Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.     

Neuropathy and levodopa in Parkinson's disease: Evidence from a multicenter study

The objectives of this study were to evaluate the risk of neuropathy in patients with Parkinson's disease (PD) and to evaluate the role of levodopa exposure as a potential risk factor. A multicenter study of 330 patients with PD and 137 healthy controls with a comparable age distribution was performed. With respect to levodopa exposure, 144 patients had long exposure (≥3 years) to levodopa (LELD), 103 patients had short exposure (<3 years) to levodopa (SELD), and 83 patients had no exposure to levodopa (NOLD). Nerve function was evaluated using the reduced total neuropathy score. Right sural sensory antidromic and peroneal motor nerve conduction studies were performed by neurophysiologists who were blinded to the existence of neuropathy clinical features or PD treatment. Overall, 19.40% of patients in the LELD group, 6.80% in the SELD group, 4.82% in the NOLD group, and 8.76% in the control group were diagnosed with neuropathy (axonal, predominantly sensory). Multivariate logistic analysis indicated that the risk of neuropathy was not influenced by disease duration, severity, or sex. The risk of neuropathy increased by approximately 8% for each year of age (P < 0.001; odds ratio [OR], 1.08; 95% confidence interval [CI], 1.037‐1.128). The risk of neuropathy was 2.38 higher in the LELD group than in the control group (P = 0.022; OR, 2.38; 95% CI, 1.130‐5.014). In a comparison between patients with and without neuropathy (Student's t test), the levodopa dose was higher (P < 0.0001), serum vitamin B12 levels were lower (P = 0.0102), and homocysteine levels were higher (P < 0.001) in the patients with neuropathy. Our results demonstrate that the duration of exposure to levodopa, along with age, is the main risk factor for the development of neuropathy. Screening for homocysteine and vitamin B12 levels and clinical‐neurophysiological monitoring for neuropathy may be advisable in patients with PD who are receiving treatment with levodopa. © 2013 International Parkinson and Movement Disorder Society     

Electrophysiological and phenotypic profiles of taxane-induced neuropathy

ObjectiveTo comprehensively describe patient-reported, functional and neurophysiological outcomes to elucidate the phenotypic profile of taxane-induced neuropathy.MethodsTaxane-treated patients (n = 47) completed cross-sectional bilateral clinical and sensory assessments and nerve conduction studies. Patients reported symptom severity via Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx13) questionnaire.ResultsSymptoms of neuropathy were reported by 81% of patients. On clinical examination, 62% had 2 or more abnormalities, with 20% indicating significant symptomatic and objective neuropathy. Nerve conduction studies were consistent with a sensory predominant axonal neuropathy. However, features more typical of entrapment neuropathy were also present in > 50%, which were not associated with overall severity of chemotherapy-induced peripheral neuropathy (CIPN) or clinical risk factors.ConclusionsThere is considerable variation in CIPN phenotypes associated with taxane-treatment. Understanding their clinical associations may assist in identification of patients at risk of severe neurotoxicity. This would enable treatment modification decisions but also limit early cessation of effective anti-cancer treatment in patients with less severe neurological sequelae.SignificanceUnderstanding the CIPN phenotype may inform treatment decisions which could impact clinical and survival outcomes.     

三叉神经病的CT/MRI评估与手术

三叉神经(第V颅神经)病并不十分罕见.自1986年1月至1996年1月对150例有三叉神经病可疑者作CT/MRI评估.本研究的目的:①第V颅神经病的临床表现;②建立一种对第V颅神经病有效的检查方法;③通过第V颅神经的节段性解剖建立一种鉴别诊断并采用相应的手术治疗.方法:采用规范式的CT/MRI检查.研究结果表明:97例发现有病变且说明第V颅神经的临床定位诊断是非常不准确的,对有第V颅神经病的人应考虑根据作者所拟定的方法进行MRI评估.     

High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.     

中西医结合治疗糖尿病足坏疽合并下肢神经病变的效果观察

目的观察中西医结合治疗糖尿病足坏疽合并下肢神经病变的临床效果。方法选择我院收治的80例糖尿病足坏疽合并下肢神经病变患者,采用随机数表法分为2组各40例,对照组采用常规西医治疗,观察组在对照组基础上进行中西医结合治疗,对比2组治疗效果。结果观察组和对照组的治疗有效率分别为95.0%、77.5%,2组比较差异有统计学意义(P0.05),治疗前2组糖尿病足Wagner分级改善情况及临床症状无明显差异(P0.05),治疗后观察组糖尿病足Wagner分级及临床症状改善情况优于对照组(P0.05)。结论对于糖尿病足坏疽合并下肢神经病变患者应用中西医结合治疗具有更好的效果,可有效改善患者的临床症状,值得临床推广。     

Myogenesis contributes to functional electrical stimulation (fes)‐induced recovery of myofiber excitability and mass of human long‐term denervated muscles in spinal cord injury (SCI)

Thalidomide is a neurotoxic immunomodulating agent currently used in Multiple Myeloma (MM). We prospectively evaluated the frequency and characteristics of peripheral neuropathy in a continuous series of 25 patients (13 M, 12 F; age 38–60, median 55 yrs) treated with thalidomide for MM. Patients underwent a neurological and neurophysiological evaluation before starting thalidomide therapy and monthly throughout duration of treatment. Sixteen patients (5 M, 11 F) developed neurophysiological characteristics of axonal sensitive damage and/or clinical peripheral neuropathy with distal sensory symptoms; treatment duration ranged between 95 and 572 days (median 298) in patients with neuropathy, and 49–264 days (median 162) in patients without neuropathy; the total amount of thalidomide taken ranged between 26 and 169 g (median 83 g) for patients with neuropathy and 13–170 g (median 51 g) for those without. In four patients, ENG alterations appeared before clinical symptoms, while in two patients they were not followed by clinical symptoms. In the remaining three patients, clinical symptoms preceded neurophysiological alterations. Age at onset of MM, disease duration before thalidomide therapy was started, total dose, duration of therapy and previous treatments were not correlated with neuropathy (multivariate logistic regression analysis). Female gender was a risk factor for developing neuropathy (OR 7.7).     

Effect of tumor necrosis factor inhibitors on rheumatoid arthritis-induced peripheral neuropathy A cohort study

In this historical cohort study,236 patients with primary rheumatoid arthritis were treated with the tumor necrosis factor inhibitors,etanercept or infliximab(n = 80),or by conventional methods(n = 156).Results revealed that 11 patients developed varying types of peripheral neuropathy at 1-2 years post-treatment(mean 16 months).The incidence of peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 8.8%(7/80),which was significantly higher than the conventional treatment group(2.6%;4/156).The relative risk of developing peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 3.41(95% confidence interval:1.03-11.31).Comparison of the tumor necrosis factor inhibitors revealed that etanercept and infliximab had no significant difference in terms of inducing peripheral neuropathy.Experimental findings indicate that tumor necrosis factor inhibitors may increase the risk of peripheral neuropathy.     

Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex

The most common type of peripheral neuropathy associated with human immunodeficiency virus (HIV) infection, predominantly sensory neuropathy, affects 10-30% of patients with acquired immunodeficiency syndrome (AIDS). From 40 individuals with peripheral neuropathy and HIV infection, we have identified 26 patients with this syndrome. All had constitutional symptoms when neuropathic symptoms developed; 20 had AIDS and six had AIDS-related complex. The most common complaint was pain on the soles. Paresthesias were frequent and usually involved the entire foot. Signs of peripheral neuropathy were present in all; the most frequent finding was absent or reduced ankle reflexes. Electrophysiologic studies revealed abnormal sensory and motor conduction, studies suggesting a dying-back axonopathy. Over time, the neuropathy progressed in all except one patient with ARC, who had spontaneous subjective improvement. Tricyclic antidepressants provided partial symptomatic relief. In three patients, the neuropathy did not change during azidothymidine treatment. Predominantly sensory neuropathy in HIV infection appears to be a distal axonal degeneration primarily involving sensory neurons. The mechanism is unknown, but the neuropathy is associated with the late manifestations of HIV infection.     

尼莫地平治疗糖尿病周围神经病变的临床研究

目的观察尼莫地平对糖尿病周围神经病变患者肌电图及血液流变学的影响。方法将71例糖尿病周围神经病变患者随机分为两组,对照组30例予以传统的治疗,治疗组41例在此基础上加用尼莫地平口服治疗;观察尼莫地平对肌电图及血液流变学的影响。结果经尼莫地平治疗6个月后,治疗组的神经症状、体征及正中神经、胫神经MCV和SCV的改善极显著(P<0.01),对血液流变学指标有明显改善(P<0.05),均优于对照组。结论尼莫地平治疗糖尿病周围神经病变有较好疗效。     

Clinical course and risk factors of neurotoxicity following cisplatin in an intensive dosing schedule

An intensive weekly regimen of cisplatin was administered to 66 patients with solid cancer in doses varying from 70 to 85 mg/m². The occurrence of sensory neuropathy was prospectively examined by assessment of neuropathic signs and symptoms and measurement of vibration perception threshold (VPT). Evaluation was performed before initiation of therapy and during follow-up until 3–12 months after the last cycle of cisplatin. A mild or moderate neuropathy developed in 47% of patients at 2 weeks after treatment This neuropathy continued to deteriorate until approximately 3 months after cessation of chemotherapy leading to a mild or moderate neuropathy in 71% of patients and a severe neuropathy in 9% of patients. Thereafter we observed a gradual but incomplete recovery. The high incidence of neuropathy we found may be explained by the prolonged observation period compared with earlier reports. The only factor correlated with severity of neuropathy was the cumulative dose of cisplatin, while there was no association with either pre-treatment VPT, age, sex, tumor type or co-treatment with etoposide. The progressing course up to approximately 3 months after the end of treatment underscores the need for prolonged follow-up in future studies on cisplatin neuropathy.-     

Plasmapheresis in the treatment of ataxic sensory neuropathy associated with Sjögren's syndrome

Sj?gren's syndrome (SS) is an important but poorly recognized cause of peripheral neuropathy. Several forms of peripheral nerve dysfunction occur, including trigeminal sensory neuropathy, mononeuropathy multiplex, distal sensorimotor polyneuropathy and pure sensory neuronopathy. The pathological findings vary and the definite treatment is not known. Here we present 4 cases of acute ataxic sensory polyneuropathy with SS, and the experience of treatment with plasmapheresis (PP). The 4 patients were all females; ages ranged from 30 to 58 years. All had prominent loss of kinesthetic and proprioceptive sensation. The course ranged from acute to subacute onset. Patients were treated with 5-9 sessions of PP. Two patients with initiation of treatment within 2 weeks of onset showed dramatic and sustained responses after PP, while the other 2 had no detectable effects. Our experience showed that PP should be considered in patients who present with sensory neuropathy associated with SS, and the treatment should be given as early as possible.     

Amyloid neuropathy mimicking chronic inflammatory demyelinating polyneuropathy

Introduction: Amyloid neuropathy is a rare peripheral neuropathy that classically presents as a progressive sensory neuropathy with prominent autonomic involvement. Methods: We describe 5 patients with amyloid neuropathy (familial amyloid polyneuropathy or acquired amyloidosis) who were initially mistaken to have chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) based on history, clinical examination, electrodiagnostic studies, and cerebrospinal fluid (CSF) analysis. Results: The diagnosis of CIDP had been retained on clinical and electrophysiological grounds for all patients, but we observed no improvement after immunomodulatory treatment. Nerve biopsy confirmed amyloid deposits in nerves, and molecular genetic analysis showed a mutation of the transthyretin (V30M) gene for 3 patients; the 2 other patients had acquired amyloidosis. Conclusions: This report emphasizes the need to look for an alternative diagnosis in CIDP patients who do not respond to treatment and to look carefully for symptoms or signs of autonomic involvement in such patients. Muscle Nerve 45: 26–31, 2012     

Peripheral Nerve Society Guideline on the classification, diagnosis, investigation, and immunosuppressive therapy of non-systemic vasculitic neuropathy: executive summary

Non-systemic vasculitic neuropathy (NSVN) is routinely considered in the differential diagnosis of progressive axonal neuropathies, especially those with asymmetric or multifocal features. Diagnostic criteria for vasculitic neuropathy, classification criteria for NSVN, and therapeutic approaches to NSVN are not standardized. The aim of this guideline was to derive recommendations on the classification, diagnosis, investigation, and treatment of NSVN based on the available evidence and, where evidence was not available, expert consensus. Experts on vasculitis, vasculitic neuropathy, and methodology systematically reviewed the literature for articles addressing diagnostic issues concerning vasculitic neuropathy and NSVN as well as treatment of NSVN and the small-to-medium vessel primary systemic vasculitides using MEDLINE, EMBASE, and the Cochrane Library. The selected articles were analyzed and classified. The group initially reached consensus on a classification of vasculitides associated with neuropathy. Non-diabetic radiculoplexus neuropathy was incorporated within NSVN. The consensus definition of pathologically definite vasculitic neuropathy required that vessel wall inflammation be accompanied by vascular damage. Diagnostic criteria for pathologically probable vasculitic neuropathy included five predictors of definite vasculitic neuropathy: vascular deposits of IgM, C3, or fibrinogen by direct immunofluorescence; hemosiderin deposits; asymmetric nerve fiber loss; prominent active axonal degeneration; and myofiber necrosis, regeneration, or infarcts in peroneus brevis muscle biopsy (Good Practice Points from class II/III evidence). A case definition of clinically probable vasculitic neuropathy in patients lacking biopsy proof incorporated clinical features typical of vasculitic neuropathy: sensory or sensory-motor involvement, asymmetric/multifocal pattern, lower-limb predominance, distal-predominance, pain, acute relapsing course, and non-demyelinating electrodiagnostic features (Good Practice Points from class II/III evidence). Proposed exclusionary criteria for NSVN--favoring the alternate diagnosis of systemic vasculitic neuropathy--were clinicopathologic evidence of other-organ involvement; anti-neutrophil cytoplasmic antibody (ANCAs); cryoglobulins; sedimentation rate ≥100 mm/h; and medical condition/drug predisposing to systemic vasculitis (Good Practice Points supported by class III evidence). Three class III studies on treatment of NSVN were identified, which were insufficient to permit a level C recommendation. Therefore, the group reviewed the literature on treatment of primary small-to-medium vessel systemic vasculitides prior to deriving Good Practice Points on treatment of NSVN. Principal treatment recommendations were: (1) corticosteroid (CS) monotherapy for at least 6 months is considered first-line; (2) combination therapy should be used for rapidly progressive NSVN and patients who progress on CS monotherapy; (3) immunosuppressive options include cyclophosphamide, azathioprine, and methotrexate; (4) cyclophosphamide is indicated for severe neuropathies, generally administered in IV pulses to reduce cumulative dose and side effects; (5) in patients achieving clinical remission with combination therapy, maintenance therapy should be continued for 18-24 months with azathioprine or methotrexate; and (6) clinical trials to address all aspects of treatment are needed.     

高压氧和神经妥乐平治疗痛性糖尿病神经病变的临床研究

目的 评价高压氧和神经妥乐平联合应用对2型糖尿病痛性神经病变的疗效.方法 41例2型糖尿病痛性神经病变患者,随机分组对照研究,对照组20例,只以神经妥乐平治疗,治疗组21例,给予高压氧与神经妥乐平联合治疗,共8周.结果 治疗组的总有效率与对照组比较差异有显著性（P＜0.01）,神经传导速度改善的有效率也有明显的提高（P＜0.01）.结论 高压氧和神经妥乐平联合应用可明显改善2型糖尿病痛性神经病变的治疗效果.     

LONG-TERM PROGNOSIS OF NEUROPATHY ASSOCIATED WITH ANTI-MAG IGM M-PROTEINS AND ITS RELATIONSHIP TO IMMUNE THERAPIES

Many data point to a pathogenetic role for IgM antibodies to the myelin‐associated glycoprotein (MAG) in the neuropathy associated with IgM monoclonal gammopathy, supporting the use of immune therapies in affected patients. Almost 50% of patients have been reported to improve with these therapies, but the effect of treatment on the long‐term prognosis of the neuropathy remains unclear. We analysed the outcome of 25 of the 26 patients (mean age at entry 65 years, range 45–85 years) with neuropathy and high anti‐MAG IgM, first examined by us between 1984 and 1994. By January 1999, after a mean follow‐up of 8.5 years (range 2–13 years) and a mean duration of neuropathy symptoms of 11.8 years (range 3–18,> 10 years in 16), 17 patients (68%) (aged 58–84 years, mean 73.4) were alive, while eight (32%) (aged 69–78 years, mean 73.1) had died 3–15 years (mean 10.6) after neuropathy onset; in none of them was death caused by the neuropathy, although in three it was possibly related to the therapy for the neuropathy. By the time of last follow‐up or patients' death, 11 patients (44%) were disabled by severe hand tremor, gait ataxia or both. The disability rates at 5, 10 and 15 years from neuropathy onset were 16, 24 and 50%, respectively. Of the 19 patients treated during the follow‐up for 0.5–11 years (mean 4 years) with various immune therapies, five reported a consistent and four a slight improvement in the neuropathy (total 47%) after one treatment or more, but in only one patient was improvement persistent throughout, to the end of follow‐up. In 10 patients (53%), severe adverse events, possibly related to therapy, occurred during treatment and were considered responsible for the patient's death in three. The neurological impairment did not differ between treated and untreated patients at the end of a similar follow‐up. Our findings indicate that (i) the majority of patients with neuropathy and anti‐MAG IgM have a favourable prognosis even after several years, and (ii) current immune therapies, though temporarily effective in half of the patients, are associated with considerable side effects which limit their prolonged use and efficacy, suggesting that until more effective or safer therapies become available, they should probably be reserved for patients impaired in their daily life or in a progressive phase of the disease.     

甲钴胺联合神经节苷酯治疗慢性酒精中毒性周围神经病的临床分析

目的观察甲钴胺联合单唾液酸四己糖神经节苷酯(神经节苷酯)治疗慢性酒精中毒性周围神经病(CAPN)的临床疗效。方法选取48例确诊为慢性酒精中毒性周围神经病患者,随机分成治疗组和对照组,对照组给予甲钴胺及常规药物治疗,治疗组在此基础上加用神经节苷酯,治疗4周后的临床疗效采用症状体征和神经传导速度进行评价。结果治疗组总有效率为91.7%,对照组总有效率66.7%,治疗组总有效率比对照组高,差异有统计学意义(P0.05)。两组患者治疗后的正中神经和腓总神经的神经传导速度都有增加,治疗组比对照组增加更明显,差异有统计学意义(P0.05)。结论甲钴胺联合神经节苷脂治疗慢性酒精中毒性周围神经病变可显著改善患者的症状体征和神经传导速度,值得临床推广应用。     

Polyneuropathy associated with interferon beta treatment in patients with multiple sclerosis

Peripheral neuropathy has been reported as a side effect of interferon alpha, but not with interferon beta (IFNbeta) treatment. The authors assessed six patients with multiple sclerosis who developed polyneuropathy, or had exacerbation of previously subclinical neuropathy, during treatment with IFNbeta. In five patients the neuropathy improved after discontinuation of treatment and in two patients it relapsed upon rechallenge.     

Rituximab in chronic immune mediated neuropathies: a systematic review

Chronic immune mediated neuropathy is a heterogenous group of peripheral nerve diseases, encompassing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), autoimmune nodopathy, multifocal motor neuropathy (MMN), and anti-myelin-associated glycoprotein (MAG) neuropathy. Rituximab (RTX) is a chimeric monoclonal antibody targeting the CD20 antigen, which has been used in the treatment of autoimmune neuropathies, although the efficacy of RTX remains unclear. A literature search was performed using Medline, Embase and Cochrane Register for studies between 2000 and 2021 using the search terms “Chronic inflammatory demyelinating polyneuropathy” OR “Multifocal motor neuropathy” OR “Myelin associated glycoprotein” OR “Distal acquired demyelinating neuropathy” OR “Multifocal acquired demyelinating sensory and motor neuropathy” OR “demyelinating neuropathy” AND “Rituximab”. Twenty-three studies were included, of which two were randomised controlled trials, 6 prospective studies and 15 retrospective studies. RTX was effective in 63% of CIDP patients, 48% of anti-MAG neuropathy, and 96% of patients with autoimmune nodopathy. Neurophysiological improvement was evident in 58% of CIDP and 40% of anti-MAG neuropathy patients. Low rates of serious adverse events (2.6%) were observed. These results indicate that RTX has potential as a treatment in immune mediated polyneuropathy, although the quality of evidence supporting its use it poor. Randomized controlled trials are required to reliably establish the efficacy and safety of RTX. Trial registration number: CRD42020179666.     

Leflunomide-related severe axonal neuropathy

INTRODUCTION: Leflunomide is a new drug for the treatment of rheumatoid arthritis. Its mechanism of action is based on lymphocyte inhibition. We report the cases of two patients treated with leflunomide who developed severe sensory-motor axonal polyneuropathy. OBSERVATION: Two women (61- and 70-year-old) presented with a sensory-motor axonal polyneuropathy beginning 5 months after onset of leflunomide treatment. Etiologic investigations were negative. The symptoms rapidly improved after withdrawing leflunomide. DISCUSSION: The analysis of drug watch data found twelve patients with leflunomide-related neuropathy. Ten of them were more than 60 years old. The mean delay for onset of neuropathy was 9 months. The neuropathy improved after treatment withdrawal in seven patients. CONCLUSION: We consider these data strongly suggest that leflunomide is a cause of axonal sensory-motor neuropathy. The prevalence of such adverse events is still unknown.