Neuropathy Screening Research Articles

Sensory neuropathy in patients with Pompe disease: a case series in Iran

BackgroundPompe disease is a glycogen storage disease primarily affecting striated muscles. Despite its main manifestation in muscles, patients with Pompe disease may exhibit non-muscle symptoms, such as hearing loss, suggesting potential involvement of sensory organs or the nervous system due to glycogen accumulation.AimsThis study aimed to evaluate the presence of concomitant small and large fiber neuropathy in patients with Pompe disease.MethodsIn this case series study, nine patients with Pompe disease without complaints of neuropathy were evaluated. Small fiber neuropathy was assessed using the Small Fiber Neuropathy Screening List (SFNSL) and SUDOSCANR, while the sympathetic system was evaluated through Sympathetic Skin Response (SSR), and large fiber neuropathy was assessed through electrodiagnostic findings.ResultsSmall fiber neuropathy was detected in seven patients (77.8%) according to the SFNSL. Three patients (3/9, approximately 30%) exhibited positive electrophysiological tests, including SSR, SUDOSCANR, and nerve conduction studies for neuropathy. They also had positive SFNSL results.ConclusionsThis study indicates that neuropathy can be a comorbid condition in Pompe disease, emphasizing the importance of screening for this disabling condition.

Diabetes Patient Counseling: The Pharmacist’s Role

A diabetic foot ulcer (DFU) is the prime cause of poor quality of life among diabetic patients. DFU leads to physical disability and an enormous economic burden on diabetic patients. The development and prognosis of DFU are preventable in most patients by modifying the risk factors for DFU. Programs intervened by clinical pharmacists can enhance rational drugs use and improve the early identification and prevention of DFU. This study intended to prove the beneficial outcome in identifying the risk factors and the provision of patient-tailored referral advice regarding DFU among diabetic patients. This cross-sectional study assessed the neuropathy through Michigan Neuropathy Screening Instrument (MNSI), Monofilament and Vibration test using Tuning Fork and Handheld Doppler for assessing the lower limb vascular disease as per NICE guideline among 137 diabetic patients. 64% of patients were found to have symptoms of neuropathy through the neuropathy assessment test whereas 36% did not have the symptoms. Foot sensory using monofilament test was found to be normal in 49.64% of DFU patients, reduced in 43.80%, and absent in 6.57% of DFU patients. The Ankle Brachial Index (ABI) was found to be normal in 48% of patients, mild in 34% of patients, moderate in 12% of patients, and incompressible in 6% of patients. Clinical Pharmacist intervened risk assessment through Hand-held Doppler, MNSI instrument, and Vibration test helped in screening the DFU patients for Neuropathy, and implementation of effective per patient-tailored education was found to be beneficial in the early identification of DFU and referral to specialty hospitals

Neuropathy among drug resistant HIV Patients treated in Jakarta

Introduction: Some people living with HIV (PLWH) receiving ART in Indonesia display poor clearance of replicating virus. This has been associated with HIV-associated sensory neuropathy. Here we assess whether treatment failure reflects the presence of drug resistance mutations. Methodology: PLWH were stratified by HIV RNA levels using a ≥ 1000 copies/mL cut-off after 5.3 (2-7.5) years on ART. Drug-resistance mutations were analyzed in seven of ten cases with a detectable viral load. The HIV pol gene was screened for mutations affecting resistance to nucleoside inhibitors (NRTI), non-nucleoside inhibitors (NNRTI) and protease inhibitors (PI). We recorded co-infections, transmission routes, and neuropathy based on the Brief Peripheral Neuropathy Screen Tool. Results: The primary HIV subtype was HIV-1 CRF01_AE, but one patient had subtype G. Polymorphisms affecting NRTI or NNRTI (6/7 cases) and protease inhibitors (1/7 cases) were identified. Three mutations affecting NRTI (M184V, M4IL, T215F), two for NNRTI (K103N, G190A) and five for protease inhibitors (M46I, I50V, I54V, V82A, N88NDGS) were evident. Subjects with resistance mutations were mostly intra-venous drug users (4/7) and had a higher risk of neuropathy (p = 0.016). Conclusions: Drug resistance mutations were present in most cases of treatment failure examined and were therefore indirectly a risk factor for peripheral neuropathy.

Relationship between nerve ultrasonography image and electrophysiology in diabetic polyneuropathy.

This study aims to investigate the association between cross-sectional area (CSA) imaging findings of nerve ultrasound and conventional nerve conduction studies (NCS) for patients with distal symmetric sensorimotor polyneuropathy (DSPN) due to type 2 diabetes mellitus. We enrolled 103 patients with type 2 diabetes mellitus and collected their demographic data, modified Michigan Neuropathy Screening Instrument (mMNSI) score, NCS, and ultrasonography images of peripheral nerves. The relationship of ultrasound variables for individual nerves and the ultrasound pattern sum score (UPSS) to conventional NCS findings was investigated. A higher grade of DSPN was associated with a notably higher CSA. Multivariate step-wise regression analysis revealed that the number of abnormal nerves was a positive independent variable for UPSS (β coefficient = 0.4205; P < 0.0001). Of the five nerves studied, abnormalities of the tibial nerve (P ≤ 0.0100) and ulnar nerve (P = 0.052) were the most significant variables. The tibial nerve exhibited the most substantial association with elevated UPSS. In addition, a strong correlation was observed between abnormal NCS findings and UPSS in patients with DSPN.

COMPARATIVE EFFECTIVENESS OF SENSORY-MOTOR INTEGRATION AND ROODS APPROACH ON SENSORY AND MOTOR ABNORMALITIES IN PATIENT WITH DIABETIC POLYNEUROPATHY

Background: Diabetic sensory-motor polyneuropathy causes a gradual loss of vibratory, thermal, tactile, and proprioceptive sensations, alongside motor symptoms such as reduced ankle reflexes, mild foot drop, and lower limb weakness, leading to functional limitations like frequent tripping and impaired pincer grasp. Effective therapeutic strategies are essential for managing these symptoms to enhance patients' quality of life. This study investigates the comparative effectiveness of sensory-motor integration and the Rood approach in managing diabetic polyneuropathy symptoms. Objective: To compare the effects of sensory-motor integration and the Rood approach in improving sensory and motor functions in patients with diabetic polyneuropathy. Methods: This single-blinded, randomized clinical trial included 64 patients with diabetic polyneuropathy recruited from Allied Hospital Faisalabad and Madina Teaching Hospital. Patients were randomly assigned to either a sensory-motor integration group or a Rood approach group. Both groups received 6 weeks of therapy, with three sessions per week. Sensory function was assessed using the Michigan Neuropathy Screening Instrument (MNSI), muscle strength via the Medical Research Council (MRC) scale, and functional mobility with the Walking Impairment Questionnaire (WIQ). Pre- and post-treatment data were analyzed using SPSS 20.0. Results: The Rood approach group demonstrated a significant improvement in MNSI History scores, decreasing from a mean of 9.26 ± 2.33 pre-treatment to 5.68 ± 1.49 post-treatment. The sensory-motor integration group showed a mean decrease from 10.21 ± 1.65 to 8.42 ± 1.43. For MRC scale scores, the Rood group improved from 46.95 ± 3.98 to 51.52 ± 3.67, while the sensory-motor integration group rose from 44.79 ± 4.05 to 46.63 ± 4.99. WIQ scores in the Rood group increased from 52.16 ± 9.19 pre-treatment to 62.47 ± 8.42 post-treatment, outperforming the sensory-motor integration group, which rose from 51.63 ± 6.63 to 54.26 ± 6.70. Conclusion: Both sensory-motor integration and the Rood approach significantly improved sensory and motor function in diabetic polyneuropathy patients. However, the Rood approach was more effective across all measured parameters, suggesting it as a preferable option for enhancing functionality and quality of life in this patient population.

Effectiveness of a web-based foot-ankle exercise program for treating ulcer risk factors in diabetic neuropathy in a randomized controlled trial

The need for strategies to prevent complications from diabetic neuropathy (DPN) is well recognized. However, foot-ankle exercise programs show weak to moderate evidence, and barriers to their implementation persist, including broad and facilitated access to exercise programs, which guarantee for equity. In this paper, we report for the first time the effectiveness of a web-based foot-ankle exercise program aiming to improve DPN-related outcomes, gait biomechanics and functional outcomes. Sixty-two participants with DPN were randomly allocated into the control group (CG; n = 31), which received the usual care, or the intervention group (IG; n = 31), which received the usual care plus a 12-week foot-ankle exercise program using a web-based software (the SOPeD software). The primary outcomes, DPN symptoms and severity, were assessed using the Brazilian version of the Michigan Neuropathy Screening Instrument and the Decision Support System for Classification of Diabetic Polyneuropathy, respectively. Secondary outcomes included tactile sensitivity (monofilaments) and vibration perception (tuning fork), functional outcomes, such as foot pain and function (Foot Health Status Questionnaire), foot muscle strength and plantar pressure during gait (emed plate), and foot-ankle kinematics and kinetics during gait. Outcomes were assessed at baseline, 12 and 24 weeks by an assessor blinded to group allocation. DPN symptoms and severity remained unchanged after the web-based foot-ankle program. However, IG showed improvements compared to CG, with greater functional reach at 12 weeks, better foot function, reduced foot pain and greater plantarflexion degree during push-off at 24 weeks. Regarding plantar loading during gait, the forefoot pressure reduced in the IG at 12 weeks compared to baseline, but at 24 weeks, forefoot load increased in the IG compared to CG. The 12-week web-based foot-ankle exercise program was feasible, acceptable, demonstrating safety with minimal adverse events, such as delayed onset muscle soreness and foot muscle cramping. While DPN-related outcomes were unaffected by the 12-week SOPeD program, modest improvements in foot pain and function, functional reach, and changes in plantar pressure and plantarflexion degree during gait were noted, mostly at 24 weeks.Trial registration: ClinicalTrials.gov, NCT04011267. Registered on 8 July 2019.

Profiles of Peripheral Neuropathy and Risk Factors in People With Treatment-Naive Type 2 Diabetes Mellitus and Prediabetes.

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) occurring in a majority of the affected people. DPN is the key initiating factor for the development of diabetic foot ulcerationand the most common cause of non-traumatic lower-limb amputations. Whether chronic hyperglycaemia per se or altered levels of intermediate conventional risk factors in these people are responsible for the increased risk of DPN, is a matter of debate. There is little data about the profile of DPN in people with treatment-naive diabetes and prediabetes in the Asian population. This study aimed to determine the frequency of early DPN among people with newly detected treatment-naive diabetes and prediabetes attending a tertiary care public hospital. The study further aimed to determine the risk factors associated with DPN and to investigate whethersuch risk factors in these people might help to explain their increased risk of peripheral neuropathy. A total of 65 consecutive people with treatment-naive T2DM with an equal number of people with prediabetes attending a tertiary care centre, diagnosed as per standard criteria, were enrolled in a non-randomised prospective study. The presence of peripheral neuropathy was assessed by the Michigan Neuropathy Screening Instrument (MNSI). Risk factor analysis for peripheral neuropathy in both groups was carried out. Statistical significance was considered with p-values of < 0.05. A total of 13 (20%) people with newly diagnosed treatment-naive T2DM and eight (12.3%) with prediabetes had DPN (MNSI score ≥ 2.5). Age (p < 0.001), high plasma glucose/glycated haemoglobin (HbA1c) (p < 0.001), BMI (p < 0.001), total cholesterol (p <0.001), albuminuria and hypertension (p < 0.001) were found to be strongly associated with early peripheral neuropathy. DPN is a frequent complication among newly diagnosed treatment-naive people with T2DM and to a lesser extent among people with prediabetes. Various anthropometric, clinical, biochemical and metabolic factors in people with hyperglycaemia could account for the increased frequency of DPN in these people.

Sural-to-medial femoral cutaneous amplitude ratio in early diagnosis of uremic neuropathy.

Medial femoral cutaneous (MFC) sensory nerve action potentials (SNAPs) can be easily recorded using distal stimulation. This study aimed to identify a new parameter using MFC SNAPs for the early electrophysiological diagnosis of length-dependent axonal polyneuropathy (LDAP) associated with uremic neuropathy. Patients with chronic renal failure who were referred to the electrodiagnostic laboratory due to symptoms suggesting polyneuropathy were included. Assessments encompassed neurological examination, Michigan Neuropathy Screening Instrument (MNSI), and Semmes-Weinstein monofilament test. Antidromic radial, median, ulnar, MFC, sural, and superficial peroneal sensory; median, ulnar, tibial, and peroneal motor nerve conduction studies were performed. Sural-to-radial amplitude ratio (SRAR) and sural-to-medial femoral cutaneous amplitude ratio (SMFCAR) were calculated, and their diagnostic sensitivities were compared with the age and sex matched healthy controls. Thirty-two chronic renal failure patients (mean age 60.0 ± 9.6 years) and 37 controls (60.6 ± 9 years) were included. MNSI indicated clinical polyneuropathy in 59.4% of patients, while sural SNAP amplitude was diagnostic in 78%. Median SRAR and SMFCAR values were significantly lower in patients than controls (p < .001 for both). The cut-off values for SMFCAR and SRAR were <1.82 and <0.30, respectively, both with a sensitivity of 59% and a specificity of 94%. Sural SNAP is the most sensitive parameter in the diagnosis of LDAP. SMFCAR is not superior to SRAR. If the sural SNAP amplitude is normal, SMFCAR can serve as an alternative to SRAR in dialysis patients with bilateral arteriovenous fistulae or in those unable to undergo radial NCS.

Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes

This review explores the complex relationship between diabetic neuropathy and cardiovascular disease (CVD). Neuropathy, a common complication of type 1 and type 2 diabetes, is divided into autonomic and peripheral types, each impacting cardiovascular health. Cardiovascular autonomic neuropathy, a form of autonomic neuropathy, is associated with various CVD complications, including arrhythmias, impaired nocturnal blood pressure regulation, and increased mortality. The prevalence of cardiovascular autonomic neuropathy varies depending on the type and duration of diabetes and is influenced by factors like glycemic control and metabolic stress. Peripheral polyneuropathy, which is often linked to diabetic foot disease, is also correlated with elevated CVD risk; research suggests shared pathophysiological mechanisms between peripheral neuropathy and cardiovascular conditions. Screening for neuropathies using tools like the Michigan Neuropathy Screening Instrument and heart rate variability analyses can facilitate early detection of CVD risk. Additionally, emerging technologies, like deep learning models, have demonstrated promise in detecting early cardiovascular patterns associated with autonomic neuropathy through electrocardiogram analysis. These findings underscore the value of integrating novel diagnostic approaches for early intervention. As CVD represents a leading cause of death among patients with diabetes, this article emphasizes the need for thorough assessment and proactive management of neuropathy to mitigate cardiovascular risk. The review recommends a multidisciplinary approach to diabetes care, including early screening, accurate risk stratification, and targeted therapeutic strategies to prevent or slow the progression of CVD in patients with autonomic and peripheral neuropathies. Further research is warranted to clarify the optimal intervention strategies for reducing CVD risk in these populations.

Correlation of Diabetic Symptoms with Severity of Diabetes Mellitus in Middle-Aged Population

Purpose: To investigate the correlation of symptoms of Diabetes with the severity of Diabetes Mellitus (DM) in Middle-aged subjects with diabetes. Participants: 68 subjects with diagnosed diabetes mellitus between the ages of 40 and 60 with/without symptoms of neuropathy were included. Participants with neurological disease, recent surgical procedures or injuries to feet, vascular disease, and cognitive impairment were excluded. Method: In a cross-sectional observational study, a total of 68 middle-aged diabetic subjects were interviewed in terms of demographic data, Fasting Blood Sugar (FBS), Post-Prandial Blood Sugar (PPBS), HBA1c, duration of diabetes, and associated medical conditions. All participants were examined by the Michigan Neuropathy Screening Instrument (MNSI). MNSI consists of 2 parts. 1) questionnaire 2) clinical examination. Analysis: Statistical analysis was done by SPSS 20 &amp; Spearman correlation test was applied. Results: In mild diabetes, hba1c has a weak positive correlation (r=0.232) with MNSI-1 and a very weak positive (0.016) correlation with MNSI-2. In moderate diabetes, hba1c has significant(p=0.003) strong positive correlation (r=0.703) with MNSI-1 and significant (p=0.019) moderate positive correlation (r=0.0596) with MNSI-2. In severe diabetes, hba1c has significant (p=0.028) moderate positive correlation (r=0.532) with MNSI-1 and significant (p=0.034) moderate positive (0.515) correlation with MNSI-2 Conclusion: Diabetic symptoms are moderately correlated with moderate &amp; severe levels of Diabetes based on hba1c in the middle-aged population. Keywords: Diabetes Mellitus, Middle age, Diabetic symptoms, Michigan Neuropathy Screening Instrument.

Promising predictors of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus

BackgroundDiabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) is a growing issue, with controversial data in the terms of prevalence and evaluation timelines. Currently, there are no clear standards for its early detection. Therefore, our aim was to assess the contribution of the Michigan neuropathy screening instrument (MNSI), lipid profile, serum neuron specific enolase (NSE), and serum heat shock protein 27 (HSP 27) to the prediction of DPN in children and adolescents with T1DM.MethodsIn this case-control study, fifty children diagnosed with T1DM for at least five years were enrolled and evaluated through complete neurological examination, MNSI, and nerve conduction study (NCS). Additionally, HbA1c, lipid profile, serum NSE, and serum HSP 27 levels were measured for patients and controls.ResultsThe prevalence of DPN in our study was 24% by NCS, and electrophysiological changes showed a statistically significant lower conduction velocity for the posterior tibial and sural nerves, as well as a prolonged latency period for the common peroneal and sural nerves in neuropathic patients. In these patients, older age, earlier age of diabetes onset, longer disease duration, higher total cholesterol, triglycerides, low density lipoprotein cholesterol, HbA1c, serum NSE, and HSP27 levels were observed. The MNSI examination score ≥ 1.5 cutoff point had an area under the curve (AUC) of 0.955, with 75% sensitivity and 94.74% specificity, according to receiver operating characteristic curve analysis. However, the questionnaire’s cutoff point of ≥ 5 had an AUC of 0.720, 75% sensitivity, and 63% specificity, with improved overall instrument performance when combining both scores. Regarding blood biomarkers, serum NSE had greater sensitivity and specificity in discriminating neuropathic patients than HSP27 (92% and 74% versus 75% and 71%, respectively). Regression analysis revealed a substantial dependency for MNSI and serum NSE in predicting DPN in patients.ConclusionsDespite limited research in pediatrics, MNSI and serum NSE are promising predictive tools for DPN in children and adolescents with T1DM, even when they are asymptomatic. Poor glycemic control and lipid profile changes may play a critical role in the development of DPN in these patients, despite conflicting results in various studies.

A cross-sectional study to assess the knowledge and risk of diabetic polyneuropathy using Michigan neuropathy screening instrument among type 2 diabetes mellitus

Diabetic polyneuropathy, arising from elevated blood sugar levels damaging nerves microvasculature, manifests as tingling, numbness, muscle weakness, coordination challenges, sensitivity alterations, digestive problems, and sexual dysfunction, necessitating meticulous blood sugar control, medications, physical therapy, lifestyle changes, and regular medical supervision for prevention and management. Aim: The aim of the study is to assess the knowledge and risk of diabetic polyneuropathy using Michigan Neuropathy screening Instrument among type ii diabetes mellitus. Methods: In this study Non Experimental Research study design and purposive sampling technique is used and a total of 599 samples were assessed. Knowledge Questionnaire and physical examination using standardized Michigan Neuropathy Screening Instrument were used . The mean score for knowledge is &lt;5 and the preliminary assessment risk score is &lt;4 and the physical examination mean score is &lt;2.5. Results: Participants above 50 years (46.6%) of age with chronicity of diabetes of 1- 10 years (77.5%) with abnormal preliminary risk score &gt;4 (32.2%) and abnormal physical examination score &gt;2.5(74.6%). Females has good knowledge on diabetic polyneuropathy and also they show high risk of developing diabetic polyneuropathy. Conclusion: The study concluded that increasing years of chronicity of diabetes develops diabetic polyneuropathy, in this study females are much prone for developing diabetic polyneuropathy.

Glycemic variability’s impact on painful diabetic peripheral neuropathy in type 2 diabetes patients

Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04–7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN.

Serum Calprotectin Level in Type 2 Diabetic Patients with and without Diabetic Peripheral Neuropathy: A Comparison Study

Abstract Background: Peripheral neuropathy is one of the microvascular complications that affects patients with diabetes mellitus and involves both sensory and motor nerves. The development and the progress of diabetic peripheral neuropathy (DPN) were ascribed to the inflammatory activity of the immune cells in the nerves. Calprotectin (CLP) is a heterodimer protein found in the membranes of monocytes and other inflammatory cells and the cytosol of neutrophils and released from them up to activation. Aim of Study: Evaluation of serum CLP level as a potential inflammatory biomarker for the occurrence of DPN in type 2 diabetic patients. Patients and Methods: one hundred and twenty-six patients diagnosed with type 2 diabetes mellitus were randomly selected from those who attended the National Diabetic Center between December 2022 and July 2023. Michigan Neuropathy Screening Instrument (MNSI) and nerve conduction study (NCS) were used for grouping the patients. Enzyme-linked immunosorbent assay technique has been used to measure serum CLP levels. Results: Serum levels of CLP showed no significant differences among patients with and those without diabetic peripheral neuropathy according to their NCS findings and the total scores for each and for both in combination according to the subgroups (P &gt; 0.05). Conclusions and Recommendations: The serum level of CLP in type 2 diabetic patients was not affected by the occurrence of diabetic peripheral neuropathy. Further studies are required on newly diagnosed patients and a larger sample size.

Efficacy and Safety of the Combination of Palmitoylethanolamide, Superoxide Dismutase, Alpha Lipoic Acid, Vitamins B12, B1, B6, E, Mg, Zn and Nicotinamide for 6 Months in People with Diabetic Neuropathy.

To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN). In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group (n = 36) or the placebo (n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire. In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p < 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p < 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p < 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p < 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups (p < 0.001, 0.025, 0.009, and <0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups. The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.

Whether coagulation dysfunction influences the onset and progression of diabetic peripheral neuropathy: A multicenter study in middle-aged and aged patients with type 2 diabetes.

Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

Prevalence of painful and painless diabetic peripheral neuropathy in the Northern Danish Region: A population-based study

BackgroundDiabetic peripheral neuropathy (DPN) is a common complication of diabetes, yet varying estimates of its prevalence exist. The present study aimed to estimate a questionnaire-centered prevalence of painful and painless DPN in the Northern Danish Region, examine its geographical distribution within the region, and investigate associations between DPN and potential risk factors. MethodsA questionnaire-based survey was sent to all persons living with diabetes in the Northern Danish Region using electronic mail. Persons with diabetes were identified using The National Health Insurance Service Registry. The survey included information on demographics, socioeconomics, municipality, diabetes type, duration, and treatment, as well as the validated questionnaires Michigan Neuropathy Screening Instrument-questionnaire (MNSIq) and the Douleur Neuropathique en 4 Questions (DN4)-interview. Possible DPN was defined as an MNSIq-score ≥ 4, while possible painful DPN was defined as pain in both feet and a DN4-interview score ≥ 3. ResultsA total of 23,206 eligible people were identified as having diabetes and approximately 33 % answered all questionnaires. The prevalence of possible DPN was 23.3 % (95 % CI: 22.4–24.3 %), while the prevalence of possible painful DPN was 18.0 % (17.1–18.8 %). The prevalence of possible DPN ranged from 22.1 % to 35.0 % between municipalities, while the prevalence of possible painful DPN ranged from 15.6 % to 20.0 %. High body-mass index, long diabetes duration, insulin use, glucagon-like-peptide-1-analogue use, and low income were associated with increased risk of DPN. ConclusionThe high prevalence of possible painless and painful DPN emphasizes the need for better prevention and careful screening even in high-income countries.

New phenotyping questionnaire for diagnosing sarcoidosis-associated small fiber neuropathy.

Small fiber neuropathy is a common complication in patients with sarcoidosis and its prevalence is estimated at 40-86%. The underlying mechanism influences the presentation of small fiber neuropathy. For example, patients with metabolic diseases are often associated with a classic length-dependent small fiber neuropathy pattern, while patients with inflammatory diseases are more often present with a non-length-dependent small fiber neuropathy. Detailed phenotyping may be useful to improve diagnostic efficiency, as a clue to underlying mechanisms and as a precondition for personalized medicine. This study examined four phenotypes distinguishing between length-dependent and non-length-dependent presentation with a new subdivision for continuous and intermittent presentation. Forty-eight sarcoid patients with symptoms and at least two clinical signs of small fiber neuropathy and normal nerve conduction studies were classified as having probable small fiber neuropathy. A new small fiber neuropathy phenotyping questionnaire has been developed that allows patients to mark the anatomical locations of pain at three different levels: the skin, muscles, and joints. The location of symptoms was used to define length dependence, and two colors were used to distinguish continuous (red) from intermittent (blue) symptoms. In addition, skin biopsy, corneal confocal microscopy, Sudoscan and water immersion skin wrinkling were used to investigate a correlation between the four phenotypes, sensory function, nerve fiber density, and autonomic nerve function. Overall, 35% of patients with probable small fiber neuropathy showed length-dependent symptoms and 44% showed non-length-dependent symptoms while 21% suffered from non-neuropathic musculoskeletal pain. The distinction between intermittent and continuous symptoms showed significantly less continuous than intermittent non-length-dependent symptoms (odds ratio = 0.3, P = 0.01). Moreover, continuous length-dependent symptoms were the only phenotype that correlated with thermal threshold testing (R = 0.3; P = 0.02) and the small fiber neuropathy screening list (R = 0.3; P = 0.03). In addition, thermal threshold testing (TTT) also correlated with the small fiber neuropathy (SFN) screening list (R = 0.3; P = 0.03). Other diagnostic methods showed no correlation with any of the four defined phenotypes. A novel finding is that TTT is only associated with continuous length-dependent pain, suggesting that TTT could result in more false negatives in patients with other pain phenotypes. Determining the pathophysiologic mechanisms could help develop new diagnostic methods. If patients suspected of SFN show symptoms without a length-dependent continuous presentation, the diagnosis should focus less on the diagnostic methods used.

Adolescent girls with type 1 diabetes develop changes in bone prior to evidence of clinical neuropathy.

Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease. We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n=21) and associated controls (n=12). Groups were well matched for age, height, strength, and physical activity. By HR-pQCT, participants with T1D had lower trabecular bone volume fraction at the distal radius (-14.6%, p-adj=0.095) and the tibia (-12.8%, p-adj=0.017) and decreased trabecular thickness (-8.3% radius, p-adj=0.007; -7.5% tibia, p-adj=0.034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (p-adj=0.024) and porosity was decreased by 52.9% with T1D (p-adj=0.012). There were no significant differences in bone density by DXA. Participants with T1D also had lower circulating levels of osteocalcin (-30%, p=0.057), and type I collagen cross-linked C-telopeptide (-36%, p=0.035), suggesting low bone formation and turnover in T1D. Based on the Michigan Neuropathy Screening Instrument, 9.5% of those with T1D had clinical evidence of diabetic peripheral neuropathy. However, consideration of neuropathy status failed to explain the widespread T1D-associated changes in bone. Our study defines early deficits in trabecular bone microarchitecture, decreased cortical porosity in the tibia, and suppression of biomarkers of bone turnover in adolescent girls with T1D, prior to the onset of symptomatic peripheral neuropathy. These findings inform our understanding of the rapid progression of skeletal disease in young girls with T1D and suggests that early detection and management strategies may help to prevent fracture and related co-morbidities later in life.

Differential associations between selenoprotein P and distal sensorimotor polyneuropathy in people with and without diabetes: KORA F4/FF4 study

BackgroundOxidative stress is a risk factor for distal sensorimotor polyneuropathy (DSPN). Selenoprotein P is a protein with antioxidant properties but has not been investigated in the context of DSPN. This study aimed to assess the associations between selenoprotein P and DSPN in people without and with type 2 diabetes (T2D). MethodsCross-sectional and prospective analyses were based on 1053 (including 217 with T2D) and 513 participants (including 79 with T2D), respectively, aged 61–82 years from the population-based KORA F4 survey. DSPN at baseline (KORA F4) and in the follow-up survey KORA FF4 was defined based on the Michigan Neuropathy Screening Instrument. Serum levels of full-length selenoprotein P were quantified by ELISA. Associations between selenoprotein P and prevalent or incident DSPN were estimated using logistic regression analysis adjusting for multiple confounders. ResultsSelenoprotein P levels were not associated with prevalent DSPN in the total sample. However, there was a significant interaction by diabetes status. Higher levels of selenoprotein P were associated with lower odds of prevalent DSPN in individuals without T2D (fully adjusted model: OR 0.825 [95 % CI 0.682, 0.998], p = 0.0476), but not in those with T2D (OR [95 % CI] 1.098 [0.829, 1.454], p = 0.5132; pinteraction = 0.0488). Selenoprotein P levels were not associated with incident DSPN over a follow-up of 6.5 years. ConclusionIn individuals without T2D from the older general population, lower selenoprotein P levels were associated with a higher prevalence of DSPN. Whether the antioxidant properties of selenoprotein P are responsible for the observed associations remains to be elucidated in future research.