Toronto Clinical Neuropathy Score Research Articles

Single simple question in axonal polyneuropathy.

The single simple question (SSQ), "What percentage of normal (0%-100%) do you feel regarding your disease?" has proven feasible and valid in assessing myasthenia gravis and a heterogeneous spectrum of neuropathies. This study explores the utility of the SSQ in axonal polyneuropathies (PNPs), encompassing diabetic neuropathy, and evaluates its responsiveness to scale changes. A retrospective chart review of 150 patients with axonal PNP responding to the SSQ was performed. Patients underwent clinical and electrophysiological evaluations, and were evaluated by clinical and disability scales, including the Medical Research Council sum score, modified Toronto Clinical Neuropathy score (mTCNS), Overall Neuropathy Limitation Scale, and Rasch-built Overall Disability Scale (RODS). The SSQ total scores correlated moderately with both the RODS score (r = .59, p < .001) and the mTCNS symptom score (r = -.43, p < .001), maintaining significance after adjustment for multiple comparisons. Longitudinally, after adjusting for multiple comparisons, the change in mTCNS symptom score retained statistical significance (adjusted p = .048). The SSQ did not show any association with electrophysiological parameters or sensory symptoms, other than a lower score in those with pain (100% with SSQ <40%, 85% with SSQ 40%-70%, and 34% with SSQ >70%). The SSQ is a feasible, valid scale that may be utilized to assess and follow patients with length-dependent axonal PNPs. Given that the SSQ is not strongly associated with clinical and disability scales or electrophysiological findings, additional investigations are required for a comprehensive assessment of PNP.

Dietary phytochemical index and its relationship with diabetic sensorimotor polyneuropathy: a case-control study

Phytochemicals are compounds found in fruits, vegetables, whole grains, nuts and legumes that are non-nutritive but have bioactive properties. A high intake of these compounds is essential for optimal health and disease prevention. No study has investigated the association between Dietary Phytochemical Index (DPI) and polyneuropathy in patients with diabetes. This study aimed to examine the association between DPI and Diabetic Sensory-motor Polyneuropathy (DSPN) in a case-control study. In this case-control study, a total of 185 diabetic patients with DSPN (case group) and 185 sex- and age-matched diabetic patients without neuropathy (control group) were enrolled in this study. Participants were 30–60 years old. A validated food frequency questionnaire was used to measure the dietary intake of all participants. Daily energy derived from phytochemical-rich foods was used to calculate the DPI score. Toronto clinical neuropathy score was applied to define DSPN. Anthropometric data and fasting blood glucose levels were measured using standard methods. The Binary logistic regression was used to estimate Crude and multivariable-adjusted OR (95% CI) for DSPN across tertiles of DPI for the whole population. In the crude model, there was a significant trend across the tertile of DPI (OR highest vs. lowest tertile of DPI = 0.33; 95%CI 0.18, 0.52; P-trend < 0.001). After controlling for age, sex, and energy, a significant reverse association was observed between DPI and DSPN (OR highest vs. lowest tertile of DPI = 0.27; 95%CI 0.15, 0·48; P-trend < 0.001). Moreover, after adjusting for a wide range of confounding variables such as energy intake, physical activity, education, smoking status, and HbA1c, participants in the third tertile of DPI had 75% reduced odds for DSPN (95%CI 0.14, 0.45; P-trend < 0.001). Finally in the full adjusted model, after further adjustment for BMI, observed significant association was remained (OR highest vs. lowest tertile of DPI: 0.24; 95% CI 0.13, 0.14; P-trend < 0.001). Higher intakes of phytochemical-rich foods are associated with lower odds of DSPN.

The Association between the Severity of Distal Sensorimotor Polyneuropathy and Increased Carotid Atherosclerosis in Individuals with Type 2 Diabetes.

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. 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. 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.

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.

Evaluation of Effectiveness and Safety of Firstline Drugs Used in the Treatment of Peripheral Neuropathy Among Elderly Population—A Randomised, Open-label, Active Comparator Study

Background Peripheral neuropathy is four times more common in geriatric age group patients compared to younger ones. Most of the trials have targeted adult population, and there is scarcity of data in the geriatric age group. Purpose A real-world study was planned on geriatric patients suffering from peripheral neuropathy to analyse the effectiveness and safety of first-line drugs used in the management of peripheral neuropathy. Methods It was a randomised, open-label, active comparator clinical trial in which first-line drugs for peripheral neuropathy were compared [amitriptyline (10 mg), duloxetine (30 mg), gabapentin (300 mg), pregabalin (75 mg)] for their effectiveness and safety. The trial duration was eight weeks. The modified Toronto Clinical Neuropathy Score (mTCNS), Verbal Rating Scale (VRS) and Geriatric Depression Scale (GDS) were used for effectiveness. Safety was assessed by monitoring adverse events. Multiple groups were compared with Kruskal–Wallis test, and post hoc analysis was performed with Dunn’s test. A p value &lt;.05 was considered significant. Results A total of 80 patients were recruited (20 patients in each arm) with a mean age of 65.4 years, and 56.3% were male. Pregabalin was superior to amitriptyline ( p = .04) and duloxetine ( p = .02) in reducing mTCNS. Similarly, pregabalin was superior to amitriptyline ( p = .041 and duloxetine ( p = .009) in reducing GDS score. All drugs were comparable in reducing VRS ( p = .17). A total of 14 adverse events were observed, out of which constipation, sedation and dizziness were common. Maximum adverse events were observed in the duloxetine arm (6/14). Conclusion Pregabalin was superior to amitriptyline and duloxetine, whereas it was comparable to gabapentin in effectiveness. Constipation was the most common adverse event, but the central nervous system was the most involved in adverse events.

Evaluation of peripheral and autonomic nervous systems dysfunctions in patients with Parkinson’s disease

BackgroundPeripheral neuropathy (PN) is increasingly recognized in Parkinson’s disease (PD). This study aimed to evaluate peripheral nerve and autonomic nervous system dysfunction in PD. Forty patients with PD (20 drug-naïve, 20 on treatment) and 20 controls underwent neurological examination, Toronto Clinical Neuropathy Score (TCNS), nerve conduction studies, autonomic function tests including (heart rate variability, Blood pressure changes with standing and sustained handgrip, and sudomotor pathways. The Ewing classification system scored each test to quantify autonomic failure severity). Laboratory tests (B12, homocysteine, methylmalonic acid).ResultsTreated patients with PD had higher MDS-UPDRS scores than drug-naïve (p = 0.001). TCNS indicated mild PN in some drug-naïve patients, and mild–moderate PN in treated patients. Nerve conduction studies showed significant sensory and motor neuropathy in treated versus drug-naïve PD and controls. Treated patients had lower B12, higher homocysteine/methylmalonic acid than other groups. Across autonomic tests, controls had the most normal results, followed by drug-naïve patients, with treated patients being most abnormal. Autonomic dysfunction correlated with disease duration, severity, L-dopa dose. Lower B12, higher homocysteine/methylmalonic acid levels were associated with greater neuropathy and disease severity.ConclusionPatients with PD show evidence of PN and autonomic dysfunction, which is milder in drug-naïve patients but worsens with disease progression and treatment. Peripheral nervous system assessments may help diagnose and monitor PD neuropathy and effects of interventions.

Cross-Sectional Study of the Relationship Between Medial Plantar Nerve Conduction Studies and Severity of Diabetic Neuropathy.

Diabetic peripheral neuropathy (DPN), a complication of diabetes, is detected only in later stages. Medial plantar nerve (MPL) can identify earlier stages of neuropathy. We evaluated the correlation of MPL sensory nerve action potentials (SNAPs) and severity of DPN measured using the Toronto Clinical Neuropathy Score (TCNS). In this hospital-based, cross-sectional study, we recruited diabetic subjects referred for suspected DPN. Neuropathy was graded with TCNS. Sural nerve conduction studies were performed using standard techniques. MPL studies were conducted using the modified Ponsford technique. All evaluations were performed on Nihon Kohden (model MEB 9200K). Averaged MPL SNAP was correlated with TCNS using Pearson's correlation coefficient. To estimate a correlation of 0.4 with 80% power (P = 0.05), we needed 46 subjects. Linear regression was conducted to adjust for age, duration, and diabetic control. Receiver operating characteristic (ROC) curve analysis was performed to obtain the cutoff for MPL SNAP values using the Youden index. Fifty-one subjects with a mean age of 53.5 years (8.7) and mean duration of diabetes of 10.2 years (7.2) were included. MPL SNAPs were recordable in 12 patients, and the mean amplitude was 5.15 (2.9) µV. There was correlation between MPL SNAP and TCNS (r = -0.43, P = 0.02). No confounding was seen. Use of MPL SNAP resulted in diagnosis of DPN in an additional six (11.8%) patients. The ROC curve suggested that MPL SNAP cutoff of 1.05 µV had an accuracy of 67% in identifying neuropathy as defined by TCNS. MPL SNAP has a moderate correlation with clinical score and identifies more diabetic neuropathy than sural nerve.

Early detection of peripheral neuropathy in patients with diabetes mellitus type 2

BackgroundEarly diagnosis of diabetic polyneuropathy (DPN) can significantly improve the prognosis and help prevent severe complications. The aim of this work was to study clinical, radiological, laboratory and neurophysiological findings for early detection of peripheral neuropathy in T2DM.MethodsA total of 60 diabetic patients were classified according to Toronto Clinical Neuropathy Score (TCNS) into: Group 1: 20 diabetic patients with no evident neuropathy. Group 2: 20 diabetic patients with mild neuropathy. Group 3: 20 diabetic patients with moderate and severe neuropathy. All patients underwent a neurological examination, nerve conduction studies and optical coherence tomography (OCT) to assess retinal nerve fiber layer (RNFL) thickness. Additionally, ELISA technique to measure serum interleukin-6 (IL-6).ResultsThe analysis of gender and age distributions among the groups revealed no significant differences. There were statistically significant differences regarding disease duration, HBA1c, body mass index Systolic and diastolic blood pressure. Group 3 had such significant impairment that resulted in an inability to record the measurements of sural nerves. The study's statistical analysis results for OCT variables, and post hoc comparisons revealed significant differences between all three groups. The results demonstrated significant variations in Serum IL6 levels among the groups, with Group 3 having the highest IL6 levels. In groups 1, 2, and 3 the area under the curve for IL-6 and RNFL showed a good differentiation ability between groups.ConclusionWe conclude that the total thickness RNFL and serum IL-6 levels are a potential biomarker in prediction the severity of DPN.

Electrophysiological grading scale for polyneuropathy severity.

To establish a simple electrophysiological scale for patients with distal symmetric axonal polyneuropathy, in order to promote standardized and informative electrodiagnostic reporting, and understand the complex relationship between electrophysiological and clinical polyneuropathy severity. We included 76 patients with distal symmetric axonal polyneuropathy, from a cohort of 151 patients with polyneuropathy prospectively recruited from November 2016 to May 2017. Patients underwent nerve conduction studies (NCS), were evaluated by the Toronto Clinical Neuropathy Score (TCNS), and additional tests. The number of abnormal NCS parameters was determined, within the range of 0-4, considering low amplitude or conduction velocity in the sural and peroneal nerve. Higher number of NCS abnormalities was associated with higher TCNS, indicating more severe polyneuropathy. Polyneuropathy severity per the TCNS was most frequently (63%-70%) mild in patients with a low (0-1) number of NCS abnormalities, and most frequently (57%-67%) severe in patients with a high number (3-4) of NCS abnormalities, while patients with an intermediate (2) number of NCS abnormalities showed mainly mild and moderate severity with equal distribution (40%). A simple NCS classification system can objectively grade polyneuropathy severity, although significant overlap exists especially at the intermediate range, underscoring the importance of clinical based scoring.

Potential predictive biomarker for diabetic peripheral neuropathy: serum neuron-specific enolase

Abstract The early stages of diabetic peripheral neuropathy (DPN) are symptomless. A reliable dependable and sensitive biomarker is needed for the purpose of early identification of diabetic peripheral neuropathy. The main objective of the study was to evaluate the accuracy of serum neuron-specific enolase (NSE) as a biomarker for early identification of diabetic peripheral neuropathy. Patient samples were collected from the National Diabetes Center, Mustansiriyah University; a case control study was done from April 2022 to November 2022, in Baghdad, Iraq. One hundred sixty individuals between 30 to 60 years-old were included. Participants were divided into three groups: group one included 40 type 2 diabetic patients with peripheral neuropathy, group two consisted of 40 type 2 diabetic patients without peripheral neuropathy and group three included 80 apparently in good health as the control. Toronto Clinical Neuropathy Scoring System (TCSS) was used for clinical evaluation of peripheral neuropathy. Glycated hemoglobin (HbA1c) was measured by the CLOVER A1c system. In addition, serum NSE levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) technique. Age, sex, and other standard variables were used as a basis for comparisons between groups. Statistically, diabetic patients with peripheral neuropathy demonstrated higher level of NSE (28.42±6.93 ng/ml) than did either diabetic patients without peripheral neuropathy (21.07±2.0 ng/ml) or controls (12.54±2.34 ng/ml) with a high degree of significance (p &lt;0.001). In the context of Discrimination between DPN patients and diabetic patients without neuropathy, the area under curve for neuron-specific enolase was 0.812, 95% confidence interval [CI] = 0.716-0.909, p &lt;0.001. Cut-off value of serum neuron-specific enolase was 22.53 ng/ml, sensitivity and specificity were 70% and 77%, respectively. In the context of discrimination between DPN and controls, the area under curve for neuron-specific enolase was 1.00, 95% confidence interval was 1.0-1.0, p &lt;0.001. At a cut-off value of serum neuron-specific enolase = 18.3 ng/ml, both the sensitivity and specificity were 100%. Neuron-specific enolase could potentially be used as a biomarker to detect early diabetic peripheral neuropathy and prevent it from developing to an advanced state.

Effects of Foot Dry Cupping in Diabetic Distal Polyneuropathy: A Pilot Controlled Clinical Trial

Background: Distal polyneuropathy is a common complication of diabetes mellitus with a considerable negative impact on the quality of life. This study aimed to evaluate the effect of dry cupping on distal polyneuropathy in diabetic patients. Methods: This controlled clinical trial was performed on 34 patients with diabetic polyneuropathy (DPN) for eight weeks. The non-invasive dry, fixed cupping therapy was performed on the sole of the right foot in the patients three times a week for 10 minutes, and the left foot of the same patient was considered as a control. The severity of diabetic neuropathy was measured using the modified Toronto Clinical Neuropathy Score (mTCNS), and the symptom and sensory test scores were determined. Results: Twenty patients (40 feet) completed the study. There was a significant difference between the control foot and the treated foot in terms of the mTCNS after four and eight weeks (P values=0.004 and 0.001, respectively), in terms of the sensory test scores after four and eight weeks (P values=0.007 and 0.005, respectively), and in terms of the symptom scores after eight weeks (P value=0.002). Conclusion: For the first time, this study demonstrated that cupping therapy might be effective as a complementary treatment in alleviating the symptoms of DPN, although understanding the underlying mechanism requires further investigation.

Effect of Adding Taurine to Gabapentin on Toronto Clinical Neuropathy Score in Patient with Diabetic Neuropathy

Diabetic neuropathy is a type of nerve damage that can occur in patients with diabetes mellitus. High blood glucose can injure nerves throughout the body. Diabetic neuropathy most often damages nerves in the legs and feet causing symptoms like pain and numbness. Taurine has been widely investigated regarding to its properties as a neuroprotective agent, antioxidant, anti-inflammatory in several neurodegenerative diseases. A sample consist of 40 participants enrolled randomly into two groups; group A, 20 patients treated with gabapentin capsules 300 mg once daily at night for 3 consecutive months, and group B, 20 patients treated with gabapentin capsules 300 mg once daily at night plus taurine 1 g thrice daily for 3 consecutive months. Adding taurine in combination with gabapentin significantly improves numbness, tingling, and temperature when compared with gabapentin alone. As well as, has a highly significant improving on ataxia. Taurine is better in improving insulin sensitivity due to lowering HbA1c level significantly, beside a medium degree in increasing insulin secretion; as evidenced by decreased fasting serum glucose, decreased HbA1c significantly, increased insulin level significantly, and increased C-peptide level. The conclusion of this study, adding taurine to patients with diabetic neuropathy has a significant improving effect on Toronto clinical neuropathy score by alleviating signs and symptoms, and improving insulin sensitivity.

Effects of vitamin D3 (cholecalciferol) supplementation on diabetic polyneuropathy in patients diagnosed with diabetes mellitus

Abstract Introduction: Peripheral sensorimotor polyneuropathy is present in nearly half of the patients diagnosed with diabetes mellitus. Over the past 10 years, animal and human studies have suggested that vitamin D3 treatment may have a role in preventing or reducing neuropathic complaints and symptoms. Material and method: Our clinical, prospective, interventional, placebo-controlled study investigated the therapeutic effect of 2.000 IU oral cholecalciferol administered for three months on diabetic polyneuropathy. Patients treated with vitamin D and B, thioctic acid, and other analgesics were excluded. Using the single-blind technique, they were randomly assigned into vitamin D-treated and placebo-treated groups. In addition to recording anamnestic data, the study included - a Toronto Clinical Neuropathy Scoring System and Michigan Neuropathy Screening Instrument based - questionnaire to assess subjective symptoms and a physical examination including sensory tests (fine touch-, temperature awareness, pain-, vibration perception). Vitamin D levels were measured. After three months of therapy, the examination was repeated. Results: Most of the patients were found to have vitamin D deficiency (36% of the total population) or insufficiency (43%). In the cholecalciferol-treated group, but not in the control group, subjective symptoms decreased in intensity and/or frequency, and a significant improvement in the overall complaint scale was observed (p = 0.006), but no change regarding the sensory tests (p &gt; 0.05). Conclusions: Our results show that oral administration of cholecalciferol for three months significantly reduced subjective symptoms and neuropathic pain as assessed by our questionnaire, however, there was no significant change in the results of the sensory tests. Vitamin D deficiency/insufficiency was common in diabetic patients (79% in our population), therefore screening is recommended.

EFFECT OF SCIATIC NERVE MOBILIZATION ON LOWER LIMB FUNCTION AMONG SUBJECTS WITH DIABETIC NEUROPATHY

The most frequent consequence that diabetes people experience is diabetic neuropathy. The form of diabetic neuropathy that occurs most frequently is distal symmetrical polyneuropathy, involving sensory, motor and autonomic fibers. Sensory disturbance is most common and may be seen as hypersensitivity to touch, burning sensation, tingling and pricking pain sensation. Techniques for nerve mobility can be utilized to lessen discomfort and enhance sensibility in the area that the nerve feeds. The goal of this study is to evaluate the impact of sciatic nerve mobilization on the performance of the lower limbs and the degree of peripheral neuropathy in diabetic neuropathy patients. A Quasi-experimental design was carried out in Saveetha physiotherapy OPD, Saveetha medical college and hospital, Chennai involving 30 patients recruited using convenient sampling procedure. The data were tabulated and analyzed using Graph pad prism. This study focuses on the Influence of sciatic nerve mobilization on lower limb mobilization among subjects with diabetic neuropathy. Key Words: Sciatic nerve mobilization, Diabetic neuropathy, Lower limb function, Dynamic gait index scale, Toronto clinical neuropathy score.

Posterior Tibial Nerve Ultrasound Assessment of Peripheral Neuropathy in Adults with Type 2 Diabetes Mellitus.

Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of type 2 diabetes mellitus (T2DM). Early detection and prompt institution of appropriate therapy could prevent undesirable outcomes such as paresthesia, pain, and amputation. Although the gold standard for diagnosing DPN is nerve conduction studies, high-resolution peripheral nerve ultrasonography may serve as a noninvasive and low-cost alternative for diagnosing and staging DPN. This study investigated the clinical utility of sonographic posterior tibial nerve cross-sectional area (PTN CSA) for diagnosing DPN in individuals with T2DM. Eighty consecutive adults with T2DM and 80 age-/sex-matched controls were recruited. Clinical information was obtained, including symptoms, disease duration, Toronto clinical neuropathy score (TCNS), and biochemical parameters. The left PTN CSA at 1 cm, 3 cm, and 5 cm above the medial malleolus (MM) was measured with a high-frequency ultrasound transducer and compared to the detection of DPN using the TCNS. Based on the TCNS, 58 (72.5%) of the T2DM group had DPN. Of these, 14 (24.1%), 16 (27.6%), and 28 (48.3%) participants had mild, moderate, and severe DPN, respectively. All the mean PTN CSA (aggregate, 1 cm, 3 cm, and 5 cm above MM) of the participants with T2DM and DPN (T2DM-DPN) were significantly higher than those of T2DM without DPN (WDPN) and controls. All the PTN CSA increased significantly with increasing severity of DPN. The PTN CSA at 3 and 5 cm levels correlated weakly but significantly with fasting plasma glucose and glycated hemoglobin levels. The PTN CSA is significantly larger in T2DM-DPN than in T2DM-WDPN and healthy controls. PTN ultrasonography can be an additional tool for screening DPN in patients with T2DM.

Structural Changes of Cutaneous Immune Cells in Patients With Type 1 Diabetes and Their Relationship With Diabetic Polyneuropathy.

Diabetic polyneuropathy (DPN) is a complication of diabetes characterized by pain or lack of peripheral sensation, but the underlying mechanisms are not yet fully understood. Recent evidence showed increased cutaneous macrophage infiltration in patients with type 2 diabetes and painful DPN, and this study aimed to understand whether the same applies to type 1 diabetes. The study included 104 participants: 26 healthy controls and 78 participants with type 1 diabetes (participants without DPN [n = 24], participants with painless DPN [n = 29], and participants with painful DPN [n = 25]). Two immune cells, dermal IBA1+ macrophages and epidermal Langerhans cells (LCs, CD207+), were visualized and quantified using immunohistological labeling and stereological counting methods on skin biopsies from the participants. The IBA1+ macrophage infiltration, LC number density, LC soma cross-sectional area, and LC processes were measured in this study. Significant difference in IBA1+ macrophage expression was seen between the groups (p = 0.003), with lower expression of IBA1 in participants with DPN. No differences in LC morphologies (LC number density, soma cross-sectional area, and process level) were found between the groups (all p > 0.05). In addition, IBA1+ macrophages, but not LCs, correlated with intraepidermal nerve fiber density, Michigan neuropathy symptom inventory, (questionnaire and total score), severity of neuropathy as assessed by the Toronto clinical neuropathy score, and vibration detection threshold in the whole study cohort. This study showed expressional differences of cutaneous IBA1+ macrophages but not LC in participants with type 1 diabetes-induced DPN compared with those in controls. The study suggests that a reduction in macrophages may play a role in the development and progression of autoimmune-induced diabetic neuropathy.

489-P: Abnormal Combined Point-of-Care-Device DPN-Check and SUDOSCAN Results Predict All-Cause Mortality in People with Diabetes

Aims: Diabetic peripheral neuropathy (DPN) has been associated with increased mortality; however, data is not available for objectively diagnosed DPN using point-of-care-devices (POCDs). We therefore examined the predictive validity of POCD-diagnosed DPN for increased mortality in a prospective study. Methods: A total of 245 consecutive people with diabetes (17 type 1 diabetes, age 62.3+14.3) attending retinal-screening had all annual review health checks in a One-stop Screening Service. DPN assessments included Toronto Clinical Neuropathy Score (TCNS) evaluation, 10g-monofilament test(10g-MFT) and two validated, objective POCDs, DPN-Check (handheld device measuring sural nerve conduction velocity/amplitude), and SUDOSCAN (measuring sudomotor function). Mortality data was collected at 7-year follow-up. Kaplan-Meier survival curves and Cox-proportional hazards models were generated to assess associations of DPN measures with all-cause mortality. Results: At follow-up, 52 [21.2% (SE 6.8%)] had died. Those who died were older at screening [72.4 (10.9) vs 59.6 (13.9) years; (p&amp;lt;0.001)]. The prevalence of screen-detected DPN was 12.6% (SE 4.4%) for 10g-MFT, 27.7% (SE 8.2%) for TCNS and 33.4% (SE 9.1%) for combined POCDs. In crude Kaplan-Meier analyses all-cause mortality risk was greater in patients with abnormal TCNS (p&amp;lt;0.001) and POCDs (p&amp;lt;0.001) but was equivalent in patients with normal or abnormal 10g-MFT (p=0.21). After adjusting for age, HbA1c and Total Cholesterol, only abnormal POCDs was significantly associated with all-cause mortality [HR 1.18 (p=0.04, 95%CI 1.00:1.39) vs TCNS [HR 1.33 (p=0.06, 95%CI 0.99:1.78)]. Conclusions: This is the first prospective study showing abnormal combined DPN-Check and SUDOSCAN results predict all-cause mortality after adjusting for other risk factors. However, 10g-MFT and TCNS that diagnose DPN late did not predict all-cause mortality. Disclosure M.Goonoo: None. D.Selvarajah: None. G.P.Sloan: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH &amp; Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter &amp; Gamble, Novo Nordisk, Berlin-Chemie AG.

Corneal Confocal Microscopy Abnormalities in Children and Adolescents With Type 1 Diabetes

ObjectiveUtility of corneal confocal microscopy (CCM) in children and adolescents with type 1 diabetes mellitus (T1DM) without neuropathic symptoms or signs and minimal abnormality in large and small nerve fiber function tests remains largely undetermined. This study aimed to evaluate the performance of CCM in comparison to thermal detection thresholds (TDT) testing and nerve conduction studies (NCS) for detecting neuropathy in children with T1DM. MethodsA cohort of children and adolescents with T1DM (n = 51) and healthy controls (n = 50) underwent evaluation for symptoms and signs of neurological deficits, including warm detection threshold, cold detection threshold, vibration perception threshold, NCS, and CCM. ResultsChildren with T1DM had no or very minimal neuropathic symptoms and deficits based on the Toronto Clinical Neuropathy Score, yet NCS abnormalities were present in 18 (35%), small fiber dysfunction defined by an abnormal TDT was found in 13 (25.5%) and CCM abnormalities were present in 25 (49%). CCM was abnormal in a majority of T1DM children with abnormal TDT (12/13, 92%) and abnormal NCS (16/18, 88%). CCM additionally was able to detect small fiber abnormalities in 13/38 (34%) in T1DM with a normal TDT and in 9/33 (27%) with normal NCS. ConclusionCCM was able to detect corneal nerve loss in children with and without abnormalities in TDT and NCS.

Case Report: Lower Extremity Paresthesia and Pain with Diabetic Polyneuropathy Combated with Complex Korean Medical Treatment

Background: Diabetic polyneuropathy is the most common complication in diabetics, occurring in 50% of all cases. About 10-20% of all diabetics are accompanied by neurological pain, showing a tendency to increase with age. Clinical aspects are very diverse, from mild abnormalities on nerve conduction tests to severe abnormalities in all sensory, motor, and autonomic nerves; however, sensory symptoms usually precede motor symptoms. Patients typically express sensory symptoms, such as positive and negative symptoms, which decrease the quality of life and have marked clinical implications, such as increased morbidity and mortality. Although Western medical drugs, such as tricyclic antidepressants, anticonvulsants, and narcotic analgesics, are used for diabetic polyneuropathy, a standard treatment has not been established.Case report: A 65-year-old male with paresthesia and pain due to diabetic polyneuropathy was treated with &lt;i&gt;Uchashinki-hwan&lt;/i&gt;, acupuncture, electroacupuncture, moxibustion, and Jungsongouhyul pharmacopuncture for 10 days. We used the Toronto Clinical Neuropathy Scoring System, EuroQol-5 Dimension, and Visual Analog Scale to evaluate symptoms. Subsequently, the Neuropathy Scoring System, EuroQol-5 Dimension, and subjective discomfort improved.Conclusion: The present case report suggests that combined Korean medicine treatment might be an effective treatment for paresthesia and pain with diabetic polyneuropathy. Several follow-up studies should be conducted to clarify the effectiveness of the treatment.

Optimal cut-off value of the Modified Toronto Clinical Neuropathy Score in the diagnosis of polyneuropathy.

The modified Toronto Clinical Neuropathy Score (mTCNS) is a valid and reliable scale for the diagnosis and staging of diabetic sensorimotor polyneuropathy (DSP). To determine the optimal diagnostic cut-off value of the mTCNS in diverse polyneuropathies. Demographics and mTCNS values were retrospectively extracted from an electronic database of 190 patients with polyneuropathy (PNP) and 20 normal controls. Sensitivity, specificity, and likelihood ratios and the area under the receiver operating characteristics (ROC) curve were determined for each diagnosis and different cut-off values of the mTCNS. Patients had clinical, electrophysiological, and functional assessments of their PNP. 43% of PNP was related to diabetes or impaired glucose tolerance. mTCNS was significantly higher in patients with PNP than in those without (15.27±8 vs 0.79±1.4, P = 0.001). The cut-off value for diagnosing PNP was ≥3 (sensitivity 98.4%, specificity 85.7%, positive likelihood ratio 6.88). The area under the ROC curve is 0.987. A value of 3 or more on the mTCNS is recommended for the diagnosis of PNP.