medRxiv - Neurology最新文献

{"title":"Beyond pain: Using Unsupervised Machine Learning to Identify Phenotypic Clusters of Small Fiber Neuropathy","authors":"Peyton J Murin, Vivian D Gao, Stefanie Geisler","doi":"10.1101/2024.09.09.24313341","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313341","url":null,"abstract":"Background and Objectives: Small fiber neuropathy (SFN) is characterized by dysfunction and loss of peripheral unmyelinated and thinly myelinated nerve fibers, resulting in a phenotype that includes varying combinations of somatosensory and dysautonomia symptoms, which can be profoundly disabling and lead to decreased quality of life. Treatment aimed mainly at pain reduction, which may not target the underlying pathophysiology, is frequently ineffective. Another impediment to the effective management of SFN may be the significant between-patient heterogeneity. Accordingly, we launched this study to gain insights into the symptomatic variability of SFN and determine if SFN patients can be sub-grouped based on clinical characteristics.\u0000Methods: To characterize the phenotype and investigate how patients with SFN differ from those with large fiber involvement, 105 patients with skin-biopsy proven SFN and 45 with mixed fiber neuropathy (MFN) were recruited. Using unsupervised machine learning, SFN patients were clustered based upon symptom concurrence and severity. Demographics, clinical data, symptoms, and skin biopsy- and laboratory findings were compared between the groups.\u0000Results: MFN- as compared to SFN patients, were more likely to be male, older, had a lower intraepidermal nerve fiber density at the ankle and more frequent abnormal immunofixation. Beyond these differences, symptom prevalence and intensities were similar in the two cohorts. SFN patients comprised three distinct phenotypic clusters, which differed significantly in symptom severity, co-occurrence, localization, and skin biopsy findings. Only one subgroup, constituting about 20% of the patient population, was characterized by intense neuropathic pain, which was always associated with several other SFN symptoms of similarly high intensities. A pauci-symptomatic cluster comprised patients who experienced few SFN symptoms, generally of low to moderate intensity. The largest cluster was characterized by intense fatigue, myalgias and subjective weakness, but lower intensities of burning pain and paresthesia. Discussion: This data-driven study introduces a new approach to subgrouping patients with SFN. Considering both neuropathic pain and pernicious symptoms beyond pain, we identified three clusters, which may be related to distinct pathophysiological mechanisms. Although additional validation will be required, our findings represent a step towards stratified treatment approaches and, ultimately, personalized treatment.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197354","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}

{"title":"Management of Dementia in a Resource-Constrained Sub-Saharan African Setting: Outcome of a Retrospective Survey of Clinical Practice in the Only Neuropsychiatric Facility in Northeastern Nigeria.","authors":"Ibrahim Abdu Wakawa, Chiadi Onyike, Mahmoud Bukar Maina","doi":"10.1101/2024.09.09.24313311","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313311","url":null,"abstract":"Introduction: Dementia prevalence is rising in sub-Saharan Africa due to a combination of factors, including population growth and aging. In resource-constrained settings, such as Northeastern Nigeria, dementia management is challenged by delayed diagnosis and limited specialist care. This study evaluates the burden of dementia and its management at the Federal Neuropsychiatric Hospital Maiduguri (FNHM), the only neuropsychiatric facility in Northeastern Nigeria. The study aims to provide insights into current dementia trends and practices and identify key areas for improvement. Methods: A retrospective analysis of patient records at FNPH Maiduguri was conducted, including patients aged 60 and above diagnosed with dementia between 1999 and 2023. Data on patient demographics, dementia subtypes, comorbidities, symptoms, diagnostic investigations, and treatment modalities were analysed. Results: The Available record from the hospital health records register showed that the total number of diagnosed cases of dementia in the FNHM is 1,216 cases with a male predominance (56%). Alzheimers disease was the most common subtype (60.5%), followed by vascular dementia (24.5%). Hypertension was the most frequently reported comorbidity (41.6%). Cognitive symptoms, particularly memory loss, were reported in all cases, while behavioural symptoms, such as agitation and hallucinations, were reported in some cases. The most commonly administered treatments included cognitive enhancers (donepezil), supplements (gingko biloba), and non-drug therapies (psychoeducation). However, 70.9% of patients were lost to follow-up, highlighting a critical gap in long-term care. Conclusion: The increasing burden of dementia at the only neuropsychiatric facility in Northeastern Nigeria highlights the urgent need for investments and targeted interventions. Enhancing patient engagement, strengthening follow-up systems, and expanding diagnostic and treatment capacities will improve care outcomes and address the growing demands for dementia management in this underserved region.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142225074","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}

{"title":"The causal relationship between cathepsins and multiple sclerosis : a mendelian randomization study","authors":"Haining Lin, Yuqing Shi, Huazhong Xiong, Dongyi Wang, Shilei Wang, Hailan Kang, ZiXu Wang, Zeyu Wang, Jixiang Ren","doi":"10.1101/2024.09.05.24313125","DOIUrl":"https://doi.org/10.1101/2024.09.05.24313125","url":null,"abstract":"Background Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease. Although some evidence indicates the potential involvement of cathepsins in the MS process, the precise nature of this involvement remains uncertain. The objective of this study was to ascertain whether there is a causal relationship between cathepsins and MS. Methods This study aimed to examine the relationship between nine cathepsins and MS, incorporating heterogeneity and sensitivity analyses into the study design. The MR study was reported according to the STROBE-MR checklist. Results The MR analysis revealed a causal relationship between cathepsin H and MS (IVW: P=0.036, OR=1.095, 95% CI=1.006-1.192); and an inverse causal relationship between cathepsin E and MS (IVW: P=0.031, OR=1.043, 95% CI=1.004-1.083). Conclusion Genetically predicted risk of developing MS was associated with increased cathepsin H, whereas elevated cathepsin E was associated with developing MS, and their causal relationships were both unidirectional.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197346","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}

{"title":"Safety and Outcomes of Valproic Acid in Subarachnoid Hemorrhage Patients: A Retrospective Study","authors":"Matthew Cobler-Lichter, Kushak Suchdev, Hayley Tatro, Ava Cascone, Joanna Yang, Janice Weinberg, Mohamad K Abdalkader, Hormuzdiyar H Dasenbrock, Charlene J Ong, Anna Cervantes-Arslanian, David Greer, Thanh N Nguyen, Ali Daneshmand, David Y Chung","doi":"10.1101/2024.09.09.24313246","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313246","url":null,"abstract":"Background and Purpose: Animal studies have suggested that valproic acid (VPA) is neuroprotective in aneurysmal subarachnoid hemorrhage (SAH). Potential mechanisms include an effect on cortical spreading depolarizations (CSD), apoptosis, blood–brain barrier integrity, and inflammatory pathways. However, the effect of VPA on SAH outcomes in humans has not been investigated. Methods: We conducted a retrospective analysis of 123 patients with nontraumatic SAH. Eighty–seven patients had an aneurysmal source and 36 patients did not have a culprit lesion identified. We used stepwise logistic regression to determine the association between VPA and the following: delayed cerebral ischemia (DCI), radiographic vasospasm, and discharge modified Rankin Scale (mRS) score > 3. Results: All 18 patients who received VPA underwent coil embolization of their aneurysm. VPA use did not have a significant association with DCI on adjusted analysis (Odds Ratio, OR = 1.07, 95% CI: 0.20 – 5.80). The association between VPA use and vasospasm was OR = 0.64 (0.19 – 1.98) and discharge mRS > 3 was OR = 0.45 (0.10 – 1.64). Increased age (OR = 1.04, 1.01 – 1.07) and Hunt and Hess (HH) grade > 3 (OR = 14.5, 4.31 – 48.6) were associated with an increased likelihood for poor discharge outcome (mRS > 3). Younger age (OR = 0.96, 0.93 – 0.99), mFS score = 4 (OR = 4.14, 1.81 – 9.45), and HH grade > 3 (OR = 2.92, 1.11 – 7.69) were all associated with subsequent development of radiographic vasospasm. There were no complications associated with VPA administration. Conclusion: We did not observe an association between VPA and the rate of DCI. There may have been a protective association on discharge outcome and radiographic vasospasm that did not reach statistical significance. We found that VPA use was safe and is plausible to be used in a population of SAH patients who have undergone endovascular treatment of their aneurysm. Larger, prospective studies are needed to determine the effect of VPA on outcome after SAH.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197347","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}

{"title":"Dynamic cerebral autoregulation during and 3 months after endovascular treatment in large-vessel occlusion stroke","authors":"Adam Vittrup Heiberg, Troels Gil Lukassen, Thomas Clement Truelsen, Henrik Gutte Borgwardt, Goetz Benndorf, Christine Sølling, Henrik Winther Schytz, Kirsten Møller, Klaus Hansen, Helle Klingenberg Iversen","doi":"10.1101/2024.09.05.24313166","DOIUrl":"https://doi.org/10.1101/2024.09.05.24313166","url":null,"abstract":"<strong>Background</strong> Acute ischemic stroke caused by large-vessel occlusion is effectively treated by endovascular treatment (EVT). However, treatment could be further refined by improved understanding of the underlying pathophysiology, including dynamic cerebral autoregulation (dCA). Near-infrared spectroscopy (NIRS) requires virtually no setup time and enables dCA investigation during EVT by measuring dynamic concentration in cortical oxygenated hemoglobin (OxyHb) continuously.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"5 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197357","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}

{"title":"Distinct brain atrophy progression subtypes underlie phenoconversion in isolated REM sleep behaviour disorder","authors":"Stephen Joza, Aline Delva, Christina Tremblay, Andrew Vo, Marie Filiatrault, Max Tweedale, John-Paul Taylor, John T. O’Brien, Michael Firbank, Alan Thomas, Paul C. Donaghy, Johannes Klein, Michele Hu, Petr Dusek, Stanislav Marecek, Zsoka Varga, Stephane Lehericy, Isabelle Arnulf, Marie Vidailhet, Jean-Christophe Corvol, Jean-François Gagnon, Ronald B. Postuma, Alain Dagher, Richard Camicioli, Howard Chertkow, Simon Lewis, Elie Matar, Kaylena A. Ehgoetz Martens, Lachlan Churchill, Michael Sommerauer, Sinah Röttgen, Per Borghammer, Karoline Knudsen, Allan K. Hansen, Dario Arnaldi, Beatrice Orso, Pietro Mattioli, Luca Roccatagliata, Oury Monchi, Shady Rahayel","doi":"10.1101/2024.09.05.24313131","DOIUrl":"https://doi.org/10.1101/2024.09.05.24313131","url":null,"abstract":"<strong>Background</strong> Synucleinopathies manifest as a spectrum of disorders that vary in features and severity, including idiopathic/isolated REM sleep behaviour disorder (iRBD) and dementia with Lewy bodies. Patterns of brain atrophy in iRBD are already reminiscent of what is later seen in overt disease and are related to cognitive impairment, being associated with the development of dementia with Lewy bodies. However, how brain atrophy begins and progresses remains unclear.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197364","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}

{"title":"The patient voice: valproate, topiramate and MHRA regulation","authors":"Jane Hanna, Faye Waddams, Sarah Jones, Rachel Arkell, Heather Angus-Leppan","doi":"10.1101/2024.09.06.24313040","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313040","url":null,"abstract":"Valproate and topiramate use are increasingly restricted by government regulations, such as those of the MHRA. The views of people with epilepsy and their families affected by these have been little studied. This qualitative study examines 19 people with epilepsy and their views on the restrictions, and examines the thematic outcomes of these views – in terms of direct damage of avoiding valproate or topiramate (including SUDEP), missed opportunities and disruption of belief systems. Recommendations to align the regulations to human rights and true informed decision making are made.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197399","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}

{"title":"Feasibility and pilot efficacy of self-applied home-based cognitive training and brain stimulation","authors":"Merle Rocke, Anna E. Fromm, Nora Jansen, Friederike Thams, Catalina Trujillo-Llano, Ulrike Grittner, Daria Antonenko, Agnes Flöel","doi":"10.1101/2024.09.06.24313172","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313172","url":null,"abstract":"<strong>Objective</strong> To assess whether home-based, self-applied cognitive training combined with tDCS in older adults is feasible (primary), acceptable, and effective (secondary).","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197359","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}

{"title":"Metabolomic and Lipidomic Analysis of Manganese-Associated Parkinsonism: a Case-Control Study in Brescia, Italy","authors":"Freeman Lewis, Daniel Shoieb, Somaiyeh Azmoun, Elena Colicino, Yan Jin, Jinhua Chi, Haiwei Gu, Donatella Placidi, Alessandro Padovani, Andrea Pilotto, Fulvio Pepe, Marinella Turla, Patrizia Crippa, Xuexia Wang, Roberto G Lucchini","doi":"10.1101/2024.09.04.24313002","DOIUrl":"https://doi.org/10.1101/2024.09.04.24313002","url":null,"abstract":"<strong>Background and Objectives</strong> Excessive Manganese (Mn) exposure is neurotoxic and can cause Mn-Induced Parkinsonism (MnIP), marked by cognitive and motor dysfunction. Although metabolomic and lipidomic research in Parkinsonism (PD) patients exists, it remains limited. This study hypothesizes distinct metabolomic and lipidomic profiles based on exposure status, disease diagnosis, and their interaction.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197388","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}

{"title":"Development and validation of domain-specific clinical prediction models of post-stroke cognitive impairment","authors":"Andrea Kusec, Kym IE Snell, Nele Demeyere","doi":"10.1101/2024.09.06.24313196","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313196","url":null,"abstract":"<strong>Background</strong> Post-stroke cognitive impairment (PSCI) is highly prevalent across multiple cognitive domains. Individualised PSCI prognosis has mainly been researched using global cognitive outcomes. Here, we develop and externally validate clinical prediction models for overall and domain-specific PSCI, including language, memory, attention, executive function, numeracy, and praxis.","PeriodicalId":501367,"journal":{"name":"medRxiv - Neurology","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197360","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}