Journal of the Peripheral Nervous System最新文献_第2页

Genetic and Clinical Spectrum of Hereditary Transthyretin Amyloidosis in Brazil 巴西遗传性甲状腺转蛋白淀粉样变性的遗传和临床谱。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2026-01-07 DOI: 10.1111/jns.70097

Gustavo Maximiano-Alves, Carolina Lavigne-Moreira, Marcus Vinicius Simões, Adilson Junior Pinto Galvão, Flavio Henrique Valicelli, Fernando Saraiva Coneglian, Elisa Vegezzi, Pedro Manoel Marques Garibaldi, Pedro José Tomaselli, Andrea Cortese, Wilson Marques Jr

Background

Transthyretin hereditary amyloidosis (ATTRv) clinical variability has been widely reported, not only across countries and variants but also among families and distinct regions within a single nation. One of the principal challenges in disease management is the accurate determination of age of onset (AOO), which is heterogeneous and has therapeutic implications given the availability of disease-modifying treatments.

Methods

This study characterizes the genetic landscape and clinical onset spectrum of ATTRv in an admixed Brazilian cohort of 175 patients.

Results

Seven TTR pathogenic variants (p.Val50Met, p.Val142Ile, p.Ile127Val, p.Ile88Leu, p.Ala39Asp, p.Phe84Leu, p.Tyr98Phe) were identified. The most common was p.Val50Met (58.8%), followed by p.Val142Ile (29.7%) and p.Ile127Val (7.4%). Notably, 44% of V122I had a neurological onset. Close clinical monitoring of presymptomatic carriers reduced age at diagnosis by 10.5 years. The median AOO was 50 years, with V30M patients presenting earlier (38.5 years) than V122I (p.Val142Ile) (60y) and I107V (p.Ile127Val) (60 years). Familial cases showed a 20.5-year earlier AOO than sporadic cases. In Brazil, late-onset (> 50 years) V30M is more common than previously reported (37.5%); ethnicity can influence AOO within the same variant, and for the first time, we show a distinct geographic pattern: early-onset V30M is more frequent in São Paulo/South, whereas late-onset V30M predominates in the central region.

Interpretation

This study emphasizes the heterogeneity of ATTRv presentation in admixed populations and underscores the need for expanded screening and multicenter studies to refine genotype–phenotypic correlations.

背景：甲状腺素遗传性淀粉样变性（ATTRv）的临床变异性已被广泛报道，不仅在国家和变异之间，而且在一个国家的家庭和不同地区之间。疾病管理的主要挑战之一是准确确定发病年龄（AOO），这是异质的，鉴于疾病改善治疗的可用性，具有治疗意义。方法：本研究在175名巴西混合队列患者中描述了ATTRv的遗传景观和临床发病谱。结果：共鉴定出7个TTR致病变异体（p.Val50Met、p.Val142Ile、p.Ile127Val、p.Ile88Leu、p.Ala39Asp、p.Phe84Leu、p.Tyr98Phe）。最常见的是p.Val50Met(58.8%)，其次是p.Val142Ile（29.7%）和p.Ile127Val（7.4%）。值得注意的是，44%的V122I患者有神经系统疾病。对症状前携带者进行密切的临床监测，可使诊断年龄降低10.5岁。中位AOO为50年，V30M患者比V122I (p.Val142Ile)（60年）和I107V (p.Ile127Val)（60年）更早出现（38.5年）。家族性病例的AOO比散发病例早20.5年。在巴西，晚发性（50岁以下）V30M比之前报道的更为常见（37.5%）；种族可以影响同一变异中的AOO，并且我们首次显示出明显的地理模式：早发性V30M在圣保罗/南部地区更为常见，而晚发性V30M在中部地区占主导地位。解释：该研究强调了混合人群中ATTRv表现的异质性，并强调了扩大筛查和多中心研究以完善基因型-表型相关性的必要性。

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引用次数: 0

Evaluation of Nicotinamide Riboside in Prevention of Small Nerve Fiber Axon Degeneration and Promotion of Nerve Regeneration 烟酰胺核苷预防神经小纤维轴突变性和促进神经再生的作用。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2026-01-07 DOI: 10.1111/jns.70101

Simone Thomas, Remi Ben-Davies, Aysel Cetinkaya-Fisgin, Xindan Hu, Xiaoling Li, Sarah Stewart, Baohan Pan, Jeffery L. Twiss, Rajiv R. Ratan, Dianna Willis, Michael Polydefkis, Ahmet Höke

Background and Aims

Recent preclinical studies have shown that nicotinamide adenine dinucleotide (NAD⁺) plays a critical role in molecular mechanisms of axon degeneration, and reductions in NAD⁺ levels are associated with axonal degeneration. Nicotinamide riboside (NR) is a safe and widely available pyridine-nucleoside form of vitamin B3 and is an NAD⁺ precursor.

Methods

To investigate if oral supplementation of synthetic NR can act as a therapeutic agent to prevent degeneration of small somatic sensory axons innervating the skin or promote regeneration of these same fibers in humans, we utilized a validated experimental model of cutaneous nerve degeneration and regeneration and conducted a placebo-controlled, double-blinded Phase 2 study.

Results

NR supplementation did not result in elevation of plasma NAD⁺ levels but resulted in a small increase in NAD⁺ in the skin samples. NR supplementation did not prevent capsaicin-induced degeneration of the epidermal sensory nerve fibers, and there was no difference in the amount of epidermal reinnervation at the 90-day visit. Although there was a small but statistically significant increase in the number of epidermal sensory nerve fibers at the 60-day visit, these results are preliminary and will need to be validated in larger studies.

Interpretation

At present oral NR supplementation, at the doses used in this study, cannot be recommended to prevent neuropathy or to improve nerve regeneration.

背景与目的：最近的临床前研究表明，烟酰胺腺嘌呤二核苷酸（NAD+）在轴突变性的分子机制中起着关键作用，NAD+水平的降低与轴突变性有关。烟酰胺核苷（Nicotinamide riboside， NR）是一种安全且广泛存在的维生素B3的吡啶核苷形式，是一种NAD+前体。方法：为了研究口服合成NR是否可以作为一种治疗药物来预防支配皮肤的小体感觉轴突的退化或促进这些纤维的再生，我们利用了一个经过验证的皮神经退化和再生的实验模型，并进行了一项安慰剂对照、双盲的2期研究。结果：NR补充没有导致血浆NAD+水平升高，但导致皮肤样本中NAD+水平小幅升高。补充NR并不能阻止辣椒素诱导的表皮感觉神经纤维变性，在90天的随访中，表皮神经再生的数量也没有差异。虽然在60天的随访中，表皮感觉神经纤维的数量有少量但统计学上显著的增加，但这些结果是初步的，需要在更大规模的研究中得到验证。解释：目前口服NR补充剂，在本研究中使用的剂量，不能被推荐用于预防神经病变或改善神经再生。

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引用次数: 0

Utility of the “Modified Erasmus GBS Respiratory Insufficiency Score” in Axonal and Demyelinating Guillain–Barré Syndrome “改良Erasmus GBS呼吸功能不全评分”在轴突和脱髓鞘格林-巴勒综合征中的应用。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2026-01-05 DOI: 10.1111/jns.70096

Yukari Sekiguchi, Sonoko Misawa, Marie Morooka, Tomoki Suichi, Yuki Shiko, Kohei Takahashi, Satoshi Kuwabara

Background

The modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) has been proposed to be a useful tool for predicting the risk of mechanical ventilation (MV) in Guillain–Barré syndrome (GBS), whereas most of the patients included in previous studies had classical demyelinating GBS. This study validated the utility of the mEGRIS in axonal, as well as demyelinating GBS, defined by electrophysiologic criteria in Japan.

Methods

Data from 214 consecutive patients diagnosed with GBS at our institution within 28 days from disease onset between 1998 and 2023 were reviewed and 200 patients with adequate data were analyzed. Acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) were diagnosed by sequential nerve conduction studies and mEGRIS was applied to each group.

Results

A total of 200 GBS patients were classified as AMAN (n = 73 [37%]), AIDP (n = 72 [36%]), or unclassified (n = 55 [28%]) and 27 (14%) patients required MV (18% of AMAN, 15% of AIDP). Patients with MV had a significantly higher mEGRIS than those without MV (17 [median range: 5–29] vs. 6 [0–22]). Approximately 81% of the patients in the moderate- or high-risk group (mEGRIS ≧ 18) required MV. Area under the curves (AUCs) of the mEGRIS prediction formulas was 0.89 (95% CI, 0.82–0.96) for total GBS group and 0.92 (95% CI, 0.85–1.00) for the AMAN group.

Interpretation

The mEGRIS is useful for predicting MV risk in patients with AMAN, as well as AIDP. Close monitoring was required for patients who were classified as moderate or high-risk by mEGRIS, irrespective of GBS subtypes.

背景：改进的Erasmus GBS呼吸功能不全评分（mEGRIS）被认为是预测格林-巴- 综合征（GBS）机械通气（MV）风险的有用工具，而先前研究中的大多数患者为典型脱髓鞘性GBS。这项研究证实了mEGRIS在轴突性和脱髓鞘性GBS（日本电生理标准定义）中的应用。方法：对1998年至2023年间在我院连续诊断为GBS的214例患者的资料进行回顾，并对200例资料充分的患者进行分析。通过序贯神经传导检查诊断急性运动轴索神经病（AMAN）和急性炎症性脱髓鞘多神经病变（AIDP），并应用mEGRIS进行观察。结果：共有200例GBS患者被分类为AMAN （n = 73[37%]）、AIDP （n = 72[36%]）或未分类（n = 55[28%]）， 27例（14%）患者需要MV（18%的AMAN， 15%的AIDP）。MV患者的mEGRIS显著高于无MV患者（17[中位范围：5-29]对6[0-22]）。中高危组（mEGRIS≧18）中约81%的患者需要MV。mEGRIS预测公式的曲线下面积（auc）在总GBS组为0.89 (95% CI, 0.82-0.96)， AMAN组为0.92 （95% CI, 0.85-1.00）。解释：mEGRIS可用于预测AMAN和AIDP患者的MV风险。对于mEGRIS分类为中度或高危的患者，无论GBS亚型如何，都需要密切监测。

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引用次数: 0

Patient Outcomes Among Medicare Beneficiaries With Guillain–Barré Syndrome 格林-巴罗综合征医疗保险受益人的患者结局。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-29 DOI: 10.1111/jns.70094

Brad Wright, Samantha R. Eiffert, Abagail Cirincione, Joshua Nardin, James F. Howard Jr, Rebecca E. Traub

Background and Aims

Understanding of population-level outcomes for patients with Guillain–Barré syndrome (GBS) remains limited. We identified which GBS patients are most likely to experience worse outcomes using the largest and most current GBS cohort in the United States.

Methods

This retrospective cohort study used 2005–2020 fee-for-service Medicare claims to identify individuals newly diagnosed with GBS (N = 16 280). We used three person-level modified Poisson regressions to estimate hospital and intensive care unit (ICU) lengths of stay and GBS episode length as a function of sociodemographic characteristics, comorbid conditions, and year of diagnosis. We also documented hospital-acquired pressure ulcers and deep vein thromboses as quality indicators.

Results

Median hospital length of stay was 9 days [IQR: 6–18 days] and median GBS episode length was 26 days [IQR: 10–60 days]. Approximately 43% of patients spent time in the ICU, with most of those stays (57%) lasting ≤ 1 week. On average, stays and episodes were significantly longer for men, those with a disability, and those diagnosed with an impulse control disorder, other nervous system diagnoses, or certain cancers, but significantly shorter for Black individuals and those dually eligible for Medicare and Medicaid. Most patients avoided developing pressure ulcers (96%) or deep vein thromboses (91%).

Interpretation

The GBS disease course varies significantly among Medicare enrollees. We identified some factors associated with worse GBS outcomes and others suggesting structural barriers to care. Our findings can improve care delivery by helping clinicians identify high-risk patients, facilitate early interventions, and reduce morbidity and mortality.

背景和目的：对格林-巴利综合征（GBS）患者人群水平结局的了解仍然有限。我们使用美国最大和最新的GBS队列来确定哪些GBS患者最有可能经历更糟糕的结果。方法：本回顾性队列研究使用2005-2020年按服务收费的医疗保险索赔来确定新诊断为GBS的个体（N = 16 280）。我们使用三个人水平的修正泊松回归来估计医院和重症监护病房（ICU）的住院时间和GBS发作时间作为社会人口学特征、合并症和诊断年份的函数。我们还记录了医院获得性压疮和深静脉血栓形成作为质量指标。结果：中位住院时间为9天[IQR: 6-18天]，中位GBS发作时间为26天[IQR: 10-60天]。大约43%的患者在ICU住院，其中大多数（57%）的住院时间≤1周。平均而言，男性、残疾人、被诊断为冲动控制障碍、其他神经系统诊断或某些癌症的人的住院时间和发作时间明显更长，但黑人和双重符合医疗保险和医疗补助资格的人的住院时间和发作时间明显更短。大多数患者避免发生压疮（96%）或深静脉血栓（91%）。解释：GBS病程在医保参保者中差异显著。我们确定了一些与更糟糕的GBS结果相关的因素，以及其他表明护理结构性障碍的因素。我们的研究结果可以帮助临床医生识别高危患者，促进早期干预，降低发病率和死亡率，从而改善护理服务。

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引用次数: 0

Prospective Evaluation of Machine-Assisted Electrophysiologic and Online Clinical Diagnostic Support Tools in Chronic Inflammatory Demyelinating Polyradiculoneuropathy 慢性炎症性脱髓鞘性多根神经病变的机器辅助电生理和在线临床诊断支持工具的前瞻性评价。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-18 DOI: 10.1111/jns.70084

Michael P. Skolka, Grace Swart, Shahar Shelly, Thapat Wannarong, Stefan Stålberg, Benjamin Stålberg, Abe Gardner, Jacob Price, Ruple S. Laughlin, Divyanshu Dubey, John R. Mills, Jay Mandrekar, Christopher J. Klein

Background and Aims

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a common, treatable, autoimmune, neuropathy frequently misdiagnosed. The complex electrodiagnostic (EDX) criteria required for diagnosis are challenging to apply in routine practice. This study evaluates the effectiveness of a machine-assisted EDX tool in real-time identification of demyelinating nerve conduction studies (NCS) stipulated by 2021-EAN/PNS CIDP criteria in conjunction with an online CIDP clinical probability calculator.

Methods

We prospectively evaluated 100 consecutive patients with referral or EDX diagnosis of polyradiculoneuropathy beginning January 1, 2024. Fifty patients were included, each from Jacksonville and Rochester Mayo Clinics. Routine electromyography (EMG) reports were compared to a machine-assisted support tool applying 2021-EAN/PNS CIDP EDX criteria to NCS assessing demyelination. The EDX-assistant performance was compared to the final clinical diagnosis and our previously reported online CIDP clinical prediction tool (https://news.mayocliniclabs.com/cidp-calculator/).

Results

Among 100 patients (60% male; median age 64), 30 had a final clinical CIDP diagnosis with 29 having intravenous immunoglobulin follow-up; 27 (93%) improved and 2 (7%) stabilized. Routine EMGs reported demyelination in 14 of 30 (47%), with 46% sensitivity and 79% specificity. The EDX-assistant identified CIDP demyelination in 28 of 30 (93%), with 93% sensitivity and 57% specificity. The clinical calculator detected CIDP in 30 of 30 (100%) with 86% specificity, increasing to 94% after excluding false positives lacking demyelinating features on the EDX tool.

Interpretation

A real-time machine-assisted EDX support tool, used with a clinical web-based calculator, streamlines CIDP assessment by improving standardized identification of 2021-EAN/PNS CIDP demyelinating NCS criteria and aiding clinical decisions.

背景和目的：慢性炎症性脱髓鞘性多根神经病变（CIDP）是一种常见的、可治疗的自身免疫性神经病变，常被误诊。诊断所需的复杂电诊断（EDX）标准在常规实践中应用具有挑战性。本研究评估了机器辅助EDX工具在2021-EAN/PNS CIDP标准规定的脱髓鞘神经传导研究（NCS）实时识别中的有效性，并结合在线CIDP临床概率计算器。方法：从2024年1月1日开始，我们前瞻性评估了100例转诊或EDX诊断为多神经根神经病变的连续患者。50名患者分别来自杰克逊维尔和罗切斯特梅奥诊所。将常规肌电图（EMG）报告与机器辅助支持工具进行比较，该工具应用2021-EAN/PNS CIDP EDX标准评估NCS脱髓鞘。将EDX-assistant的表现与最终临床诊断和我们之前报道的在线CIDP临床预测工具（https://news.mayocliniclabs.com/cidp-calculator/）.Results)进行比较：在100例患者中（60%为男性，中位年龄64岁），30例最终临床CIDP诊断，29例进行静脉免疫球蛋白随访；27例（93%）好转，2例（7%）稳定。常规肌电图显示30例中有14例（47%）脱髓鞘，敏感性46%，特异性79%。EDX-assistant在30例中有28例（93%）诊断出CIDP脱髓鞘，灵敏度为93%，特异性为57%。临床计算器在30例（100%）中检测出CIDP，特异性为86%，在排除EDX工具上缺乏脱髓鞘特征的假阳性后，特异性增加到94%。解释：实时机器辅助EDX支持工具与临床基于网络的计算器一起使用，通过改进2021-EAN/PNS CIDP脱髓鞘NCS标准的标准化识别并辅助临床决策，简化了CIDP评估。

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引用次数: 0

Longitudinal Assessment of Quality of Life and Functionality by CAP-PRI in Patients With Active Chronic Inflammatory Demyelinating Polyradiculoneuropathy CAP-PRI对活动性慢性炎症性脱髓鞘性多根神经病变患者的生活质量和功能的纵向评估。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-18 DOI: 10.1111/jns.70091

Ivo Bozovic, Kelly Gwathmey, Stojan Peric, Aleksandra Kacar, Jelena Lazovic, Reza Sadjadi, Ivana Basta

Background and Aims

In most studies to date, generic health-related quality of life (QoL) questionnaires have been used in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Unfortunately, these tools are often considered insufficient for capturing the unique characteristics of this specific, rare disease. The Chronic Acquired Polyneuropathy Patient-Reported Index (CAP-PRI) is a measure which specifically targets patients with chronic immune-mediated polyneuropathies. This is the first study which longitudinally assessed QoL and functionality by CAP-PRI in patients with active CIDP.

Methods

CAP-PRI testing was conducted at three time points (baseline, year one and year four) in 57 CIDP patients with active disease at baseline. In addition, the Medical Research Council Sum Score (MRC-SS), Inflammatory Neuropathy Cause and Treatment (INCAT) disability score, Inflammatory Rasch-built Overall Disability Scale (I-RODS), and the generic QOL instrument, the Short Form 36 (SF-36) were used in all tested patients at all three time points.

Results

At the baseline and two other time points, CAP-PRI showed strong correlations with impairment (MRC-SS), functionality (INCAT, I-RODS), and the SF-36. At year one and year four, CAP-PRI was able to make a differentiation between patients whose impairment/disability improved compared to patients who deteriorated, and it performed better than SF-36. One- and four-year changes in CAP-PRI correlated with a change in MRC-SS, INCAT, and I-RODS.

Interpretation

CAP-PRI is a highly reliable and sensitive measure for assessing QoL in patients with active CIDP. Its consistent performance over time supports its utility in monitoring CIDP patients with active disease in clinical and research settings.

背景和目的：在迄今为止的大多数研究中，通用的健康相关生活质量（QoL）问卷调查已用于慢性炎症性脱髓鞘性多根神经病变（CIDP）患者。不幸的是，这些工具通常被认为不足以捕捉这种特殊的罕见疾病的独特特征。慢性获得性多神经病变患者报告指数（CAP-PRI）是一种专门针对慢性免疫介导的多神经病变患者的指标。这是第一个通过CAP-PRI对活动性CIDP患者的生活质量和功能进行纵向评估的研究。方法：在三个时间点（基线、第1年和第4年）对57例基线时疾病活动性的CIDP患者进行CAP-PRI测试。此外，医学研究委员会总评分（MRC-SS）、炎症性神经病变病因和治疗（INCAT）残疾评分、炎症性rasch构建的整体残疾量表（I-RODS）和通用的生活质量量表短表36 （SF-36）在所有三个时间点被用于所有被测试的患者。结果：在基线和其他两个时间点，CAP-PRI显示与损伤（MRC-SS）、功能（INCAT, I-RODS）和SF-36有很强的相关性。在第一年和第四年，CAP-PRI能够区分损伤/残疾改善的患者与恶化的患者，并且它比SF-36表现更好。1年和4年CAP-PRI的变化与MRC-SS、INCAT和i - rod的变化相关。CAP-PRI是一种高度可靠和敏感的评估活动性CIDP患者生活质量的方法。随着时间的推移，它的一贯表现支持了它在临床和研究环境中监测患有活动性疾病的CIDP患者的效用。

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引用次数: 0

Impact of High-Dose Tafamidis on Hereditary ATTR (ATTRv) Amyloidosis With Central Nervous System Involvement: Two Case Reports With Clinical, Radiological and Cerebrospinal Fluid Follow Up 高剂量他法非地对遗传性ATTR （ATTRv）淀粉样变性伴中枢神经系统的影响：2例临床、影像学和脑脊液随访报告

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-11 DOI: 10.1111/jns.70088

Victor Jia Wei Zhang, Laura Mantoan Ritter, Chandrashekar Hoskote, Ata Siddiqui, Michael Lunn, Julian Gillmore, Mary M. Reilly

Background

Treatment options for central nervous system (CNS) manifestations of ATTRv amyloidosis remain limited, with no disease-modifying therapy. However, previous case series have indicated that tafamidis (a transthyretin stabiliser) crosses the blood–brain barrier in small quantities. We present long-term follow-up data on two patients with CNS manifestations of ATTRv who received high-dose (61 mg) oral tafamidis.

Methods

Patient one is a 48-year-old man with p.Gly73Ala ATTRv peripheral neuropathy and commenced on gene-silencing therapy. He was subsequently diagnosed with early ATTRv CNS involvement, prompting the addition of tafamidis since age 45. Patient two is a 27-year-old woman with p.Gly67Arg ATTRv with significant CNS involvement resulting in epilepsy and encephalopathy. Since age 21, she has been on gene-silencing therapy and tafamidis.

Results

Following 3 years of therapy, patient one has remained clinically asymptomatic. However, brain magnetic resonance imaging (MRI) and cerebrospinal fluid assessment have demonstrated progression of his CNS ATTRv. Followed 6 years of therapy, patient two has continued to have seizures requiring escalation of anti-seizure medications and MRI brain has shown progression of CNS disease.

Conclusions

In our two patients, progression of CNS disease occurred whilst on high-dose tafamidis, highlighting the importance of further studies into the monitoring and treatment of CNS manifestations of ATTRv.

背景：ATTRv淀粉样变的中枢神经系统（CNS）表现的治疗选择仍然有限，没有疾病改善治疗。然而，先前的病例系列表明，他法底斯（一种甲状腺素转运稳定剂）穿过血脑屏障的量很小。我们对两名接受高剂量（61 mg）口服他法非地的有中枢神经系统表现的ATTRv患者进行了长期随访。方法患者1为48岁男性p.Gly73Ala ATTRv周围神经病变患者，开始接受基因沉默治疗。随后，他被诊断为早期ATTRv中枢神经系统受累，促使他在45岁时增加了他法底肌。患者2为一名27岁女性，患有p.Gly67Arg ATTRv，伴有明显的中枢神经系统受累，导致癫痫和脑病。从21岁开始，她就一直在接受基因沉默疗法和塔法米底疗法。结果经3年治疗，患者1无临床症状。然而，脑磁共振成像（MRI）和脑脊液评估显示他的中枢神经系统ATTRv进展。经过6年的治疗，患者2持续出现癫痫发作，需要增加抗癫痫药物治疗，MRI显示中枢神经系统疾病进展。在我们的两例患者中，高剂量他法非底斯治疗期间发生了中枢神经系统疾病的进展，这突出了进一步研究ATTRv中枢神经系统表现的监测和治疗的重要性。

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引用次数: 0

Blood 1-Deoxysphingolipid Levels Are Associated With Epidermal Denervation in Small Fiber Neuropathy 血1-脱氧鞘脂水平与小纤维神经病表皮失神经支配有关。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-11 DOI: 10.1111/jns.70089

Luisa Kreß, Caren Meyer zu Altenschildesche, Nadine Egenolf, Claudia Sommer, Thorsten Hornemann, Nurcan Üçeyler

Background and Aims

Dysfunctional sphingolipid metabolism leads to nerve fiber degeneration, particularly of small caliber Aδ and C fibers, in hereditary sensory and autonomic neuropathies. We aimed to investigate the association of blood 1-deoxysphingolipid (1-deoxySL) profiles and skin denervation in idiopathic small fiber neuropathy (SFN).

Methods

Seventy-five patients with idiopathic SFN were recruited prospectively. Patients underwent a skin punch biopsy at the lower leg and upper thigh for intraepidermal nerve fiber density (IENFD) quantification. IENFD was correlated with individual blood 1-deoxySL levels, amino acid profiles, and determinants of glucose and lipoprotein metabolism.

Results

Median distal IENFD in SFN patients was 5.3 fibers/mm. In 38/75 (51%) patients, IENFD was ≤ 5.3 fibers/mm (i.e., “low fiber density,” LFD), while in 37/75 (49%) patients, IENFD was > 5.3 fibers/mm (i.e., “high fiber density,” HFD). 1-deoxySL was higher in patients with LFD compared to HFD (p < 0.05). Fasting plasma glucose was also higher in patients with LFD than in patients with HFD (p < 0.01), while HDL was lower in patients with LFD compared to HFD (p < 0.001).

Interpretation

1-deoxySL, lipoprotein metabolism, and glucose levels are associated with the extent of epidermal denervation in SFN, supporting the role of this metabolic axis in small nerve fiber pathology.

背景和目的：在遗传性感觉和自主神经病变中，鞘脂代谢功能障碍导致神经纤维变性，特别是小口径Aδ和C纤维变性。我们旨在研究特发性小纤维神经病（SFN）患者血液1-脱氧鞘脂（1-deoxySL）谱与皮肤去神经支配的关系。方法：前瞻性招募75例特发性SFN患者。患者在小腿和大腿上部进行皮肤穿刺活检，以量化表皮内神经纤维密度（IENFD）。IENFD与个体血液1-脱氧ysl水平、氨基酸谱以及葡萄糖和脂蛋白代谢的决定因素相关。结果：SFN患者中位远端IENFD为5.3纤维/mm。在38/75（51%）的患者中，IENFD≤5.3纤维/mm（即“低纤维密度”LFD），而在37/75（49%）的患者中，IENFD为bb0 5.3纤维/mm（即“高纤维密度”HFD）。解释：1-deoxySL、脂蛋白代谢和葡萄糖水平与SFN中表皮失神经支配的程度相关，支持该代谢轴在小神经纤维病理中的作用。

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引用次数: 0

Nonsystemic Vasculitic Neuropathy—A Brazilian Case Series 非全身性血管性神经病-巴西病例系列。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-09 DOI: 10.1111/jns.70086

Victor Evangelista Rodrigues Pereira, Roberto Pereira Santos, Marcos Raimundo Gomes de Freitas, Manuella Lima Gomes Ochtrop, Ana Caroline Siquara-De-Souza, Salim L. Balassiano, Marcia Rodrigues Jardim

Background and Aims

Vasculitides are a heterogeneous group of immune-mediated inflammatory disorders that compromise the vascuar wall, leading to luminal narrowing and tissue ischemia. When inflammation selectively affects the vasa nervorum without systemic involvement, it results in nonsystemic vasculitic neuropathy (NSVN), an underrecognized condition. NSVN presents diagnostic challenges due to its variable clinical manifestations and reliance on nerve biopsy for definitive diagnosis. This study aimed to characterize the clinical, neurophysiological, and histopathological features of NSVN in a Brazilian cohort.

Methods

We conducted a cross-sectional, ambispective cohort study combining retrospective chart review and prospective patient assessments. Inclusion required histopathological confirmation of isolated peripheral nerve vasculitis; cases with systemic or secondary vasculitis were excluded. Data collection included clinical evaluation, neurophysiology, and nerve biopsy.

Results

A total of 14 patients were included (9 female, 64%; mean age: 61). Most (n = 8, 57%) had subacute onset of painful sensory or sensorimotor deficits. Multiple mononeuropathies predominated (n = 11, 78%), but a subset exhibited chronic progression (n = 5, 35%) and axonal polyneuropathy (n = 3, 21%). Electrophysiological studies revealed a consistent axonal pattern. Biopsies confirmed possible vasculitis in six (43%), and probable vasculitis in six (42%), with only two (14%) fulfilling criteria for definite vasculitis. Serologies were nonspecific. Treatment involved corticosteroid pulse therapy, with immunosuppression in refractory cases.

Interpretation

These findings highlight that NSVN often presents with painful sensorimotor symptoms and may clinically mimic progressive axonal polyneuropathies. Given its potential for significant morbidity if left untreated, early recognition and consideration of nerve biopsy remain critical. The diagnostic complexity and variability in presentation suggest that NSVN may be underrecognized. We hope this cohort contributes to a broader understanding of its clinical spectrum and informs future diagnostic strategies.

背景和目的：血管炎是一种异质免疫介导的炎症性疾病，损害血管壁，导致管腔狭窄和组织缺血。当炎症选择性地影响血管神经而不累及全身时，它会导致非全身性血管性神经病（NSVN），这是一种未被认识的疾病。NSVN由于其多变的临床表现和对神经活检的明确诊断的依赖，提出了诊断挑战。本研究旨在描述巴西队列中NSVN的临床、神经生理和组织病理学特征。方法：我们进行了一项横断面、双视角队列研究，结合回顾性图表回顾和前瞻性患者评估。孤立性周围神经血管炎需要组织病理学证实；排除全身性或继发性血管炎病例。数据收集包括临床评估、神经生理学和神经活检。结果：共纳入14例患者，其中女性9例，占64%，平均年龄61岁。大多数（n = 8.57%）有亚急性发作的疼痛感觉或感觉运动缺陷。多发性单神经病变占主导地位（n = 11,78%），但一小部分表现为慢性进展（n = 5,35%）和轴突多神经病变（n = 3,21%）。电生理研究显示了一致的轴突模式。活检证实6例（43%）可能有血管炎，6例（42%）可能有血管炎，只有2例（14%）符合明确的血管炎标准。血清学无特异性。治疗包括皮质类固醇脉冲治疗，对难治性病例进行免疫抑制。解释：这些发现强调NSVN通常表现为疼痛的感觉运动症状，并且在临床上可能类似于进行性轴突多发性神经病。如果不及时治疗，其潜在的显著发病率，早期识别和考虑神经活检仍然是至关重要的。诊断的复杂性和表现的可变性表明NSVN可能未被充分认识。我们希望这个队列有助于更广泛地了解其临床谱，并告知未来的诊断策略。

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引用次数: 0

Novel Dominant Splicing Variant in MPZ Associated With Unusual Charcot–Marie–Tooth Disease 与不寻常的腓骨-玛丽-牙病相关的MPZ显性剪接新变异。

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-12-09 DOI: 10.1111/jns.70085

Anthony Maino, Florence Hazane-Puch, Philippe Petiot, Nathalie Roux-Buisson, John Rendu, Julien Fauré, Gaëlle Hardy

Background and Aims

Variants in the myelin protein zero coding MPZ gene are responsible for a broad spectrum of peripheral demyelinating and axonal neuropathies, including different types of Charcot–Marie–Tooth diseases, challenging for genotype–phenotype correlation.

Methods

Minigene splicing reporter assay was used to unveil the pathogenic mechanism of a novel MPZ(NM_000530.8) c.234 + 1G>C p.(?) heterozygous splice variant.

Results

The variant was identified in a 47-year-old female patient presenting with atypical clinical features, including balance disturbance with positive Romberg, absent Achilles tendon reflexes, distal hypoesthesia and bulbar involvement, including dysarthria and dysphagia. Electromyography revealed a sensory-motor neuropathy with moderately reduced nerve conduction velocities. In silico analysis predicted this variant to disrupt the consensual donor splice site located in intron 2 of MPZ. Minigene construction confirmed the functional impact of this variant, revealing exon 2 skipping and the apparition of a premature termination codon.

Interpretation

This case expends the genotype–phenotype correlations of MPZ-related Charcot–Marie–Tooth diseases, associating atypical mild phenotype with a rare splice dominant variant, and provides new insights into MPZ haploinsufficiency and pathogenic mechanisms.

背景和目的：髓鞘蛋白零编码MPZ基因的变异是广泛的外周脱髓鞘和轴突神经病变的原因，包括不同类型的沙科-玛丽-牙病，对基因型-表型相关性具有挑战性。方法：采用Minigene剪接报告基因试验，揭示新型MPZ(NM_000530.8) C .234 + 1G>C . p.（?）杂合剪接变异的致病机制。结果：该变异在一名47岁女性患者中被发现，其临床特征不典型，包括平衡障碍，Romberg阳性，跟腱反射缺失，远端感觉减退和球受累，包括构音障碍和吞咽困难。肌电图显示感觉-运动神经病变，神经传导速度中度降低。计算机分析预测这种变异会破坏位于MPZ内含子2上的供体剪接位点。miniigene的构建证实了该变异的功能影响，揭示了外显子2的跳跃和一个过早终止密码子的出现。解释：本病例扩展了MPZ相关沙克-玛丽-图斯病的基因型-表型相关性，将非典型轻度表型与罕见的剪接显性变异联系起来，并为MPZ单倍性不足和致病机制提供了新的见解。

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引用次数: 0