细胞因子与2型糖尿病周围神经病变的相关性研究

目的 观察细胞因子TNF-α、IL-1β和IL-6在2型糖尿病周围神经病变患者的表达并分析其相关性.方法 收集在本院住院治疗的120例2型糖尿病患者及60例正常体检者的病史和临床生化资料,2型糖尿病患者根据有无周围神经病变分成两组:单纯2型糖尿病组与2型糖尿病周围神经病变组.ELISA法分别测定两组患者的细胞因子TNF-α、IL- 1β和IL-6.采用多因素相关分析方法,分析细胞因子与2型糖尿病周围神经病变之间的关系.结果 对照正常组与单纯2型糖尿病组,FBG、PPG、HbAlc、Hs-CRP、TNF-α和IL- 1β在2型糖尿病周围神经病变组表达明显增高,具有统计学意义(P＜0.05).多因素相关分析显示Hs-CRP、TNF-α和HbAlc对2型糖尿病是否合并周围神经病变均有独立作用.结论 免疫炎性反应参与了2型糖尿病周围神经病变的发生.     

The carcinomatous neuromyopathy of oat cell lung cancer

A prospective controlled clinical-neurophysiological-pathological study of 71 patients with oat cell carcinoma of the lung revealed no increased incidence of peripheral neuropathy at the initial stages of illness. All patients developed neuropathy by the time they had lost 15% of their body weight, but the neuropathy was less severe than in 20 age-matched alcoholic patients with an equal degree of weight loss. The weight loss and peripheral neuropathy progressed with atrophy of type II (adenosine triphosphatase-positive) muscle fibers out of proportion to the patient's loss of body weight. By 40% body weight loss, all the patients had moderate symmetrical peripheral neuropathy, 6 had proximal brachial or lumbosacral plexus metastases, and 9 had distal pressure palsies. Mononeuritis multiplex developed in only 1 patient, who had diabetes mellitus. Two patients developed Eaton-Lambert syndrome, which resolved in 1 when chemotherapy controlled the systemic tumor, with no protein in the tumor postmortem which could produce the characteristic electromyographic findings of the syndrome.     

Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

Charcot-Marie-Tooth disease type 1A(CMT1A) is caused by duplication of the peripheral myelin protein 22(PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1 A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1 A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1 A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.     

糖尿病患者的运动神经传导速度和脑干听觉诱发电位研究

对46例临床确诊的Ⅱ型糖尿病患者进行了运动神经传导速度(MCV)测定,其中20例同时作了脑干听觉诱发电位(BAEP)检查。结果发现MCV减慢,异常率是78.26%,下肢异常率高于上肢,而且大多数是多发性神经病。MCV使糖尿病周围神经病的诊断率由39%上升至78.26%,并能初步了解神经病变的范围。BAEP的异常率是60%,它可反映中枢神经系统的功能性损害。研究发现患者的MCV和BAEP与血糖值及病程长短无显著关系。本文认为MCV和BAEP对早期诊断糖尿病患者的周围神经病变和中枢神经病变是有价值的。     

Diabetes mellitus may affect short‐term outcome of Guillain‐Barré syndrome

We sought to determine influence of diabetes mellitus on Guillain‐Barré syndrome (GBS) course and short‐term prognosis. Among the 257 GBS patients included in this retrospective study, diabetes mellitus was present in 17%. The degree of disability at admission and on discharge was assessed according to the GBS Disability Scale (mild disability = 0–3, severe disability = 4–6). Even after correction for age, diabetes mellitus was significantly associated with more severe disability at nadir (odds ratio, OR = 3.4, p < 0.05) and on discharge (OR = 2.0, p < 0.05). Linear regression analysis with multiple factors included showed that age and presence of diabetes were significant predictors of severe disability at nadir (adjusted R² = 0.21, p < 0.05), and on discharge (adjusted R² = 0.19, p < 0.05). The presence of diabetes mellitus affects short‐term prognosis of GBS, independent of age.     

Peripheral and central neurologic complications in type 2 diabetes mellitus: no association in individual patients

Diabetes mellitus is associated with end-organ complications in the peripheral and central nervous system. It is unknown if these complications share a common aetiology, and if they co-occur in the same patient. The aim of the present study was to relate different measures of peripheral neuropathy in patients with type 2 diabetes mellitus (DM2) to cognition and brain MRI. A standardized neurological examination and questionnaire, neuropsychological examination and brain MRI were performed in 122 patients with DM2 and 56 matched controls. Measures of peripheral neuropathy were vibration threshold, a sensory examination sum score and the Toronto Clinical Neuropathy Scoring System. Neuropsychological test scores were expressed in standardized z-values across five predetermined cognitive domains. White matter lesions and cortical and subcortical atrophy were rated on MRI. Overall 38% of the patients with DM2 and 12% of the controls were classified as having any neuropathy (p<0.001). Patients with DM2 had a lower performance on the neuropsychological tests, more white matter lesions (p<0.01) and more atrophy (p<0.01) than controls. Within the DM2 group none of the measures of peripheral neuropathy was related to MRI abnormalities or cognitive dysfunction (linear regression analyses, adjusted for age, education, sex). We conclude that peripheral neuropathy in patients with DM2 is not related to cognitive dysfunction and brain abnormalities. This indicates that central and peripheral neurological complications of DM2 might have different etiologies.     

First pathological report of a de novo CD5‐positive diffuse large B‐cell lymphoma patient presenting with Guillain–Barré syndrome‐like neuropathy due to neurolymphomatosis

Peripheral neuropathy occurs in approximately 5% of the patients with lymphoma. Two major causes of peripheral neuropathy associated with lymphoma are neurolymphomatosis and paraneoplastic neuropathy such as demyelinating neuropathy. The differential diagnosis between neurolymphomatosis and demyelinating neuropathy is difficult, because electrophysiological findings suggestive of demyelination are frequently observed even in patients with neurolymphomatosis. Here, we report a patient with de novo CD5‐positive diffuse large B‐cell lymphoma (DLBCL) who presented with Guillain–Barré syndrome (GBS)‐like neuropathy. Demyelination due to paraneoplastic neuropathy was clinically suspected. However, autopsy demonstrated that the cause of the neuropathy was neurolymphomatosis. Clinical courses of neurolymphomatosis vary and neurolymphomatosis cases presenting with GBS‐like neuropathy are reported. In addition, DLBCL is the most frequent histological type of malignant lymphoma that develops neurolymphomatosis. Furthermore, “CD5‐positive” DLBCL may tend to develop neurolymphomatosis. If a patient with “CD5‐positive” DLBCL develops peripheral neuropathy, neurolymphomatosis should be considered and imaging studies performed and, if possible, nerve tissue biopsy, regardless of clinical symptoms of the neuropathy. To our knowledge, this is the first report of a patient with de novo CD5‐positive DLBCL with neurolymphomatosis who presented with GBS‐like neuropathy.     

PERIPHERAL NEUROPATHY IN MOUSE HEREDITARY DIABETES MELLITUS. II. ULTRASTRUCTURAL CORRELATES OF DEGENERATIVE AND REGENERATIVE CHANGES

Carson K.A., Bossen E.H. & Hanker J.S. (1980) Neuropathology and Applied Neurobiology 6,361–374
Peripheral neuropathy in mouse hereditary diabetes mellitus. II. Ultrastructural correlates of degenerative and regenerative changes
The fine structural changes in some peripheral nerves and sensory ganglia from mice (C57BL/K & J, db/db) with an hereditary diabetic syndrome, similar to human maturity-onset diabetes mellitus, were studied during development of the mild peripheral neuropathy. The abnormalities observed included axonal degeneration, disruption of myelin, accumulation of electron-dense material in axons, satellite cells and Schwann cells, increased frequency of it granules of Reich in Schwann cells, enlarged mitochondria, and proliferated and thickened Schwann cell basal laminae. Distal hind limb nerves were most affected. Sensory ganglion neurons were normal except for occasional chro-matolytic cells, so that nerve cell loss was not present in this peripheral neuropathy. Morphological indications of Schwann cell hyperplasia, hypertrophy, and axonal sprouting supported the contention that a continuous cycle of axonal degeneration and regeneration was occurring. The ultrastructural changes and accumulation of electron-opaque, lipid material suggested that a defect in lipid metabolism, secondary to the diabetic condition, could be an important factor in the peripheral neuropathy in the diabetic mouse.     

Peripheral neuropathy in the spontaneously diabetic WBN/Kob rat

We report that the morphological characteristics of the periperhal neuropathy in WBN/Kob rat, a diabetic animal model that develops persistent diabetes, were primary segmental demyelination and secondary axonal degeneration. These findings are similar to those in human patients with diabetes mellitus and unlike those in rodents with streptozotosin-induced diabetes. However, these changes were also indistinguishable from those of age-dependent neuropathy. In the spontaneous peripheral motor neuropathy of rats, pressure neuropathy from housing in wire-mesh cages has also been reported to be indistinguishable from the peripheral neuropathy in plantar nerve or tibial nerve. Therefore, we examined phrenic nerves that were free from the pressure of body weight in rats and described the changes with light and electron microscopy. The morphological changes of the nerve fibers consisted of myelin blebbing or distention, and early remyelination. The changes were seen with age. On morphometric analysis, a marked reduction of fiber occupancy was observed in WBN/Kob rats over 23 months old. The present study demonstrated that the peripheral neuropathy of WBN/Kob rats is myelinopathy. Since the phrenic nerve was not affected by pressure neuropathy anatomically, this study indicates that the peripheral neuropathy of WBN/Kob rats is not pressure neuropathy. Received: 15 January 1996 / Revised, accepted: 13 June 1996     

Diabetic neuropathy and braille ability

Thirty-five individuals with visual impairment due to diabetic retinopathy underwent neurologic examination with special emphasis on two-point discrimination and nerve conduction studies to determine whether concomitant peripheral neuropathy would interfere with their ability to read braille. Twenty-two individuals with insulin-dependent diabetes mellitus (9 men and 13 women) and 13 with noninsulin-dependent diabetes mellitus (4 men and 9 women) were evaluated. All had peripheral neuropathy; there were 4 with stage 1, 29 with stage 2, and 2 with stage 3 neuropathy. Two-point discriminatory ability appeared to be relatively well-preserved and at least 25 of the 35 individuals were able to learn to read standard or jumbo braille. Individuals with abnormalities in two-point discrimination (greater than 5 mm) were found to have abnormalities in braille reading. Individuals with visual impairment due to diabetes should not be discouraged from undertaking braille on the basis of apparent polyneuropathy.     

Pseudo‐Guillain‐Barre Syndrome Due to “Whippet”‐Induced Myeloneuropathy

Guillain‐Barre syndrome (GBS) is the rubric encompassing highly variable phenotypic subgroups of acute, postinfectious, immune‐mediated peripheral neuropathy. The hallmark of GBS phenomenology is a rapidly progressive ascending lower extremity weakness. GBS taxonomy includes a motor and sensory axonal neuropathy (AMSAN). Nitrous oxide (NO) abuse may create a pattern of neurological dysfunction almost identical to subacute combined degeneration. We report an adult with myeloneuropathy due to NO abuse that mimicked the presenting features of the GBS‐subtype AMSAN.     

2型糖尿病患者合并周围神经病变相关危险因素分析

目的 探讨2型糖尿病周围神经病变的相关危险因素.方法 选取2型糖尿病（DM）患者114例为研究对象,根据有无合并周围神经病变将其分为糖尿病周围神经病变组（DPN组）和非糖尿病周围神经病变组（NDPN组）.分析患者临床资料,探讨2型糖尿病周围神经病变相关因素.结果 （1） DPN组与NDPN组病患年龄、病程、FPG、2hPG、HbA1C、尿 A/C 差异均有统计学意义（P〈0.05）.（2）Logistic分析显示糖尿病病程、年龄、糖化血红蛋白（HbA1C）是糖尿病周围神经病变的独立危险因素.结论 糖尿病病程、年龄、空腹血糖、餐后 2 h血糖、糖化血红蛋白等是 2 型糖尿病并周围神经病变的相关危险因素.其中年龄大、病程长、高HbA1C的糖尿病患者发生 DPN 的风险增加.提示临床医生应在糖尿病早期对DPN和相关危险因素进行预防和干预.     

Progression in idiopathic,diabetic, paraproteinemic,alcoholic, and B12 deficiency neuropathy

We determined prospectively the clinical and electrophysiological progression of idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy in 606 subjects over 3 years. We hypothesized that idiopathic peripheral neuropathy would demonstrate slower progression when compared with other etiologies. Laboratory assessments were used to determine the etiology of peripheral neuropathy at baseline and after 3 years. When compared with peripheral neuropathy related to type 1 or type 2 diabetes mellitus, subjects with idiopathic peripheral neuropathy progressed much slower, but demonstrated similar rates of progression to that of the other groups. Overall, detectable progression was minimal over 3 years. After 3 years, only 3% of cases of idiopathic peripheral neuropathy had any potentially identifiable causes discovered. Clinical and electrophysiological detection of very slow progression for these five types of peripheral neuropathy is possible using currently established clinical scales and standard electrophysiological techniques.     

Human neurolymphomatosis in a patient with chronic lymphatic leukemia

A 62-year-old woman with chronic lymphatic leukemia (CLL) (RAI stage IV) with multiple organ involvement and diabetes mellitus, three months prior to death presented with a symmetrical sensory neuropathy of the upper extremities with little motor impairment and, two months later, sensory atactic neuropathy of the lower limbs. No cranial nerve or CNS impairment was noted. Clinical diagnosis was predominantly sensory neuropathy, but nerve conduction velocities were normal on upper limbs and moderately abnormal on lower limbs, the latter attributing to long lasting diabetes mellitus. The women died from acute subarachnoid hemorrhage. Autopsy revealed CLL of B-cell type with generalized organ involvement and acute craniospinal subarachnoid hemorrhage from ruptured cerebral aneurysm. There was selective neoplastic infiltration of the dorsal root ganglia and peripheral nerves, particularly the median nerve. Although selective infiltration of peripheral nerves by B-cell lymphoma cells was not associated with myelo-axonal degeneration, the relationship of this case to human neurolymphomatosis is discussed.     

α?硫酸锌联合神经妥乐平对2型糖尿病合并周围神经病变患者血清GGT MDA及GSH-Px水平的影响

目的探讨α-硫酸锌联合神经妥乐平对Ⅱ型糖尿病合并周围神经病变患者血清谷氨酰转肽酶(gamma-glutamyl transferase,GGT)、丙二醛(malondialdehyde,MDA)及谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)水平的影响。方法选取我院收治的100例Ⅱ型糖尿病合并周围神经病变患者,随机分成观察组和对照组各50例,对照组给予神经妥乐平进行治疗,观察组在对照组基础上给予α-硫酸锌治疗,评价2组临床疗效、血清GGT、MDA及GSH-Px水平和安全性。结果观察组临床疗效显著优于对照组,差异有统计学意义(P0.05);治疗前,2组血清GGT、MDA及GSH-Px水平比较无统计学意义(P0.05),治疗后2组GGT、MDA水平均显著降低,GSH-Px水平显著升高,且观察组各指标显著优于对照组,差异有统计学意义(P0.05);2组不良反应发生情况比较无统计学意义(P0.05)。结论α-硫酸锌联合神经妥乐平治疗Ⅱ型糖尿病合并周围神经病变疗效显著,可显著降低血清GGT、MDA水平,并提高GSH-Px水平,减轻氧化应激反应,安全性较高,值得临床推广。     

Prevalence of peripheral neuropathy with insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is rare in Chinese children. There have been no reports on the prevalence of peripheral neuropathy in Chinese children with IDDM. This study aimed to determine prevalence of subclinical peripheral neuropathy in Chinese children with IDDM. Motor and sensory nerve conduction studies of both median, ulnar, peroneal, and tibial (motor nerves) and median, ulnar, and sural (sensory nerves) were performed in 38 children with IDDM (18 males, 20 females). The age was 4-21 years (mean = 12.7 years; median = 12 years, 6 months). The duration of diabetes was less than 5 years in 15, 5-10 years in 14, and more than 10 years in nine. Neurophysiologic evidence of subclinical peripheral neuropathy was present in 26 patients (68.4%) of which motor, sensory, or motor and sensory involvement was 26 (68.4%), eight (21.1%), and 26 (68.4%), respectively. Twelve (31.6%) and 14 (36.8%) children had mild and moderate degrees of peripheral neuropathy, respectively. Among the 26 children with abnormal nerve-conduction studies, two (7.7%) had symptoms of numbness and pain in the lower limbs. Thus, two children had symptomatic neuropathy and most (n = 24) had asymptomatic peripheral neuropathy. Two children had systemic hypertension, and one (3.8%) had laboratory evidence of early renal complications. Analysis of demographic and laboratory risk factors for the development of subclinical peripheral neuropathy revealed that the age of onset, duration of diabetes, level of hemoglobin A1c, triglyceride, cholesterol, serum creatinine, and urea, microalbumin/creatinine ratio, and urinary microalbumin excretion rate were significantly related to the development of subclinical peripheral neuropathy in specific nerves.     

Hcy和Cys-C水平与糖尿病周围神经病变的相关性研究

目的 探讨2型糖尿病(T2DM)周围神经病变患者血浆同型半胱氨酸(Hcy)、胱抑素C(Cys-C)的水平变化及其意义。方法 选取2016年1月～2016年12月本院确诊的T2DM周围神经病变患者88例(DPN组),另选88例年龄、性别与之匹配的单纯T2DM患者(对照组),检测并比较2组的血浆Hcy、Cys-C的水平,采用非条件Logistic回归分析T2DM患者并发周围神经病变的危险因素。结果 DPN组的糖尿病病程、HbA1c测定值均高于对照组(P<0.05); DPN组的HDL-C水平低于对照组(P<0.05); DPN组的血浆Hcy、Cys-C的水平均高于对照组(P<0.05); 糖尿病患者并发周围神经病变的危险因素为糖尿病病程(OR=1.829)、HbA1c(OR=1.558)、Hcy(OR=1.629)、Cys-C(OR=1.733)(P<0.05)。结论 血浆Hcy、Cys-C高水平是糖尿病患者并发周围神经病变的独立危险因素。     

Uncommon early-onset neuropathy in diabetic patients

An acute neuropathy rarely occurs early in the course of diabetes mellitus. Five cases are described of adult patients who developed a peripheral neuropathy at the time or shortly after the onset or discovery of diabetes mellitus. Patient 1, an 80-year-old woman who developed a subacute tetraparesis with proximal and distal muscle weakness with normal cranial nerves, proved to have insulin-requiring diabetes mellitus. In the other patients, all men aged 23–34 years, symptomatic neuropathy occurred simultaneously (patient 2) or 1–6 months after the onset of insulin-dependent diabetes mellitus (IDDM) (patients 3–5). Patients 2 and 3 developed a symptomatic multifocal neuropathy; patients 4 and 5, a painful distal symmetrical sensory polyneuropathy (DSSP) shortly after beginning treatment with insulin. Nerve biopsy showed active axonal lesions in patients 2 and 5 and mixed axonal and demyelinating lesions in the others, with severe axon loss in patients 4 and 5. Vasculitic lesions were found in patient 2, who improved without additional treatment. Neurological examination remained unchanged after 2 years in patients 3–5. Although a coincidence cannot be excluded for patients 1–3, whose neuropathy was not of the pattern commonly found in diabetes, it is suggested that acute disequilibrium in the diabetic status may facilitate the occurrence of a variety of neuropathies. Alternatively, the autoimmune process which led to IDDM may also trigger an autoimmune neuropathy with vasculitis (patient 2) or demyelinative nerve lesions. Only the distal symmetrical sensory polyneuropathy with severe axonal lesions observed in patients 4 and 5 seems directly related to diabetes mellitus. In spite of their occurrence shortly after beginning insulin therapy, the role of treatment with insulin in the onset is uncertain. Received: 29 November 1996 Received in revised form: 4 September 1997 Accepted: 10 Oktober 1997     

Quantitative sensory testing and risk factors of diabetic sensory neuropathy

The goal of this study was to identify risk factors for diabetic peripheral sensory neuropathy in type 2 diabetes mellitus in a Chinese population. Peripheral sensory neuropathy was detected by quantitative sensory testing (5.07/10 g monofilament, neurometer and 128-Hz Riedel Seiffert graduated tuning fork). Those who had two or more abnormal quantitative sensory testings were defined as having diabetic sensory neuropathy. Of the 558 non-insulin dependent diabetes mellitits subjects, 62 (11.1%) had peripheral neuropathy. In 59 (10.6%) detection was by monofilament testing, 45 (8.1%) by graduated tuning fork, and 189 (33.9%) by neurometer. In a multivariate logistic regression model, age and insulin therapy were significantly associated with peripheral neuropathy. Age, serum triglyceride, height, and fasting plasma glucose were independently associated with large fiber neuropathy. Our results confirm the previously identifed multiple risk factors of diabetic neuropathy. Different quantitative sensory testings detect different nerve fiber defects. The weak correlation between these tests indicates the need to use more than one test in screening for diabetic neuropathy. Received: 2 June 1998 Received in revised form: 23 September 1998 Accepted: 10 October 1998     

Autonomic dysfunction and hemodynamics in vitamin B12 deficiency

Orthostatic hypotension in patients with cobalamin (Cbl) deficiency has been reported previously in isolated cases but we are not aware of detailed systematic studies of hemodynamic and autonomic nervous system function in patients with cobalamin deficiency. We investigated hemodynamic and autonomic responses to 60 degrees passive head up tilt (HUT) in 21 patients with vitamin B12 deficiency, 21 healthy age-matched control subjects and 9 age-matched patients with diabetes mellitus (DM) and established diabetic neuropathy. To systematically assess hemodynamic and autonomic nervous system function, we performed measurements of heart rate, beat-to-beat systolic and diastolic blood pressure, stroke index, cardiac index, total peripheral resistance index, total power, low (LF) and high (HF) frequency oscillatory component of heart rate variability, LF/HF ratio and spontaneous baroreflex sensitivity. As compared to controls, we found a significant fall of systolic blood pressure during 60 consecutive beats directly after head up tilt; furthermore, a significantly blunted fall of stroke index, cardiac index and a lack of increase of total peripheral resistance index for the duration of tilt in patients with diabetes mellitus and in patients with vitamin B12 deficiency. As compared to controls, we observed an altered response of spectral indices of sympathetic activation and vagal withdrawal and an impaired modulation of baroreflex sensitivity during head up tilt suggestive of a complex modification in the neural control activities in patients with cobalamin deficiency, which was comparable to that observed in patients with diabetes mellitus and established autonomic neuropathy. The results suggest that vitamin B12 deficiency causes autonomic dysfunction with similar hemodynamic consequences and patterns of autonomic failure as seen in diabetic autonomic neuropathy. Defective sympathetic activation may be the cause for orthostatic hypotension, which is occasionally seen in patients with vitamin B12 deficiency. It is concluded that patients with orthostatic hypotension should be screened for cobalamin deficiency.