糖尿病周围神经病的电生理诊断研究进展

糖尿病周围神经病(DPN)是糖尿病最常见的慢性并发症,其发病率高达60%～90%[1,2]。DPN可与糖尿病同时发生,亦可为糖尿病的首发症状或在糖尿病控制良好的情况下出现,是足部溃疡、感染和截肢发生的主要原因之一。DPN发病机制复杂,目前尚不完全清楚,多认为与多羟基途径的过度     

糖尿病周围神经病病变中施万细胞凋亡信号传导通路的研究进展

糖尿病周围神经病(DPN)是最常见的糖尿病性神经病变,其具体发病机制目前仍不明确,目前认为施万细胞(SC)凋亡是DPN发生、发展的重要环节,了解施万细胞凋亡信号传导通路,对于了解DPN的发病机制及治疗对策十分重要。本文就施万细胞凋亡信号传导通路的研究进展进行综述。     

运动对糖尿病周围神经病影响的研究进展

正糖尿病周围神经病(Diabetic peripheral neuropathy,DPN)是糖尿病的常见并发症之一,它是指在排除其他病因的情况下糖尿病患者出现的与周围神经功能障碍相关的症状或体征,可累及感觉,运动以及自主神经,其中最常见为多发、对称性神经病变和植物神经病变。目前,有关糖尿病周围神经病的发病机制尚未完全明确,治疗措施除营养神经,改善循环外也无特殊治疗。运动疗法作为糖尿病管理的五个要点之一,很多国家已经将相关体育运动列为T2DM重要的非药物治疗方案~([1])。有研究表明运动有助于改善糖尿病周围神经病变,为研究运动对DPN的影响,作者查阅了近年的相关研究,对DPN的发病机制及运动强度、运动方式对与DPN     

糖尿病周围神经病变的药物治疗进展

糖尿病周围神经病变(DPN)的发病与长期严重的高血糖及由此导致的代谢障碍、微循环异常、神经营养因子缺乏、氧化应激自由基增多和自身免疫紊乱等多因素有关,其药物治疗临床上缺乏特异性方法,良好的血糖控制是治疗基础,尚需对症治疗痛性糖尿病神经病变,本文就针对DPN致病机制的药物进展综述如下.……     

高压氧治疗糖尿病周围神经病机制研究

糖尿病周围神经病(DPN)是糖尿病最常见的并发症之一。高压氧在治疗DPN过程中有着其独特的作用,可通过多种机制改善DPN的症状,延缓疾病进展。本文综述了高压氧治疗DPN在微循环、血管活性因子、氧化应激、代谢、免疫以及神经营养因子等方面的作用机制和相关进展,以及其在临床上的疗效,最后对高压氧治疗DPN进行了总结,并提出进一步的研究方向。     

糖尿病周围神经病发病机制探讨

据统计,1995年世界范围内糖尿病(DM)人数为1亿3千5百万人,到2025年糖尿病人数将呈戏剧性增加到3亿人。其中,糖尿病周围神经病(DPN)患者占50％-80％。如果DM的发病过程不被制止,它将严重影响人类健康状况及生活质量。目前DPN治疗比较棘手,主要原因在于其发病机制尚不十分清楚,但经过长期研究已逐渐认为与以下几个方面有关:     

前列腺素E1、氯沙坦与弥可保合用治疗糖尿病周围神经病变的疗效

糖尿病周围神经病变（DPN）是糖尿病常见的慢性并发症之一，其发病机制与代谢紊乱、微血管病变及神经生长因子减少等因素有关。此外还可能与血脂、血液流变学异常伴发的营养障碍和维生素缺乏等因素有关。因而仅针对某个病理作用环节的单独用药取得的临床疗效还不能令人满意。为此，本文试用前列腺素E1、氯沙坦合用神经修复剂弥可保对DPN患者进行临床治疗研究，取得较好疗效。现总结报道如下。     

丁苯肽联合硫辛酸治疗糖尿病周围神经病变的疗效观察

正糖尿病周围神经病变是糖尿病最常见的慢性并发症之一,病变主要累及中枢神经和周围神经,以周围神经病变(DPN)最常见。流行病学调查研究显示,约1/3的糖尿病患者合并DPN,临床表现包括剧烈的神经性疼痛、乏力、糖尿病足溃疡和截肢等,显著降低患者的生活质量,增加患者的心理障碍和病死率。但其发病机制尚未完全清楚,目前归因于糖、脂代谢紊乱、神经营养因子缺乏、神经轴突转运异常及     

糖尿病大鼠周围神经bFGF的动态表达及巴曲酶对其的影响

目的探讨碱性成纤维生长因子(bFGF)在糖尿病周围神经病(DPN)大鼠中的动态变化规律;观察巴曲酶对bFGF的影响及其机制,为临床上治疗DPN提供理论依据。方法将大鼠腹腔注射链脲佐菌素制作实验性糖尿病模型,分别于成模后2m和3m时腹腔注射巴曲酶进行干预。通过免疫组织化学和原位杂交双重检测bF-GF在坐骨神经中的表达。结果DM造模后2m时坐骨神经中bFGF的含量明显减少,且随时间变化有统计学差异,巴曲酶治疗后bFGF的表达明显增加。结论DPN大鼠坐骨神经中bFGF表达减少可能参与DPN的发病机制。巴曲酶对DPN有保护作用,其机制可能包括对bFGF的调节。     

糖尿病大鼠周围神经NGF的动态表达及巴曲酶对其影响

目的探讨神经生长因子（NGF）在糖尿病周围神经病（DPN）大鼠中的动态变化规律,初步证实巴曲酶对NGF的影响并探讨其机制,为临床上治疗DPN提供理论依据。方法将大鼠腹腔注射链脲佐菌素制作实验性糖尿病模型,再分别于成模后2个月和3个月时腹腔注射巴曲酶进行干预。通过免疫组织化学和原位杂交双重检测NGF在坐骨神经中的表达。结果DM造模后2个月时坐骨神经中NGF的含量明显减少,且随时间变化有统计学差异,而巴曲酶治疗后NGF的表达明显增加。结论DPN大鼠坐骨神经中NGF表达减少可能参与DPN的发病机制。巴曲酶对DPN有保护作用,其机制可能包括对NGF的调节。     

Purple pigments: The pathophysiology of acute porphyric neuropathy

The porphyrias are inherited metabolic disorders arising from disturbance in the haem biosynthesis pathway. The neuropathy associated with acute intermittent porphyria (AIP) occurs due to mutation involving the enzyme porphobilinogen deaminase (PBGD) and is characterised by motor-predominant features. Definitive diagnosis often encompasses a combination of biochemical, enzyme analysis and genetic testing, with clinical neurophysiological findings of a predominantly motor axonal neuropathy. Symptomatic and supportive treatment are the mainstays during an acute attack. If administered early, intravenous haemin may prevent progression of neuropathy. While the pathophysiology of AIP neuropathy remains unclear, axonal dysfunction appears intrinsically linked to the effects of neural energy deficits acquired through haem deficiency coupled to the neurotoxic effects of porphyrin precursors. The present review will provide an overview of AIP neuropathy, including discussion of recent advances in understanding developed through neurophysiological approaches that have further delineated the pathophysiology of axonal degeneration.     

Medication-induced peripheral neuropathy

Although not very common, medication-induced neuropathy is a treatable condition and, therefore, is important to identify. Medications continue to grow in number and expand in usage; consequently, toxic neuropathy continues to be relevant to neurologists. Many agents have toxicities that are tolerated because the treatments are necessary, such as therapies for HIV and malignancy. Additional agents to prevent or ameliorate the toxic neuropathy are being sought and trials are ongoing. Certain patients, however, may be at high risk for peripheral nerve toxicity due to genetic factors or another underlying neuropathy. Newer drug-delivery methods, such as viral transfection, may produce less toxicity in the future. The underlying pathomechanisms remain incompletely elucidated; however, apoptosis is emerging as an important final pathway in some forms of toxic neuropathy. Although most cases demonstrate acute or subacute onset after exposure, recent experiences with statin drugs raise the possibility of occult toxic causes of chronic idiopathic neuropathy.     

Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy

Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicative of a functional impairment and that this results in a chronic axonal energy deficiency that is the cause of the neuropathy's symptoms. However, the significance of mitochondrial swelling and vacuolation is ambiguous and a test of the hypothesis requires a direct assessment of the effects of chemotherapy on mitochondrial function. The results of such an assessment are reported here. Mitochondrial respiration and ATP production were measured in rat sciatic nerve samples taken 1–2 days after and 3–4 weeks after induction of painful peripheral neuropathy with paclitaxel and oxaliplatin. Significant deficits in Complex I-mediated and Complex II-mediated respiration and significant deficits in ATP production were found for both drugs at both time points. In addition, prophylactic treatment with acetyl-l-carnitine, which inhibited the development of paclitaxel-evoked and oxaliplatin-evoked neuropathy, prevented the deficits in mitochondrial function. These results implicate mitotoxicity as a possible cause of chemotherapy-evoked chronic sensory peripheral neuropathy.     

OXIDATIVE STRESS AND DIABETIC NEUROPATHY: PATHOPHYSIOLOGICAL MECHANISMS AND TREATMENT PERSPECTIVES

Increased oxidative stress is a mechanism that probably plays a major role in the development of diabetic complications, including peripheral neuropathy. This review summarises recent data from in vitro and in vivo studies that have been performed both to understand this aspect of the pathophysiology of diabetic neuropathy and to develop therapeutic modalities for its prevention or treatment. Extensive animal studies have demonstrated that oxidative stress may be a final common pathway in the development of diabetic neuropathy, and that antioxidants can prevent or reverse hyperglycaemia-induced nerve dysfunction. Most probably, the effects of antioxidants are mediated by correction of nutritive blood flow, although direct effects on endoneurial oxidative state are not excluded. In a limited number of clinical studies, antioxidant drugs including alpha-lipoic acid and vitamin E were found to reduce neuropathic symptoms or to correct nerve conduction velocity. These data are promising, and additional larger studies with alpha-lipoic acid are currently being performed.     

Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes

High glucose driven reactive oxygen intermediates production and inflammatory damage are recognized contributors of nerve dysfunction and subsequent damage in diabetic neuropathy. Sulforaphane, a known chemotherapeutic agent holds a promise for diabetic neuropathy because of its dual antioxidant and anti-inflammatory activities. The present study investigated the effect of sulforaphane in streptozotocin (STZ) induced diabetic neuropathy in rats. For in vitro experiments neuro2a cells were incubated with sulforaphane in the presence of normal (5.5 mM) and high glucose (30 mM). For in vivo studies, sulforaphane (0.5 and 1 mg/kg) was administered six weeks post diabetes induction for two weeks. Motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and pain behavior were improved and malondialdehyde (MDA) level was reduced by sulforaphane. Antioxidant effect of sulforaphane is derived from nuclear erythroid 2-related factor 2 (Nrf2) activation as demonstrated by increased expression of Nrf2 and downstream targets hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1) in neuro2a cells and sciatic nerve of diabetic animals. Nuclear factor-kappa B (NF-κB) inhibition seemed to be responsible for antiinflammatory activity of sulforaphane as there was reduction in NF-κB expression and IκB kinase (IKK) phosphorylation along with abrogation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) levels. Here in this study we provide an evidence that sulforaphane is effective in reversing the various deficits in experimental diabetic neuropathy. This study supports the defensive role of Nrf2 in neurons under conditions of oxidative stress and also suggests that the NF-κB pathway is an important modulator of inflammatory damage in diabetic neuropathy.     

Central and peripheral SEP defects in neurologically symptomatic and asymptomatic subjects with low vitamin B12 levels

Somatosensory evoked potentials (SEPs) following median nerve stimulation were abnormal in 7 patients with sensory impairment due to vitamin B12 deficiency. Extensor plantar reflexes indicated a central sensory pathway lesion in 4 cases and absent tendon jerks suggested peripheral neuropathy in 4, but median nerve SEPs indicated a predominantly central lesion without marked peripheral nerve involvement in 6 and an axonal neuropathy without CNS involvement in 1. The latter had evidence of central slowing of conduction in SEPs following posterior tibial nerve stimulation. Consequently, it is suggested that the brunt of sensory pathway involvement usually falls on the CNS, although peripheral neuropathy may occur as the major abnormality in some cases. In 2 patients SEPs showed a marked improvement following treatment with vitamin B12 injections, one consistent with restored central conduction and the other with recovery from peripheral neuropathy. No peripheral or central SEP abnormalities were seen in 18 dairy-produce eating vegetarians with low vitamin B12 levels, although 6 reported mild sensory symptoms suggestive of peripheral neuropathy and 3 had corroborative clinical signs.     

Optic neuropathy associated with CANOMAD: description of 2 cases

CANOMAD is a chronic ataxic neuropathy associated with IgM paraproteinemia and reactivity against disialosyl gangliosides. Ophthalmoplegia is a typical feature, but optic pathway involvement has not been reported previously. We describe 2 cases of CANOMAD associated with optic neuropathy. Severe visual loss was present in 1 case. We postulate that optic nerve damage may be related to antibody reactivity against gangliosides. Our report broadens the spectrum of cranial nerve involvement in this rare entity.     

Childhood giant axonal neuropathy. Case report and review of the literature

Giant axonal neuropathy (GAN) is a rare autosomal recessive childhood disorder characterized by a peripheral neuropathy and features of central nervous system involvement. Typically seen are distal axonal swellings filled with 8-10 nm in diameter neurofilaments in central and peripheral axons, and intermediate filament collections in several other cell types. Many neurotoxins produce a morphologically similar neuropathy in humans and experimental animals. Defective nerve fiber energy metabolism has been postulated as a cause in these toxic neuropathies. It is possible that GAN represents an inborn error of metabolism of enzyme-linked sulfhydryl containing proteins, resulting in impaired production of energy necessary for the normal organization of intermediate filaments.