Motor function in diabetic neuropathy

In contrast to sensory and autonomic disturbances motor function has seldomly been studied in diabetic neuropathy. Recently quantitative studies of long-term type 1 diabetic patients have shown that the strength of the ankle and knee extensors and flexors are moderately impaired. The weakness is closely related to the severity of neuropathy. Applying quantitative electromyography the degree of reinnervation is related to the muscle strength in diabetic patients suggesting the reinnervation to be insufficient. Magnetic resonance imaging of the distal part of the leg has revealed substantial muscular atrophy closely related to the degree of muscle weakness. The present findings indicate that diabetic neuropathy often is a mixed sensory-motor neuropathy.     

Electrophysiological signs of permanent axonal loss in a follow-up study of patients with Guillain-Barré syndrome

The neurophysiological mechanisms for persisting impairment of motor function after Guillain-Barre syndrome (GBS) were assessed in 37 unselected patients 1-13 years after diagnosis. For evaluation of reinnervation and axonal loss, macroelectromyography (macro-EMG) including measurement of fiber density (FD) was performed. Data from neuropathy symptom score, neuropathy disability score, nerve conduction studies, and quantitative sensory examination were ranked and summed to a neuropathy rank sum score (NRSS). The isokinetic muscle strength at the ankle was measured. Signs of axonal loss with increase of either macro motor unit potential (macro-MUP) amplitude or FD occurred in 76% of patients. The macro-MUP amplitude correlated with muscle strength and with NRSS. Patients with evidence of residual neuropathy had increased macro-MUP amplitude and FD as well as decreased muscle strength compared to patients without evidence of residual neuropathy. We conclude that axonal loss takes place in a substantial number of GBS patients and is associated with permanent muscle weakness caused by insufficient reinnervation. Possible patterns of pathology are discussed in relation to the macro-EMG findings.     

Intraepidermal nerve fiber density as a marker of early diabetic neuropathy

The purpose of the study was to reliably identify an early stage of diabetic polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic subjects who had no clinical or electrophysiological evidence of small- or large-fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic subjects was 9.1+/-5.0 mm and that of controls, 13.0+/-4.8 mm (P<0.001). The thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by ankle IENFD) was 2.39+/-1.30 in diabetic subjects and 1.77+/-0.58 in controls (P<0.001), indicating a length-dependent reduction of IENFD in diabetics. Ankle IENFD remained significantly lower and the IENFD ratio higher in diabetic subjects after adjusting for age. Two subjects had parasympathetic dysfunction, two had retinopathy, and two early nephropathy. Age, height, weight, duration of diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We used receiver operating characteristic (ROC) curves to describe and compare the utility of various threshold values of ankle IENFD and IENFD ratio for the diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus, asymptomatic diabetics have a measurable, length-dependent reduction of distal epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable identification and quantitation of nascent diabetic neuropathy may have potential therapeutic implications.     

Effects of uridine in the treatment of diabetic neuropathy: an electrophysiological study

The authors performed a controlled double-blind neurophysiological study (uridine vs placebo) in 40 diabetic patients with peripheral neuropathy. Twenty subjects were treated with uridine and 20 with placebo. The neurophysiological evaluation consisted of a study of the MCV of the median nerve, the common Peroneal, the posterior Tibial, the SCV of the radial nerve, the median and the sural as well as the amplitudes of the motor and sensory responses. The nerves examined were on the dominant side. The evaluations were performed at baseline and after 60, 120, 180 days of therapy with a follow up control after 90 days from the completion of therapy. No statistically significant modifications were observed in the placebo group. In the drug group, the neurophysiological parameters improved significantly from the 120th day post therapy compared with baseline and were maintained through to follow up. The authors discuss the results which demonstrated that treatment with uridine can bring about a neurophysiological improvement in peripheral nerves.     

单纤维肌电图对糖尿病周围神经病变的应用价值

目的探讨单纤维肌电图(SFEMG)对糖尿病周围神经病变(DPN)的应用价值。方法应用SFEMG检测129例DPN患者的优势侧指总伸肌颤抖(jitter)和纤维密度(FD),按常规方法行神经传导速度(NCS)检测。比较SFEMG和NCS的异常检出率,并分析jitter值与血糖化血红蛋白(HbA1C)和预后的关系。结果 SFEMG异常检出率(91.5%)显著高于NCS(78.3%)(P<0.01)。HbA1C轻度升高组SFEMG异常检出率(86.4%)显著高于NCS异常检出率(69.7%)(χ2=7.69,P<0.01),而HbA1C重度升高组差异无统计学意义。jitter值与HbA1C水平呈正相关(r=0.3132,P<0.05)。jitter值正常及轻度异常患者治疗有效率(82.3%)及治愈率(30.6%)均显著高于明显异常者(54.2%,11.9%)(χ2=11.02,P<0.01;χ2=6.32,P<0.05)。结论 SFEMG对DPN的诊断意义显著,并且可用于DPN的预后判断。     

Subclinical diabetic neuropathy with normal conventional electrophysiological study

Background For early detection and prevention of diabetic neuropathy, it is important to identify subclinical diabetic neuropathy. Routine nerve conduction study often fails to detect early stage of neuropathy. Objectives The purpose of this study is to evaluate the clinical usefulness of electrophysiological indexes in detecting early diabetic neuropathy with no objective clinical or electrophysiological abnormalities. Materials and Methods Nerve conduction study of upper/lower limbs was investigated in 31 subclinical diabetic neuropathy patients with normal nerve conduction studies(group I), 38 clinical diabetic neuropathy patients with normal nerve conduction studies(group II) and 31 normal controls. Residual latency (RL), terminal latency index (TLI) and modified F raito (MFR) were calculated and compared among groups. Results Compared with controls, MFR of lower limbs and TLI of both upper/lower limbs were significantly decreased in both group I and II (p<0.05). RL was increased in both groups, but the difference was not statistically significant. Comparing the indexes between group I and II, there was no significant difference. Conclusions RL, TLI and MFR, which reflect distal conduction slowing, may be useful indexes to identify subclinical diabetic neuropathy. The results also suggest that electrophysiological changes that are obscured in routine nerve conduction study are present before the clinical manifestation. Presented at the American Academy of Neurology annual meeting, Miami, Florida, April 13, 2005. Received in revised form: 22 March 2006     

Regional distribution of slow-twitch muscle fibers after reinnervation in adult rat hindlimb muscles

In adult rats, the sciatic nerve was unilaterally sectioned and reunited above the knee. Following a survival time of 21 weeks, five muscles were removed from both lower hindlimbs after determining their intra-limb positions. In each muscle, cryostat sections from seven equidistant proximo-distal levels were stained for myofibrillar ATPase. Intramuscular positions were determined for all slow-twitch type I fibers. Within each muscle, type I fibers were heterogeneously distributed, and the direction of type I fiber accumulation was, on average, almost identical in reinnervated muscles and contralateral controls. Furthermore, as in controls, a proximo-distal decline of type I fiber density was found in reinnervated muscles. Compared to contralateral controls, reinnervated muscles consistently showed a very high number of type I fibers at close interfiber distances, indicating respecification of muscle fiber types by the ingrowing nerve fibers. The results suggest that slow-twitch motor axons preferentially grew back toward the original slow-twitch muscle regions.     

Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy

As the occurrence of restless legs syndrome (RLS) in diabetes is controversial, the aim of this study was to assess the prevalence of RLS in a cohort of patients with diabetic neuropathy and to analyze the features of the associated neuropathy. We investigated the occurrence of RLS diagnosed in accordance with the criteria of the International Restless Legs Syndrome Study Group in a cohort of patients with polyneuropathy and mononeuropathy multiplex associated with diabetes mellitus (DM), or impaired glucose tolerance (IGT), or impaired fasting glucose (IFG) in a retrospective study. RLS was present in 33/99 patients with neuropathy associated with DM/IGT/IFG (84 with distal polyneuropathy and 15 with multiple mononeuropathy). Comparing patients with or without RLS, small fiber sensory neuropathy was more common in the RLS patients (15/33 vs. 15/66), as were symptoms of burning feet (10/33 vs. 6/66). In several patients, RLS was responsive to neuropathic pain medications. The frequent occurrence of RLS in association with thermal dysesthesias may reflect the involvement of small sensory fibers in the form of hyperexcitable C fibers or A-delta fiber deafferentation. We suggest that RLS may be triggered by abnormal sensory inputs from small fibers, especially involved in neuropathy associated with DM/IGT/IFG. Our data show that RLS is a relevant feature of diabetic neuropathy, as a frequent and potentially treatable manifestation of small fiber involvement in the course of DM and IGT/IFG.     

单纤维肌电图对糖尿病周围神经病的诊断价值

目的 探讨单纤维肌电图（SFEMG）在糖尿病周围神经病（DPN）中的应用。方法 采用Viking Ⅳ肌电图仪,测定36例2型糖尿病患者指总伸肌的颤抖和纤维密度（FD）,同时进行常规神经传导检测（NCS）并测量空腹血糖和糖化血红蛋白（HbA1C)。结果 颤抖和FD具有相关性,且均与HbA1C呈正相关。18例NCS异常者,颤抖值均超过正常范围（11例伴阻滞）,14例FD增加;18例NCS正常者,7例颤抖值增大（3例伴阻滞）,5例FD增加。结论 颤抖和FD所反映的失神经－神经再支配与代谢状况相关联;SFEMG是DPN早期诊断的敏感手段,可发现糖尿病亚临床周围神经病变。     

Postpolio muscular dysfunction: Relationships between muscle energy metabolism,subjective symptoms,magnetic resonance imaging,electromyography, and muscle strength

Eleven patients with previous polio were studied. The concentration of energy-related metabolites and energy charge was measured from the vastus lateralis muscle, as was isometric muscle strength of knee extension. Cross-sectional area of the quadriceps femoris muscle was calculated from magnetic resonance imaging. Reinnervation was studied using macroelectromyography. Muscle weakness, pain, and newly acquired muscle weakness in the legs was estimated by the patients. The findings in the legs in which the patients experienced new loss of muscle function were compared with the stable legs. There were no significant differences between these groups in any of the objectively measured variables. Only hip pain correlated with new loss of muscle function. Creatine phosphate was decreased in 5 patients. The symptoms and subjective muscle strength did not correlate with any of the objective measurements. There were no significant relationships between energy-related metabolites and postpolio symptoms. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1341–1351, 1997     

Phenotyping animal models of diabetic neuropathy: a consensus statement of the diabetic neuropathy study group of the EASD (Neurodiab)

NIDDK, JDRF, and the Diabetic Neuropathy Study Group of EASD sponsored a meeting to explore the current status of animal models of diabetic peripheral neuropathy. The goal of the workshop was to develop a set of consensus criteria for the phenotyping of rodent models of diabetic neuropathy. The discussion was divided into five areas: (1) status of commonly used rodent models of diabetes, (2) nerve structure, (3) electrophysiological assessments of nerve function, (4) behavioral assessments of nerve function, and (5) the role of biomarkers in disease phenotyping. Participants discussed the current understanding of each area, gold standards (if applicable) for assessments of function, improvements of existing techniques, and utility of known and exploratory biomarkers. The research opportunities in each area were outlined, providing a possible roadmap for future studies. The meeting concluded with a discussion on the merits and limitations of a unified approach to phenotyping rodent models of diabetic neuropathy and a consensus formed on the definition of the minimum criteria required for establishing the presence of the disease. A neuropathy phenotype in rodents was defined as the presence of statistically different values between diabetic and control animals in 2 of 3 assessments (nocifensive behavior, nerve conduction velocities, or nerve structure). The participants propose that this framework would allow different research groups to compare and share data, with an emphasis on data targeted toward the therapeutic efficacy of drug interventions.     

Hip strength: Ankle proprioceptive threshold ratio predicts falls and injury in diabetic neuropathy

Introduction: We determined lower limb neuromuscular capacities associated with falls and fall‐related injuries in older people with declining peripheral nerve function. Methods: Thirty‐two subjects (67.4 ± 13.4 years; 19 with type 2 diabetes), representing a spectrum of peripheral neurologic function, were evaluated with frontal plane proprioceptive thresholds at the ankle, frontal plane motor function at the ankle and hip, and prospective follow‐up for 1 year. Results: Falls and fall‐related injuries were reported by 20 (62.5%) and 14 (43.8%) subjects, respectively. The ratio of hip adductor rate of torque development to ankle proprioceptive threshold (Hip^STR/Ank_PRO) predicted falls (pseudo‐R² = .726) and injury (pseudo‐R² = .382). No other variable maintained significance in the presence of Hip^STR/Ank_PRO. Conclusions: Fall and injury risk in the population studied is related inversely to Hip^STR/Ank_PRO. Increasing rapidly available hip strength in patients with neuropathic ankle sensory impairment may decrease risk of falls and related injuries. Muscle Nerve 50 : 437–442, 2014     

Muscle fiber conduction velocity in situ (MFCV) in denervation, reinnervation and disuse atrophy

OBJECTIVES: Muscle fiber conduction velocity (MFCV) was performed in disuse atrophy, in denervated muscle and during reinnervation as a possible index of muscle atrophy, and to clarify the evolution of the fiber size. MATERIAL AND METHODS: MFCV was performed in 12 patients with complete denervation of biceps brachii muscle and during various stages of reinnervation. Twenty-one patients with disuse quadriceps atrophy were also tested. Invasive MFCV was performed according to the method reported elsewhere (2). RESULTS: MFCV decreased significantly in denervated muscles. Reduction of MFCV was found during the first weeks and was progressive. Peak frequency in histograms decreased and the normal Gaussian distribution was lost. MFCV increased progressively after reinnervation with coexistence of slow and significant increase of faster MFCV. MFCV decreased significantly also during the first weeks after immobilization and improved by rehabilitation therapy. CONCLUSION: MFCV is a reliable method to test the muscle fiber size after denervation and immobilization, and its evolution by reinnervation and therapy.     

Follow-up of advanced diabetic neuropathy

Background The course of advanced diabetic neuropathy (DN) is largely unknown. Aim To find variables allowing the follow–up of late stages of DN. Methods Thirty diabetic patients with DN were observed. Patients were examined at intervals of 6 months over a period of 2 years. The compound muscle action potentials (CMAPs) were recorded in extensor digitorum brevis (EDB) and flexor hallucis brevis (FHB) muscles. Clinical severity of DN, nerve conduction studies (NCS), quantitative sensory testing (QST) and heart rate variability (HRV) were evaluated. The data were compared with age– and sex–matched controls. Results All measures were sensitive to the detection of DN. Significant deterioration during follow–up was exclusively found in CMAP analysis of the EDB (p < 0.05) and FHB muscles (p < 0.03). NCS, QST and HRV remained unchanged within the 2 years of observation. Coincidental changes might occur, if only two time points are chosen for followup. Conclusion Our results indicate that ongoing axonopathy predominates in advanced DN. Repeated testing helps to minimize the impact of coincidental or chance changes in DN follow–up studies.     

Gabapentin in acute painful diabetic neuropathy

Sir, Acute painful diabetic neuropathy (APDN) is an uncommon syndrome originally recognized by Ellenberg (1974) and termed ‘diabetic neuropathic cachexia’. It has been described in diabetic patients and also in females with diabetes and anorexia nervosa (Steele et al., 1987). Its clinical features consist in an unremitting burning pain in the lower limbs, which is more troublesome at night (Thomas and Griffin, 1995). We present the case of a woman with APDN who improved and became asymptomatic with low doses of gabapentin.     

Reduced skeletal muscle quantity and quality in patients with diabetic polyneuropathy assessed by magnetic resonance imaging

Introduction: The aim of this study was to determine whether diabetic polyneuropathy (DPN) is associated with reduced muscle quality using MRI. Methods: MRIs of the tibialis anterior (TA) muscle were recorded from 9 individuals (5 men) with DPN (～65 years) and 8 (4 men) age‐ and gender‐matched controls. A magnetization transfer ratio (MTR) and T2 relaxation times of the TA were calculated. Results: Despite equal voluntary activation, the DPN group was ～37% weaker than controls, with a significantly lower proportion (～8%) of contractile tissue and lower MTR (0.28 ± 0.03 vs. 0.32 ± 0.02 percent units). T2 relaxation time was significantly longer in the DPN group (77 ± 16 ms) compared with controls (63 ± 6 ms). Conclusions: These findings indicate a reduction in the structural integrity and myocellular protein density in the TA of those with DPN. Thus, muscle weakness in DPN is likely due to both a loss of muscle mass and a reduction in contractile quality. Muscle Nerve 53 : 726–732, 2016     

Sensory reinnervation of cat peroneus brevis muscle spindles after nerve crush

Results are presented of examining the postcrush sensory reinnervation of cat peroneus brevis muscle spindles previously investigated physiologically by Hyde and Scott. It is shown that primary and secondary endings were successfully restored in their final form in the early stages of recovery. The primary endings were shorter than normal and had fewer transverse bands; 12% were judged to be hyperinnervated. Some secondary endings showed signs of growth through the primary region apparently designed to establish secondary terminals in the opposite pole. This is compared with the collateral regeneration of intact motor axons in partially denervated muscle. It is concluded that the defects observed in the regenerated sensory endings had no effect on their functional recovery.     

Obturator neuropathy: causes and outcome

To study causes of obturator neuropathy and to correlate them with outcome, we retrospectively studied patients seen at the Mayo Clinic electromyography (EMG) laboratory from 1975 through 1999 with a diagnosis of obturator neuropathy. Twenty-two patients with obturator neuropathy were identified. The clinical outcome of patients with acute obturator neuropathy treated conservatively was good regardless of etiology or severity.     

Antihypoxic treatment at an early stage of diabetic neuropathy: an electrophysiological study with sabeluzole

Thirty-seven non-IDDM patients at an early stage of polyneuropathy, defined as the presence of symptoms for less than two years, as well as an abnormal perception threshold and/or abnormal thermal discrimination threshold, were treated with sabeluzole, a new antihypoxic drug, or placebo for 1 year in a double-blind, placebo-controlled study. They were examined neurophysiologically every 3 months, when motor (tibial, ulnar) nerve and sensory (sural, ulnar) nerve conduction velocities, H-reflex of the soleus muscle, SF-EMG of the anterior tibial muscle, static and dynamic pupillometry were measured. Statistical analysis did not show significant differences in nerve function between the sabeluzole group and the placebo group. There were also no significant changes within each group over the 1-year period. The results of the present study show no beneficial effect of sabeluzole on peripheral nerve function in patients at an early stage of diabetic polyneuropathy.     

Time course of sprouting during muscle reinnervation in vitamin E-deficient rats

A typical aspect of motoneuron plasticity is the sprouting which occurs during muscle reinnervation, resulting in a transitory multiple innervation of the muscle cells. In order to verify the effect of a decreased protection from free radical attack on the sprouting, the multiple innervation in the extensor digitorum longus muscle, following sciatic nerve crush and regeneration, was studied in vitamin E-deficient rats. Thus, the innervated end-plates and the end-plates with multiple innervation were studied with histochemical and electrophysiological techniques. The percentage of innervated end-plates was similar in both groups at 30 as well as at 60 days after nerve crush. Nevertheless, multiple innervation was found in a larger part of the muscle and it lasted longer in the deficient rats. This finding is discussed in relation to some of the major hypotheses of sprouting; it may be relevant in the treatment of some lesions of peripheral nerve.