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Cardiovascular autonomic neuropathy in patients with type 2 diabetes with and without sensorimotor polyneuropathy 伴有和不伴有感觉运动多神经病变的2型糖尿病患者的心血管自主神经病变
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-07-14 DOI: 10.1111/jns.12580
Emil Peters, Mustapha Itani, Alexander G. Kristensen, Astrid Juhl Terkelsen, Thomas Krøigård, Hatice Tankisi, Troels S. Jensen, Nanna B. Finnerup, Sandra Sif Gylfadottir

Background and Aims

Cardiovascular autonomic neuropathy (CAN) in patients with diabetes is associated with poor prognosis. We aimed to assess signs of CAN and autonomic symptoms and to investigate the impact of sensorimotor neuropathy on CAN by examining type 2 diabetes patients with (DPN [distal sensorimotor polyneuropathy]) and without distal sensorimotor polyneuropathy (noDPN) and healthy controls (HC). Secondarily, we aimed to describe the characteristics of patients with CAN.

Methods

A population of 374 subjects from a previously described cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) were included. Subjects were examined with the Vagus™ device for the diagnosis of CAN, where two or more abnormal cardiovascular autonomic reflex tests indicate definite CAN. Autonomic symptoms were assessed with Composite Autonomic Symptom Score 31 (COMPASS 31) questionnaire. DPN was defined according to the Toronto consensus panel definition.

Results

Definite CAN was present in 22% with DPN, 7% without DPN and 3% of HC, and 91% of patients with definite CAN had DPN. Patients with DPN and definite CAN reported higher COMPASS 31 scores compared to patients with noDPN (20.0 vs. 8.3, p < 0.001) and no CAN (22.1 vs. 12.3, p = 0.01). CAN was associated with HbA1c and age in a multivariate logistic regression analysis but was not associated with IEFND or triglycerides.

Interpretation

One in five patients with DPN have CAN and specific CAN characteristics may help identify patients at risk for developing this severe diabetic complication. Autonomic symptoms were strongly associated with having both DPN and CAN, but too unspecific for diagnosing CAN.

背景与目的糖尿病患者心血管自主神经病变(CAN)与不良预后相关。我们旨在通过检查伴有远端感觉运动多神经病变(DPN)、无远端感觉运动多神经病变(noDPN)和健康对照(HC)的2型糖尿病患者,评估CAN的体征和自主神经症状,并研究感觉运动神经病变对CAN的影响。其次,我们旨在描述CAN患者的特征。方法从丹麦2型糖尿病战略研究中心(DD2)先前描述的队列中纳入374名受试者。受试者使用Vagus™设备进行检查以诊断CAN,当两项或两项以上的心血管自主反射测试异常表明明确的CAN时。采用自主神经症状综合评分31 (COMPASS 31)问卷评估自主神经症状。DPN是根据多伦多共识小组定义定义的。结果明确的CAN在22%的DPN患者、7%的非DPN患者和3%的HC患者中存在,91%的明确CAN患者患有DPN。DPN和明确CAN患者的COMPASS 31评分高于noDPN患者(20.0比8.3,p < 0.001)和无CAN患者(22.1比12.3,p = 0.01)。在多变量logistic回归分析中,CAN与HbA1c和年龄相关,但与IEFND或甘油三酯无关。五分之一的DPN患者患有CAN,特定的CAN特征可能有助于识别有发生这种严重糖尿病并发症风险的患者。自主神经症状与患有DPN和CAN密切相关,但对于诊断CAN过于特异性。
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引用次数: 0
Phenotypic features of RETREG1-related hereditary sensory autonomic neuropathy retreg1相关遗传性感觉自主神经病变的表型特征
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-07-14 DOI: 10.1111/jns.12581
Arman Çakar, Gulandam Bagırova, Hacer Durmuş, Oya Uyguner, Yeşim Parman

Background and Aims

Homozygous loss-of-function mutations in the RETREG1 gene result in Hereditary Sensory Autonomic Neuropathy Type 2B. Clinical features include pain loss, autonomic disturbances, and upper motor neuron features.

Methods

We evaluated the clinical and genetic features of seven patients from four families with RETREG1 variants.

Results

Five patients were male. The median age of disease onset was 7.00 ± 2.81 (between 2 and 10 years). A combination of painless wounds, trophic changes, and foot ulcerations was the presenting symptom in five patients and walking difficulties in two. Motor symptoms were present in five patients. In a median disease duration of 30.00 ± 12.88 years, five patients had osteomyelitis, and three had toe amputations. A history of renal disease was present in one family. In another family, three affected siblings had short stature and a history of delayed puberty. Although sensory signs predominated the clinical findings, various degrees of motor signs such as muscle weakness, spasticity, and brisk tendon reflexes were noted in all patients. Nerve conduction studies showed axonal sensory-motor neuropathy in five patients and sensory neuropathy in two. Three pathogenic variants were identified in the RETREG1 gene. Two unrelated patients had a homozygous c.433C > T/p.(Gln145*), one a homozygous c.826delA/p.(Ser276Valfs*8), and the last had a novel homozygous c.102delC/p.(Ala35Glnfs*349) variants.

Interpretation

In our study, all patients showed signs and symptoms consistent with pain insensitivity. Although shadowed by sensory symptoms, motor signs were noted in our patients. Further studies are necessary to clarify the causal relationship between extra-neurological features and RETREG1 mutations.

背景与目的RETREG1基因的纯合子功能丧失突变可导致遗传性感觉自主神经病变2B型。临床特征包括疼痛丧失、自主神经紊乱和上运动神经元特征。方法分析来自4个家族的7例RETREG1变异患者的临床和遗传特征。结果男性5例。发病年龄中位数为7.00±2.81岁(2 ~ 10岁)。无痛伤口、营养改变和足部溃疡是5例患者的主要症状,2例患者行走困难。5例患者出现运动症状。病程中位数为30.00±12.88年,5例患者发生骨髓炎,3例患者截肢。1个家族有肾脏疾病史。在另一个家庭中,三个受影响的兄弟姐妹身材矮小,并且有青春期延迟的历史。虽然临床表现以感觉体征为主,但所有患者均有不同程度的运动体征,如肌肉无力、痉挛和肌腱反射快。神经传导研究显示轴突感觉-运动神经病变5例,感觉神经病变2例。在RETREG1基因中鉴定出三种致病变异。2例无亲缘关系的患者为纯合子c.433C > T/p.(Gln145*), 1例为纯合子c.826delA/p.(Ser276Valfs*8),最后1例为新型纯合子c.102delC/p.(Ala35Glnfs*349)。在我们的研究中,所有患者都表现出与疼痛不敏感相一致的体征和症状。虽然被感觉症状所掩盖,但我们的患者也注意到运动体征。需要进一步的研究来阐明神经外特征与RETREG1突变之间的因果关系。
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引用次数: 0
Somatosensory profiling of patients undergoing alcohol withdrawal: Do neuropathic pain and sensory loss represent a problem? 酒精戒断患者的体感特征分析:神经性疼痛和感觉丧失是否代表一个问题?
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-07-07 DOI: 10.1111/jns.12578
Aurore Fernandez, Guillaume Graf, Aurélie Lasserre, Jean-Bernard Daeppen, Paul Chu Sin Chung, Chantal Berna, Marc R. Suter

Introduction

Chronic heavy alcohol use is known to cause neurological complications such as peripheral neuropathy. Concerning the pathophysiology, few sural nerve and skin biopsy studies showed that small fibers might be selectively vulnerable to degeneration in alcohol-related peripheral neuropathy. Pain has rarely been properly evaluated in this pathology. The present study aims at assessing pain intensity, potential neuropathic characteristics as well as the functionality of both small and large nerve sensitive fibers.

Methods

In this observational study, 27 consecutive adult patients, hospitalized for alcohol withdrawal and 13 healthy controls were recruited. All the participants underwent a quantitative sensory testing (QST) according to the standardized protocol of the German Research Network Neuropathic Pain, a neurological examination and filled standardized questionnaires assessing alcohol consumption and dependence as well as pain characteristics and psychological comorbidities.

Results

Nearly half of the patients (13/27) reported pain. Yet, pain intensity was weak, leading to a low interference with daily life, and its characteristics did not support a neuropathic component. A functional impairment of small nerve fibers was frequently described, with thermal hypoesthesia observed in 52% of patients. Patients with a higher alcohol consumption over the last 2 years showed a greater impairment of small fiber function.

Discussion

Patients report pain but it is however unlikely to be caused by peripheral neuropathy given the non-length-dependent distribution and the absence of neuropathic pain features. Chronic pain in AUD deserves to be better evaluated and managed as it represents an opportunity to improve long-term clinical outcomes, potentially participating to relapse prevention.

众所周知,长期大量饮酒可引起神经系统并发症,如周围神经病变。在病理生理学方面,很少有腓肠神经和皮肤活检研究表明,小纤维可能选择性地易发生酒精相关周围神经病变的变性。在这种病理中,疼痛很少得到适当的评估。本研究旨在评估疼痛强度,潜在的神经病变特征以及小神经和大神经敏感纤维的功能。方法在本观察性研究中,连续招募27例因酒精戒断住院的成年患者和13名健康对照者。根据德国神经性疼痛研究网络的标准化方案,所有参与者都进行了定量感觉测试(QST),进行了神经学检查,并填写了评估酒精消耗和依赖、疼痛特征和心理合并症的标准化问卷。结果近一半(13/27)的患者报告疼痛。然而,疼痛强度较弱,导致对日常生活的干扰较低,其特征不支持神经性成分。小神经纤维的功能损伤经常被描述,52%的患者观察到热感觉减退。在过去2年中,高饮酒量的患者显示出更大的小纤维功能损害。患者报告疼痛,但考虑到非长度依赖性分布和缺乏神经性疼痛特征,疼痛不太可能由周围神经病变引起。AUD的慢性疼痛值得更好地评估和管理,因为它代表了改善长期临床结果的机会,可能参与复发预防。
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引用次数: 0
Assessing diabetic polyneuropathy in Spanish-speaking patients: Translation and validation of the Toronto Clinical Neuropathy Score 评估西班牙语患者的糖尿病多发性神经病变:多伦多临床神经病评分的翻译和验证
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-06-24 DOI: 10.1111/jns.12577
Juan Francisco Idiáquez Rios, Ignacio Acosta, Alberto Prat, Francesca Gattini, Francisca Pino, Carolina Barnett-Tapia

Background and Aims

Diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes. The Toronto Clinical Neuropathy Score (TCNS) is a useful tool for detecting DSP. However, it is not available in Spanish. The study aimed to translate and culturally adapt the TCNS and modified (mTCNS) scales into Spanish and evaluate their measurement properties.

Methods

A multistep forward-backward method was used for translation and cultural adaptation. A panel of physicians subjected the final Spanish versions of TCNS and mTCNS (TCÑS, mTCÑS) to cognitive debriefing. Consecutive patients with diabetes mellitus and DSP were recruited from an outpatient clinic, and the TCÑS and mTCÑS were tested for construct validity, along with other measures.

Results

The internal consistency of both TCÑS and mTCÑS was excellent, as evidenced by Cronbach's Alpha coefficients of 0.83 and 0.85, respectively. Furthermore, there was a robust positive correlation between TCÑS and mTCÑS. In addition, TCÑS was found to exhibit a strong negative correlation with sural sensory nerve action potential amplitude (r = −0.9206) and peroneal compound motor action potential amplitude (r = −0.729), while demonstrating a positive and strong correlation with the Michigan Neuropathy Screening Instrument (r = 0.713).

Interpretation

The TCÑS and mTCÑS are reliable and valid translations of the original TCNS. The TCÑS and mTCÑS can be used to diagnose and measure the severity of neuropathy in Spanish-speaking patients with diabetes.

背景与目的糖尿病感觉运动多神经病变(DSP)是糖尿病的常见并发症。多伦多临床神经病评分(Toronto Clinical Neuropathy Score, TCNS)是检测DSP的有效工具。然而,它没有西班牙语版本。本研究旨在将TCNS和修正(mTCNS)量表翻译成西班牙语并进行文化适应,并评估其测量特性。方法采用多步前退法进行翻译和文化适应。一组医生对最终的西班牙语版本的TCNS和mTCNS (TCÑS, mTCÑS)进行认知情况汇报。从门诊连续招募糖尿病和DSP患者,并对TCÑS和mTCÑS以及其他措施进行结构效度检验。结果TCÑS和mTCÑS的内部一致性较好,Cronbach’s Alpha系数分别为0.83和0.85。此外,TCÑS和mTCÑS之间存在显著的正相关。此外,TCÑS与腓肠感觉神经动作电位幅值(r =−0.9206)和腓肠复合运动动作电位幅值(r =−0.729)呈强负相关,而与密歇根神经病变筛查仪呈强正相关(r = 0.713)。TCÑS和mTCÑS是对原TCNS的可靠、有效的翻译。TCÑS和mTCÑS可用于诊断和测量西班牙语糖尿病患者神经病变的严重程度。
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引用次数: 0
Serum neurofilament light chain measurements following nerve trauma 神经损伤后血清神经丝轻链测量
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-06-22 DOI: 10.1111/jns.12576
Matthew Wilcox, Melissa L. D. Rayner, Owein Guillemot-Legris, Isobel Platt, Hazel Brown, Tom Quick, James B. Phillips

Background

Optimal functional recovery following peripheral nerve injuries (PNIs) is dependent upon early recognition and prompt referral to specialist centres for appropriate surgical intervention. Technologies which facilitate the early detection of PNI would allow faster referral rates and encourage improvements in patient outcomes. Serum Neurofilament light chain (NfL) measurements are cheaper to perform, easier to access and interpret than many conventional methods used for nerve injury diagnosis, such as electromyography and/or magnetic resonance imaging assessments, but changes in serum NfL levels following traumatic PNI have not been investigated. This pre-clinical study aimed to determine whether serum NfL levels can: (1) detect the presence of a nerve trauma and (2) delineate between different severities of nerve trauma.

Methods

A rat sciatic nerve crush and common peroneal nerve crush were implemented as controlled animal models of nerve injury. At 1-, 3-, 7- and 21-days post-injury, serum samples were retrieved for analysis using the SIMOA® NfL analyser kit. Nerve samples were also retrieved for histological analysis. Static sciatic index (SSI) was measured at regular time intervals following injury.

Results

Significant 45-fold and 20-fold increases in NfL serum levels were seen 1-day post-injury following sciatic and common peroneal nerve injury, respectively. This corresponded with an eightfold higher volume of axons injured in the sciatic compared to the common peroneal nerve (p < .001). SSI measurements post-injury revealed greater reduction in function in the sciatic crush group compared with the common peroneal crush group.

Conclusions

NfL serum measurements represent a promising method for detecting traumatic PNI and stratifying their severity. Clinical translation of these findings could provide a powerful tool to improve the surgical management of nerve-injured patients.

背景:周围神经损伤(PNIs)后的最佳功能恢复取决于早期识别和及时转诊到专科中心进行适当的手术干预。有助于早期发现PNI的技术将加快转诊率,并鼓励改善患者的预后。血清神经丝轻链(NfL)测量比许多用于神经损伤诊断的传统方法(如肌电图和/或磁共振成像评估)更便宜,更容易获取和解释,但尚未研究创伤性PNI后血清NfL水平的变化。这项临床前研究旨在确定血清NfL水平是否可以:(1)检测神经损伤的存在,(2)区分不同程度的神经损伤。方法采用大鼠坐骨神经压迫和腓总神经压迫作为神经损伤的对照动物模型。在损伤后1、3、7和21天,提取血清样本,使用SIMOA®NfL分析仪试剂盒进行分析。同时提取神经样本进行组织学分析。在损伤后定期测量静态坐骨指数(SSI)。结果坐骨神经和腓总神经损伤后1天血清NfL水平分别升高45倍和20倍。与腓总神经相比,坐骨神经的轴突损伤量增加了8倍(p < .001)。损伤后SSI测量显示,与普通腓骨挤压组相比,坐骨挤压组的功能下降更大。结论NfL血清检测是一种检测外伤性PNI并区分其严重程度的有效方法。这些发现的临床翻译可以为改善神经损伤患者的外科治疗提供有力的工具。
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引用次数: 0
Plasma neurofilament light chain concentrations are elevated in youth-onset type 2 diabetes and associated with neuropathy 青年期2型糖尿病患者血浆神经丝轻链浓度升高,并与神经病变相关。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-06-21 DOI: 10.1111/jns.12575
Vera Fridman, Stefan Sillau, Alanna Ritchie, Jacob Bockhorst, Christina Coughlan, Paula Araya, Joaquin M. Espinosa, Keith Smith, Ethan M. Lange, Leslie A. Lange, Laure El Ghormli, Kimberly L. Drews, Philip Zeitler, Jane E. B. Reusch

Background and Aims

The lack of easily measurable biomarkers remains a challenge in executing clinical trials for diabetic neuropathy (DN). Plasma Neurofilament light chain (NFL) concentration is a promising biomarker in immune-mediated neuropathies. Longitudinal studies evaluating NFL in DN have not been performed.

Methods

A nested case–control study was performed on participants with youth-onset type 2 diabetes enrolled in the prospective Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Plasma NFL concentrations were measured at 4-year intervals from 2008 to 2020 in 50 participants who developed DN and 50 participants with type 2 diabetes who did not develop DN.

Results

NFL concentrations were similar in the DN and no DN groups at the first assessment. Concentrations were higher in DN participants at all subsequent assessment periods (all p < .01). NFL concentrations increased over time in both groups, with higher degrees of change in DN participants (interaction p = .045). A doubling of the NFL value at Assessment 2 in those without DN increased the odds of ultimate DN outcome by an estimated ratio of 2.86 (95% CI: [1.30, 6.33], p = .0046). At the final study visit, positive Spearman correlations (controlled for age, sex, diabetes duration, and BMI) were observed between NFL and HbA1c (0.48, p < .0001), total cholesterol (0.25, p = .018), and low-density lipoprotein (LDL (0.30, p = .0037)). Negative correlations were observed with measures of heart rate variability (−0.42 to −0.46, p = <.0001).

Interpretation

The findings that NFL concentrations are elevated in individuals with youth-onset type 2 diabetes, and increase more rapidly in those who develop DN, suggest that NFL could be a valuable biomarker for DN.

背景和目的:在糖尿病神经病变(DN)的临床试验中,缺乏易于测量的生物标志物仍然是一个挑战。血浆神经丝轻链(NFL)浓度是免疫介导的神经病变中一种很有前途的生物标志物。尚未进行评估DN中NFL的纵向研究。方法:对参与青少年2型糖尿病前瞻性治疗方案(TODAY)研究的青年发病2型糖尿病参与者进行嵌套病例对照研究。从2008年到2020年,每隔4年测量50名患DN的参与者和50名未患DN的2型糖尿病参与者的血浆NFL浓度。结果:在第一次评估时,DN组和无DN组的NFL浓度相似。DN参与者在随后的所有评估期内的浓度都较高(所有p 解释:研究结果表明,青年期2型糖尿病患者的NFL浓度升高,而DN患者的NFL浓度增加更快,这表明NFL可能是DN的一个有价值的生物标志物。
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引用次数: 1
Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial 透明质酸酶促进的皮下免疫球蛋白10%作为慢性炎症性脱髓鞘性多根神经病变的维持治疗:ADVANCE-CIDP 1随机对照试验
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-06-14 DOI: 10.1111/jns.12573
Vera Bril, Robert D. M. Hadden, Thomas H. Brannagan III, Michal Bar, Elisabeth Chroni, Konrad Rejdak, Alberto Rivero, Henning Andersen, Norman Latov, Todd Levine, Mamatha Pasnoor, Sabrina Sacconi, Nizar Souayah, Colin Anderson-Smits, Kim Duff, Erin Greco, Shabbir Hasan, Zhaoyang Li, Leman Yel, Hakan Ay

Background and Aims

ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse.

Methods

ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0–7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints.

Results

Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: −21.8% [−34.5%, −7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common.

Interpretation

fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.

背景与目的ADVANCE-CIDP 1评估促性皮下免疫球蛋白(fSCIG;人免疫球蛋白G 10%联合重组人透明质酸酶预防慢性炎症性脱髓鞘性多根神经病变(CIDP)复发的有效性和安全性。ADVANCE-CIDP 1是一项3期、双盲、安慰剂对照试验,在21个国家的54个地点进行。符合条件的成年人有明确或可能的CIDP,调整炎症性神经病变病因和治疗(INCAT)残疾评分为0-7分(含),并在筛查前接受稳定静脉注射免疫球蛋白(IVIG)≥12周。停止IVIG后,患者按1:1随机分配至fSCIG 10%或安慰剂组,持续6个月或直到复发/停药。10%的fSCIG以与预随机IVIG相同的剂量(或匹配的安慰剂体积)和间隔给予。主要结局是在修改意向治疗人群中经历CIDP复发的患者比例(与皮下治疗前基线相比,调整后的INCAT评分增加≥1分)。次要终点包括复发时间和安全性终点。结果132例患者(平均年龄54.4岁,56.1%为男性)接受fSCIG 10% (n = 62)或安慰剂(n = 70)治疗。与安慰剂相比,fSCIG组CIDP复发率降低10% (n = 6 [9.7%;95%置信区间4.5%,19.6%]vs n = 22 [31.4%;21.8%, 43.0%];绝对的区别:−−−34.5%,7.9%,21.8% p = .0045)。随着时间的推移,安慰剂组的复发概率比fSCIG组高10% (p = 0.002)。fSCIG组不良事件(ae)发生率为10%(79.0%)高于安慰剂组(57.1%),但严重(1.6% vs 8.6%)和严重(3.2% vs 7.1%)不良事件发生率较低。解释fSCIG预防CIDP复发的效果比安慰剂高10%,支持其作为维持CIDP治疗的潜力。
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引用次数: 1
Imbalance and lower limb tremor in chronic inflammatory demyelinating polyradiculoneuropathy 慢性炎性脱髓鞘性多根神经病变的失衡和下肢震颤
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-06-14 DOI: 10.1111/jns.12574
Matthew Silsby, Con Yiannikas, Alessandro F. Fois, Karl Ng, Matthew C. Kiernan, Victor S. C. Fung, Steve Vucic

Background and Aims

Imbalance is a prominent symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although upper limb tremor in CIDP is described, lower limb tremor has not been assessed. The aim of this study was to determine whether lower limb tremor was present in CIDP and assess potential relationships with imbalance.

Methods

This was a cross-sectional observational study of prospectively recruited consecutive patients with typical CIDP (N = 25). Clinical phenotyping, lower limb nerve conduction and tremor studies, and posturography analyses were performed. The Berg Balance Scale (BBS) divided CIDP patients into those with “good” and “poor” balance.

Results

Lower limb tremor was evident in 32% of CIDP patients and associated with poor balance (BBSTremor 35 [23–46], BBSNo Tremor 52 [44–55], p = .035). Tremor frequency was 10.2–12.5 Hz with legs outstretched and on standing, apart from four patients with a lower frequency tremor (3.8–4.6 Hz) while standing. Posturography analysis revealed a high-frequency spectral peak in the vertical axis in 44% of CIDP patients (16.0 ± 0.4 Hz). This was more likely in those with “good” balance (40% vs. 4%, p = .013).

Interpretation

Lower limb tremor is present in one third of CIDP patients and is associated with poor balance. A high-frequency peak on posturography is associated with better balance in CIDP. Lower limb tremor and posturography assessments could serve as important biomarkers of balance in a clinical setting.

背景与目的失衡是慢性炎症性脱髓鞘性多根神经病变(CIDP)的一个突出症状。虽然对CIDP的上肢震颤进行了描述,但下肢震颤尚未得到评估。本研究的目的是确定下肢震颤是否存在于CIDP中,并评估其与失衡的潜在关系。方法前瞻性连续招募典型CIDP患者(N = 25)进行横断面观察性研究。临床表型,下肢神经传导和震颤研究,以及姿势分析。伯格平衡量表(BBS)将CIDP患者分为“良好”和“差”两组。结果32%的CIDP患者下肢震颤明显,并伴有平衡不良(bbs震颤35 [23-46],BBSNo震颤52 [44-55],p = 0.035)。除了4名站立时震颤频率较低(3.8-4.6 Hz)的患者外,双腿伸展和站立时震颤频率为10.2-12.5 Hz。体位照相分析显示44%的CIDP患者在纵轴处出现高频频谱峰(16.0±0.4 Hz)。这在那些“良好”平衡的人身上更有可能发生(40%对4%,p = 0.013)。解释:三分之一的CIDP患者存在下肢震颤,并伴有平衡能力差。姿势照相的高频峰值与CIDP中更好的平衡有关。下肢震颤和体位学评估可以作为临床平衡的重要生物标志物。
{"title":"Imbalance and lower limb tremor in chronic inflammatory demyelinating polyradiculoneuropathy","authors":"Matthew Silsby,&nbsp;Con Yiannikas,&nbsp;Alessandro F. Fois,&nbsp;Karl Ng,&nbsp;Matthew C. Kiernan,&nbsp;Victor S. C. Fung,&nbsp;Steve Vucic","doi":"10.1111/jns.12574","DOIUrl":"10.1111/jns.12574","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Imbalance is a prominent symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although upper limb tremor in CIDP is described, lower limb tremor has not been assessed. The aim of this study was to determine whether lower limb tremor was present in CIDP and assess potential relationships with imbalance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a cross-sectional observational study of prospectively recruited consecutive patients with typical CIDP (<i>N</i> = 25). Clinical phenotyping, lower limb nerve conduction and tremor studies, and posturography analyses were performed. The Berg Balance Scale (BBS) divided CIDP patients into those with “good” and “poor” balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lower limb tremor was evident in 32% of CIDP patients and associated with poor balance (BBS<sub>Tremor</sub> 35 [23–46], BBS<sub>No Tremor</sub> 52 [44–55], <i>p</i> = .035). Tremor frequency was 10.2–12.5 Hz with legs outstretched and on standing, apart from four patients with a lower frequency tremor (3.8–4.6 Hz) while standing. Posturography analysis revealed a high-frequency spectral peak in the vertical axis in 44% of CIDP patients (16.0 ± 0.4 Hz). This was more likely in those with “good” balance (40% vs. 4%, <i>p</i> = .013).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Lower limb tremor is present in one third of CIDP patients and is associated with poor balance. A high-frequency peak on posturography is associated with better balance in CIDP. Lower limb tremor and posturography assessments could serve as important biomarkers of balance in a clinical setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12574","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10184231","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}
引用次数: 2
EGR2 gene-linked hereditary neuropathies present with a bimodal age distribution at symptoms onset EGR2基因相关的遗传性神经病在症状发作时呈现双峰年龄分布
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-06-12 DOI: 10.1111/jns.12572
Andoni Echaniz-Laguna, Cécile Cauquil, Jean-Baptiste Chanson, Céline Tard, Lucie Guyant-Marechal, Thierry Kuntzer, Ioana Maria Ion, Anne-Sophie Lia, Jérôme Bouligand, Vianney Poinsignon

Background

Mutations in the Early-Growth Response 2 (EGR2) gene cause various hereditary neuropathies, including demyelinating Charcot–Marie-Tooth (CMT) disease type 1D (CMT1D), congenital hypomyelinating neuropathy type 1 (CHN1), Déjerine–Sottas syndrome (DSS), and axonal CMT (CMT2).

Methods

In this study, we identified 14 patients with heterozygous EGR2 mutations diagnosed between 2000 and 2022.

Results

Mean age was 44 years (15–70), 10 patients were female (71%), and mean disease duration was 28 years (1–56). Disease onset was before age 15 years in nine cases (64%), after age 35 years in four cases (28%), and one patient aged 26 years was asymptomatic (7%). All symptomatic patients had pes cavus and distal lower limbs weakness (100%). Distal lower limbs sensory symptoms were observed in 86% of cases, hand atrophy in 71%, and scoliosis in 21%. Nerve conduction studies showed a predominantly demyelinating sensorimotor neuropathy in all cases (100%), and five patients needed walking assistance after a mean disease duration of 50 years (47–56) (36%). Three patients were misdiagnosed as inflammatory neuropathy and treated with immunosuppressive drugs for years before diagnosis was corrected. Two patients presented with an additional neurologic disorder, including Steinert's myotonic dystrophy and spinocerebellar ataxia (14%). Eight EGR2 gene mutations were found, including four previously undescribed.

Interpretation.

Our findings demonstrate EGR2 gene-related hereditary neuropathies are rare and slowly progressive demyelinating neuropathies with two major clinical presentations, including a childhood-onset variant and an adult-onset variant which may mimic inflammatory neuropathy. Our study also expands the genotypic spectrum of EGR2 gene mutations.

早期生长反应2 (EGR2)基因突变可导致多种遗传性神经病变,包括脱髓鞘性沙科-玛丽-图斯病(CMT) 1D型(CMT1D)、先天性低髓鞘神经病变1型(CHN1)、dsamjerine - sottas综合征(DSS)和轴突性CMT (CMT2)。方法在本研究中,我们确定了2000年至2022年间诊断为EGR2杂合突变的14例患者。结果平均年龄44岁(15 ~ 70岁),女性10例(71%),平均病程28年(1 ~ 56岁)。发病年龄为15岁前9例(64%),35岁后4例(28%),26岁1例无症状(7%)。所有有症状的患者均有足弓足和下肢远端无力(100%)。86%的患者出现下肢远端感觉症状,71%的患者出现手部萎缩,21%的患者出现脊柱侧凸。神经传导研究显示所有病例(100%)主要为脱髓鞘感觉运动神经病变,5例患者在平均病程50年(47-56年)(36%)后需要行走辅助。3例患者被误诊为炎症性神经病变,经免疫抑制药物治疗多年后才得到纠正。2例患者表现出额外的神经系统疾病,包括Steinert's肌强直性营养不良和脊髓小脑性共济失调(14%)。发现了8个EGR2基因突变,其中包括4个以前未描述过的突变。解释。我们的研究结果表明,EGR2基因相关的遗传性神经病是一种罕见的缓慢进展的脱髓鞘性神经病,有两种主要的临床表现,包括儿童期发病的变体和成人发病的变体,可能模仿炎症性神经病。我们的研究也扩大了EGR2基因突变的基因型谱。
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引用次数: 0
CYBA allelic variants are associated with severity and recovery in Guillain–Barré syndrome CYBA等位基因变异与格林-巴-巴综合征的严重程度和恢复有关
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-06-08 DOI: 10.1111/jns.12571
Andreas Törnell, Nina Lagerström, Natalia Mossberg, Roberta Kiffin, Helen Farman, Jan Lycke, Oluf Andersen, Markus Axelsson, Kristoffer Hellstrand, Anna Martner

Background and Aims

Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent Campylobacter jejuni infection are associated with severe GBS, but the detailed mechanisms of nerve damage are only partly explored. Pro-inflammatory myeloid cells express NADPH oxidases (NOX) that generate tissue-toxic reactive oxygen species (ROS) that are implicated in neurodegenerative diseases. This study analyzed the impact of variants of the gene encoding the functional NOX subunit CYBA (p22phox) on acute severity, axonal damage, and recovery in adult GBS patients.

Methods

Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within CYBA using real-time quantitative polymerase chain reaction. Serum neurofilament light chain was quantified by single molecule array. Patients were followed for severity and motor function recovery for up to 13 years.

Results

CYBA genotypes linked to reduced formation of ROS, i.e. rs1049254/G and rs4673/A, were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. Residual disability at follow-up was confined to patients carrying CYBA alleles associated with high formation of ROS.

Interpretation

These findings implicate NOX-derived ROS in GBS pathophysiology and CYBA alleles as biomarkers of severity.

背景和目的吉兰-巴勒综合征(GBS)是一种罕见的急性神经病变,以上升肌无力为特征。年龄、轴突GBS变异和先前的空肠弯曲杆菌感染与严重的GBS有关,但神经损伤的详细机制仅被部分探索。促炎髓细胞表达NADPH氧化酶(NOX),产生与神经退行性疾病有关的组织毒性活性氧(ROS)。本研究分析了编码功能性NOX亚基CYBA (p22phox)的基因变异对成人GBS患者急性严重程度、轴突损伤和康复的影响。方法提取121例患者的DNA,采用实时定量聚合酶链反应对CYBA中rs1049254和rs4673等位基因变异进行基因分型。采用单分子阵列法定量血清神经丝轻链。随访患者的严重程度和运动功能恢复长达13年。结果与ROS形成减少相关的CYBA基因型rs1049254/G和rs4673/A与无辅助通气、较短的血清神经丝轻链正常化时间和较短的运动功能恢复时间显著相关。随访时的残障局限于携带与ROS高形成相关的CYBA等位基因的患者。这些发现暗示GBS病理生理和CYBA等位基因中nox衍生的ROS是严重程度的生物标志物。
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引用次数: 0
期刊
Journal of the Peripheral Nervous System
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