Pub Date : 2024-08-06DOI: 10.1016/j.jns.2024.123172
Background
Highly active (HA) relapsing remitting multiple sclerosis (RRMS) is associated with frequent relapses and high burden of disease/disability. Natalizumab is licensed for HA RRMS, including rapidly evolving severe (RES) (≥2 relapses in previous year) and sub-optimally treated (SOT) (≥1 relapse in previous year despite treatment) populations. However, there is limited RCT evidence in the SOT subpopulation.
Objective
To review the non-RCT evidence for natalizumab in SOT HA RRMS.
Methods
Databases were searched to January 2023 for non-randomised studies of natalizumab in HA RRMS. Studies in patients with ≥1 relapse during previous treatment were eligible for inclusion. Meta-analyses were conducted to compare natalizumab with platform and higher efficacy disease-modifying therapies, with sensitivity analysis restricted to studies of low risk of bias.
Results
Included comparative studies (n = 16) showed natalizumab had lower relapse rates, disease activity and MRI (radiological) outcomes compared with platform and higher efficacy therapy. Case series (n = 11) showed natalizumab was associated with high rates of freedom from relapse and clinical/radiological disease activity and reductions in annualised relapse rate and disability progression.
Conclusions
Literature reviewed indicates that natalizumab is more effective than other included treatments for SOT patients. Findings were consistent with studies in the broad HA RRMS population, suggesting that natalizumab may have similar efficacy for SOT and RES HA RRMS.
背景高活动性(HA)复发缓解型多发性硬化症(RRMS)与频繁复发和高疾病/残疾负担有关。纳他珠单抗获准用于HA RRMS,包括快速发展的重症(RES)(前一年复发≥2次)和次优治疗(SOT)(尽管接受了治疗,但前一年复发≥1次)人群。方法检索了截至2023年1月有关纳他珠单抗治疗HA RRMS的非随机研究数据库。符合纳入条件的研究对象为既往治疗期间复发≥1次的患者。结果纳入的比较研究(n = 16)显示,与平台疗法和高效疗法相比,纳他珠单抗的复发率、疾病活动性和MRI(放射学)结果较低。病例系列研究(n = 11)显示,纳他珠单抗的复发率和临床/放射学疾病活动率较高,年复发率和残疾进展率也有所降低。结论综述的文献表明,纳他珠单抗对SOT和RES HA RRMS患者的疗效优于其他治疗方法。研究结果与对广泛的HA RRMS人群的研究结果一致,表明纳他珠单抗对SOT和RES HA RRMS可能具有相似的疗效。
{"title":"Literature review and meta-analysis of natalizumab therapy for the treatment of highly active relapsing remitting multiple sclerosis in the ‘suboptimal therapy’ patient population","authors":"","doi":"10.1016/j.jns.2024.123172","DOIUrl":"10.1016/j.jns.2024.123172","url":null,"abstract":"<div><h3>Background</h3><p>Highly active (HA) relapsing remitting multiple sclerosis (RRMS) is associated with frequent relapses and high burden of disease/disability. Natalizumab is licensed for HA RRMS, including rapidly evolving severe (RES) (≥2 relapses in previous year) and sub-optimally treated (SOT) (≥1 relapse in previous year despite treatment) populations. However, there is limited RCT evidence in the SOT subpopulation.</p></div><div><h3>Objective</h3><p>To review the non-RCT evidence for natalizumab in SOT HA RRMS.</p></div><div><h3>Methods</h3><p>Databases were searched to January 2023 for non-randomised studies of natalizumab in HA RRMS. Studies in patients with ≥1 relapse during previous treatment were eligible for inclusion. Meta-analyses were conducted to compare natalizumab with platform and higher efficacy disease-modifying therapies, with sensitivity analysis restricted to studies of low risk of bias.</p></div><div><h3>Results</h3><p>Included comparative studies (<em>n</em> = 16) showed natalizumab had lower relapse rates, disease activity and MRI (radiological) outcomes compared with platform and higher efficacy therapy. Case series (<em>n</em> = 11) showed natalizumab was associated with high rates of freedom from relapse and clinical/radiological disease activity and reductions in annualised relapse rate and disability progression.</p></div><div><h3>Conclusions</h3><p>Literature reviewed indicates that natalizumab is more effective than other included treatments for SOT patients. Findings were consistent with studies in the broad HA RRMS population, suggesting that natalizumab may have similar efficacy for SOT and RES HA RRMS.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022510X24003071/pdfft?md5=379dd39647af789f9e6f1bf6fc079e7c&pid=1-s2.0-S0022510X24003071-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.jns.2024.123161
Multiple Sclerosis (MS) is a complex neurological disease which prevalence is increasing worldwide. The impact of environmental factors on MS susceptibility has already been defined and highlighted in many previous reports, particularly vitamin D or ultraviolet B light exposure, Epstein–Barr virus (EBV) infection, obesity, and smoking. There is increasing evidence that environmental and lifestyle factors are not only important in triggering MS but are also implicated in MS progression. Low sun exposure and vitamin D deficiency exhibit a strong relationship with disease progression in both animal and human studies. The gestational period seems also to impact long-term disease progression as January's babies had a higher risk of requiring walking assistance than those born in other months. The implication of EBV in neurodegeneration and MS progression was also suggested even though its specific targets and mechanisms are still unclear. Cigarette smoking is correlated with faster clinical progression. The association of obesity and smoking seems to be associated with a faster progression and an increased rate of brain atrophy. Although the effect of air pollution on MS pathogenesis remains not fully understood, exposure to polluted air can stimulate several mechanisms that might contribute to MS severity. People with MS with active disease have an altered microbiota compared to patients in the remission phase. Cardiovascular comorbidities, epilepsy, and depression are also associated with a more severe disability accrual. Knowledge about MS modifiable risk factors of progression need to be incorporated into everyday clinical practice in order to ameliorate disease outcomes.
多发性硬化症(MS)是一种复杂的神经系统疾病,其发病率在全球范围内呈上升趋势。环境因素对多发性硬化症易感性的影响已在以往的许多报告中得到明确和强调,尤其是维生素 D 或紫外线 B 暴露、Epstein-Barr 病毒(EBV)感染、肥胖和吸烟。越来越多的证据表明,环境和生活方式因素不仅是诱发多发性硬化症的重要因素,而且还与多发性硬化症的进展有关。在动物和人体研究中,日晒不足和维生素 D 缺乏与疾病进展有密切关系。妊娠期似乎也会影响疾病的长期发展,因为一月份出生的婴儿比其他月份出生的婴儿需要辅助行走的风险更高。尽管EB病毒的具体靶点和机制尚不清楚,但它对神经变性和多发性硬化症的进展也有影响。吸烟与临床进展加快有关。肥胖和吸烟似乎与进展加快和脑萎缩率增加有关。虽然空气污染对多发性硬化症发病机制的影响仍未完全明了,但暴露于污染的空气中会刺激多种机制,可能会导致多发性硬化症的严重程度。与处于缓解期的多发性硬化症患者相比,处于活动期的多发性硬化症患者的微生物群发生了改变。心血管合并症、癫痫和抑郁症也与更严重的残疾累积有关。需要将有关多发性硬化症可改变病情发展风险因素的知识纳入日常临床实践,以改善疾病预后。
{"title":"Environmental factors related to multiple sclerosis progression","authors":"","doi":"10.1016/j.jns.2024.123161","DOIUrl":"10.1016/j.jns.2024.123161","url":null,"abstract":"<div><p>Multiple Sclerosis (MS) is a complex neurological disease which prevalence is increasing worldwide. The impact of environmental factors on MS susceptibility has already been defined and highlighted in many previous reports, particularly vitamin D or ultraviolet B light exposure, Epstein–Barr virus (EBV) infection, obesity, and smoking. There is increasing evidence that environmental and lifestyle factors are not only important in triggering MS but are also implicated in MS progression. Low sun exposure and vitamin D deficiency exhibit a strong relationship with disease progression in both animal and human studies. The gestational period seems also to impact long-term disease progression as January's babies had a higher risk of requiring walking assistance than those born in other months. The implication of EBV in neurodegeneration and MS progression was also suggested even though its specific targets and mechanisms are still unclear. Cigarette smoking is correlated with faster clinical progression. The association of obesity and smoking seems to be associated with a faster progression and an increased rate of brain atrophy. Although the effect of air pollution on MS pathogenesis remains not fully understood, exposure to polluted air can stimulate several mechanisms that might contribute to MS severity. People with MS with active disease have an altered microbiota compared to patients in the remission phase. Cardiovascular comorbidities, epilepsy, and depression are also associated with a more severe disability accrual. Knowledge about MS modifiable risk factors of progression need to be incorporated into everyday clinical practice in order to ameliorate disease outcomes.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141964202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.jns.2024.123163
Background
Vascular mild cognitive impairment (VMCI) is a transitional condition that may evolve into Vascular Dementia(VaD). Hippocampal volume (HV) is suggested as an early marker for VaD, the role of white matter lesions (WMLs) in neurodegeneration remains debated.
Objectives
Evaluate HV and WMLs as predictive markers of VaD in VMCI patients by assessing: (i)baseline differences in HV and WMLs between converters to VaD and non-converters, (ii) predictive power of HV and WMLs for VaD, (iii) associations between HV, WMLs, and cognitive decline, (iv)the role of WMLs on HV.
Methods
This longitudinal multicenter study included 110 VMCI subjects (mean age:74.33 ± 6.63 years, 60males/50females) from the VMCI-Tuscany Study database. Subjects underwent brain MRI and cognitive testing, with 2-year follow-up data on VaD progression. HV and WMLs were semi-automatically segmented and measured. ANCOVA assessed group differences, while linear and logistic regression models evaluated predictive power.
Results
After 2 years, 32/110 VMCI patients progressed to VaD. Converting patients had lower HV(p = 0.015) and higher lesion volumes in the posterior thalamic radiation (p = 0.046), splenium of the corpus callosum (p = 0.016), cingulate gyrus (p = 0.041), and cingulum hippocampus(p = 0.038). HV alone did not fully explain progression (p = 0.059), but combined with WMLs volume, the model was significant (p = 0.035). The best prediction model (p = 0.001) included total HV (p = 0.004) and total WMLs volume of the posterior thalamic radiation (p = 0.005) and cingulate gyrus (p = 0.005), achieving 80% precision, 81% specificity, and 74% sensitivity. Lower HV were linked to poorer performance on the Rey Auditory-Verbal Learning Test delayed recall (RAVLT) and Mini Mental State Examination (MMSE).
Conclusions
HV and WMLs are significant predictors of progression from VMCI to VaD. Lower HV correlate with worse cognitive performance on RAVLT and MMSE tests.
{"title":"Hippocampal atrophy and white matter lesions characteristics can predict evolution to dementia in patients with vascular mild cognitive impairment","authors":"","doi":"10.1016/j.jns.2024.123163","DOIUrl":"10.1016/j.jns.2024.123163","url":null,"abstract":"<div><h3>Background</h3><p>Vascular mild cognitive impairment (VMCI) is a transitional condition that may evolve into Vascular Dementia(VaD). Hippocampal volume (HV) is suggested as an early marker for VaD, the role of white matter lesions (WMLs) in neurodegeneration remains debated.</p></div><div><h3>Objectives</h3><p>Evaluate HV and WMLs as predictive markers of VaD in VMCI patients by assessing: (i)baseline differences in HV and WMLs between converters to VaD and non-converters, (ii) predictive power of HV and WMLs for VaD, (iii) associations between HV, WMLs, and cognitive decline, (iv)the role of WMLs on HV.</p></div><div><h3>Methods</h3><p>This longitudinal multicenter study included 110 VMCI subjects (mean age:74.33 ± 6.63 years, 60males/50females) from the VMCI-Tuscany Study database. Subjects underwent brain MRI and cognitive testing, with 2-year follow-up data on VaD progression. HV and WMLs were semi-automatically segmented and measured. ANCOVA assessed group differences, while linear and logistic regression models evaluated predictive power<strong>.</strong></p></div><div><h3>Results</h3><p>After 2 years, 32/110 VMCI patients progressed to VaD. Converting patients had lower HV(<em>p</em> = 0.015) and higher lesion volumes in the posterior thalamic radiation (<em>p</em> = 0.046), splenium of the corpus callosum (<em>p</em> = 0.016), cingulate gyrus (<em>p</em> = 0.041), and cingulum hippocampus(<em>p</em> = 0.038). HV alone did not fully explain progression (<em>p</em> = 0.059), but combined with WMLs volume, the model was significant (<em>p</em> = 0.035). The best prediction model (<em>p</em> = 0.001) included total HV (<em>p</em> = 0.004) and total WMLs volume of the posterior thalamic radiation (<em>p</em> = 0.005) and cingulate gyrus (p = 0.005), achieving 80% precision, 81% specificity, and 74% sensitivity. Lower HV were linked to poorer performance on the Rey Auditory-Verbal Learning Test delayed recall (RAVLT) and Mini Mental State Examination (MMSE).</p></div><div><h3>Conclusions</h3><p>HV and WMLs are significant predictors of progression from VMCI to VaD. Lower HV correlate with worse cognitive performance on RAVLT and MMSE tests.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022510X24002983/pdfft?md5=35966eafc36f362559b78b91dc6ed0bf&pid=1-s2.0-S0022510X24002983-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1016/j.jns.2024.123166
Introduction
Gerstmann–Sträussler–Scheinker disease (GSS) is an autosomal-dominant inherited prion disease most often associated with the human prion protein gene (PRNP)-P102L mutation. Although patients manifest considerable phenotypic heterogeneity, the involvement of the nigrostriatal system has not been well-studied.
Methods
We performed dopamine transporter single-photon emission computed tomography (DAT-SPECT) using 123I-ioflupane to investigate the nigrostriatal system function in nine patients with the PRNP-P102L mutation. We also examined the pathological findings in another patient whose predominant feature was ataxia and who died 5 years after disease onset.
Results
Striatum uptake of 123I-ioflupane indicated by specific binding ratio (SBR) values was significantly reduced in two patients. The DAT-SPECT examination was performed 6 months after disease onset in one of these patients who manifested rapidly developing cognitive decline mimicking Creutzfeldt–Jakob disease. DAT-SPECT was also performed 9 years after disease onset in another patient who manifested the conventional features of GSS involving ataxia and dementia in the initial phase but showed akinetic mutism at the examination time. Another patient examined 2 years after disease onset who predominantly manifested ataxia showed marginally abnormal SBR values. An autopsy case showed moderate neuronal loss in the substantia nigra, and the degree of neuronal loss was similar in most other parts of the brain.
Conclusion
Nigrostriatal system involvement may occur in patients with GSS associated with the PRNP-P102L mutation, even though parkinsonism is not the predominant feature.
{"title":"Involvement of the nigrostriatal system in Gerstman–Sträussler–Scheinker disease with the PRNP-P102L mutation","authors":"","doi":"10.1016/j.jns.2024.123166","DOIUrl":"10.1016/j.jns.2024.123166","url":null,"abstract":"<div><h3>Introduction</h3><p>Gerstmann–Sträussler–Scheinker disease (GSS) is an autosomal-dominant inherited prion disease most often associated with the human prion protein gene (<em>PRNP)</em>-P102L mutation. Although patients manifest considerable phenotypic heterogeneity, the involvement of the nigrostriatal system has not been well-studied.</p></div><div><h3>Methods</h3><p>We performed dopamine transporter single-photon emission computed tomography (DAT-SPECT) using <sup>123</sup>I-ioflupane to investigate the nigrostriatal system function in nine patients with the <em>PRNP</em>-P102L mutation. We also examined the pathological findings in another patient whose predominant feature was ataxia and who died 5 years after disease onset.</p></div><div><h3>Results</h3><p>Striatum uptake of <sup>123</sup>I-ioflupane indicated by specific binding ratio (SBR) values was significantly reduced in two patients. The DAT-SPECT examination was performed 6 months after disease onset in one of these patients who manifested rapidly developing cognitive decline mimicking Creutzfeldt–Jakob disease. DAT-SPECT was also performed 9 years after disease onset in another patient who manifested the conventional features of GSS involving ataxia and dementia in the initial phase but showed akinetic mutism at the examination time. Another patient examined 2 years after disease onset who predominantly manifested ataxia showed marginally abnormal SBR values. An autopsy case showed moderate neuronal loss in the substantia nigra, and the degree of neuronal loss was similar in most other parts of the brain.</p></div><div><h3>Conclusion</h3><p>Nigrostriatal system involvement may occur in patients with GSS associated with the <em>PRNP</em>-P102L mutation, even though parkinsonism is not the predominant feature.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1016/j.jns.2024.123165
Introduction
A major component of Lewy bodies is phosphorylated α-synuclein. This post-translational modification of α-synuclein, phosphorylation, may consume a great amount of serum phosphorus. We aimed to investigate serum phosphorus levels and their associations with clinical phenotype and the degeneration of cardiac sympathetic and nigrostriatal dopaminergic neurons in patients with Parkinson's disease (PD).
Materials and methods
We examined serum phosphorus levels in 127 participants (drug-naïve PD, 97; age- and sex-matched controls, 30). Associations of serum phosphorus levels with clinical features, heart-to-mediastinum (H/M) ratio on cardiac 123I-metaiodobenzylguanidine scintigraphy and striatal specific binding ratio of 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) were examined.
Results
Serum phosphorus levels were 3.4 ± 0.5 mg/dL in patients with PD and were not different from those in controls after controlling for age and sex (p = 0.850). Serum phosphorus levels were significantly lower in patients with PD and decreased H/M ratio than in those with PD and normal H/M ratio (3.3 ± 0.4 mg/dL vs. 3.6 ± 0.5 mg/dL, p = 0.003). Lower serum phosphorus levels were significantly associated with more severe degeneration of nigrostriatal dopaminergic neurons in patients with PD and decreased H/M ratio. However, this association was not observed in patients with PD and normal H/M ratio.
Conclusions
Serum phosphorus levels and their association with nigrostriatal dopaminergic degeneration are different between patients with decreased H/M ratio and those with normal H/M ratio. Serum phosphorus levels may reflect the degree of nigrostriatal dopaminergic degeneration in patients with decreased H/M ratio, namely, Body-First PD.
简介路易体的主要成分是磷酸化的α-突触核蛋白。α-突触核蛋白的这种翻译后修饰(磷酸化)可能会消耗大量的血清磷。我们旨在研究帕金森病(PD)患者的血清磷水平及其与临床表型、心交感神经和黑质纹状体多巴胺能神经元变性的关系:我们检测了127名参与者(药物治疗无效的帕金森病患者97名;年龄和性别匹配的对照组30名)的血清磷水平。研究了血清磷水平与临床特征、心脏123I-甲碘代苄基胍闪烁照相术(H/M)心胸比和123I-2-甲氧羰基-3-(4-碘苯基)-N-(3-氟丙基)正丙烷(123I-FP-CIT)纹状体特异性结合率的关系:帕金森病患者的血清磷水平为 3.4 ± 0.5 mg/dL,在控制年龄和性别后,与对照组无差异(p = 0.850)。患有帕金森病且H/M比值下降的患者血清磷水平明显低于患有帕金森病且H/M比值正常的患者(3.3 ± 0.4 mg/dL vs. 3.6 ± 0.5 mg/dL, p = 0.003)。血清磷水平较低与帕金森病患者黑质多巴胺能神经元变性更严重和H/M比值降低有显著相关性。结论:血清磷水平及其与黑质多巴胺能神经元变性的关系是一个重要的研究课题:结论:血清磷水平及其与黑质多巴胺能变性的关系在H/M比值降低和H/M比值正常的患者中有所不同。血清磷水平可反映H/M比值降低患者(即体先型帕金森病患者)的黑质多巴胺能退化程度。
{"title":"Serum phosphorus levels associated with nigrostriatal dopaminergic deficits in drug-naïve Parkinson's disease","authors":"","doi":"10.1016/j.jns.2024.123165","DOIUrl":"10.1016/j.jns.2024.123165","url":null,"abstract":"<div><h3>Introduction</h3><p>A major component of Lewy bodies is phosphorylated α-synuclein. This post-translational modification of α-synuclein, phosphorylation, may consume a great amount of serum phosphorus. We aimed to investigate serum phosphorus levels and their associations with clinical phenotype and the degeneration of cardiac sympathetic and nigrostriatal dopaminergic neurons in patients with Parkinson's disease (PD).</p></div><div><h3>Materials and methods</h3><p>We examined serum phosphorus levels in 127 participants (drug-naïve PD, 97; age- and sex-matched controls, 30). Associations of serum phosphorus levels with clinical features, heart-to-mediastinum (H/M) ratio on cardiac <sup>123</sup>I-metaiodobenzylguanidine scintigraphy and striatal specific binding ratio of <sup>123</sup>I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (<sup>123</sup>I-FP-CIT) were examined.</p></div><div><h3>Results</h3><p>Serum phosphorus levels were 3.4 ± 0.5 mg/dL in patients with PD and were not different from those in controls after controlling for age and sex (<em>p</em> = 0.850). Serum phosphorus levels were significantly lower in patients with PD and decreased H/M ratio than in those with PD and normal H/M ratio (3.3 ± 0.4 mg/dL vs. 3.6 ± 0.5 mg/dL, <em>p</em> = 0.003). Lower serum phosphorus levels were significantly associated with more severe degeneration of nigrostriatal dopaminergic neurons in patients with PD and decreased H/M ratio. However, this association was not observed in patients with PD and normal H/M ratio.</p></div><div><h3>Conclusions</h3><p>Serum phosphorus levels and their association with nigrostriatal dopaminergic degeneration are different between patients with decreased H/M ratio and those with normal H/M ratio. Serum phosphorus levels may reflect the degree of nigrostriatal dopaminergic degeneration in patients with decreased H/M ratio, namely, Body-First PD.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1016/j.jns.2024.123162
Introduction
Headache disorders are the largest contributor to all years lived with disability attributed to neurological disorders. In sub-Saharan Africa (SSA), with 1.2 billion inhabitants, headache prevalence is similar to that of Western countries but with widely inadequate access to care. Cost of transport to healthcare facilities hampers access to care, leading to abandonment and low retention. The aim of this observational study in Malawi was to investigate cost of transport and its likely impact on implementation of WHO's-Intersectoral Global Action Plan (IGAP) in an HIV+ population also complaining of, and requiring treatment for, an active headache disorder.
Methods
The study was conducted at the Disease Relief through Excellent and Advanced Means (DREAM) centre in Blantyre, Malawi, in collaboration with the Global Campaign against Headache as an extension of a previous study. Enquiries about distance and costs of travel were added to the previously published questionnaire.
Results
We included 495 consecutive HIV+ patients aged 6–65 years who had been followed for at least 1 year. One-year prevalence of any headache was 76.6%; 28.7% missed at least one appointment because of transport costs. Higher costs of transport were associated with higher probability of missing visits (p < 0.001), while costs were higher for those living in rural areas than for those in urban (p < 0.001).
Conclusions
Awareness of cost and affordability of transport in SSA may suggest strategies to improve access to headache care. Given the disability attributable to headache, this is necessary if the IGAP strategic objectives and targets are to be achieved.
{"title":"Cost of transport is a barrier to access to headache care in sub-Saharan Africa: An observational study in an HIV-positive population","authors":"","doi":"10.1016/j.jns.2024.123162","DOIUrl":"10.1016/j.jns.2024.123162","url":null,"abstract":"<div><h3>Introduction</h3><p>Headache disorders are the largest contributor to all years lived with disability attributed to neurological disorders. In sub-Saharan Africa (SSA), with 1.2 billion inhabitants, headache prevalence is similar to that of Western countries but with widely inadequate access to care. Cost of transport to healthcare facilities hampers access to care, leading to abandonment and low retention. The aim of this observational study in Malawi was to investigate cost of transport and its likely impact on implementation of WHO's-Intersectoral Global Action Plan (IGAP) in an HIV+ population also complaining of, and requiring treatment for, an active headache disorder.</p></div><div><h3>Methods</h3><p>The study was conducted at the Disease Relief through Excellent and Advanced Means (DREAM) centre in Blantyre, Malawi, in collaboration with the Global Campaign against Headache as an extension of a previous study. Enquiries about distance and costs of travel were added to the previously published questionnaire.</p></div><div><h3>Results</h3><p>We included 495 consecutive HIV+ patients aged 6–65 years who had been followed for at least 1 year. One-year prevalence of any headache was 76.6%; 28.7% missed at least one appointment because of transport costs. Higher costs of transport were associated with higher probability of missing visits (<em>p</em> < 0.001), while costs were higher for those living in rural areas than for those in urban (p < 0.001).</p></div><div><h3>Conclusions</h3><p>Awareness of cost and affordability of transport in SSA may suggest strategies to improve access to headache care. Given the disability attributable to headache, this is necessary if the IGAP strategic objectives and targets are to be achieved.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-05DOI: 10.1016/j.jns.2024.123167
Compelling evidence has been presented in favor of herpes simplex virus type 1 (HSV1) being one of the causative agents of Alzheimer's disease (AD). The success of HSV1 as a pathogen relates to its sophisticated strategies to evade host immunosurveillance. One strategy involves encoding a decoy Fcγ receptor (FcγR) that thwarts the Fcγ-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), a potent host immunosurveillance mechanism against virally infected cells. The decoy FcγR binds to antibodies of all IgG subclasses, except IgG3; therefore, IgG3 would be expected to play an important role in viral clearance by neutralization and ADCC, and thus contribute to protection from HSV1-spurred diseases. Previous studies have shown significant association between anti-HSV1 IgG3 antibodies and cortical thinning of the areas of the brain typically altered in AD and also targeted by HSV1. The aim of the present investigation was to determine whether GM (γ marker) 5 and GM 21 allotypes, hereditary allelic determinants expressed on IgG3, together with brain biomarkers of neural integrity, contributed to neurodegeneration—as measured by mini-mental state examination (MMSE) score—in patients with AD. Multiple regression analyses showed that the homozygous GM 5/5 genotype, preserved right hippocampus, and right insula thickness were associated with higher MMSE scores (p < 0.001), whereas the opposite pattern and GM 5/21 genotype were associated with worse clinical profiles. Influence of GM 5/21-expressing IgG3 antibodies on the ADCC of HSV1-infected neurons could, at least partially, explain these results.
{"title":"Biomarkers of neural integrity and immunoglobulin genes influence neurodegeneration in Alzheimer's disease","authors":"","doi":"10.1016/j.jns.2024.123167","DOIUrl":"10.1016/j.jns.2024.123167","url":null,"abstract":"<div><p>Compelling evidence has been presented in favor of herpes simplex virus type 1 (HSV1) being one of the causative agents of Alzheimer's disease (AD). The success of HSV1 as a pathogen relates to its sophisticated strategies to evade host immunosurveillance. One strategy involves encoding a decoy Fcγ receptor (FcγR) that thwarts the Fcγ-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), a potent host immunosurveillance mechanism against virally infected cells. The decoy FcγR binds to antibodies of all IgG subclasses, except IgG3; therefore, IgG3 would be expected to play an important role in viral clearance by neutralization and ADCC, and thus contribute to protection from HSV1-spurred diseases. Previous studies have shown significant association between anti-HSV1 IgG3 antibodies and cortical thinning of the areas of the brain typically altered in AD and also targeted by HSV1. The aim of the present investigation was to determine whether GM (γ marker) 5 and GM 21 allotypes, hereditary allelic determinants expressed on IgG3, together with brain biomarkers of neural integrity, contributed to neurodegeneration—as measured by mini-mental state examination (MMSE) score—in patients with AD. Multiple regression analyses showed that the homozygous GM 5/5 genotype, preserved right hippocampus, and right insula thickness were associated with higher MMSE scores (<em>p</em> < 0.001), whereas the opposite pattern and GM 5/21 genotype were associated with worse clinical profiles. Influence of GM 5/21-expressing IgG3 antibodies on the ADCC of HSV1-infected neurons could, at least partially, explain these results.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.jns.2024.123155
Introduction
Atypical Parkinsonian Syndromes(APS) are challenging neurodegenerative disorders due to their heterogeneous phenotypic overlaps.So far,there are no validated biomarkers that can accurately predict disease progression,and survival studies were highly different and contradictory.
Aim
To investigate clinical and molecular survival factors among Tunisian APS patients.
Methods
A retrospective study included Tunisian APS-patients.Using clinical and molecular parameters,survival was explored by Kaplan-Meier analysis.
Results
We included 409-APS patients divided into 166-DLB,112-PSP,81-MSA and 50-CBS.Survival rate was similar in synucleinopathies, while it differed in tauopathies,being shorter in PSP compared to CBS.Median survival in DLB was different according to gender(p = 0.0048),early parkinsonism and cognitive disorders. Among MSA, prognosis was worse in MSA-C-patients(p = 0.012) and those with stridor(p = 0.0049),oculomotor and neuropsychiatric disorders. For tauopathies, survival was shorter in PSP-RS(p = 0.027),cerebellar phenotype, those with tremor and swallowing problems at onset, early parkinsonism and memory impairment. For CBS,prognosis was worse in patients with tremor,swallowing and cognitive problems.Significant differences were noted in terms of survival across APS non-carriers of APOE-ε4(p < 0.001) as well APS patients carriers of MAPT-H1.PSP patients had lower survival rate according to MAPT haplotype carriage. Moreover, the number of copies had an influence as patients with H1/H2-MAPT profile had better prognosis than those with H1/H1.
Conclusion
This study determined survival rates in APS subgroups,which were comparable across synucleinopathies but shorter in PSP and longer in CBS.It also characterized demographic,phenotypic,and genetic profiles identifying more aggressive forms within APS subgroups.These findings address clinical gaps,aiding counseling for patients and families and guiding clinical management.Furthermore,they could facilitate patient stratification in clinical trials where mortality is an outcome measure.
{"title":"Clinical and molecular predictors of survival among atypical parkinsonian syndromes in a North African tertiary referral center","authors":"","doi":"10.1016/j.jns.2024.123155","DOIUrl":"10.1016/j.jns.2024.123155","url":null,"abstract":"<div><h3>Introduction</h3><p>Atypical Parkinsonian Syndromes(APS) are challenging neurodegenerative disorders due to their heterogeneous phenotypic overlaps.So far,there are no validated biomarkers that can accurately predict disease progression,and survival studies were highly different and contradictory.</p></div><div><h3>Aim</h3><p>To investigate clinical and molecular survival factors among Tunisian APS patients.</p></div><div><h3>Methods</h3><p>A retrospective study included Tunisian APS-patients.Using clinical and molecular parameters,survival was explored by Kaplan-Meier analysis.</p></div><div><h3>Results</h3><p>We included 409-APS patients divided into 166-DLB,112-PSP,81-MSA and 50-CBS.Survival rate was similar in synucleinopathies, while it differed in tauopathies,being shorter in PSP compared to CBS.Median survival in DLB was different according to gender(<em>p</em> = 0.0048),early parkinsonism and cognitive disorders. Among MSA, prognosis was worse in MSA-C-patients(<em>p</em> = 0.012) and those with stridor(<em>p</em> = 0.0049),oculomotor and neuropsychiatric disorders. For tauopathies, survival was shorter in PSP-RS(<em>p</em> = 0.027),cerebellar phenotype, those with tremor and swallowing problems at onset, early parkinsonism and memory impairment. For CBS,prognosis was worse in patients with tremor,swallowing and cognitive problems.Significant differences were noted in terms of survival across APS non-carriers of <em>APOE-</em>ε4(<em>p</em> < 0.001) as well APS patients carriers of <em>MAPT-</em>H1.PSP patients had lower survival rate according to <em>MAPT</em> haplotype carriage. Moreover, the number of copies had an influence as patients with H1/H2-<em>MAPT</em> profile had better prognosis than those with H1/H1.</p></div><div><h3>Conclusion</h3><p>This study determined survival rates in APS subgroups,which were comparable across synucleinopathies but shorter in PSP and longer in CBS.It also characterized demographic,phenotypic,and genetic profiles identifying more aggressive forms within APS subgroups.These findings address clinical gaps,aiding counseling for patients and families and guiding clinical management.Furthermore,they could facilitate patient stratification in clinical trials where mortality is an outcome measure.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.jns.2024.123154
Introduction/Aims
The common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG).
Methods
A total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation.
Results
Among the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use.
Discussion
Regarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use.
{"title":"Worsening of myasthenic symptoms associated with statins","authors":"","doi":"10.1016/j.jns.2024.123154","DOIUrl":"10.1016/j.jns.2024.123154","url":null,"abstract":"<div><h3>Introduction/Aims</h3><p>The common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG).</p></div><div><h3>Methods</h3><p>A total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation.</p></div><div><h3>Results</h3><p>Among the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use.</p></div><div><h3>Discussion</h3><p>Regarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1016/j.jns.2024.123148
Background
Early detection of Alzheimer's disease (AD) is one of the critical components of the global response to the growing dementia crisis. Analysis of serial position performance in story recall tests has yielded sensitive metrics for the prediction of AD at low cost. In this study, we examined whether serial position markers in two story recall tests (the logical memory test, LMT, and the Craft Story 21 test, CST) were sensitive to cross-sectional biomarker-based assessment of in vivo neuropathology.
Methods
Participants were selected from the Wisconsin Registry of Alzheimer's Prevention (n = 288; WRAP) and the Alzheimer's Disease Research Center (n = 156; ADRC), both from the University of Wisconsin–Madison. Average age at PET was 68.9 (6.7) and 67.0 (8.0), respectively. Data included tau and PiB PET, and LMT for WRAP participants and CST for ADRC participants. Two sets of Bayesian analyses (logistic regressions and ANCOVAs) were conducted within each cohort, separately.
Results
Results indicated that the A+T+ classification was best predicted, cross-sectionally, by the recency ratio (Rr), indexing how much of the end of the story was forgotten between initial learning and delayed assessment. Rr outperformed traditional scores and discriminated between A+T+ and A+T−/A-T-, in both cohorts.
Conclusions
Overall, this study confirms that serial position analysis of LMT and CST data, and particularly Rr as an index of recency loss, is a valuable tool for the identification of in vivo tau pathology in individuals free of dementia. Diagnostic considerations are discussed.
背景:早期发现阿尔茨海默病(AD)是全球应对日益严重的痴呆症危机的关键组成部分之一。对故事回忆测试中的序列位置表现进行分析,能以低成本获得预测阿尔茨海默病的敏感指标。在这项研究中,我们研究了两种故事回忆测试(逻辑记忆测试 LMT 和 Craft Story 21 测试 CST)中的序列位置标记是否对基于生物标记的体内神经病理学横断面评估敏感:参与者选自威斯康星大学麦迪逊分校的威斯康星阿尔茨海默氏症预防登记处(288 人;WRAP)和阿尔茨海默氏症研究中心(156 人;ADRC)。PET时的平均年龄分别为68.9(6.7)岁和67.0(8.0)岁。数据包括 tau 和 PiB PET,以及 WRAP 参与者的 LMT 和 ADRC 参与者的 CST。在每个队列中分别进行了两组贝叶斯分析(逻辑回归和方差分析):结果表明,从横截面来看,A+T+分类的最佳预测指标是重现率(Rr),即在初始学习和延迟评估之间故事结尾被遗忘的程度。在两个组群中,Rr的表现均优于传统评分,并能区分A+T+和A+T-/A-T-:总之,本研究证实了 LMT 和 CST 数据的序列位置分析,尤其是作为复发性丧失指数的 Rr,是识别无痴呆症患者体内 tau 病理学的重要工具。本文还讨论了诊断方面的注意事项。
{"title":"Story recall performance and AT classification via positron emission tomography: A comparison of logical memory and Craft Story 21","authors":"","doi":"10.1016/j.jns.2024.123148","DOIUrl":"10.1016/j.jns.2024.123148","url":null,"abstract":"<div><h3>Background</h3><p>Early detection of Alzheimer's disease (AD) is one of the critical components of the global response to the growing dementia crisis. Analysis of serial position performance in story recall tests has yielded sensitive metrics for the prediction of AD at low cost. In this study, we examined whether serial position markers in two story recall tests (the logical memory test, LMT, and the Craft Story 21 test, CST) were sensitive to cross-sectional biomarker-based assessment of in vivo neuropathology.</p></div><div><h3>Methods</h3><p>Participants were selected from the Wisconsin Registry of Alzheimer's Prevention (<em>n</em> = 288; WRAP) and the Alzheimer's Disease Research Center (<em>n</em> = 156; ADRC), both from the University of Wisconsin–Madison. Average age at PET was 68.9 (6.7) and 67.0 (8.0), respectively. Data included tau and PiB PET, and LMT for WRAP participants and CST for ADRC participants. Two sets of Bayesian analyses (logistic regressions and ANCOVAs) were conducted within each cohort, separately.</p></div><div><h3>Results</h3><p>Results indicated that the A+T+ classification was best predicted, cross-sectionally, by the recency ratio (Rr), indexing how much of the end of the story was forgotten between initial learning and delayed assessment. Rr outperformed traditional scores and discriminated between A+T+ and A+T−/A-T-, in both cohorts.</p></div><div><h3>Conclusions</h3><p>Overall, this study confirms that serial position analysis of LMT and CST data, and particularly Rr as an index of recency loss, is a valuable tool for the identification of in vivo tau pathology in individuals free of dementia. Diagnostic considerations are discussed.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022510X24002831/pdfft?md5=223b11f2df052645d049d536c64f0784&pid=1-s2.0-S0022510X24002831-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}