Neuropathy Disability Score Research Articles

Electrochemical skin conductance to detect sudomotor dysfunction, peripheral neuropathy and the risk of foot ulceration among Saudi patients with diabetes mellitus.

BackgroundSudomotor dysfunction is manifested clinically as abnormal sweating leading to dryness of feet skin and increased risk of foot ulceration. The aim of this study was to test the performance of foot electrochemical skin conductance (ESC) to detect diabetic peripheral neuropathy and the risk of foot ulceration against traditional methods in Saudi patients with diabetes mellitus.MethodsThis cross-sectional study was conducted on 296 Saudi patients with diabetes mellitus. Painful neuropathic symptoms were evaluated using the neuropathy symptom score (NSS). The risk of foot ulceration and diabetic peripheral neuropathy were determined using the neuropathy disability score (NDS). Vibration perception threshold (VPT) was assessed using neurothesiometer. Neurophysiological assessment of the right and left sural, peroneal and tibial nerves was performed in 222 participants. Diabetic peripheral neuropathy was defined according to the definition of the American Academy of Neurology. ESC was measured with Sudoscan.ResultsFeet-ESC decreased as the scores of sensory and motor function tests increased. Feet-ESC decreased as the NSS, NDS and severity of diabetic peripheral neuropathy increased. Sensitivity of feet-ESC < 50μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 90.1, 61 and 63.8 % respectively and specificity 77, 85 and 81.9 % respectively. Sensitivity of feet-ESC < 70μS to detect diabetic peripheral neuropathy assessed by VPT ≥ 25 V, NDS ≥ 3, NDS ≥ 6 was 100, 80.6 and 80.9 % respectively. Sensitivity and specificity of feet-ESC < 70μS to detect confirmed-diabetic peripheral neuropathy were 67.5 and 58.9 % respectively.ConclusionSudoscan a simple and objective tool can be used to detect diabetic peripheral neuropathy and the risk of foot ulceration among patients with diabetes mellitus. Prospective studies to confirm our results are warranted.

Serum levels of TGF-β1 in patients of diabetic peripheral neuropathy and its correlation with nerve conduction velocity in type 2 diabetes mellitus

To correlate serum levels of TGF-β1 with motor and sensory nerve conduction velocities in patients of type 2 diabetes mellitus The study was conducted in diagnosed type 2 diabetes mellitus patients which were divided in patients with clinically detectable peripheral neuropathy of shorter duration (n=37) and longer duration (n=27). They were compared with patients without clinical neuropathy (n=22). Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TGF-β1. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study In patients of type 2 diabetes mellitus with clinically detectable and serum TGF-β1 showed positive correlation with nerve conduction velocities High level of TGF-β1 in serum of T2DM patients with neuropathy show possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy.

Neuropad for the detection of cardiovascular autonomic neuropathy in patients with type 2 diabetes

BackgroundCardiovascular autonomic neuropathy (CAN) is a prevalent and neglected chronic complication of diabetes, with a large impact on morbidity and mortality. Part of the reason why it is not detected and treated opportunely is because of the complexity of the tests required for its diagnosis. We evaluated the Neuropad®, a test based on sudomotor function, as a screening tool for CAN in adult patients with type 2 diabetes in Bogotá, Colombia. MethodsThis was a cross-sectional evaluation of Neuropad® for the detection of CAN. Patients were 20–75years of age and did not suffer from any other type of neuropathy. CAN was diagnosed using the Ewing battery of tests for R-R variability during deep breathing, Valsalva and lying-to-standing maneuvers. Additionally, distal symmetric polyneuropathy (DSP) was diagnosed using a sign-based scale (Michigan Neuropathy Disability Score – NDS) and a symptom-based score (Total Symptom Score – TSS). The primary outcome was the sensitivity and specificity of the Neuropad® for the diagnosis of CAN, and secondary outcomes were the sensitivity and specificity of Neuropad® for DSP. ResultsWe studied 154 patients (74 men and 80 women). Prevalence of CAN was extremely high (68.0% of study participants), but also DSP was prevalent, particularly according to the signs-based definition (45%). The sensitivity of the Neuropad® for any degree of CAN was 70.1%, being slightly higher for the deep breathing and Valsalva tests than for lying-to-standing. The specificity of the Neuropad® for any type of CAN was only 37.0%, as expected for a screening exam. The negative predictive value was higher for the deep breathing and Valsalva tests (69.4 and 81.6%, respectively). Neuropad showed also a good sensitivity and negative predictive value for DSP. The sensitivity and specificity of Neuropad were better among men, and among patients with diabetes duration above the group median. ConclusionsThe Neuropad is a simple and inexpensive device that demonstrated an adequate performance as a screening tool for cardiovascular autonomic neuropathy in Latin American patients with DM2.

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

Diabetic peripheral neuropathy, is it an autoimmune disease?

BackgroundAutoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. ObjectivesThis study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. Research design and methodsA case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. ResultsAntinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (p<0.001). The odds of positive values of ANA in the neuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). ConclusionThe study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers.

ASSESSMENT OF THE RELATIONSHIP BETWEEN SUBCUTANEOUS FAT TISSUE AND RESULTS OF ELECTROMYONEUROGRAPHY

In this cross-sectional study we assessed the associations between the amplitude and the velocity of the potential and the volume of subcutaneous fat tissue in order to answer the question on whether the results of electroneuromyography should be adjusted for the volume of subcutaneous fat tissue in analytical studies. The sample consisted of 570 individuals who were covered by the seriveces of the policlinic of the International Kazakh-Turkish University, Turkestan, Kazakhstan. Peripheral neuropathy was assessed using a modified Neuropathy Disability Score (NDSm). The volume of the subcutaneous fat tissue was calculated using the formula proposed by Bonora (1995). Associations between the volume of subcutaneous fat tissue and the indices of the electroneuromyography were assessed using multivariable linear regression analyses. Amplitude and velocity of the potential were separately used as dependent variables. Crude and adjusted regression coefficients were calculated with 95 % confidence intervals (CI). Analyses were performed separately for participants with and without other symptoms of peripheral neuropathy. The prevalence of peripheral neuropathy in the sample was 11.4 (95 % CI: 9.1; 14.3) %. We observed inverse and statistically significant associations between the volume of subcutaneous fat tissue and the amplitude of the potential in n. peroneus, n. tibialis and n. suralis among the individuals with and without other signs of peripheral neuropathy. However, we did not observe independent associations between the velocity of the electric wave and the volume of subcutaneous fat tissue. The results of our study demonstrate the need in additional adjustment for the volume of subcutaneous fat tissue in studies in studies with the use of electroneuromyography for example is studies on neuropathy among patients with Type II diabetes mellitus or metabolic syndrome to control for the confounding effect of the former.

Clinical diagnosis of distal diabetic polyneuropathy using neurological examination scores: correlation with nerve conduction studies

The aim of this study was to diagnose diabetic sensorimotor polyneuropathy using neurological examination scores and to correlate the findings with nerve conduction studies (NCS). Thirty patients with type 2 diabetes were included in the study. Detection and grading of neuropathy were carried out based on the Diabetic Neuropathy Symptom (DNS) Score, modified Neuropathy Symptom Score (NSS), Diabetic Neuropathy Examination (DNE), and modified Neuropathy Disability Score (NDS). For the NCS, amplitudes, velocities, and latencies of seven nerves — that is, four motor (median, ulnar, tibial, and common peroneal) and three sensory (median, ulnar, and sural) nerves — were recorded. If the patient had two or more abnormal findings in any of these nerves, the patient was diagnosed as having peripheral sensorimotor neuropathy. Thereafter, the sensitivity, specificity, and diagnostic efficacy of each neurological score were recorded taking NCS as the gold standard. Diabetic sensorimotor polyneuropathy was diagnosed clinically and electrophysiologically in 17 patients (56.7%). However, there were nine cases (30%) of subclinical neuropathy. Neurological examination scores were significantly correlated with each other and with individual variables of NCS and the nerve conduction sum score. Taking the NCS as gold standard, DNS, modified NSS, DNE, and modified NDS had 65.4, 61.5, 30.8, and 61.5% sensitivity and 100, 75, 100, and 100% specificity, respectively. Their diagnostic efficacies were 70, 63.3, 40, and 66.7%, respectively. Neurological examination scores can detect and grade neuropathy in the majority of cases. However, NCS was accurate for detection of diabetic sensorimotor polyneuropathy, especially for the subclinical neuropathies.

Altered glutathione system is associated with the presence of distal symmetric peripheral polyneuropathy in type 2 diabetic subjects

Distal symmetric peripheral polyneuropathy (DSPN) is a highly prevalent complication of diabetes. However, underlying pathophysiological mechanisms are multiple and not well understood. The aim of our study was to analyze the oxidative stress levels in circulating mononuclear cells by measuring the glutathione system, malondialdehyde and oxidized-LDL, in 60 type 2 diabetic patients from a well-characterized cohort of 196 type 2 diabetic patients. Using a nested case–control design, we studied 30 type 2 diabetic patients with distal symmetric polyneuropathy and 30 diabetic controls without this complication, according to the Neuropathy Disability Score. We have found that diabetic patients with distal symmetric polyneuropathy showed significantly lower values of reduced glutathione (GSH) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio. These data indicate an increased consumption of glutathione in mononuclear cells from patients with distal symmetric polyneuropathy. No significant differences were found in malondialdehyde or in oxidized-LDL levels comparing both groups. These data show an altered glutathione response in circulating monocytes from diabetic patients with distal symmetric polyneuropathy.

Is cognitive impairment associated with the presence and severity of peripheral neuropathy in patients with type 2 diabetes mellitus?

BackgroundPeripheral Diabetic Neuropathy (PDN) and cognitive impairment are complications of Diabetes Mellitus (DM) that seem to share several underlying mechanisms. The aim of this study was to investigate whether diabetic patients would have worse cognitive function than non diabetic individuals and within diabetic patients, whether those with PDN would present an even more significant cognitive impairment.FindingsNinety four (94) outpatients with Type 2 DM were sequentially evaluated. Also, Fifty four (54) healthy individuals were sequentially selected to match the diabetic group. For the assessment of neuropathy, Portuguese versions of the Neuropathy Disability Score (NDS) and Neuropathy Symptom Score (NSS) were used. Global cognitive function was assessed by using the Portuguese Version of the Mini-Mental State Examination (MMSE), Trail Making Tests A and B and Verbal Fluency Test. Significantly lower scores were found in the Type 2 DM group in comparison to control group in the MMSE (25.7 [16–30] vs 27.6 [19–30]; p <0.001). Within T2DM group, forty five (45) patients were diagnosed with PDN. No differences were found between patients with and without PDN in all cognitive tests (p >0.05 in all comparison). No correlation was also found among NSS, NDS and any of the cognitive tests.ConclusionAlthough diabetic patients do have a worse cognitive function, this impairment does not seem to be related to the presence and/or severity of PDN.

Screening techniques to identify occurrence of peripheral neuropathy among diabetic patients

Background Neuropathy is the greatest source of morbidity associated with diabetes, affecting up to 50% of those with long-standing disease, and pain as a symptom of neuropathy may be seen in as many as one third of all patients with diabetes. Aim: - The aim of this study was screen the occurrence of peripheral neuropathy among diabetic patients. Subjects and methods The design used for conduction of this study was prospective (cohort) study). Subjects: - A total 300 adults diabetic patients. Tools of data collection:-Tool I Diabetic patient knowledge scaduale, Tool II Diabetic foot examination checklist. It contained two items. General examination Highet , weight , BMI , heart rate , blood pressure, specific foot examination, diagnosis of diabetic peripheral neuropathy using neuropathy symptoms score (NSS),neuropathy disability score (NDS),Pressure perception using 10gm Semmes Winston monofilament on10 sites in two feet and sensory assessment Results: -. The patients who had ≥ 3in total score of neuropathy symptoms score (NSS) were 23%, (10.3%) had total score ≥6 in neuropathy disability score. Loss of protective sensation was common in (11.0%) of patients. The total patients diagnosed with neuropathy (Abnormal with one of these three parameters) were 27 .3 % of studied sample. Also the study reveals that assessment of foot pressure perception using 10gm monofilament had the best sensitivity.Conclusion based on the findings it was concluded that diabetic peripheral neuropathy was diagnosed in one third of studied sample ,10gm monofilament had the best sensitivity Recommendations .All patients with diabetes should be screened at least annually for presence of diabetic peripheral neuropathy. Foot care education must be provided to every diabetic patient with regular confirmation

Assessment of Peripheral Neuropathy Using Measurement of the Current Perception Threshold with the Neurometer® in patients with type 1 diabetes mellitus

ObjectiveThe aim of this study is to evaluate the role of current perception threshold (CPT) measurement in peripheral neuropathy in type 1 diabetic patients by using the Neurometer®, a nerve measuring instrument. Methods52 patients with type 1 diabetes mellitus with a disease duration of less than five years and normal neuropathy symptom score (NSS), neuropathy disability score (NDS) and sensory nerve conduction velocity (SCV), and 40 healthy controls were enrolled in this study. Measurement of CPT using the Neurometer® at 2000, 250 and 5Hz assesses function in the bilateral median nerve and sural nerve in all studied cases. We also evaluated the glycated hemoglobin, microalbuminuria, urinary albumin/creatinine ratio and other metabolism indexes of all patients. ResultsThe CPT of the bilateral median nerve and sural nerve was significantly lower in diabetic patients (P<0.01). Moreover, the number of median nerve injuries in the diabetic group (left side 8/52, right side 8/52) is significantly different from the number of its ipsilateral sural nerve injuries (left side 28/52, right side 22/52) (left side P<0.01, right side P<0.01). By comparing those with DPN and those without DPN in the diabetic group, DPN groups had significantly higher glycated hemoglobin (t=2.518, P<0.05). Using binary logistic regression, high glycated hemoglobin was identified to be an independent risk factor of DPN incidence (OR (95% CI): 1.317 (1.013 −1.712), P<0.05). ConclusionThese data suggest that CPT is useful in early detection of peripheral neuropathy in patients with type 1 diabetes mellitus. Patients with diabetic peripheral neuropathy, the lower limb nerve is more vulnerable than the upper limb nerve. In addition, patients with DPN had higher glycated hemoglobin which is an independent risk factor of DPN.

Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria.

ObjectiveCorneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria.Materials and MethodsAll participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)].Results53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria.ConclusionsIVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.

Diabetic foot syndrome and corneal subbasal nerve plexus changes in congolese patients with type 2 diabetes.

BackgroundTo study the severity of diabetic neuropathy, diabetic retinopathy and grades of diabetic foot syndrome for correlations with corneal subbasal nerve plexus (SBP) changes in Congolese patients with type 2 diabetes.Methodology/Principal FindingsTwenty-eight type 2 diabetes patients with diabetes-related foot ulceration were recruited in a diabetic care unit in Kinshasa, Democratic Republic of Congo. Corneal SBP was investigated by confocal laser-scanning microscopy to analyse nerve fibre density (NFD) [µm/ µm²], number of branches [n] and number of connectivity points [n]. Foot ulceration was graded using the Wagner ulcer classification. Corneal sensitivity (Cochet-Bonnet), Neuropathy Symptom Score (NSS), Neuropathy Disability Score (NDS), ankle-brachial index (ABI) and ophthalmological status were evaluated. Foot ulceration was ranked as mild (Wagner 0-1: 13 patients/46.4%), moderate (Wagner 2-3: 10 patients/35.7%) and severe (Wagner 4-5: 5 patients/17.9%). The correlation between Wagner Score and NFD (p=0.017, r = - 0,454), NDS and NFD (p=0,039, r = - 0.400) as well as Wagner Score and HbA1c (p=0,007, r = - 0.477) was stated. Significant differences in confocal SBP parameters were observed between Wagner 0-1 and Wagner 4 5 (number of branches (p=0.012), number of connectivity points (p=0.001), nerve fibre density (p=0.033)) and ABI (p=0.030), and between Wagner 2-3 and Wagner 4-5 (number of branches (p=0.003), number of connectivity points (p=0.005) and nerve fibre density (p=0.014)). Differences in NDS (p=0.001) and corneal sensation (p=0.032) were significant between Wagner 0-1 and Wagner 2-3. Patients with diabetic retinopathy had significantly longer diabetes duration (p=0.03) and higher NDS (p=0.01), but showed no differences in SBP morphology or corneal sensation.Conclusions/SignificanceWhile confirming the diabetic aetiology of foot ulceration due to medial arterial calcification, this study indicates that the grade of diabetic foot syndrome correlates with corneal SBP changes and corneal sensation in patients in sub-Saharan Africa.

Treatment for IgG and IgA paraproteinaemic neuropathy.

Paraproteinaemic neuropathy refers to those neuropathies associated with a monoclonal gammopathy or paraprotein. The most common of these present with a chronic, predominantly sensory, symmetrical neuropathy, similar to chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but with relatively more sensory involvement, both clinically and neurophysiologically. The optimal treatment for neuropathies associated with IgG and IgA monoclonal gammopathy of uncertain significance is not known. This is an update of a review first published in 2007. To assess the effects of any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. On 18 January 2014 we searched the Cochrane Neuromuscular Disease Group Trials Specialized Register, CENTRAL, MEDLINE and EMBASE. We also checked bibliographies for controlled trials of treatments for IgG or IgA paraproteinaemic peripheral neuropathy. We checked clinical trials registries for ongoing studies in November 2014. We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs using any treatment for IgG or IgA paraproteinaemic peripheral neuropathy. We excluded people with IgM paraproteins. We excluded people where the monoclonal gammopathy was considered secondary to an underlying disorder. We included participants of any age with a diagnosis of monoclonal gammopathy of uncertain significance with a paraprotein of the IgG or IgA class and a neuropathy. Included participants were not required to fulfil specific electrophysiological diagnostic criteria. We used standard Cochrane methodology to select studies, extract data and analyse results. One trial author provided additional data and clarification. We identified one RCT, with 18 participants, that fulfilled the predetermined inclusion criteria. The trial compared plasma exchange to sham plasma exchange in participants with IgG or IgA paraproteinaemic neuropathy over a three-week follow-up period. We identified four other studies but these were not RCTs or quasi-RCTs. The included RCT did not report our predefined primary outcome measure, change in disability six months after randomisation. The trial revealed a modest benefit of plasma exchange in the weakness component of the Neuropathy Disability Score (NDS, now the Neuropathy Impairment Score); the mean improvement with plasma exchange was 17 points (95% confidence interval (CI) 5.2 to 28.8 points) versus 1 point (95% CI -7.7 to 9.7 points) in the sham exchange group at three weeks' follow-up (mean difference (MD) 16.00; 95% CI 1.37 to 30.63, low quality evidence). There was no statistically significant difference in the overall NDS (MD 18.00; 95% CI -2.03 to 38.03, low quality evidence), vibration thresholds or neurophysiological indices. Adverse events were not reported. The trial was at low risk of bias overall, although limitations of trial size and duration reduce the quality of the evidence in support of its conclusions. The evidence from RCTs for the treatment of IgG or IgA paraproteinaemic neuropathy is currently inadequate. More RCTs of treatments are required. These should have adequate follow-up periods and contain larger numbers of participants, perhaps through multicentre collaboration, considering the relative infrequency of this condition. Observational or open trial data provide limited support for the use of treatments such as plasma exchange, cyclophosphamide combined with prednisolone, intravenous immunoglobulin, and corticosteroids. These interventions show potential therapeutic promise but the potential benefits must be weighed against adverse effects. Their optimal use and the long-term benefits need to be considered and validated with well-designed RCTs.

Peripheral neuropathy is associated with insulin resistance independent of metabolic syndrome.

BackgroundTo determine the association of insulin resistance, metabolic syndrome (MetS) with peripheral neuropathy (PN).MethodsThis cross-sectional study consisted of 2035 subjects in Shanghai who were classified as with MetS and without MetS. The new International Diabetes Federation (IDF) criterion was used to define MetS. HOMA-IR was applied to evaluate insulin resistance. All subjects underwent complete foot examination. PN was assessed according to the neuropathy symptom and neuropathy disability scores. Binary logistic regression was performed to analyze the contributions of insulin resistance, features of MetS to PN.Results(1) The percentage of PN was 4.0% in our study. Patients with MetS (47.7%) had a higher percentage of PN (5.5% vs. 2.6%, respectively, P = 0.001). With the components of MetS increased (non-MetS, three, four, five), a linear increase in the proportion of peripheral neuropathy was observed (2.6%, 4.8%, 5.6% and 7.2%; respectively, P for trend = 0.001). (2) In patients with PN, the average age of patients was significantly older than the corresponding non-PN patients. Waist circumference, fasting blood glucose, HbA1c, proportion of treatment for diabetes and hypertension were significantly higher in PN group compared with non-PN group in MetS patients. (3) The frequency of dysglycemia was the highest in PN patients both with and without MetS (96.2% and 82.1%, P = 0.084). (4) After adjusting for gender and smoking history, the PN was associated with MetS [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2, 3.2; P = 0.006], and age (OR 1.1; 95% CI 1.1, 1.1; P < 0.001). When HOMA-IR was added to this binary logistic regression, the association of PN with MetS disappeared (P = 0.110), but the PN was still associated with HOMA-IR (OR 1.2; 95% CI 1.1, 1.4, P < 0.001).ConclusionsIn metabolic syndrome, insulin resistance might play an important role in the development of peripheral neuropathy.

Clinical neuropathy scales in neuropathy associated with impaired glucose tolerance

AimsDisagreement exists on effective and sensitive outcome measures in neuropathy associated with impaired glucose tolerance (IGT). Nerve conduction studies and skin biopsies are costly, invasive and may have their problems with reproducibility and clinical applicability. A clinical measure of neuropathy that has sufficient sensitivity and correlates to invasive measures would enable significant future research. MethodsData was collected prospectively on patients with IGT and symptomatic early neuropathy (neuropathy symptoms <2years) and normal controls. The seven scales that were examined were the Neuropathy Impairment Score of the Lower Limb (NIS-LL), Michigan Diabetic Neuropathy Score (MNDS), modified Toronto Clinical Neuropathy Scale (mTCNS), Total Neuropathy Score (Clinical) (TNSc), The Utah Early Neuropathy Scale (UENS), the Early Neuropathy Score (ENS), and the Neuropathy Disability Score (NDS). ResultsAll seven clinical scales were determined to be excellent in discriminating between patients with neuropathy from controls without neuropathy. The strongest discrimination was seen with the mTCNS. The best sensitivity and specificity for the range of scores obtained, as determined by using receiver operating characteristic curves, was seen for the mTCNS followed by the TNSc. Most scales show a stronger correlation with measures of large rather than small fiber neuropathy. ConclusionsAll seven scales identify patients with neuropathy. For the purpose of screening potential patients for a clinical study, the mTCNS followed by the TNSc would be most helpful to select patients with neuropathy.

Prospective Evaluation of the Effect of Short-Term Oral Vitamin D Supplementation on Peripheral Neuropathy in Type 2 Diabetes Mellitus

Objective: We aimed to assess the efficacy of short-term oral vitamin D supplementation on peripheral neuropathy in patients with type 2 diabetes. Materials and Methods: This prospective, placebo-controlled trial included 112 type 2 diabetic patients with diabetic peripheral neuropathy (DPN) and vitamin D [25(OH)D] deficiency. Patients were sequentially assigned to a treatment group (n = 57) and a placebo group (n = 55). DPN was assessed using a neuropathy symptom score (NSS), a neuropathy disability score (NDS) and a nerve conduction study (NCS). Vitamin D status was determined by measuring the serum total 25(OH)D concentration. Patients received either oral vitamin D₃ capsules or starch capsules once weekly for 8 weeks. The primary outcome was changes in NSS and NDS from baseline. The secondary outcome was changes in the NCS result. Results: Serum 25(OH)D concentrations significantly improved after oral vitamin D supplementation in the treatment group when compared to the placebo group (32.8 ± 23.7 vs. 1.1 ± 3.6, p < 0.0001). Similarly, the improvement in NSS values was significantly greater in the treatment group than in the placebo group (-1.49 ± 1.37 vs. -0.20 ± 0.59, p < 0.001). No improvement was observed for NDS and NCS between the 2 groups after treatment. Conclusion: Short-term oral vitamin D₃ supplementation improved vitamin D status and the symptoms of neuropathy in patients with type 2 diabetes.

Automated Quantification of Neuropad Improves Its Diagnostic Ability in Patients with Diabetic Neuropathy

Neuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics)) outputs to diagnose diabetic peripheral neuropathy (DPN). 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS), peroneal motor nerve conduction velocity (PMNCV), sural nerve action potential (SNAP), Deep Breathing-Heart Rate Variability (DB-HRV), intraepidermal nerve fibre density (IENFD), and corneal confocal microscopy (CCM). 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%), CNFD (88%, 78%), and SNAP (88%, 83%), whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV) and 80% for small fibre neuropathy (CNFD). The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%, P = 0.0003) and CNFD (AUC: 82%, P = 0.01) was better than for PMNCV (AUC: 60%). The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics) improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.

The ISIS-TTRRx-CS2 phase 3 study in patients with familial amyloid polyneuropathy: Baseline results of the first 100 patients for the NIS, NIS+7 and mNIS+7 using different methods of scoring: identification of consistencies and key differences

Background Familial amyloid polyneuropathy (FAP) is a devastating disease with continuous progression over time leading to complete disability, bedridden status, and ultimately death within 10 to 15 years from symptom onset. In order to document disease progression, it is necessary to have valid instruments which allow assessment of the severity of the sensory, motor and autonomic neuropathy components of the disease. Over the last decades, multiple related instruments have been used and modifications developed to measure disease progression in FAP patients in clinical trial settings. These include the Neuropathy Impairment Score (NIS), originally called Neuropathy Disability Score, the Neuropathy Impairment Score for the Lower Limbs (NIS-LL), the Neuropathy Impairment Score +7 (NIS+7) and the modified NIS +7 (mNIS+7). The NIS scores were first used to quantitate neuropathic impairment in a series of therapeutic trials in chronic inflammatory demyelinating polyradiculoneuropathy and were also used as primary endpoints in clinical trials for FAP in the completed diflunisal (NIS+7) and tafamidis (NIS-LL) Phase 3 trials. Building on experience from these trials, modifications to the NIS+7 were developed (Suanprasert et al, 2014, J Neurol Sci) and are currently being applied in the ongoing ISIS-TTRRx-CS2 (mNIS+7 Isis) and patisiran (mNIS+7 ALN) Phase 3 trials. Even though the mNIS+7 Isis and mNIS+7 ALN scores are very similar, they are not identical. The details in the assessment and scoring for the various versions of the NIS based scores are described and their scoring methods applied to baseline data collected on the first 100 patients in the ISIS-TTRRx-CS2 trial to better understand and illustrate the key differences.

Clinical, electrophysiological and skin biopsy studies of peripheral neuropathy with small fibers involvement: a report of 34 cases

To explore the relationship between clinical features, electrophysiology and intraepidermal nerve fiber density (IENFD) in peripheral neuropathy with small fibers involvement and determine the diagnostic value of 13-item small-fiber neuropathy and symptoms inventory questionnaire (SFN-SIQ) and neuropathy symptom score [lower limb] (NSS [LL]) in small fiber neuropathy (SFN). A total of 34 consecutive patients with peripheral neuropathy with symptoms of small fibers were enrolled and divided into two groups of small fiber injury and small and large fiber injury.SFN-SIQ, NSS [LL] and neuropathy disability score [lower limb] (NDS [LL]) were administered.Nerve conduction studies and skin biopsy were conducted in unilateral lower limb. The relationship between IENFD and these scales was assessed by partial correlation.Receiver operating characteristic analysis was applied for evaluating the diagnostic value of SFN-SIQ and NSS [LL] in small fiber injury. Independent sample t test was used to compare various parameters of two groups. And similar statistical method was used for IENFD abnormal and normal groups to detect the clinicoelectrophysiological differences. According to the international normative reference of IENFD, 13 patients could be diagnosed with peripheral neuropathy with small fibers involvement. IENFD was moderately correlated with SFN-SIQ (r = 0.437, P = 0.012) and marginally correlated with NSS [LL] (r = 0.334, P = 0.062). The diagnostic value of SFN-SIQ and NSS [LL] was moderate for small fiber injury (Az = 0.753, P = 0.012 for SFN-SIQ, Az = 0.712, P = 0.040 for NSS [LL]) and the best diagnostic indicator of each scale was 6. The value of NDS [LL] was apparently elevated in small and large fiber injury group versus small fiber injury group (t = -5.605, P < 0.001). The IENFD abnormal group had a higher NSS [LL] value than that of the IENFD normal group (t = -2.047, P = 0.049). No differences of electrophysiological parameters existed between IENFD abnormal and normal groups. Chinese normative reference of IENFD should be formulated for the diagnosis of small fiber neuropathy. SFN-SIQ and NSS [LL] may screen for small fiber neuropathy and both are convenient during patient follow-ups.Large sample studies are warranted to further evaluate the clinical values of SFN-SIQ and NSS [LL].