cortices, becoming smaller when moving outward from cortical lesions (cortical lesions: 10.38 ± 0.209 μm, “inner” layer: 10.19 ± 0.140 μm, “outer” layer: 10.07 ± 0.149 μm, normal-appearing cortex: 9.99 ± 0.127 μm).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Cortical cell body loss in multiple sclerosis is most pronounced in cortical lesions and also present in normal-appearing cortex. Gradients of diffusion microstructural alterations moving outward from cortical lesions toward normal-appearing cortex highlight the potential of high-gradient diffusion MRI to identify both focal and diffuse cortical pathology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"4-16"},"PeriodicalIF":4.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise as an abortive treatment for cluster headaches: Insights from a large patient registry","authors":"Mi-Kyoung Kang,&nbsp;Yooha Hong,&nbsp;Soo-Jin Cho","doi":"10.1002/acn3.52263","DOIUrl":"10.1002/acn3.52263","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to evaluate the potential of exercise as an abortive treatment for patients with cluster headache (CH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional survey was conducted among CH patients at a single center in Korea. Demographics and headache characteristics were compared between those who found exercise effective and those who did not. We analyzed the type and intensity of exercise used. Headache improvement was measured as intensity reduction, with ≥50% improvement defined as a reduction in intensity by half or more. Exercise intensity was categorized as moderate (“possible to talk but hard to sing”) or high (“difficult to speak without pausing”). Case reports of patients exercising during CH attacks were also reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 167 registered CH patients, 136 patients provided responses about exercise during CH attacks; 39.7% (54/136) attempted exercise as treatment. Improvement was reported by 42.6% (23/54), with ≥50% improvement in 29.6% (16/54). Patients who found exercise effective had lower Headache Impact Test-6 scores. Effective exercises included running (39.1%), squats (30.4%), and stair climbing (21.7%), with high-intensity exercise effective for 52.2% and moderate intensity for 43.5%. Among the 23 patients who benefited from exercise, 18 reported their most effective treatment, which were exercise alone in 50% (9/18), followed by exercise with triptans in 38.9% (7/18), and oxygen with or without triptans in 5.5% (1/18).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>About 40% of CH patients attempted exercise for acute CH management, with 30% experiencing over 50% improvement. While evidence is limited, exercise may help alleviate headaches and could be considered an adjunctive treatment for CH attacks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"149-157"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of combined low-dose rituximab regimen for chronic inflammatory demyelinating polyradiculoneuropathy","authors":"Ying Du,&nbsp;Qi Yan,&nbsp;Chuan Li,&nbsp;Wenping Zhu,&nbsp;Chao Zhao,&nbsp;Yunfeng Hao,&nbsp;Lin Li,&nbsp;Dan Yao,&nbsp;Xuan Zhou,&nbsp;Ying Li,&nbsp;Yuting Dang,&nbsp;Rong Zhang,&nbsp;Lin Han,&nbsp;Yuanyuan Wang,&nbsp;Tao Hou,&nbsp;Juan Li,&nbsp;Hailin Li,&nbsp;Panpan Jiang,&nbsp;Pei Wang,&nbsp;Fenying Chen,&nbsp;Tingge Zhu,&nbsp;Juntong Liu,&nbsp;Shuyu Liu,&nbsp;Lan Gao,&nbsp;Yingjun Zhao,&nbsp;Wei Zhang","doi":"10.1002/acn3.52270","DOIUrl":"10.1002/acn3.52270","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine the efficacy and safety of combined low-dose rituximab with conventional therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Total 73 patients with CIDP were enrolled for the retrospective cohort study, and divided into conventional first-line therapy cohort (<i>n</i> = 40) and combined low-dose rituximab (100 mg per infusion) cohort (<i>n</i> = 33). The outcome measures include scores of I-RODS, mRS, INCAT, ONLS, TSS, and COMPASS 31 scale at baseline and regular four visits (4, 16, 28, and 52 weeks), as well as proportion of favorable response and outcome, corticosteroids dosage, and deterioration occurrence during follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to conventional therapy cohort, combined rituximab cohort presented better improvements and higher proportion of favorable response in scales assessments at each visit, as well as significantly reduced corticosteroids dosage and deterioration occurrence during the follow-up. Analyses of subgroups showed better improvements in both typical CIDP and CIDP variants in combined rituximab cohort than those in conventional therapy cohort, but had no differences between each other. Early initiating combined rituximab regimen (&lt;10 weeks) showed better improvements than delayed initiation (≥10 weeks) at the first three visits within 28 weeks, while had no difference in favorable prognoses at the last visit of 52 weeks after once reinfusion. No rituximab correlated serious adverse events were reported in our patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our simplified regimen of combined low-dose rituximab has been firstly demonstrated for the better efficacy and safety than conventional therapy in CIDP treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"180-191"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter hyperintensities and cholinergic degeneration as Lewy body disease","authors":"Sungwoo Kang,&nbsp;Seun Jeon,&nbsp;Yeoju Kim,&nbsp;Su-Hee Jeon,&nbsp;Minsun Choi,&nbsp;Young-gun Lee,&nbsp;Mijin Yun,&nbsp;Byoung Seok Ye","doi":"10.1002/acn3.52257","DOIUrl":"10.1002/acn3.52257","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Although basal forebrain (BF) cholinergic degeneration and white matter hyperintensities (WMHs) are important in neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), their relationships with dopaminergic degeneration and clinical manifestations remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 407 patients with cognitive impairment meeting the diagnostic criteria for AD, DLB, or both (AD+DLB) were assessed. All participants underwent 3T MRI, dopamine transporter (DAT) positron emission tomography, neuropsychological tests, and assessments for parkinsonism, cognitive fluctuation, visual hallucination, and rapid eye movement sleep behavior disorder (RBD). General linear and logistic regression models were used to investigate the relationships among BF volume, DAT uptake in the anterior caudate (DAT-AC), WMH volumes in anterior, posterior, periventricular, and deep regions, and clinical manifestations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DAT-AC was positively associated with BF volume and negatively associated with anterior periventricular WMH volume, but not with deep WMHs. Both deep and periventricular WMHs volumes were associated with hypertension and the number of microbleeds and lacunae. Lower BF volume and DAT-AC were independently associated with increased risk of cognitive fluctuation and visual hallucination, whereas lower DAT-AC was additionally associated with increased risk of RBD and greater parkinsonian severity. Both lower BF volume and DAT-AC were independently associated with widespread cognitive impairment, whereas higher anterior periventricular WMH volume was associated with executive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>BF cholinergic degeneration and anterior periventricular WMHs are closely associated with dopaminergic degeneration. Anterior periventricular WMHs may represent axonal alterations caused by the interplay between Lewy body-related degeneration and vascular pathologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"97-109"},"PeriodicalIF":4.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laser interstitial thermal therapy in the management of bottom-of-sulcus dysplasia-related epilepsy","authors":"Bowen Yang,&nbsp;Chao Zhang,&nbsp;Xiu Wang,&nbsp;Baotian Zhao,&nbsp;Jiajie Mo,&nbsp;Weiyuan Luo,&nbsp;Xiaoqiu Shao,&nbsp;Jianguo Zhang,&nbsp;Kai Zhang,&nbsp;Wenhan Hu","doi":"10.1002/acn3.52258","DOIUrl":"10.1002/acn3.52258","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study assessed the efficacy and safety of magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) versus open surgery (OS) for the treatment of patients with bottom-of-sulcus dysplasia (BOSD)-related epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-two patients underwent MRgLITT, while 39 underwent OS. Postoperative seizure-free rates were analyzed using Kaplan–Meier curves. The removal ratio, which represents the extent of damage, was calculated based on preoperative lesion volume and postoperative removal volume. Other outcomes, including adverse events, operative time, and hospital stay, were also compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Kaplan–Meier curves indicated the seizure-free rates were comparable between the MRgLITT group (90.9%, 26.5 [23.0, 35.1] months) and OS group (89.7%, 25.2 [16.2, 34.6] months) at the final follow-up (<i>p</i> = 0.901, log-rank test). The removal ratio of MRgLITT (1.3 [1.1, 1.7]) was significantly lower (<i>p</i> = 0.007) than that of OS (5.8 [3.6, 8.5]). A comparison of postoperative neurological deficits, infection rates, and fever rates revealed no significant differences between MRgLITT and OS groups. The operative time (hours) of MRgLITT (3.0, [2.1, 4.9]) was significantly shorter (<i>p</i> = 0.007) than that of OS (3.5 [3.0, 4.5]). The hospital stay (days) after MRgLITT (6 [5.0, 7.5]) was significantly shorter (<i>p</i> &lt; 0.001) than that of OS (11.0 [9.0, 13.5]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>MRgLITT has advantages over OS, including comparable seizure control and adverse event profiles, along with reduced removal ratios, shorter operative time, and shorter hospital stays.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"110-120"},"PeriodicalIF":4.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating ITM2B-associated ataxia in a Taiwanese cerebellar ataxia cohort","authors":"Shih-Yu Fang,&nbsp;Cheng-Tsung Hsiao,&nbsp;Kang-Yang Jih,&nbsp;Yu-Sheun Tsai,&nbsp;Kuan-Lin Lai,&nbsp;Cheng-Ta Chou,&nbsp;Yi-Chu Liao,&nbsp;Yi-Chung Lee","doi":"10.1002/acn3.52265","DOIUrl":"10.1002/acn3.52265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The genetic causes of a significant number of patients with cerebellar ataxia remain unsolved. Variations in the <i>ITM2B</i> gene, typically linked to dominantly inherited dementia, can sometimes present with cerebellar ataxia as an early symptom. This study aims to investigate the role of <i>ITM2B</i> variations in a Taiwanese cohort with unsolved cerebellar ataxia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic analysis of <i>ITM2B</i> was performed in 212 unrelated Taiwanese patients with unsolved cerebellar ataxia. Eight short tandem repeat markers flanking <i>ITM2B</i> were genotyped to analyze the associated haplotype. Affected carriers underwent comprehensive clinical evaluations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A heterozygous <i>ITM2B</i> variant, c.800G&gt;T (p.(Ter267LeuextTer11)), was identified in three patients. Haplotype analysis demonstrated a shared haplotype linked to this variant in the three families, suggesting a founder effect. The three probands and additional three affected relatives presented with cerebellar ataxia and unsteady gait with an average onset age of 43.2 years. Most participants had no cognitive impairment at symptom onset but experienced memory decline, oculomotor disturbances, lower limb spasticity, and extensor plantar responses within 2–5 years. Magnetic resonance imaging and spectroscopy revealed progressive extension of white matter hyperintensity over periventricular and subcortical regions, subtle hippocampal atrophy, preserved cerebellar volumes, and decreased N-acetylaspartate/creatine ratio over the vermis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p><i>ITM2B</i> mutations accounted for 1.4% of cerebellar ataxia cases in the Taiwanese cohort, with patients carrying <i>ITM2B</i> c.800G&gt;T descending from a common ancestor. This study underscores the importance of considering <i>ITM2B</i> variations as a potential cause of cerebellar ataxia, even in the absence of dementia at the initial presentation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"158-168"},"PeriodicalIF":4.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral hypoperfusion reduces tau accumulation","authors":"Ghupurjan Gheni,&nbsp;Mitsuru Shinohara,&nbsp;Masami Masuda-Suzukake,&nbsp;Akihiko Shindo,&nbsp;Atsushi Watanabe,&nbsp;Kaori Kawai,&nbsp;Guojun Bu,&nbsp;Hidekazu Tomimoto,&nbsp;Masato Hasegawa,&nbsp;Naoyuki Sato","doi":"10.1002/acn3.52247","DOIUrl":"10.1002/acn3.52247","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) often coexists with cerebrovascular diseases. However, the impact of cerebrovascular diseases such as stroke on AD pathology remains poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study examines the correlation between cerebrovascular diseases and AD pathology. The research was carried out using clinical and neuropathological data collected from the National Alzheimer's Coordinating Center (NACC) database and an animal model in which bilateral common carotid artery stenosis surgery was performed, following the injection of tau seeds into the brains of wild-type mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis of the NACC database suggests that clinical stroke history and lacunar infarcts are associated with lower neurofibrillary tangle pathology. An animal model demonstrates that chronic cerebral hypoperfusion reduces tau pathology, which was observed in not only neurons but also astrocytes, microglia, and oligodendrocytes. Furthermore, we found that astrocytes and microglia were activated in response to tau pathology and chronic cerebral hypoperfusion. Additionally, cerebral hypoperfusion increased a lysosomal enzyme, cathepsin D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These data together indicate that cerebral hypoperfusion reduces tau accumulation likely through an increase in microglial phagocytic activity towards tau and an elevation in degradation through cathepsin D. This study contributes to understanding the relationship between tau pathology and cerebrovascular diseases in older people with multimorbidity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 1","pages":"69-85"},"PeriodicalIF":4.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain lesion characteristics in Chinese multiple sclerosis patients: A 7-T MRI cohort study","authors":"Lei Su,&nbsp;Zhe Zhang,&nbsp;Chenyang Gao,&nbsp;Ai Guo,&nbsp;Mengting Zhang,&nbsp;Xiaoyu Shi,&nbsp;Xinyao Liu,&nbsp;Tian Song,&nbsp;Wangshu Xu,&nbsp;Huabing Wang,&nbsp;Joseph Kuchling,&nbsp;Jing Jing,&nbsp;De-Cai Tian,&nbsp;Yaou Liu,&nbsp;Yunyun Duan,&nbsp;Friedemann Paul,&nbsp;Fu-Dong Shi","doi":"10.1002/acn3.52256","DOIUrl":"10.1002/acn3.52256","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Prevalence, susceptibility genes, and clinical and radiological features may differ across different ethnic groups of multiple sclerosis (MS). We aim to characterize brain lesions in Chinese patients with MS by use of 7-T MRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MS participants were enrolled from the ongoing China National Registry of Neuro-Inflammatory Diseases (CNRID) cohort. 7-T MRI of the brain was performed. Each lesion was evaluated according to a standardized procedure. Central vein sign (CVS) and paramagnetic rim lesions were identified. The characteristics of lesions at patient-level and at lesion-level from previous 7-T MRI literature were also summarized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 120 MS patients. Their mean (SD) age was 34.6 (9.4) years. The female-to-male ratio was 1.7:1 and mean disease duration of patients with MS was 5.5 ± 6.1 years. The median EDSS score was 2 (range, 0–8). A total of 8502 lesions were identified with a median lesion count of 45 (IQR, 18–90) (range, 2–370). The median (IQR) percentage for these special locations were as follows: cortical lesions (CLs) 2.7% (0%–5.7%), juxtacortical lesions 16.2% (7.8%–25.7%), periventricular lesions 30.2% (17.2%–38.7%), and infratentorial lesions 5.8% (0.4%–11.9%). CLs occurred in 70 (58%) patients, accounting for only 443 (5%) of the total lesions. Out of the 443 CLs, 309 (69.8%) were leukocortical lesions. CVS appeared in 5392 (63%) lesions from 117 (98%) patients. 1792 (21%) lesions and 104 (87%) patients exhibited a paramagnetic rim.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our study elaborated on the lesion features of Chinese patients with MS by use of 7-T MRI. Lesion burden is heavy in Chinese patients with MS. The median lesion count and proportion of PRL are high. The reported heavy lesion burden calls for ramping up regional and global efforts to care for MS patients. The management and research of Chinese population with MS needs to be further strengthened.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"12 2","pages":"300-310"},"PeriodicalIF":4.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of DL-3-N-butylphthalide in the treatment of ischemic poststroke aphasia: A randomized clinical trial","authors":"Jing Tian,&nbsp;Peng Yang,&nbsp;Jianing Yang,&nbsp;Rui Wang,&nbsp;Biyi Zhou,&nbsp;Kun Zhang,&nbsp;Yanying Zhao,&nbsp;Binbin Wang,&nbsp;Lijuan Liu,&nbsp;Ruomeng Chen,&nbsp;Haoran Wu,&nbsp;Ruihan Miao,&nbsp;Li Guo,&nbsp;Xiaoyun Liu","doi":"10.1002/acn3.52238","DOIUrl":"10.1002/acn3.52238","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Poststroke aphasia (PSA) has a high prevalence and requires a long recovery period, severely impairing life and work. Its existing behavioral interventions, principally speech and language therapy, are limited by numerous factors. The aims of this study are to evaluate the efficacy and safety of DL-3-N-butylphthalein (NBP) and explore its mechanism in the treatment of ischemic PSA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients hospitalized in the Second Hospital of Hebei Medical University in China were randomly administered NBP soft capsules or placebo orally for 6 months from July 1, 2021, to February 25, 2023. Language skills were assessed using the Western Aphasia Battery-Aphasia Quotient (WAB-AQ). We collected plasma samples and detected neurotransmitters by liquid chromatography-mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 118 out of 124 patients were included in the outcome analysis. Compared with the control group, AQ values in the NBP group significantly improved at 6 months (<i>U</i> = 1187.5, <i>p</i> = 0.003). After eliminating baseline interference, NBP treatment was independently associated with the 6-month AQ improvement [mean difference (MD) 0.106, 95% confidence interval (CI) 0.018, 0.195, <i>p</i> = 0.019]. We observed no statistically significant difference between the groups in abnormal liver function at 1 month [relative risk (RR) 1.07, 95% CI 0.89, 1.28] and 6 months [RR 0.99, 95% CI 0.86, 1.42]. Statistically significant differences were observed in tyrosine (<i>p</i> = 0.043) and 5-hydroxytryptophan (<i>p</i> = 0.041) between the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>NBP treatment might promote the recovery of WAB-AQ in patients with ischemic PSA by increasing levels of monoamine neurotransmitters.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 12","pages":"3300-3309"},"PeriodicalIF":4.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}