Peripheral Neuropathy Associated With Antiglutamic Acid Decarboxylase Antibodies

Autoantibodies to glutamic acid decarboxylase are found in some rare neurological diseases. However, acute peripheral neuropathy associated with antiglutamic acid decarboxylase autoimmunity has not been reported previously. Here we report a case of a patient who presented with acute cranial and peripheral neuropathy in association with the presence of serum antiglutamic acid decarboxylase antibodies. A 13-year-old boy was admitted to our pediatric neurology clinic with diplopia due to sixth cranial nerve palsy and ascending motor weakness in all extremities. The nerve conduction studies showed bilateral motor and sensory demyelinating neuropathy. Full recovery was achieved following intravenous immunoglobulin treatment. Glutamic acid decarboxylase autoimmunity–associated neurological diseases spectrum may also include acute demyelinating peripheral neuropathy.     

A Case Of Paraneoplastic Neuropathy (PN) And Anti-Glycolipid Antibodies (GLA)

Subacute sensory neuronopathy (SSN) is most commonly seen in association with small cell carcinoma of the lung (SCLC), however lower motor neuron syndrome with or without upper motor neuron involvement may occur. Anti-neuronal antibodies, called “anti-Hu”, can be frequently demonstrated. Other antibodies that react with the carbohydrate epitope of ganglioside GM1, associated with primary motor PN, are not frequent. We describe a 73-year-old man with subacute onset of paraesthesiae starting in his finger and toes and spreading proximally. A few months later he developed generalized muscle weakness and was admitted to another hospital. On examination he was unable to write, as well as to stand or walk without support. Tendon reflexes were absent. He had no cranial nerve involvement and had no complain of pain. Pinprick, vibration and four limb positions were impaired distally. CSF study revealed increased protein (90 mg/dl) and lymphocytes (14/mm³). SCLC was identified in paratracheal lymphnodes and treated with chemotherapy (Carboplatinum and Etopoxide) and mediastinum irradiation (36 Gray). No clinical improvement was observed after i.v. immunoglobulins (400 mg/kg/day for 5 days). He was wheelchair-bound and unable to feed himself or to recognize the four limb position when he was admitted in the Neurological Department, University of Verona. Eye movements and winking were markedly reduced. Median (48.6 m/s) and ulnar (46 m/s) nerve study revealed slow conductions. ESP were undetectable. SSEP could not be evoked from the four limbs. Cyclophosphamide (250 mg/day for 5 days), monthly plasma exchange associated with prednisone for six months, and Azatioprine were used. Ambigous low titre of antibodies against neuronal nuclei was identified but anti-Hu antibodies were not detected. The serum antibody titres against glycolipids (GM1, GM2, GM3, GQ1b, GD1a, GD1b, sulfatides) were elevated (>1:720) and had no substantial change at the bimonthly controls in the last 36 months. As negative control case for GLa, we used the Hu-negative serum from a patient who had electrophysiologically confirmed selective sensory involvement associated with SCLC and long survival (29 months). We hypothesized that the neurological course with prominent motor deficit is probably related to serum anti-GL antibody specificities. The presence of ganglioside mimicry in the SCLC (Fuentes et al., Lung Cancer, 1997) appears to be determinant for the induction of anti-GLa. However the anti-neural immune-response may be related to host factors.     

Ulnar Neuropathy At Elbow (UNE): Clinical And Electrophysiological Study Of 279 Cases

It is well known that in a small proportion of patients with peripheral neuropathy a cause is not found; on the other hand, it is also possible that extensive investigations reveal more than one possible cause of peripheral neuropathy, especially in older patients, raising a different kind of diagnostic problem. The aim of this study was to investigate the occurrence of “multifactorial neuropathy” in a population of patients with peripheral neuropathy, and the modalities of interaction when various causes are implicated in determining the features of neuropathy. In a series of 62 consecutive patients with peripheral neuropathy who underwent an extensive diagnostic work-up, more than one possible cause for a single patient was found in 24 patients (38.7%), and at least 3 causes in 9 patients (14.5%). Common causes of neuropathy, such as diabetes, alcohol, drugs, Charcot-Marie-Tooth disease, and cryoglobulinemia were more often implicated in multifactorial neuropathy. In 8 additional patients, neuropathic motor and sensory impairment was complicated by coexistent diseases (Parkinson's disease, osteoarthrosis, lumbal stenosis). Patients with multifactorial neuropathy were older than patients with neuropathy due to a single cause (mean age: 66.8 ± 9.6 vs. 62.2 ± 11.9), and had a significantly greater disability on Rankin scale (28/32 with Rankin grade 2 or more, vs. 15/30; p = 0.002). Possible mechanisms of interaction between two or more causes of neuropathy are the following: a primary neuropathic condition is worsened or revealed by an additional superimposed cause; two coexisting causes concur to determine the features of neuropathy, for instance influencing respectively motor and sensory symptoms; a unique cause produces neuropathic damage through different mechanisms (this is typically the case of malignancies, and in particular lymphoma); the significance of some potential factors of neuropathic damage, such as monoclonal gammopathy, may be difficult to be ascertained, thus their role as a cause of neuropathy remains elusive. In addition, the disability due to neuropathy may be complicated by other concurrent neurologic or non-neurologic conditions causing additional motor or sensory impairment. Thus it is also advisable to have a complete screening in patients with an obvious cause of peripheral neuropathy, as it could be made worse by another coexistent cause, and in older patients this evenience is not uncommon. This is especially important when a treatable additional cause is revealed.     

Neuropathy Associated With Anti-Chondroitin Sulfate C IgM Antibodies

Chondroitin Sulfate C (ChS-C), is a glycosaminoglycan present in the membranes of neurons and axons. Anti-ChS-C IgM antibodies have been reported in patients with predominantly sensory neuropathy (PN) often associated with IgM monoclonal gammopathy, but also in some neurological controls. In order to evaluate the frequency and clinical correlate of anti-ChS-C IgM antibodies, we tested them by a new Covalink ELISA technique in sera from 206 patients with IgM monoclonal gammopathy including 79 with PN (PN+IgM) with unknown IgM reactivity, 65 with PN with antibodies to the myelin-associated glycoprotein and 62 without PN, and from 33 patients with PN of other causes, 30 with other neurological and non-neurological diseases and 23 normal subjects. We only found high titers of anti-ChS-C IgM in two patients (1/128,000 and 1/256,000 respectively) with IgM monoclonal gammopathy: one had Waldenström Macroglobulinemia diagnosed seven years before and a 3 year history of slowly progressive limb weakness, finger paresthesias, unsteady gait and occasional nocturnal cramps. Neurological examination revealed a predominantly large-fiber sensory neuropathy with mild distal atrophy and weakness in upper and lower limbs. Electrophysiological and morphological studies were suggestive of a predominantly demyelinating neuropathy. The other patient had IgM MGUS without PN at the time of antibody testing but developed finger paresthesias seven years later, when he had decreased position sense and abnormal sensory nerve conduction studies. In conclusion high titers of anti-ChS-C IgM, though infrequent, were always associated with the presence or development of sensory PN in patients with IgM M-protein, supporting a possible role for these antibodies in the neuropathy.     

肿瘤化疗药物诱导性周围神经病的临床横断面研究

目的:分析抗肿瘤药物导致的周围神经病(CIPN)临床特征及其发病时的药物累积剂量。方法:连续收集2009年3月至2010年2月于化疗后发生周围神经损害的84例肿瘤患者。对纳入的患者进行周围神经病量表(MNSI、MDNS、FACT/GOG-NTX)评估和肌电图检查。按责任药物将患者分为:奥沙利铂组、顺铂组、紫杉醇组、长春新碱组、沙利度胺组和联合用药组(紫杉醇+卡铂,紫杉醇+顺铂),分析不同责任药物所致CIPN的特征及其与累积剂量的相关性。结果:84例患者临床主要表现为肢体远端感觉障碍,少数患者伴疼痛和(或)肌力减退,肌电图结果异常者占82.14%。84例患者中使用奥沙利铂者60例,累积剂量(1089.26±310.31)mg/m~2;长春新碱8例,累积剂量(5.14±1.07)mg/m~3;紫杉醇4例,累积剂量(640.00±306.17)mg/m~2;顺铂3例,累积剂量(360.00±120.00)mg/m~2。奥沙利铂组周围神经病量表分值与药物累积剂量呈正相关。结论:CIPN具有剂量依赖性特点,常见的责任药物为奥沙利铂、长春新碱、紫杉醇、顺铂。     

丁咯地尔与肌氨肽苷联合治疗糖尿病周围神经病疗效观察

目的:观察丁咯地尔与肌氨肽苷联合治疗糖尿病周围神经病变的疗效。方法:86例患者随机分为治疗组和对照组各43例。治疗组:在常规治疗基础上应用丁咯地尔150mg加入生理盐水250ml、肌氨肽苷8ml加入生理盐水250ml中静脉滴注,每日一次;对照组:在常规治疗基础上维生素B1100mg、维生素B12500μg肌肉注射,每日一次。连续治疗4周。结果:治疗组:显效29例,有效9例,无效5例;总有效率88.3%,明显高于对照组的62.8%,经秩和检验P<0.01,且未见明显副作用。结论:丁咯地尔与肌氨肽苷联合治疗糖尿病周围神经病变是较理想的药物。     

Axonal Neuropathy Associated With Cold Agglutinins: A Vasculitic-Ischaemic Neuropathy

Cold agglutinin (CA) disease is an autoimmune hemolytic process characterized by chronic anemia, hemoglobinuria, cold induced rash, and acrocyanosis of exposed body parts. Although few cases of peripheral neuropathies have been observed in patients with CA, the mechanism of peripheral nervous system involvement is still uncertain. However, similar to other neuropathies due to IgM paraproteinaemia, such as anti-myelin associated glycoprotein, or anti-acidic glycolipid sulphate-3-glucuronyl paragloboside, the direct effect of the antibody on nerve constituents is considered the pathogenetic mechanism causing the demyelinating neuropathy. We report a patient with CA and sensorimotor peripheral neuropathy with electrophysiological and histological findings of a severe acute axonal neuropathy. Pathological findings show vascular damage in the nerve, suggesting a major role for ischaemic/vasculitic pathogenetic mechanism of the peripheral neuropathy in CA.     

Frontal Executive Impairment Associated With Paraneoplastic Cerebellar Degeneration: A Case Study

Paraneoplastic cerebellar degeneration (PCD) is a rare cause of profound cerebellar dysfunction. Degenerative disorders of the cerebellum can cause cognitive and behavioral changes but the neuropsychological and behavioral sequelae of PCD are not well described. In this article, we detail selective frontal-executive disturbance, psychomotor slowing and affective change in a patient with PCD in whom there is no apparent extracerebellar involvement. The pattern of deficits suggests that PCD may be clinically dissociable from other forms of paraneoplastic encephalitis and correspond closely with the recently proposed “cerebellar-affective syndrome.” The results underline the importance of the cerebellum in regulating cognitive function.     

Immunopathogenetic Role Of The M-Protein In Neuropathy Associated With IgA Monoclonal Gammopathy

Neuropathy has been reported in some patients with IgA monoclonal gammopathy of undetermined significance (MGUS) but the clinical and pathogenetic relevance of this association remains unclear. This is because the clinical and electrophysiological features of the neuropathy in reported patients were quite heterogeneous and only occasionally endoneurial deposits or anti-neural reactivity of IgA M-proteins were found. In order to clarify the possible role of IgA M-proteins in the neuropathy we studied their reactivity with nerve antigens in 12 patients with neuropathy associated with IgA MGUS and in 15 patients with IgA MGUS without clinical or electrophysiological evidence of neuropathy. Patients' sera were tested for IgA reactivity with the glycolipids GM1, GM2, GD1a, GD1b, GQ1b and sulfatides by ELISA and with central (CNS) and peripheral nervous system (PNS) myelin and whole nerve homogenates by Western Blot. No IgA reactivity with any of the gangliosides tested or sulfatide was detected by ELISA in patients with neuropathy and IgA MGUS. By Western blot only one neuropathy patient had an intense IgA reactivity with several protein bands of the molecular weight (MW) of 80 to 200 kD, including high MW neurofilaments. A similar though less intense IgA reactivity with the same bands was detected in one patient without neuropathy. No other reactivity with neural proteins was detected in patients' sera more frequently or more intensely than in controls. The clinical features of the neuropathy in the four patients whose clinical reports were available showed an usually mild, predominantly motor (2) or sensory (1) or mixed (1) impairment, while electrophysiological studies showed a predominant axonal (2), demyelinating (1) or mixed (1) neuropathy. In the only patient in whom sural nerve biopsy was performed no endoneurial deposits of IgA were found. The heterogeneity of the clinical and electrophysiological findings in these patients together with the lack of a consistent pattern of IgA reactivity with neural antigens in the 12 patients examined fail to support, at least in these patients, a possible immunopathogenetic role of the IgA M-proteins in the neuropathy.     

Peripheral Neuropathy And Monoclonal Igm Gammopathy: Clinical And Laboratory Data From A Neurological Unit In A General Hospital

BACKGROUND: It has been known for decades that monoclonal IgM gammopathies are associated with peripheral neuropathies. However, available data are from ultraspecialized laboratories, while little is reported about their epidemiology. PATIENTS AND mETHODS: Since 1988 we have recorded a registry of the patients referred for a peripheral neuropathy. Database included clinical, electrophysiological, laboratory, immunological and pathological data. All the patients were followed-up with clinical visits or at least phone interview every six months. In case of death we evaluated death certificates and contacted general practitioners. Results: In the period from 1988–1999 we saw and followed-up 512 patients with clinical ascertained peripheral neuropathy. Of those patients, 35 (6.8%) had a MGUS: 18 IgG, 10 IgM, and 7 IgA. The patients with IgM paraprotein were all men, except 1 woman, aged 48 to 71 years at the onset of symptoms. Eight patients had a predominantly sensitive neuropathy and two patients a motor neuropathy. Of the 8 patients with sensitive neuropathy, 3 had a demyelinating disease and antiMAG antibodies, 4 an axonal disease and antisulphatide antibodies, and 1 an axonal neuropathy with both antiMAG and antisulphatide antibodies. The two patients with motor neuropathy had both an axonal disease and anti-GM1 antibodies. The patients with sensory neuropathy were treated with periodic plasmaphoresis plus i.v. cyclophosphamide every 4–6 months. The patients with motor neuropathy were treated every month with i.v. immunoglobulins alternated with i.v. cyclophosphamide. Follow-up of those patients lasted 12 to 108 months. Four patients died: 3 with antisulfatide antibodies because of a developing cancer (2 a primary hepatic cancer and 1 a bladder neoplasm) and 1 with anti-GM1 antibodies for respiratory failure. The remaining patients showed a slowly progressive invalidating disease especially with the loss of hand ability. Conclusions: The patients with monoclonal IgM gammopathy are a minority among those observed because of a peripheral neuropathy in a General Hospital. Prognosis is severe either because of growing dependency or of life shortening (directly or for developing cancer). Aggressive therapies probably deserve multicentric studies.     

脂质沉积性肌病合并周围神经病的临床和神经电生理研究

目的研究脂质沉积性肌病合并周围神经损害和不伴周围神经损害的临床及神经电生理特点。方法对19例病理证实的脂质沉积性肌病中7例合并周围神经损害（第一组）和12例不伴周围神经损害的患者（第二组）进行了常规肌电图、正中神经和胜后神经感觉传导速度及运动末端潜伏期测定。结果发现临床上两组不同卢、是前者病程较后者长（P＜0．01）；肌电图提示运动单位动作电位（MUAPS）时限第一组较第二组宽，去除多相波后更明显（P＜0．01），部分合并神经源性损害；神经传导速度测定结果提示，第一组可见感觉和运动神经传导速度减慢及感觉神经动作电位波幅降低。结论对临床上有典型的肌病症状、电生理为肌源性损害合并神经源性损害或单纯神经源性损害应考虑脂质沉积性肌病的可能，肌肉和周围神经活检是非常必要的。     

Height Measurement Of Patients With Neuromuscular Disease And Contractures

Patients with neuromuscular diseases frequently have joint contractures, which preclude standard measurements of standing height. Standing height, arm-span, forearm and ulnar-segment measurements were taken of 116 normal children without contractures. Measurement of the forearm segment had the highest correlation with standing height, but it requires a special ruler. Arm-span measurement had good correlation with standing height, although this cannot be used if elbow or shoulder contractures are present; in such patients ulnar segment measurement can be used, but it has the lowest correlation with standing height.     

糖尿病周围神经病97例临床特征与神经电生理分析

目的:探讨糖尿病周围神经病(DPN)患者的临床特征与神经电生理变化。方法:分析97例DPN患者的临床特征,比较DPN组和对照组的神经传导速度(NCV)、远端潜伏期、远端波幅3个参数。结果:①临床特征以肢体麻木(59%)最多见、其次为疼痛(42%)。②患者组NCV、远端波幅值低于对照组,远端潜伏期比对照组延长;两组3个参数比较,除腓总神经远端波幅、尺神经感觉传导速度和正中、尺、腓肠神经远端潜伏期外,差异均有统计学意义(P<0.05)。结论:①DPN患者临床特征以肢体麻木和疼痛最多见;②检测NCV、远端潜伏期、远端波幅,能较早发现临床患者。     

Elevation Of Electric Gustatory Threshold In Type 2 Diabetic Patients With Neuropathy

To specify the diabetic complications related to taste function in type 2 diabetes mellitus, electrogustometry was performed in 49 patients and 48 normal subjects. The results showed that the electric gustatory threshold (EGT) rose with aging. The EGT in normal subjects was, on average, not changed compared to the diabetics without complications (6.29 dB vs 6.3 dB), but the EGT was significantly higher in diabetic patients with neuropathy compared to the normal (13.3 dB vs 6.29 dB p < 0.05). The EGT was significantly higher in diabetic patients with both neuropathy and retinopathy (18.1 dB vs 6.29 p < 0.05). In the patients with chronic renal failure due to chronic glomerulonephritis treated with hemodialysis, the EGT was not changed compared to the normal (3.8 dB vs 6.29 dB), but the EGT in the diabetic renal failure treated with hemodialysis was much higher compared to the CGN patients (19.1 dB vs 3.0 dB). Thus, the electric gustatory threshold is a sensitive indicator of diabetic complications.     

Immunological Study Of Hereditary Motor And Sensory Neuropathy Type 1 A (HMSN1 A)

Ganglioside mimicry in the lipopolysaccharide (LPS) fraction of Campylobacter jejuni isolated from Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) patients was compared with isolates from patients with an uncomplicated enteritis. The antibody response to C. jejuni LPS and gangliosides in neuropathy patients and controls was compared as well. LPS from GBS and MFS-associated isolates more frequently contained ganglioside-like epitopes compared to control isolates. Almost all neuropathy patients showed a strong antibody response against LPS and multiple gangliosides in contrast to enteritis patients. Isolates from GBS patients more frequently had a GM1-like epitope than isolates from MFS patients. GQ1b-like epitopes were present in all MFS-associated isolates and was associated with anti-GQ1b antibody reactivity and the presence of oculomotor symptoms. These results demonstrate that the expression of ganglioside mimics is a risk factor for the development of post-Campylobacter neuropathy. This study provides additional evidence for the hypothesis that the LPS fraction determines the antiganglioside specificity and clinical features in post-Campylobacter neuropathy patients.     

变应性肉芽肿性血管炎14例临床表现及周围神经损害

目的分析变应性肉芽肿性血管炎(Churg-Strauss sydrome,CSS)的临床特点以及周围神经受损的表现,以提高诊治水平。方法收集自2005年1月~2016年12月在北京大学第三医院收治的14例CSS患者的临床资料,回顾性分析其临床表现及周围神经受损的情况。结果 14例CSS患者中男性10例(71.4%),年龄20~78岁(53.6±16.2);外周血嗜酸性粒细胞平均升高20.7%(10.3%~55%);呼吸系统是最常受累的器官(100%),哮喘9例(64.3%),肺部浸润12例(85.7%);6例(42.9%)存在周围神经受损,以四肢周围神经尤其是下肢神经轴索损害为主,同时累及运动与感觉神经;CSS起病初期误诊率高达64.3%,起病至确诊间隔平均15.9 m(1~72 m)。结论 CSS是一种误诊率较高的全身多系统受累的血管炎,存在嗜酸性粒细胞升高,且临床和电生理结果提示非对称性以轴索损害为主的周围神经病患者,需注意CSS的可能。     

丁基苯酞治疗糖尿病性周围神经病的疗效观察

目的 观察丁基苯酞对糖尿病性周围神经病的治疗作用.方法 糖尿病性周围神经病变患者85例,随机分为丁基苯酞治疗组(43例)及对照组(42例),丁基苯酞治疗组口服丁基苯酞200 mg、甲钴胺0.5 mg、呋喃硫胺片25 mg及维生素B6片20 mg,均3次/d,疗程3周;对照组单纯使用维生素.比较两组治疗前后以及两组间治疗后有效率和神经传导速度的变化.结果 治疗后两组神经症状及体征均有明显改善,治疗组总有效率为81.4%,明显高于对照组(59.5%,P<0.05).对照组除正中神经(MCV)外,两组治疗后感觉及运动神经传导速度均较治疗前明显增快(P<0.05,P<0.01).治疗组治疗后感觉及运动神经传导速度明显高于对照组(P<0.05).结论 丁基苯酞合并B族维生素对糖尿病性周围神经病有较好的治疗作用.