Journal of the Peripheral Nervous System最新文献

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The NCX1 calcium exchanger is implicated in delayed axotomy after peripheral nerve stretch injury. NCX1 钙交换器与周围神经拉伸损伤后的延迟轴突切断有关。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-10-14 DOI: 10.1111/jns.12663
Bradley Wilhelmy, Volodymyr Gerzanich, J Marc Simard, Jesse A Stokum
{"title":"The NCX1 calcium exchanger is implicated in delayed axotomy after peripheral nerve stretch injury.","authors":"Bradley Wilhelmy, Volodymyr Gerzanich, J Marc Simard, Jesse A Stokum","doi":"10.1111/jns.12663","DOIUrl":"https://doi.org/10.1111/jns.12663","url":null,"abstract":"<p><strong>Background and aims: </strong>After peripheral nerve stretch injury, most degenerating axons are thought to become disconnected at the time of injury, referred to as primary axotomy. The possibility of secondary axotomy-a delayed and potentially reversible form of disconnection-has not been evaluated. Here, we investigated secondary axotomy in a rat model of sciatic nerve stretch injury. We also evaluated whether axon sparing and functional improvement results from pharmacological blockade of the sodium-calcium exchanger 1 (NCX1), which is widely believed to contribute to traumatic axon degeneration but was previously only investigated in vitro.</p><p><strong>Methods: </strong>We studied peripheral nerve secondary axotomy in a clinically relevant rat model of sciatic nerve rapid stretch injury with immunolabeling and fluorescence microscopy. The role of NCX1 in secondary axotomy was studied with pharmacological inhibition with SEA0400 and immunolabeling, immunoblot, and behavioral assays.</p><p><strong>Results: </strong>We found that early after injury, many axons remained in-continuity and that degeneration of axons was delayed, consistent with the occurrence of secondary axotomy. βAPP, a marker of secondary axotomy, accumulated at regions of axon swelling and disconnection, and NCX1 was upregulated and co-localized to βAPP axonal swellings. Pharmacological blockade of NCX1 after injury reduced calpain activation, proteolytic degradation of neurofilaments, βAPP accumulation, distal axon degeneration, and improved hindlimb function.</p><p><strong>Interpretation: </strong>Our data demonstrate a major role for secondary axotomy in peripheral nerve stretch injury and identify NCX1 as a promising therapeutic target to reduce secondary axotomy and improve functional outcome after nerve injury.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468725","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}
引用次数: 0
Patient-reported disease burden in the Accelerate Clinical Trials in Charcot-Marie-Tooth Disease Study. Charcot-Marie-Tooth 病加速临床试验研究中患者报告的疾病负担。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-10-10 DOI: 10.1111/jns.12662
T Rehbein, J Purks, N Dilek, S Behrens-Spraggins, J E Sowden, K J Eichinger, J Burns, D Pareyson, S S Scherer, M M Reilly, M E Shy, M P McDermott, C R Heatwole, D N Herrmann
{"title":"Patient-reported disease burden in the Accelerate Clinical Trials in Charcot-Marie-Tooth Disease Study.","authors":"T Rehbein, J Purks, N Dilek, S Behrens-Spraggins, J E Sowden, K J Eichinger, J Burns, D Pareyson, S S Scherer, M M Reilly, M E Shy, M P McDermott, C R Heatwole, D N Herrmann","doi":"10.1111/jns.12662","DOIUrl":"https://doi.org/10.1111/jns.12662","url":null,"abstract":"<p><strong>Background and aims: </strong>The Charcot-Marie-Tooth Disease Health Index (CMT-HI) is a disease-specific, patient-reported disease burden measure. As part of an international clinical trial readiness study, individuals with CMT1A (ages 18-75 years) underwent clinical outcome assessments (COAs), including the CMT-HI, to capture their longitudinal perspective on the disease burden.</p><p><strong>Methods: </strong>Two hundred and fifteen participants underwent serial COAs including the CMT-HI, CMT Functional Outcome Measure (CMT-FOM), CMT Neuropathy Score (CMTNSv2R), and CMT Exam Score (CMTES/CMTES-R). Correlations between the total and subscale scores for the CMT-HI and other COAs were determined. Changes in the CMT-HI scores over 12 months were assessed using paired t-tests. The minimum clinically important difference (MCID) for the CMT-HI and its subscales were calculated by anchoring to a participant global impression of change scale.</p><p><strong>Results: </strong>At baseline, CMT1A participants were 44.5 ± 15 years old (range: 18-75) and 58% were women. The mean CMT-HI was 25.7 ± 18.8 (range: 0-91.9; 100 reflecting maximal disease burden). The CMT-HI correlated with the CMT-FOM (r = .54, p < .0001), CMTNSv2R (r = .48, p < .0001), and CMTES/CMTES-R (r = .52/r = .54, p < .0001). Disease burden was greater in women than in men (CMT-HI 29.1 ± 19.1 vs. 21.2 ± 17.3, p = .001). Over 12 months, there was a nonsignificant mean increase in CMT-HI of 0.40 ± 10.0 (n = 189, p = .89). The MCID for the CMT-HI total score was 3.8 points (95% CI: 1.7-5.9).</p><p><strong>Discussion: </strong>Patient-reported disease burden in CMT1A as measured by the CMT-HI is associated with measures of neurologic impairment and physical functioning. Women reported a higher disease burden than men. These data will inform the design of clinical trials in CMT1A.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400611","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}
引用次数: 0
Association of dynamic hepatic metabolism with clinical outcomes in patients with severe Guillain-Barré syndrome: A prospective cohort study from multi-centers in China. 动态肝代谢与重症格林-巴利综合征患者临床预后的关系:中国多中心前瞻性队列研究。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-09-29 DOI: 10.1111/jns.12661
Jiali Xie, Huan Yu, Wenjing Lv, Kezheng Li, Hui Li, Yingxiao Ji, Yunlei Cai, Yifan Cheng, Longfeng Luo, Chunxue Wu, Yiting Xu, Lihuai Du, Yinuo Chen, Chunyang Pang, Binbin Deng
{"title":"Association of dynamic hepatic metabolism with clinical outcomes in patients with severe Guillain-Barré syndrome: A prospective cohort study from multi-centers in China.","authors":"Jiali Xie, Huan Yu, Wenjing Lv, Kezheng Li, Hui Li, Yingxiao Ji, Yunlei Cai, Yifan Cheng, Longfeng Luo, Chunxue Wu, Yiting Xu, Lihuai Du, Yinuo Chen, Chunyang Pang, Binbin Deng","doi":"10.1111/jns.12661","DOIUrl":"https://doi.org/10.1111/jns.12661","url":null,"abstract":"<p><strong>Background and aims: </strong>Little is known about the ability of serological biomarkers to monitor clinical outcomes in patients with Guillain-Barré syndrome (GBS). The objective of this study was to determine the associations of liver function, easily available and convenient biomarkers, with the clinical course and outcome of severe GBS in patients.</p><p><strong>Methods: </strong>A prospective data collection was conducted in a cohort of 343 GBS patients from multi-centers between September 2019 and December 2023. Serum samples were obtained at four-time points for mechanical ventilation (MV) patients and two-time points for non-MV patients. The primary endpoint was the need for MV during hospitalization, while secondary outcomes included the ability to walk independently and the mortality at 26-week follow-up.</p><p><strong>Results: </strong>(i) A total of 208 patients were eligible, of whom 50 required MV with a median (interquartile range) ventilation duration of 15 (8-27) days. (ii) Hypohepatia, as evidenced by reduced total protein (OR 0.913 [95% CI 0.862-0.967]) and albumin (0.775 [0.679-0.884]) 1 week after treatment, along with raised liver enzymes (2.732 [1.007-7.413]), was associated with the risk of MV after adjusting for confounders. (iii) After 26-week follow-up, patients with hypohepatia were less likely to regain independent walking and exhibited higher mortality in survival analysis (all log-rank p < .05). (iv) In a cross-sectional study spanning up to 4 years of follow-up, patients with prolonged MV (≥15 days) experienced a longer time to regain independent ambulation than those with shorter MV (167 [46-316] vs. 69 [24-106], p = .036). However, no relationships between liver function and prolonged MV were revealed.</p><p><strong>Interpretation: </strong>Dynamically monitoring hepatic metabolism and promptly adjusting, it can aid the improvement of GBS in patients.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349158","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}
引用次数: 0
Oxygen matters: Unraveling the role of oxygen in the neuronal response to cisplatin. 氧气很重要揭示氧气在神经元对顺铂反应中的作用。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-09-27 DOI: 10.1111/jns.12659
Jose Crugeiras, Aina Calls, Estefanía Contreras, Montse Alemany, Xavier Navarro, Victor J Yuste, Oriol Casanovas, Esther Udina, Jordi Bruna
{"title":"Oxygen matters: Unraveling the role of oxygen in the neuronal response to cisplatin.","authors":"Jose Crugeiras, Aina Calls, Estefanía Contreras, Montse Alemany, Xavier Navarro, Victor J Yuste, Oriol Casanovas, Esther Udina, Jordi Bruna","doi":"10.1111/jns.12659","DOIUrl":"https://doi.org/10.1111/jns.12659","url":null,"abstract":"<p><strong>Background and aims: </strong>Cell culture is a fundamental experimental tool for understanding cell physiology. However, translating these findings to in vivo settings has proven challenging. Replicating donor tissue conditions, including oxygen levels, is crucial for achieving meaningful results. Nevertheless, oxygen culture conditions are often overlooked, particularly in the context of chemotherapy-induced neurotoxicity.</p><p><strong>Methods: </strong>In this study, we investigated the role of oxygen levels in primary neuronal cultures by comparing neuronal performance under cisplatin exposure (1 μg/mL) in supraphysiological normoxia (representing atmospheric conditions in a standard incubator; 18.5% O<sub>2</sub>) and physioxia (representing physiologic oxygen conditions in nervous tissue; 5% O<sub>2</sub>). Experiments were also conducted to assess survival, neurite development, senescence marker expression, and proinflammatory cytokine secretion.</p><p><strong>Results: </strong>Under control conditions, both oxygen concentration conditions exhibited similar behaviors. However, after cisplatin administration, sensory neurons cultured under supraphysiological normoxic conditions show higher mortality, exhibit an evolutionarily proinflammatory cytokine profile over time, and activate apoptotic-regulated neuron death markers. In contrast, under physiological conditions, neurons treated with cisplatin exhibited senescence marker expression and an attenuated inflammatory secretome.</p><p><strong>Interpretation: </strong>These results underscore the critical role of oxygen in neuronal culture, particularly in studying compounds where neuronal damage is mechanistically linked to oxidative stress. Even at identical doses of evaluated neurotoxic drugs, distinct cellular phenotypic fates can emerge, impacting translatability to the in vivo setting.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349159","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}
引用次数: 0
Correction to "Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study". 更正 "皮肤活组织切片中表皮内神经纤维的自动免疫组化:概念验证研究"。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-09-20 DOI: 10.1111/jns.12658
{"title":"Correction to \"Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study\".","authors":"","doi":"10.1111/jns.12658","DOIUrl":"https://doi.org/10.1111/jns.12658","url":null,"abstract":"","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290008","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}
引用次数: 0
Clinical and genetic features of CMT2T in Italian patients confirm the importance of MME pathogenic variants in idiopathic, late‐onset axonal neuropathies 意大利 CMT2T 患者的临床和遗传特征证实了 MME 致病变体在特发性晚发性轴索神经病中的重要性
IF 3.8 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-09-09 DOI: 10.1111/jns.12657
Alessandro Geroldi, Andrea La Barbera, Alessia Mammi, Paola Origone, Andrea Gaudio, Clarissa Ponti, Francesca Sanguineri, Sabrina Matà, Martina Sperti, Ilaria Carboni, Emilia Bellone, Fabio Gotta, Chiara Gemelli, Sara Massucco, Guglielmino Valeria, Lucio Marinelli, Marina Grandis, Giulia Bisogni, Mario Sabatelli, Giuseppe Piscosquito, Gabriella Esposito, Angelo Schenone, Fiore Manganelli, Paola Mandich, Stefano Tozza, Marco Luigetti
{"title":"Clinical and genetic features of CMT2T in Italian patients confirm the importance of MME pathogenic variants in idiopathic, late‐onset axonal neuropathies","authors":"Alessandro Geroldi, Andrea La Barbera, Alessia Mammi, Paola Origone, Andrea Gaudio, Clarissa Ponti, Francesca Sanguineri, Sabrina Matà, Martina Sperti, Ilaria Carboni, Emilia Bellone, Fabio Gotta, Chiara Gemelli, Sara Massucco, Guglielmino Valeria, Lucio Marinelli, Marina Grandis, Giulia Bisogni, Mario Sabatelli, Giuseppe Piscosquito, Gabriella Esposito, Angelo Schenone, Fiore Manganelli, Paola Mandich, Stefano Tozza, Marco Luigetti","doi":"10.1111/jns.12657","DOIUrl":"https://doi.org/10.1111/jns.12657","url":null,"abstract":"Background and AimsSince 2016, biallelic mutations in the membrane metalloendopeptidase (<jats:italic>MME)</jats:italic> gene have been associated with late‐onset recessive CMT2 (CMT2T). More recently, heterozygous mutations have also been identified in familial and sporadic patients with late‐onset axonal neuropathy, ranging from subclinical to severe. This indicates that the heterozygous <jats:italic>MME</jats:italic> variants may not be fully penetrant, or alternatively, that they may be a potential risk factor for neuropathy. Here, we describe the clinical, neurophysiological, and genetic findings of 32 CM2T Italian patients.MethodsThe patients were recruited from four different Italian referral centers. Following a comprehensive battery of neurological, electrophysiological, and laboratory examinations, the patients' DNA was subjected to sequencing in order to identify any variants in the gene. Bioinformatic and modeling analyses were performed to evaluate the identified variants' effects.ResultsWe observe a relatively mild axonal sensory‐motor neuropathy with a greater impairment of the lower extremities. Biallelic and monoallelic patients exhibit comparable disease severity, with an earlier onset observed in those with biallelic variants. When considering a subgroup with more than 10 years of disease, it becomes evident that biallelic patients exhibit a more severe form of neuropathy. This suggests that they are more prone to quick progression.InterpretationCM2T has been definitively defined as a late‐onset neuropathy, with a typical onset in the fifth to sixth decades of life and a more rapidly progressing worsening for biallelic patients. CMT2T can be included in the neuropathies of the elderly, particularly if <jats:italic>MME</jats:italic> variants heterozygous patients are included.","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"41 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142197531","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}
引用次数: 0
Nerve ultrasound in CANVAS-spectrum disease: Reduced nerve size distinguishes genetically confirmed CANVAS from other axonal polyneuropathies. CANVAS 光谱病的神经超声:减小的神经尺寸可将经基因证实的 CANVAS 与其他轴索型多发性神经病区分开来。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-09-02 DOI: 10.1111/jns.12655
Alessandro Salvalaggio, Mario Cacciavillani, Benedetta Tierro, Daniele Coraci, Riccardo Currò, Moreno Ferrarini, Elena Pegoraro, Luca Bello, Gian Maria Fabrizi, Alessandro Filla, Luca Padua, Fiore Manganelli, Andrea Cortese, Chiara Briani
{"title":"Nerve ultrasound in CANVAS-spectrum disease: Reduced nerve size distinguishes genetically confirmed CANVAS from other axonal polyneuropathies.","authors":"Alessandro Salvalaggio, Mario Cacciavillani, Benedetta Tierro, Daniele Coraci, Riccardo Currò, Moreno Ferrarini, Elena Pegoraro, Luca Bello, Gian Maria Fabrizi, Alessandro Filla, Luca Padua, Fiore Manganelli, Andrea Cortese, Chiara Briani","doi":"10.1111/jns.12655","DOIUrl":"https://doi.org/10.1111/jns.12655","url":null,"abstract":"<p><strong>Background and aims: </strong>Ultrasound nerve cross-sectional area (CSA) of patients affected with axonal neuropathy usually shows normal value. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) seems to represent an exception, showing smaller CSA, but previous reports did not test for biallelic RFC1 gene repeat expansions.</p><p><strong>Methods: </strong>We compared nerve CSA from CANVAS patients (tested positive for biallelic RFC1 gene repeat expansions) with the CSA from a group of patients with chronic idiopathic axonal polyneuropathy (CIAP) who tested negative for RFC1 gene repeat expansions, hereditary axonal neuropathy (Charcot-Marie-Tooth type 2, CMT2), and Friedreich ataxia (FRDA).</p><p><strong>Results: </strong>We enrolled 15 CANVAS patients (eight men, mean age 66.3 ± 11.5 years, mean disease duration 9.3 ± 4.1 years), affected with sensory axonal neuronopathy. Controls consisted of 13 CIAP (mean age 68.5 ± 12.8 years, seven men), seven CMT2 (mean age 47.9 ± 18.1 years, four men), 12 FRDA (mean age 33.7 ± 8.8, five men). Nerve ultrasound was performed at median, ulnar, sciatic, sural, and tibial nerves and brachial plexus, bilaterally. The nerve CSA from CANVAS patients was significantly smaller than the one from the other cohorts at several sites with significant and high accuracy at Receiver-operating characteristic (ROC) curve analyses. RFC1 AAGGG pentanucleotide expansion, disease duration, and disability did not correlate with CSA at any site, after Bonferroni correction.</p><p><strong>Interpretation: </strong>Decreased sonographic nerve sizes, in arms and legs, in patients with sensory neuropathy and normal motor conduction studies could point to CANVAS-spectrum disease and help guide appropriate genetic testing.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108739","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}
引用次数: 0
Peripheral neuropathy, an independent risk factor for falls in the elderly, impairs stepping as a postural control mechanism: A case-cohort study. 周围神经病变是老年人跌倒的一个独立风险因素,会损害作为姿势控制机制的步态:一项病例队列研究。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-09-01 DOI: 10.1111/jns.12656
Felix Kohle, Christopher Stark, Heinz-Dieter Klünter, Daniel Wernicke, Gilbert Wunderlich, Gereon R Fink, Jens P Klussmann, Michael Schroeter, Helmar C Lehmann
{"title":"Peripheral neuropathy, an independent risk factor for falls in the elderly, impairs stepping as a postural control mechanism: A case-cohort study.","authors":"Felix Kohle, Christopher Stark, Heinz-Dieter Klünter, Daniel Wernicke, Gilbert Wunderlich, Gereon R Fink, Jens P Klussmann, Michael Schroeter, Helmar C Lehmann","doi":"10.1111/jns.12656","DOIUrl":"https://doi.org/10.1111/jns.12656","url":null,"abstract":"<p><strong>Background/aims: </strong>Peripheral neuropathies perturbate the sensorimotor system, causing difficulties in walking-related motor tasks and, eventually, falls. Falls result in functional dependency and reliance on healthcare, especially in older persons. We investigated if peripheral neuropathy is a genuine risk factor for falls in the elderly and if quantification of postural control via posturography is helpful in identifying subjects at risk of falls.</p><p><strong>Methods: </strong>Seventeen older persons with a clinical polyneuropathic syndrome of the lower limbs and converging electrophysiology were compared with 14 older persons without polyneuropathy. All participants were characterized via quantitative motor and sensory testing, neuropsychological assessment, and self-questionnaires. Video-nystagmography and caloric test excluded vestibulocochlear dysfunction. For further analysis, all subjects were stratified into fallers and non-fallers. Overall, 28 patients underwent computerized dynamic posturography for individual fall risk assessment. Regression analyses were performed to identify risk factors and predictive posturography parameters.</p><p><strong>Results: </strong>Neuropathy is an independent risk factor for falls in the elderly, while no differences were observed for age, gender, weight, frailty, DemTect test, timed \"Up & Go\" test, and dizziness-related handicap score. In computerized dynamic posturography, fallers stepped more often to regain postural control in challenging conditions, while the Rhythmic Weight Shift test showed a lack of anterior-posterior bidirectional voluntary control.</p><p><strong>Interpretation: </strong>Our study confirms peripheral neuropathy as a risk factor for older persons' falls. Fallers frequently used stepping to regain postural control. The voluntary control of this coping movement was impaired. Further investigations into these parameters' value in predicting the risk of falls in the elderly are warranted.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108740","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}
引用次数: 0
Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy. 辐射诱发周围神经病变的新型大鼠模型中的痛觉过敏、感觉运动损伤和肌力下降。
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-08-24 DOI: 10.1111/jns.12654
Allison B Vittert, Melissa Daniel, Shelby R Svientek, Mary Jane Risch, Noah S Nelson, Alexis Donneys, Amir Dehdashtian, Gina N Sacks, Steven R Buchman, Stephen W P Kemp
{"title":"Pain hypersensitivity, sensorimotor impairment, and decreased muscle force in a novel rat model of radiation-induced peripheral neuropathy.","authors":"Allison B Vittert, Melissa Daniel, Shelby R Svientek, Mary Jane Risch, Noah S Nelson, Alexis Donneys, Amir Dehdashtian, Gina N Sacks, Steven R Buchman, Stephen W P Kemp","doi":"10.1111/jns.12654","DOIUrl":"https://doi.org/10.1111/jns.12654","url":null,"abstract":"<p><strong>Introduction: </strong>Radiation-induced peripheral neuropathy is a rare, but serious complication often resulting in profound morbidity, life-long disability, and chronic debilitating pain. Unfortunately, this type of peripheral neuropathy is usually progressive, and almost always irreversible. To date, a standardized rat model of radiation-induced peripheral neuropathy has not been established. The purpose of the present study was to examine neuropathic pain, sensorimotor impairment, and muscle force parameters following the administration of a clinically relevant radiation dose in a rat model.</p><p><strong>Methods: </strong>Ten rats were randomly assigned to one of two experimental groups: (1) radiation and (2) sham-radiated controls. Radiated animals were given a clinically relevant dose of 35 Gray (Gy) divided into five daily doses of 7 Gy/day. This regimen represents a human equivalent dose of 70 Gy, approximating the same dosage utilized for radiotherapy in oncologic patients. Sham-radiated controls were anesthetized and placed in the radiation apparatus but were not given radiation. All animals were tested for baseline values in both sensorimotor and pain behavioral tests. Sensorimotor testing consisted of the evaluation of walking tracks with the calculation of the Sciatic Functional Index (SFI). Pain-related behavioral measures consisted of mechanical allodynia (von Frey test), cold allodynia (Acetone test), and thermal allodynia (Hargreaves test). Animals were tested serially over an 8-week period. At the study endpoint, electrophysiological and muscle force assessments were completed, and histomorphometric analysis was performed on all sciatic nerves.</p><p><strong>Results: </strong>Animals that underwent radiation treatment displayed significantly greater pain hypersensitivity to mechanical stimulation as compared to sham radiated controls from weeks 4 to 8 of testing. SFI values indicated sensorimotor impairments in the overground gait of radiated animals as compared to non-radiated animals. Furthermore, radiated animals displayed reduced twitch and tetanic muscle force when compared to sham radiated controls.</p><p><strong>Conclusions: </strong>A clinically relevant human equivalent dose of fractionated 35 Gy in rats established significant pain hypersensitivity, impairments in sensorimotor locomotion, and decreased muscle force capacity. This novel rodent model of radiation-induced peripheral neuropathy can be utilized to assess the potential efficacy of therapeutic treatments to either prevent or remediate this clinically debilitating condition.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046778","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}
引用次数: 0
Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study 皮肤活检中表皮内神经纤维的自动免疫组化:概念验证研究
IF 3.9 3区 医学
Journal of the Peripheral Nervous System Pub Date : 2024-08-20 DOI: 10.1111/jns.12650
Jamie Burgess, Anne Marshall, Leandros Rapteas, J. Hamill Kevin, Andrew Marshall, Rayaz A. Malik, Bernhard Frank, Uazman Alam
{"title":"Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study","authors":"Jamie Burgess,&nbsp;Anne Marshall,&nbsp;Leandros Rapteas,&nbsp;J. Hamill Kevin,&nbsp;Andrew Marshall,&nbsp;Rayaz A. Malik,&nbsp;Bernhard Frank,&nbsp;Uazman Alam","doi":"10.1111/jns.12650","DOIUrl":"10.1111/jns.12650","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra-epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Skin biopsies (<i>n</i> = 274) from 100 participants (fibromyalgia syndrome <i>n</i> = 62; idiopathic small fibre neuropathy: <i>n</i> = 16; healthy volunteers: <i>n</i> = 22) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two-way mixed-effects model to evaluate inter- and intra-observer variability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The automated staining system reproduced intra-epidermal nerve fibre density (IENFD) counts consistent with free-floating sections (mean ± standard deviation: free-floating: 5.6 ± 3.4 fibres/mm; automated: 5.9 ± 3.2 fibres/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at −0.00005 established non-inferiority against a margin of −0.4 (<i>p</i> = .08). Specifically, the inter-class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9–1), indicating excellent agreement between free-floating and automated methods. The inter- and intra-class coefficient between examiners were both 99% (95% CI: 0.9–0.1) for IENFD, demonstrating high reliability using sections stained using the automated method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Automated immunohistochemistry provides high-throughput reliable and reproducible intra-epidermal nerve fibre quantification. This method, although currently proof-of-concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"329-338"},"PeriodicalIF":3.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008980","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}
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