Distal Symmetric Polyneuropathy Research Articles

A Practical Approach to Diagnosing Peripheral Neuropathies.

Polyneuropathies are common, with the incidence increasing with older age. The causes of polyneuropathies are diverse and numerous, and it can be challenging for clinicians to determine the etiology of a particular patient's neuropathy. In this article, we systematically detail a practical approach to polyneuropathies, beginning with the most important aspects of the workup, the history and physical. We then discuss the limited diagnostic approach required for patients who present with a distal symmetric polyneuropathy and the more comprehensive approach for patients who present with other neuropathy subtypes.

Comparison of intraepidermal nerve fiber density and confocal corneal microscopy for neuropathy.

Compare the diagnostic characteristics of intraepidermal nerve fiber density (IENFD) and confocal corneal microscopy (CCM) for distal symmetric polyneuropathy (DSP) and small fiber neuropathy (SFN). Participants with obesity were recruited from bariatric surgery clinics and testing was performed prior to surgery. DSP and SFN were determined using the Toronto consensus definitions of probable neuropathy. IENFD was assessed from 3 mm punch biopsies of the distal leg and proximal thigh. CCM was performed on both eyes with manual and automated counting. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was also completed. Diagnostic capability was determined using areas under the receiver operating characteristics curve (AUC) from logistic regression. We enrolled 140 participants (mean [standard deviation [SD]] age: 50.3 years [7.1], 77.1% female, BMI: 44.4 kg/m2 [6.7]). In this population, 22.9% had DSP and 14.3% had SFN. Distal leg IENFD had the largest AUC (95% confidence interval) for DSP (0.78, 0.68-0.89) and SFN (0.85, 0.75-0.96). Proximal thigh IENFD (DSP: AUC: 0.59, 0.48-0.69, SFN: AUC: 0.59, 0.46-0.73) and CCM metrics (DSP: AUC range: 0.55-0.60, SFN: AUC range: 0.45-0.62) had poorer diagnostic capability than distal leg IENFD for DSP/SFN (P < 0.05). MNSIq had similar diagnostic capability to distal leg IENFD for both DSP/SFN (DSP: AUC: 0.76, 0.68-0.85, SFN: AUC: 0.81, 0.73-0.88). More participants (52%) preferred skin biopsies to CCM. Distal leg IENFD was the best quantitative measure of DSP/SFN. CCM had poor diagnostic characteristics and fewer patients preferred this test to IENFD. The MNSIq had similar diagnostic characteristics to distal leg IENFD, indicating its value as a diagnostic tool in the clinical setting. clinicaltrials.gov: NCT03617185.

Diabetic Charcot neuroarthropathy: A threat to both limb and life.

Diabetic Charcot neuroarthropathy (DCN), first described in 1936, occurs in less than 1% of diabetic patients, but in those diabetic subjects with distal symmetrical polyneuropathy, the overall incidence increases to 30% and the risk is even greater in those with type 1 diabetes. Factors that precipitate DCN are trauma, ischaemia due to arterio-venous shunting, increased osteoclastic activity and inflammation. DCN usually presents with a painless swollen foot and/or ankle which is 'hot to the touch'. These clinical findings are soon followed by characteristic magnetic resonance imaging (MRI) abnormalities and later X-ray changes. The joints that are most typically involved in chronological order are the tarsometatarsals followed by the naviculocuniform, sub-tarsal, talonavicular and metatarsal and tarsophalangeal. The cornerstone of therapy is prolonged (3-12 months) offloading with immobilization. Bisphosphonates may possibly accelerate recovery, whereas other unproven possible therapies include rhPTH, 1-34, calcitonin and methylprednisolone, which are not only ineffective but in some cases may also prolong the time to healing. Denosumab is potentially an efficacious, if unproven, therapy to accelerate healing. The risk of amputation is high and increases in the presence of a foot ulcer. DCN is associated with manifestations of autonomic neuropathy, including cardiac denervation, so that the risks of a cardiac event and heart failure are increased with DCN. Mortality is also increased with DCN, especially in the presence of a foot ulcer. To avoid the recurrence of DCN and especially to lower the risk of the recurrence of a foot ulcer recurrence reconstructive, surgery may be needed.

Low serum CTRP3 is related to more severe distal symmetric polyneuropathy in type 2 diabetes patients.

Distal symmetric polyneuropathy (DSPN) is one of the most common chronic complications in patients with type 2 diabetes mellitus (T2DM). Our previous study found that serum C1q tumor necrosis factor-related protein 3 (CTRP3) levels were decreased in type 2 diabetic patients. Thus, this study was designed to reveal the relationship between low serum CTRP3 and the prevalence and severity of DSPN. A total of 178 cases of patients with T2DM were enrolled in the study. The subjects were divided into the DSPN group (n = 89) and the non-DSPN group (n = 89). Both anthropometric parameters and neurologic symptoms were recorded. Furthermore, neurologic signs, the neuropathy symptom score (NSS), and the neuropathy disability score (NDS) were assessed. Biochemical indexes, fasting insulin, and C peptide were measured. Serum CTRP3 concentrations were assayed using the ELISA method. Serum CTRP3 levels decreased significantly in the DSPN group compared with the non-DSPN group (P < 0.05). CTRP3 was negatively associated with the number of positive signs, NSS score, and NDS score in patients with DSPN (all P < 0.05). Interestingly, the higher the NSS score or NDS score, the lower were the levels of serum CTRP3 (all P < 0.05). Moreover, patients with lower CTRP3 levels (< 7.58ng/ml) had a higher rate of neurologic signs (all P < 0.05). Binary logistic regression analysis showed that CTRP3 independently predicted the occurrence of DSPN (β = -0.316, P < 0.001). ROC curve analysis revealed that the best cut-off value of CTRP3 for the prediction of DSPN was 7.55ng/ml (sensitivity 78.7%, specificity 79.8%), the area under the curve (AUC) was 0.763 (95% CI 0.689-0.838, P < 0.001). Low serum CTRP3 could be a predictor for the occurrence and progression of DSPN in Chinese patients with T2DM.

Pain Detect as A Tool for The Screening of Neuropathic Pain in Patients with Diabetes Mellitus

Background: Diabetic neuropathy (DN) is a prevalent long-term complication of diabetes mellitus (DM), affecting more than 50% of patients. In addition, several studies also showed that distal symmetric polyneuropathy (DSPN) accounts for 75% of all DN cases. To facilitate the treatment of DN, painDETECT questionnaire, a self-reported tool with 85% sensitivity and 80% specificity, has been recommended for detecting neuropathic component in pain. Objective: This study aimed to promptly diagnose DN using painDETECT questionnaire in DM patients. Methods: The study procedures were carried out using a descriptive, cross-sectional design with 67 DM patients from Cibabat Regional Hospital Department of Internal Medicine outpatient clinic through consecutive sampling in October–November 2022. Primary data were obtained using the adapted and validated Indonesian painDETECT questionnaire. Results: Among the 67 patients, 32.9% experienced neuropathic pain with a score of 19–38, indicating the involvement of &gt;90% of neuropathic pain components. Sensory deficits, such as numbness, burning sensation, pins-and-needles, and allodynia, were observed in 86.3%, 90.1%, and 72.7% of patients with neuropathic pain, respectively. In addition, a total of 59.7% of participants (n=40) reported the presence of mild pain (NRS 3). Conclusion: Based on the results, the majority of patients had complaints of neuropathic or mild pain (40 subjects; 59.7%). Among the 22 patients experiencing neuropathic pain, 54.5% reported mild intensity.

An Overview on Diabetic Neuropathy.

The term "Diabetic neuropathy" refers to a collection of clinical and subclinical symptoms caused by problems with the peripheral nervous system. Diabetes, which affects approximately 381 million people worldwide, is the source of dysfunction due to the emergence of microvascular complications. It is anticipated that in the next ten years, Diabetic neuropathy will manifest in about 50% of patients who are currently diagnosed with diabetes. Clinical diagnosis can be established by getting a thorough patient history and exploring the symptoms to rule out alternative causes. Although distal symmetrical polyneuropathy, or just, is the most common and well-researched variant of the disorder, this review will concentrate on it. The multifactorial pathogenesis is linked to various inflammatory, vascular, metabolic, and neurodegenerative illnesses. The three fundamental molecular alterations that lead to the development of diabetic neuropathic pain are oxidative stress, endothelial dysfunction, and chronic inflammation. These three elements are crucial in the development of polyneuropathy because their combination might result in direct axonal damage and nerve ischemia. The purpose of this article was to provide a narrative review of diabetic neuropathy. We provide an overview of the most recent data on biomarkers, the pathogenesis of the illness, the most recent epidemiology of diabetic neuropathy, and the existing screening and diagnosis outcome measures used in both clinical and research contexts.

SiRNA Treatments for Diabetic Neuropathy: Obstacles and Delivery Techniques.

Targeting genes using siRNA shows promise as an approach to alleviate symptoms of diabetic neuropathy. It focuses on neuropathies and distal symmetric polyneuropathy (DSPN) to explore the potential use of small interfering RNA (siRNA) as a treatment for diabetic neuropathy. Timely identification and management of neuropathy play a critical role in mitigating potential complications. RNAi success depends on understanding factors affecting small interfering RNA (siRNA) functionality and specificity. These include sequence space restrictions, structural and sequence features, mechanisms for nonspecific gene modulation, and chemical modifications. Addressing these factors enhances siRNA performance for efficient gene silencing and confidence in RNAi-mediated genomic studies. Diabetic retinopathy, particularly in South Asian, African, Latin American, and indigenous populations, is a significant concern due to its association with diabetes. Ethnicity plays a crucial role in its development and progression. Despite declining rates in the US, global trends remain concerning, and further research is needed to understand regional differences and reinforce ethnicity-based screening and treatment protocols. In this regard, siRNA emerges as a valuable instrument for early intervention strategies. While presenting promising therapeutic applications, siRNA utilization encounters challenges within insect pest control contexts, thereby providing insights into enhancing its delivery mechanisms for neuropathy treatment purposes. Recent advancements in delivery modalities, such as nanoparticles, allow for the controlled release of siRNA. More investigation is necessary to grasp the safety and efficacy of siRNA technology fully. It holds promise in transforming the treatment of diabetic neuropathy by honing in on particular genes and tackling issues such as inflammation and oxidative stress. Continuous advancements in delivery techniques have the potential to enhance patient results significantly. SiRNA targets genes in diabetic neuropathy, curbing nerve damage and pain and potentially preventing or delaying the condition. Customized treatments based on genetic variations hold promise for symptom management and enhancing quality of life.

A Study on Autonomic Dysfunction in Type 2 Diabetes Mellitus with Peripheral Neuropathy

Abstract Introduction: Subclinical Autonomic Neuropathy is found in association with distal symmetric polyneuropathy in diabetic patients. The Aim of this study was to compare the Cardiac Autonomic Function Test parameters in Type 2 Diabetes Mellitus patients with and without Distal Peripheral Neuropathy. The Primary Objective was to compare the mean of Valsalva ratio in Type 2 Diabetes Mellitus patients with and without Distal Peripheral Neuropathy. The secondary Objective of this study was to find the correlation between Michigan Neuropathic Screening Instrument Score and Autonomic Function test parameters in type 2 Diabetes Mellitus patients. Methods: This was a single centre, cross sectional study conducted from July 2022 to Feb 2023. The study was commenced after obtaining Institute Ethics Committee clearance. Subjects who satisfied the inclusion and exclusion criteria, and gave informed consent for participation in this study were eligible for enrolment. The inclusion Criteria were patients aged between 18 and 65 years with diagnosis of Diabetes mellitus. The number required to study Diabetic patients with peripheral neuropathy was 34 and for Diabetic patients without peripheral neuropathy was 34. Total sample size of 68 patients was taken. Once the patient was enrolled a detailed history, clinical examination, ANS testing and MSNI scoring was done as per attached pre verified proforma duly vetted by institutional scientific committee.Patients were asked to refrain from vigorous exercise for the 24 hours before to the cardiovascular testing as well as from eating, drinking, or smoking for at least 2 hours before the autonomic testing. At the conclusion of the checkup, all antidiabetic and other prescriptions were given. After data collection, test for normality of data was done. Appropriate statistical tests were applied according to data distribution and analysed by using SPSS criteria 2011. Results: A total of 68 patients, 34 with symptoms of Diabetic Peripheral Neuropathy and 34 without Diabetic Peripheral Neuropathy were studied from July 2022 to December 2023. The age, BMI, duration of disease, HbA1c, resting systolic blood pressure and heart rate didn’t show any significant difference between the two groups and thus the groups were comparable. The median (interquartile range) of MNSI score of diabetic patients without neuropathy was 1(1,1) and diabetic patients with neuropathy was 8 (7,9) with p value &lt; 0.005. There was a significant difference in E: I ratio (P&lt;0.0001) between diabetic patients with and without neuropathy. The mean ± SD of Valsalva ratio, in diabetic patients without neuropathy was 1.632 ± 0.115 and with neuropathy was 1.366 ± 0.045. There was a significant difference in Valsalva ratio (P&lt;0.0001). There was a good negative correlation between MNSI score and Valsalva ratio with r= -0.769 and p value &lt; 0.0001 in Type 2 Diabetes mellitus patients. Conclusion: This study found that the Cardiac Autonomic Function Test parameters in Type 2 Diabetes Mellitus patients with and without Distal Peripheral Neuropathy, were significantly deranged in patients with symptomatic DPN. The mean of Valsalva ratio was significantly different in two study groups. The correlation between Michigan Neuropathy Screening Instrument Score and Autonomic Function test parameters in Type 2 Diabetes Mellitus patients showed strong negative correlation. The patients with symptomatic DSN were found to have higher MSNI scores, who in turn were having severe cardiac autonomic dysfunction. Recommendation of Study: Mean Valsalva ratio and MNSI testing are recommended to be used as a screening tool to assess cardiac autonomic functions as a low cost tool in patients of T2DM having symptoms suggestive of DSN.

Prevalence and Risk Factors of Distal Symmetric Polyneuropathy Among Predominantly Non-Hispanic Black, Low-Income Patients.

Distal symmetric polyneuropathy (DSP) is a disabling, often painful condition associated with falls and reduced quality of life. Non-Hispanic Black people and people with low income are underrepresented in existing DSP studies; therefore, it is unknown whether data accurately reflect the prevalence, risk factors, and burden of disease in these populations. Patients older than 40 years presenting to an outpatient internal medicine clinic predominantly serving Medicaid patients in Flint, Michigan, were enrolled in a cross-sectional study. Demographics, clinical characteristics, including medication use, anthropomorphic measurements, fasting lipids, and hemoglobin A1c were collected. DSP was defined using the modified Toronto Clinical Neuropathy Score (mTCNS). Multivariable logistic regression was performed to model DSP and undiagnosed DSP as a function of potential risk factors age, metabolic syndrome, and race. DSP burden was measured using Peripheral Neuropathy Quality of Life Instrument-97. Two hundred participants were enrolled, and 169 (85%) completed all data collection. The population was 55% female of mean age (SD) 58.2 years (10.4) and 69% non-Hispanic Black. Among the population, 50% had diabetes, 67% had metabolic syndrome, and 47% had a household income <$20,000. DSP was present in 73% of the population, of which 75% were previously undiagnosed. Neuropathic pain was documented in 57% of participants with DSP. DSP based on mTCNS criteria was associated with older age (odds ratio [OR] 1.1 [95% confidence interval (CI) 1.03-1.2]) and metabolic syndrome (OR 4.4 [1.1-18.1]). Non-Hispanic Black participants had lower odds of DSP (OR 0.1 [0.01-0.4]) than non-Hispanic White and Hispanic participants. DSP burden was high, including increased pain, health-related worry, and poorer quality of life (all p < 0.001). DSP is extremely common and often underrecognized in this predominantly non-Hispanic Black, low-income population and leads to substantial disease burden. Metabolic syndrome is a highly prevalent, modifiable risk factor in this population that should be managed to lower DSP prevalence.

Pathogenic Mechanisms of Diabetic Neuropathy

Diabetes stands as the predominant cause of peripheral neuropathy, and diabetic neuropathy (DN) is an early-onset and most frequent complication of diabetes. Distal symmetric polyneuropathy is the major form of DN; however, various patterns of nerve injury can manifest. Growing evidence suggests that hyperglycemia-related metabolic disorders in neurons, Schwann cells, and vascular endothelial cells play a major role in the development and progression of DN; however, its pathogenesis and development of disease-modifying therapies warrant further investigation. Herein, recent studies regarding the possible pathogenic factors of DN (polyol and other collateral glycolysis pathways, glycation, oxidative stress, Rho/Rho kinase signaling pathways, etc.) and therapeutic strategies targeting these factors are introduced.

Novel strategy: Identifying new markers for demyelination in diabetic distal symmetrical polyneuropathy

ObjectiveTo develop a novel strategy for identifying acquired demyelination in diabetic distal symmetrical polyneuropathy (DSP). BackgroundMotor nerve conduction velocity (CV) slowing in diabetic DSP exceeds expectations for pure axonal loss thus implicating superimposed acquired demyelination. MethodsAfter establishing demyelination confidence intervals by regression analysis of nerve conduction data from chronic inflammatory demyelinating polyneuropathy (CIDP), we prospectively studied CV slowing in 90 diabetic DSP patients with and without at least one motor nerve exhibiting CV slowing (groups A and B) into the demyelination range by American Academy of Neurology (AAN) criteria respectively and 95 amyotrophic lateral sclerosis (ALS) patients. Simultaneously, secretory phospholipase A2 (sPLA2) activity was assessed in both diabetic groups and 46 healthy controls. ResultsNo ALS patient exhibited CV slowing in more than two motor nerves based on AAN criteria or the confidence intervals. Group A demonstrated a significantly higher percentage of patients as compared to group B fulfilling the above criteria, with an additional criterion of at least one motor nerve exhibiting CV slowing in the demyelinating range and a corresponding F response in the demyelinating range by AAN criteria (70.3 % vs. 1.9 %; p < 0.0001). Urine sPLA2 activity was increased significantly in diabetic groups as compared to healthy controls (942.9 ± 978.0 vs. 591.6 ± 390.2 pmol/min/ml, p < 0.05), and in group A compared to Group B (1328.3 ± 1274.2 vs. 673.8 ± 576.9 pmol/min/ml, p < 0.01). More patients with elevated sPLA2 activity and more than 2 motor nerves with CV slowing in the AAN or the confidence intervals were identified in group A as compared to group B (35.1 % vs. 5.7 %, p < 0.001). Furthermore, 13.5 % of patients in diabetic DSP Group A, and no patients in diabetic DSP Group B, fulfilled an additional criterion of more than one motor nerve with CV slowing into the demyelinating range with its corresponding F response into the demyelinating range by AAN criteria. ConclusionA combination of regression analysis of electrodiagnostic data and a urine biological marker of systemic inflammation identifies a subgroup of diabetic DSP with superimposed acquired demyelination that may respond favorably to immunomodulatory therapy.

Contemporary prevalence of diabetic neuropathies in individuals with type 1 and type 2 diabetes in a Danish tertiary outpatient clinic

BackgroundPopulation-based prevalence estimates of distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathy (DAN) are scares. Here we present neuropathy estimates and describe their overlap in a large cohort of people with type 1 and type 2 diabetes. MethodsIn a large population of outpatient participants, DPN was assessed using vibration perception threshold, sural nerve function, touch, pain and thermal sensation. Definite DPN was defined by the Toronto Consensus Criteria. Painful DPN was defined by Douleur Neuropathique 4 Questions. DAN measures were: cardiovascular reflex tests, electrochemical skin conductance, and gastroparesis cardinal symptom index. ResultsWe included 822 individuals with type 1 (mean age (±SD) 54 ± 16 years, median [IQR] diabetes duration 26 [15–40] years) and 899 with type 2 diabetes (mean age 67 ± 11 years, median diabetes duration 16 [11−22] years).Definite DPN was prevalent in 54 % and 68 %, and painful DPN was in 5 % and 15 % of type 1 and type 2 participants, respectively. The prevalence of DAN varied between 6 and 39 % for type 1 and 9–49 % for type 2 diabetes. DPN without other neuropathy was present in 45 % with T1D and 50 % with T2D. ConclusionThe prevalence of DPN and DAN was high. DPN and DAN co-existed in only 50 % of cases.

Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy – A Danes cohort study

ObjectiveWe investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) – Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. Research design and methodsCross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation.Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. ResultsWe included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. ConclusionsA high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

Perceived Stress and its Association with Sleep Quality in Patients with Neuropathic Pain and Distal Symmetric Polyneuropathy (P3-11.020)

Perceived Stress and its Association with Sleep Quality in Patients with Neuropathic Pain and Distal Symmetric Polyneuropathy (P3-11.020)

Natural History of Acquired Demyelination in Diabetic Distal Symmetric Polyneuropathy (P9-11.014)

Natural History of Acquired Demyelination in Diabetic Distal Symmetric Polyneuropathy (P9-11.014)

Regression Equation Analysis Enhances Detection of Conduction Slowing Beyond Exclusive Axonal Loss in Diabetic Distal Symmetrical Polyneuropathy (P1-11.012)

Regression Equation Analysis Enhances Detection of Conduction Slowing Beyond Exclusive Axonal Loss in Diabetic Distal Symmetrical Polyneuropathy (P1-11.012)

Identification of New Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing: A Prospective Proteomics Analysis (P8-11.003)

Identification of New Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing: A Prospective Proteomics Analysis (P8-11.003)

Is There an Association Between Serum Neurofilament Light Chain Levels and Conduction Slowing in Type 2 Diabetic Distal Symmetrical Polyneuropathy? (P3-4.003)

Is There an Association Between Serum Neurofilament Light Chain Levels and Conduction Slowing in Type 2 Diabetic Distal Symmetrical Polyneuropathy? (P3-4.003)

Clinical and Biological Markers of Conduction Slowing in Diabetic Distal Symmetrical Polyneuropathy: A Prospective Study (P8-11.012)

Clinical and Biological Markers of Conduction Slowing in Diabetic Distal Symmetrical Polyneuropathy: A Prospective Study (P8-11.012)

Lipidomic Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing (P8-11.015)

Lipidomic Biomarkers in Diabetic Distal Symmetrical Polyneuropathy with Conduction Slowing (P8-11.015)