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Keywords = Toronto Clinical Neuropathy Score

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14 pages, 787 KB  
Article
The Assessment of the Autonomic Polyneuropathy Through Sudoscan and Vitamin B12 in Patients with Type 2 Diabetes Mellitus and High Cardiovascular Risk or Established Cardiovascular Disease
by Cristina Mocanu (Chitan), Teodor Salmen, Anca Pantea Stoian and Cristian Serafinceanu
Biomedicines 2026, 14(1), 18; https://doi.org/10.3390/biomedicines14010018 - 21 Dec 2025
Viewed by 520
Abstract
Background: Diabetes Mellitus (DM) is frequently associated with diabetic peripheral neuropathy (DPN) and cardiovascular diseases (CVD). The aim of this study is to assess the relationship between DPN symptoms, vitamin B12 level, and autonomic neuropathy in DM patients with high and very high [...] Read more.
Background: Diabetes Mellitus (DM) is frequently associated with diabetic peripheral neuropathy (DPN) and cardiovascular diseases (CVD). The aim of this study is to assess the relationship between DPN symptoms, vitamin B12 level, and autonomic neuropathy in DM patients with high and very high CV risk or established CVD. Material and Methods: A cross-sectional analysis of 164 patients from the Outpatient DM Department of Suceava County Hospital from September 2025 was performed. The clinical, paraclinical, and demographic data were collected, including Toronto Clinical Neuropathy Score (TCNS), Sudoscan, Orthostatic Hypotension (OH), and B12 level. Results: In total, 65.9% of patients had DPN; the mean HbA1c was 8.22% ± 1.74. No significant correlation was obtained between autonomic neuropathy (Sudoscan) and DPN severity (p = 0.163) or between vitamin B12 and DPN (p = 0.6). Vitamin B12 was associated with CV risk assessed with Sudosan (p = 0.04). OH had limited diagnostic significance for autonomic dysfunction. Conclusions: No strong link was detected between B12 levels and DPN; thus, it cannot be considered a predictive marker. Objective DPN screening remains essential. Sudoscan is practical and non-invasive in assessing autonomic neuropathy, but only when combined with TCNS may it increase the DPN screening and risk stratification in high-CV-risk populations with DM. Full article
(This article belongs to the Special Issue Molecular and Histopathological Background of Diabetic Neuropathy)
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18 pages, 841 KB  
Article
Effect of Cocoa Supplementation on the Biochemical and Clinical Profile and the Somatosensory Processing of Diabetic Peripheral and Autonomic Neuropathy: A Randomized Clinical Trial
by Rebeca Kababie-Ameo, Gabriela Gutiérrez-Salmeán, Luisa Fernanda Salinas-Hernández, Virgilio Eduardo Trujillo-Condes, Israel Ramírez-Sánchez and Carlos A. Cuellar
Int. J. Mol. Sci. 2025, 26(16), 8033; https://doi.org/10.3390/ijms26168033 - 20 Aug 2025
Viewed by 3679
Abstract
Peripheral and autonomic neuropathy are common in type 2 diabetes; they are associated with oxidative stress and inflammation. Cocoa, rich in polyphenols, may offer neuroprotective benefits. This study evaluated the effect of cocoa supplementation on the biochemical, clinical, and somatosensory profile of neuropathy [...] Read more.
Peripheral and autonomic neuropathy are common in type 2 diabetes; they are associated with oxidative stress and inflammation. Cocoa, rich in polyphenols, may offer neuroprotective benefits. This study evaluated the effect of cocoa supplementation on the biochemical, clinical, and somatosensory profile of neuropathy in individuals with type 2 diabetes. A 12-week, double-blind controlled trial involved 39 subjects randomized to receive cocoa capsules (50 mg polyphenols) or placebo (methylcellulose). Evaluations included glycemic and lipid profiles, neutrophil/lymphocyte ratio, blood pressure, standardized questionnaires, anthropometric measurements, and the rate-dependent depression of the H-reflex. In the cocoa group, the Toronto score decreased by 2.63 points and the BEST score decreased by 1.45 points. In the placebo group, these reductions were 1.84 and 2.21 points, respectively. Neither difference was statistically significant between groups (p > 0.05). Quality-of-Life questionnaire score decreased by 9.2 points in the cocoa group, but without significant difference to the placebo group (p = 0.501). Fasting glucose and HbA1c levels decreased in the placebo group by 38 mg/dL (0.28%) but were not significantly different from the cocoa group (p > 0.05). No other intra- or inter-group differences were significant (p > 0.05). Cocoa supplementation did not show significant improvements over the placebo in the measured outcomes. Both groups showed persistent abnormalities in spinal somatosensory processing, with an RDD of the H-reflex ≥ 0.5. Full article
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15 pages, 2794 KB  
Article
Clinical Trial: Effect of Autologous Dendritic Cell Administration on Improving Neuropathy Symptoms and Inflammatory Biomarkers in Diabetic Neuropathy
by Erwin Setiawan, Chrismis Novalinda Ginting, Jonny Jonny, Bhimo Aji Hernowo and Terawan Agus Putranto
Curr. Issues Mol. Biol. 2024, 46(12), 14366-14380; https://doi.org/10.3390/cimb46120861 - 20 Dec 2024
Viewed by 1771
Abstract
Type 2 diabetes mellitus (T2DM) is a global health concern, with diabetic neuropathy (DN) being a prevalent complication. Current DN treatments focus on blood glucose control and pain management, which show limited efficacy. This study explored the effects of autologous dendritic cell (DC) [...] Read more.
Type 2 diabetes mellitus (T2DM) is a global health concern, with diabetic neuropathy (DN) being a prevalent complication. Current DN treatments focus on blood glucose control and pain management, which show limited efficacy. This study explored the effects of autologous dendritic cell (DC) administration on improving DN symptoms. A quasi-experimental clinical trial was conducted on 28 DN patients at Gatot Soebroto Army Hospital. Patients received autologous DC administration, with their Toronto Clinical Neuropathy Score (TCNS), Transforming Growth Factor-β (TGF-β), and Vascular Cell Adhesion Molecule-1 (VCAM-1) levels measured before and at four weeks after treatment. The results show an average TCNS reduction from 8.93 to 7.5 (p < 0.001). TGF-β levels increased slightly from 41.16 ng/mL to 44.18 ng/mL (p > 0.05). VCAM-1 levels increased from 1389.75 ng/mL to 1403.85 ng/mL. Correlation analysis showed that TGF-β levels had a significant negative correlation with the TCNS (r = −0.353; p = 0.033) and VCAM-1 levels (r = −0.521; p = 0.002). Autologous DC administration significantly improves DN. While the changes in TGF-β and VCAM-1 levels were not statistically significant, their trends suggest that there was an anti-inflammatory effect. These findings highlight the potential of autologous DC therapy as a complementary approach to manage DN through inflammation reduction and nerve repair. Full article
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12 pages, 263 KB  
Article
The Association between the Severity of Distal Sensorimotor Polyneuropathy and Increased Carotid Atherosclerosis in Individuals with Type 2 Diabetes
by Dong-Yi Hsieh, Yun-Ru Lai, Chih-Cheng Huang, Chi-Ping Ting, Wen-Chan Chiu, Yung-Nien Chen, Chia-Yi Lien, Ben-Chung Cheng, Ting-Yin Lin, Hui Ching Chiang and Cheng-Hsien Lu
Diagnostics 2024, 14(17), 1922; https://doi.org/10.3390/diagnostics14171922 - 31 Aug 2024
Viewed by 2113
Abstract
Background: Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive [...] Read more.
Background: Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. Results: Individuals with DSPN exhibited lower EDV in the CCA and ICA (p < 0.0001 and p = 0.002), higher PI and RI in both CCA and ICA (all p < 0.0001), and higher CPS (p = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all p < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. Conclusions: Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
13 pages, 579 KB  
Article
The Effects of Indoxyl Sulfate and Oxidative Stress on the Severity of Peripheral Nerve Dysfunction in Patients with Chronic Kidney Diseases
by Yun-Ru Lai, Ben-Chung Cheng, Chia-Ni Lin, Wen-Chan Chiu, Ting-Yin Lin, Hui-Ching Chiang, Chun-En Aurea Kuo, Chih-Cheng Huang and Cheng-Hsien Lu
Antioxidants 2022, 11(12), 2350; https://doi.org/10.3390/antiox11122350 - 28 Nov 2022
Cited by 7 | Viewed by 2654
Abstract
Pieces of evidence support the view that the accumulation of uremic toxins enhances oxidative stress and downstream regulation of signaling pathways, contributing to both endothelial microangiography and cell dysfunction. This study is to address the impact of protein-binding uremic toxins on the severity [...] Read more.
Pieces of evidence support the view that the accumulation of uremic toxins enhances oxidative stress and downstream regulation of signaling pathways, contributing to both endothelial microangiography and cell dysfunction. This study is to address the impact of protein-binding uremic toxins on the severity of peripheral nerve function in patients with chronic kidney disease (CKD). Fifty-four patients with CKD were included in the Toronto Clinical Neuropathy Score (TCNS), nerve conduction study (NCS), and laboratory studies including protein-binding uremic toxin (indoxyl sulfate [IS] and p-cresyl sulfate [PCS]), oxidative stress (Thiol and thiobarbituric acid reacting substances [TBARS]), and endothelial dysfunction (serum intercellular adhesion molecule 1 [sICAM-1] and serum vascular adhesion molecule 1 [sVCAM-1]) at enrollment. We used composite amplitude scores (CAS) to analyze the severity of nerve conductions on peripheral nerve function. TCNS and CAS were higher in the diabetic CKD group (p = 0.02 and 0.01, respectively). The NCS revealed the compound muscle action potential of ulnar and peroneal nerves and the sensory nerve action potential of ulnar and sural nerves (p = 0.004, p = 0.004, p = 0.004, and p = 0.001, respectively), which was found to be significantly low in the diabetic group. CAS was significantly correlated with age (r = 0.27, p = 0.04), urine albumin-creatinine ratio (UACR) (r = 0.29, p = 0.046), free-form IS (r = 0.39, p = 0.009), sICAM-1 (r = 0.31, p = 0.02), sVCAM-1 (r = 0.44, p < 0.0001), TBARS (r = 0.35, p = 0.002), and thiols (r = −0.28, p = 0.045). Linear regression revealed that only TBARS and free-form IS were strongly associated with CAS. The mediation analysis shows that the sVCAM-1 level serves as the mediator between higher IS and higher CAS. IS and oxidative stress contribute to the severity of peripheral nerve dysfunction in patients with CKD, and chronic glycemic impairment can worsen the conditions. Full article
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11 pages, 1337 KB  
Article
SUDOSCAN, an Innovative, Simple and Non-Invasive Medical Device for Assessing Sudomotor Function
by Dana Elena Gavan, Alexandru Gavan, Cosmina Ioana Bondor, Bogdan Florea, Frank Lee Bowling, Georgeta Victoria Inceu and Liora Colobatiu
Sensors 2022, 22(19), 7571; https://doi.org/10.3390/s22197571 - 6 Oct 2022
Cited by 17 | Viewed by 5806
Abstract
Diabetic autonomic neuropathy is probably the most undiagnosed but serious complication of diabetes. The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the [...] Read more.
Diabetic autonomic neuropathy is probably the most undiagnosed but serious complication of diabetes. The main objectives were to assess the prevalence of peripheral and autonomic neuropathy in a population of diabetic patients, analyze it in a real-life outpatient unit scenario and determine the feasibility of performing SUDOSCAN tests together with widely used tests for neuropathy. A total of 33 patients were included in the study. Different scoring systems (the Toronto Clinical Neuropathy Score—TCNS; the Neuropathy Disability Score—NDS; and the Neuropathy Symptom Score—NSS) were applied to record diabetic neuropathy (DN), while the SUDOSCAN medical device was used to assess sudomotor function, detect diabetic autonomic neuropathy and screen for cardiac autonomic neuropathy (CAN). Fifteen (45.5%) patients had sudomotor dysfunction. The SUDOSCAN CAN risk score was positively correlated with the hands’ electrochemical sweat conductance (ESC), diastolic blood pressure (DBP), the level of the glycated hemoglobin, as well as with the TCNS, NDS and NSS. Performing SUDOSCAN tests together with other tests for DN proved to be a feasible approach that could be used in daily clinical practice in order to screen for DN, as well as for the early screening of CAN, before more complex and time-consuming tests. Full article
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50 pages, 11489 KB  
Systematic Review
Oral Administration of East Asian Herbal Medicine for Peripheral Neuropathy: A Systematic Review and Meta-Analysis with Association Rule Analysis to Identify Core Herb Combinations
by Hee-Geun Jo and Donghun Lee
Pharmaceuticals 2021, 14(11), 1202; https://doi.org/10.3390/ph14111202 - 22 Nov 2021
Cited by 13 | Viewed by 6179
Abstract
This review aimed to comprehensively assess the efficacy and safety of oral East Asian herbal medicine (EAHM) for overall peripheral neuropathy (PN). In addition, an Apriori algorithm-based association rule analysis was performed to identify the core herb combination, thereby further generating useful hypotheses [...] Read more.
This review aimed to comprehensively assess the efficacy and safety of oral East Asian herbal medicine (EAHM) for overall peripheral neuropathy (PN). In addition, an Apriori algorithm-based association rule analysis was performed to identify the core herb combination, thereby further generating useful hypotheses for subsequent drug discovery. A total of 10 databases were searched electronically from inception to July 2021. Randomized clinical trials (RCTs) comparing EAHM with conventional analgesic medication or usual care for managing PN were included. The RCT quality was appraised using RoB 2.0, and the random effects model was used to calculate the effect sizes of the included RCTs. The overall quality of evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation. By analyzing the constituent herb data, the potential association rules of core herb combinations were explored. A total of 67 RCTs involving 5753 patients were included in this systematic review. In a meta-analysis, EAHM monotherapy and combined EAHM and western medicine therapy demonstrated substantially improved sensory nerve conduction velocity, motor nerve conduction velocity, and response rate. Moreover, EAHM significantly improved the incidence rate, pain intensity, Toronto clinical scoring system, and Michigan diabetic neuropathy score. The evidence grade was moderate to low due to the substantial heterogeneity among the studies. Nine association rules were identified by performing the association rule analysis on the extraction data of 156 EAHM herbs. Therefore, the constituents of the herb combinations with consistent association rules were Astragali Radix, Cinnamomi Ramulus, and Spatholobi Calulis. This meta-analysis supports the hypothesis that EAHM monotherapy and combined therapy may be beneficial for PN patients, and follow-up research should be conducted to confirm the precise action target of the core herb. Full article
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14 pages, 1291 KB  
Article
Large-Fiber Neuropathy in Parkinson’s Disease: Clinical, Biological, and Electroneurographic Assessment of a Romanian Cohort
by Oana Maria Vanta, Nicoleta Tohanean, Sebastian Pintea and Lacramioara Perju-Dumbrava
J. Clin. Med. 2019, 8(10), 1533; https://doi.org/10.3390/jcm8101533 - 24 Sep 2019
Cited by 9 | Viewed by 3706
Abstract
(1) Background: Increased attention has lately been given to polyneuropathy in Parkinson’s Disease (PD). Several papers postulated that large-fiber neuropathy (PNP) in PD is related to vitamin B12 deficiency and L-Dopa exposure. (2) Methods: Using a cross-sectional, observational study, we evaluated 73 PD [...] Read more.
(1) Background: Increased attention has lately been given to polyneuropathy in Parkinson’s Disease (PD). Several papers postulated that large-fiber neuropathy (PNP) in PD is related to vitamin B12 deficiency and L-Dopa exposure. (2) Methods: Using a cross-sectional, observational study, we evaluated 73 PD patients without a previously known cause of PNP using clinical scores (UPDRS II and III and Toronto Clinical Scoring System), biological evaluation of vitamin B12 and folic acid, and nerve conduction studies to assess the prevalence and features of PNP. (3) Results: The prevalence of PNP was 49.3% in the study group. In the L-Dopa group, the frequency of PNP was 67.3% as compared to PNP in the non-L-Dopa group, where one subject had PNP (χ2 = 23.41, p < 0.01). PNP was predominantly sensory with mild to moderate axonal loss. Cyanocobalamin correlated with L-Dopa daily dose (r = −0.287, p < 0.05) and L-Dopa duration of administration (r = −0.316, p < 0.05). L-Dopa daily dose correlated with the amplitudes of sensory nerve action potentials of the superficial peroneal and radial nerves (r = −0.312, p < 0.05) (r = −0.336, p < 0.05), respectively. (4) Conclusions: PNP is more frequent in L-Dopa-treated patients than in L-Dopa-naïve patients. The results imply that longer exposure to high doses of L-Dopa may cause vitamin B12 and folate imbalance and PNP, secondarily. Full article
(This article belongs to the Section Clinical Neurology)
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