Neuropathy Score Research Articles

Increased prevalence of mild myopathic changes in the post-COVID-19 duration

ABSTRACT Objective There are reports of peripheral nerve and muscle involvement during or after coronavirus disease 2019 (COVID-19), even following a mild infection. Here, we aimed to analyze the objective findings regarding peripheral nerve, neuromuscular junction, and muscle function using electrophysiology in patients with a previous COVID-19 infection. Methods All consecutive patients with a history of COVID-19 were questioned for post-COVID-19 duration-related neurological complaints via Composite Autonomic Symptom Score-31 (COMPASS-31), modified Toronto Neuropathy score (mTORONTO), and Fatigue Severity Scale (FSS). Patients were dichotomized into two groups based on their scores in the questionnaire. Group 1 (patients with high scores in any area of the questionnaire) and Group 2 (patients with normal scores in all sections of the questionnaire). In the second step, Group 1 was invited to a preplanned hospital visit for electrophysiological analysis, including nerve conduction studies, repetitive nerve stimulation, needle electromyography (EMG), quantitative motor unit potential analysis (qMUP), and single fiber EMG. We included 106 patients in the study. According to the questionnaire, 38 patients constituted Group 1, and 68 formed Group 2. Results Of the 38 patients, 14 accepted and underwent preplanned electrophysiological examinations. Needle EMG revealed small, short, polyphasic MUPs with early recruitment, and qMUP analysis demonstrated an increased percentage of polyphasic potentials in three patients. The examinations in other patients were unremarkable. Conclusions The high prevalence of complaints and objective myopathic findings in our cohort implicated the role of muscle involvement in the post-COVID-19 duration. Considering the socioeconomic and psychological burden of the post-COVID-19 duration among individuals and societies, a better understanding of the symptoms and myopathy is warranted.

Randomized controlled trial on the effect of 1-hour infusion of vincristine versus push injection on neuropathy in children with cancer (final analysis).

Vincristine is an integral component of treatment for children with cancer. Its main dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1-hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short-term outcomes (median follow-up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1-hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow-up 20 months), which includes treatment outcome as a secondary objective (follow-up 3 years). VIPN was measured 1-7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed. Forty-five participants per randomization group were included. There was no significant effect of 1-hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one-hour group (rate ratio 0.52, 95% confidence interval 0.33-0.80, p = 0.003). Four patients in the one-hour group and one patient in the push group relapsed. Two patients in the one-hour group died. 1-hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1-hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile.

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 > 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.

Determinants and Stratification of Microvascular Complications of Type 2 Diabetes Mellitus.

Background Diabetes mellitus (DM) is a prevalent metabolic disorder characterized by high blood sugar levels. It is classified into type 1 (T1DM) and type 2 (T2DM), which have different mechanisms and complications. The global prevalence of diabetes, particularly T2DM, has increased significantly in recent decades, leading to a need for standardized data collection of macrovascular and microvascular complications to track disease progression and guide treatment options. This study aims to assess and correlate the prevalence and severity of microvascular complications in patients with T2DM. Methodology This observational, cross-sectional study was conducted at Poonam Multispeciality Hospital in Ahmedabad, India. A total of 4,123 diabetic patients admitted to the hospital were included. Information on sociodemographics and medical history was collected using standardized forms. Fundus photography and fluorescein angiography were performed to assess diabetic retinopathy, and estimated glomerular filtration rate and albumin-to-creatinine ratio were measured to evaluate renal function. Neurological examinations were conducted to score diabetic neuropathy. Chi-square tests were used to determine associations between medical history with diabetic retinopathy and nephropathy, and t-tests were used to compare diabetic neuropathy scores. Kendall's Tau correlation was used to determine correlations between diabetic retinopathy and nephropathy. P-values <0.05 were considered statistically significant. Results The overall prevalence of diabetic retinopathy, nephropathy, and neuropathy was 37.5%. Of the patients included, 47.9% had diabetic nephropathy and 28.9% had diabetic neuropathy. A significant association was observed between the severity of diabetic retinopathy and age, body mass index, duration of diabetes, and hemoglobin A1c (HbA1C) levels. Similarly, significant associations were found between these factors and the severity of diabetic nephropathy. Unpaired t-tests revealed significant differences in diabetic neuropathy examination scores based on the duration of diabetes and Hba1C levels. Moreover, correlation analysis indicated a low, positive correlation between diabetic retinopathy and diabetic nephropathy. Conclusions This study provides insights into the prevalence, severity, and associations of microvascular complications in patients with T2DM, contributing to the understanding and management of these conditions. Additionally, the research revealed a direct association between diabetic retinopathy and different stages of chronic kidney disease determined by the Kidney Disease Improving Global Outcome guidelines.

Studies to Assess the Utility of Serum Neurofilament Light Chain as a Biomarker in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and disabling dose-limiting toxicities of chemotherapy. We report here the results of two separate non-interventional studies (49 patients), which evaluated blood neurofilament light chain (NfL) as a biomarker of CIPN in breast cancer patients treated with paclitaxel. All patients underwent a standard treatment protocol that was established independently of the present studies. NfL was measured in serum using an ultrasensitive single-molecule array and compared with the self-administered European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (CIPN20) and Total Neuropathy Score clinical version (TNSc), a clinician-reported measure of neuropathy progression. The TNSc increased with cumulative dose compared with baseline, and the NfL concentrations were also strongly associated with the cumulative dose of chemotherapy. The analysis showed a correlation between TNSc and NfL. Both TNSc and NfL showed weak to moderate associations with CIPN20 subscores, with a better association for the CIPN20 sensory compared with motor and autonomic subscores. Data from the two studies provide evidence that serum NfL has the potential to be used as a biomarker to monitor and mitigate CIPN. However, studies with additional patients planned in the ongoing clinical trial will determine the universal application of NfL as a biomarker in CIPN.

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.

Dual mapping of MTHFR C677T (A1298C) and BDNF G196A (Val66Met) polymorphisms in patients with diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is a loss of distal sensory function in the lower limbs that is accompanied by pain and severe morbidity. The goal of this study was to perform a screening of the MTHFR C677T (A1298C) and BDNF G196A (Val66Met) polymorphisms and determine their possible relationships using biochemical blood tests and clinical presentations of symptoms in Jordanian patients with DPN. A cross-sectional study was conducted, and medical records were used to identify and recruit patients with DPN and collect their demographic and clinical characteristics. The total neuropathy score (TNSr) was used to assess the severity of sensory symptoms. In addition, direct sequencing was performed after Polymerase Chain Reaction (PCR) amplification to screen the two single nucleotide polymorphisms (SNPs) of interest. Ninety patients with DPN participated in the study. The MTHFR-SNP variant (CT) and (TT) genotypes were identified in 39 (43.3%) and 19 (21.1%) patients, respectively. On the other hand, the BDNF-SNP variant (GA) and (AA) genotypes were identified in 22 (24.4%) and 11 (12.2%) patients, respectively. The distributions of the genotype frequencies of the MTHFR-SNP and BDNF-SNP variants statistically differed between patients with DPN and the control group (p < 0.0001, p < 0.002). Moreover, patients carrying variant genotypes of the two analyzed SNPs were more likely to have unsatisfactory HbA1c levels (> 7 mg/dl, p = 0.029) and moderate to severe symptoms (TNSr score 8-24). The results of this study show that the MTHFR C>T-677 SNP and the BDNF G>A-196 SNP can be used as genetic risk markers for DPN. Assessing patients' genetic-metabolic risk profiles is recommended for providing personalized treatment.

492-P: Utility of Measures of Nerve Fiber Function and Structure for the Diagnosis of Diabetic Peripheral Neuropathy

Introduction: Identifying diabetic neuropathy (DPN) in the clinic is challenging. The purpose of this study is to investigate the utility of various diagnostic tools for the detection of DPN Methods: The following measures were assessed in controls and patients with type 2 diabetes with and without DPN: clinical neuropathy scores, quantitative sensory testing, corneal confocal microscopy, and sudomotor function. Receiver operating characteristics and areas under the curve with sensitivity and specificity were calculated Results: See Table and Figure Conclusions: Functional measures were more sensitive but less specific than structural ones. Similar to other studies, our study shows that no individual test is reliable per-se. Future studies are needed to investigate the best combination of tests for assessing DPN. Disclosure C.M.Casellini: None. H.Parson: None. C.Cushman: None. A.M.Ingram: None. J.L.Pettaway: None. T.Sears: None. E.S.Siraj: Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk, Boehringer Ingelheim and Eli Lilly Alliance.

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.

Plasma neurofilament light chain level is not a biomarker of Charcot-Marie-Tooth disease progression: Results of 3-year follow-up study.

Charcot-Marie-Tooth disease (CMT) is a hereditary, slowly progressive neuropathy. Currently, there are no effective pharmacological treatments or sensitive disease activity biomarkers available. The aim of this study was to demonstrate the change in plasma neurofilament light chain (NfL) over time in a CMT cohort and analyse the association between CMT severity and NfL level. Initially, 101 CMT patients and 64 controls were enrolled in the study. Repeated evaluation was performed in 73 patients and 28 controls at a 3-year interval. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Plasma NfL concentration was measured using the Simoa (single molecule array) NfL assay. Plasma NfL concentration was increased in the CMT group compared with controls (p < 0.001). Overall NfL level increased over the 3-year interval in both CMT (p = 0.012) and control (p = 0.001) groups. However, in 22 of 73 CMT patients and seven of 28 controls, the NfL level decreased from the baseline. Analysing the association between 3-year change in plasma NfL and disease severity (CMTNSv2), there was no correlation in the CMT group (r = 0.228, p = 0.052) or different CMT subgroups. Our study verifies increased plasma NfL concentrations in patients with CMT compared with controls. Longitudinal 3-year data showed a variable change in NfL levels between CMT subtypes. There was no association between change in NfL over time and disease severity. These findings suggests that NfL is not a biomarker for CMT progression.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Few quality of life (QoL) data are available for diffuse large B-cell lymphoma (DLBCL) patients during the first year of diagnosis. Due to the disease and treatment, patients can adapt to their condition and then change their criteria to assess QoL over time, resulting in a response shift (RS) effect. This study aims to provide QoL level for DLBCL patients at diagnosis and after 1 year, and to assess the occurrence of a RS effect. Methods: Data from DLBCL patients prospectively included in the French multicentric cohort REALYSA were used. QoL was collected at diagnosis and at 1 year using the EORTC QLQ-C30 and QLQ-NHL-HG29 (non-Hodgkin high-grade lymphoma) questionnaires. The recently validated QLQ-NHL-HG29 specific questionnaire assesses 5 symptomatic dimensions: symptom burden (SB), neuropathy (NP), physical condition/fatigue (PC), emotional impact (EI), worries/fears about health and functioning (WF). A score is generated per dimension on a 0 to 100 scale. Analyses were done on patients who received standard first-line immunochemotherapy regimen, with QoL questionnaire at diagnosis and at 1 year, and without relapse before 1 year questionnaire completion to avoid bias related to second line therapy. Scores were reported according to age, gender, performance status (PS) and disease stage. We examined the prevalence of clinically important problems/symptoms on QLQ-C30 scales at patient level using validated thresholds (Giesinger et al. J Clin Epidemiol. 2020). The potential occurrence of a RS effect was explored using the Oort procedure. Results: Between Nov 2018 and Dec 2021, 3116 patients were enrolled in REALYSA including 1198 DLBCL. Among 964 patients without relapse at 1 year, 523 had completed questionnaires at baseline and 1 year. For Global QoL, 57% of patients presented clinically important problems at baseline and 42% at 1 year. Regarding the QLQ-NHL-HG29, the mean PC score was 32 (SD 25) [PS 0–1 vs. 2: 29 (SD 24) vs. 47 (SD 25)] at baseline and 23 (SD 21) [PS 0–1 vs. 2: 22 (SD 20) vs. 27 (SD 22)] at 1 year; the mean NP score was 12 (SD 20) [PS 0–1 vs. 2: 11 (SD 19) vs. 16 (SD 26)] at baseline and 23 (SD 28) [PS 0–1 vs. 2: 23 (SD 27) vs. 24 (SD 29)] at 1 year. Among the QLQ-NHL-HG29, a RS effect was observed for NP, PC and WF. The highest effect was observed for NP (Figure 1), suggesting that there is no increase in NP level at 1 year compared to baseline (mean change of -1 points (SD 1)). If no RS effect was considered, it would have been concluded that the NP level had increased at 1 year compared to diagnosis (mean change of 12 points (SD 11)). The research was funded by: Institut National du Cancer (INCa, N°2021-130) Keyword: Aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

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.

Indirect treatment comparison (ITC) of the efficacy of vutrisiran and tafamidis for hereditary transthyretin-mediated amyloidosis with polyneuropathy

ABSTRACT Background Vutrisiran and tafamidis are approved therapies for treating hereditary transthyretin-mediated (ATTRv/hATTR) amyloidosis with polyneuropathy, a rapidly progressive and fatal disease. To assist healthcare decision-makers, an indirect treatment comparison (ITC) was undertaken to explore the comparative efficacy of vutrisiran and tafamidis. Research design and methods Individual patient data (vutrisiran vs. placebo) and published results (tafamidis vs. placebo) from phase 3 randomized controlled trials were used in a Bucher analysis to assess differences in treatment effects between vutrisiran and tafamidis on: Neuropathy Impairment Score-Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) score, NIS-LL Response, and modified Body Mass Index (mBMI). Results Greater treatment effects were observed at 18 months with vutrisiran vs. tafamidis for all endpoints, with statistically significant improvements in polyneuropathy (relative mean change in NIS-LL: −5.3 [95% confidence interval (CI): −9.4, −1.2; p = 0.011]), health-related quality of life (HRQOL, relative mean change in Norfolk QOL-DN: −18.3 [95% CI: −28.6, −8.0; p < 0.001]), and nutritional status (relative mean change in mBMI: 63.9 [95% CI: 10.1, 117.7; p = 0.020]). Conclusions This analysis suggests vutrisiran has greater efficacy on multiple measures of polyneuropathy impairment and HRQOL compared to tafamidis in patients with ATTRv amyloidosis with polyneuropathy.

Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.

Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D). Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention. Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both. Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients. https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.

The Association between Waist Hip Ratio and Severity of Diabetic Peripheral Neuropaty in Diabetes Melitus Type 2 by Using Toronto Clinical Scoring System

Introduction: Diabetic neuropathy is a common and progressive microvascular complication of diabetes, so early detection and prevention is very important. Other modifiable risk factors such as hypertension, dyslipidemia, or central obesity can be managed. Central obesity with insulin resistance is a key pathophysiological factor in the metabolic syndrome. Waist hip ratio (WHR) has been proposed as a tool for detecting central obesity. Toronto Clinical Scoring System (TCSS) is a diabetic neuropathy scoring system that has high sensitivity and specificity. The aim of this study was to determine the relationship between waist hip ratio and the severity of peripheral diabetic neuropathy in type 2 Diabetes Melitus (DM) according to the Toronto Clinical Scoring System (TCSS). Method: This study used a cross-sectional design. Sampling was conducted at the Endocrinology Polyclinic and Neurology Polyclinic Hospital H. Adam Malik Medan. The research sample was taken as many as 45 subjects consecutively. TCSS examination is performed to diagnose and determine the severity of diabetic neuropathy Therefore, waist hip ratio was calculated to assess central obesity. Data analysis using Chi Square test. Results: On the demographic characteristics of the research subjects were male, age range 51-60 years, high school education level, not working, history of DM 5-10 years. The mean value of WHR is 0.87±0.051. Median TCSS Score 10 (6-16). The majority of subjects had mild diabetic peripheral neuropathy. Patients with central obesity had a grading of neuropathy that was classified as severe as many as 13 people (56.5%), moderate as many as 7 people (30.4%), and mild as many as 3 people (13.0%). While patients who are not obese have a grading of neuropathy that is classified as severe as many as 1 person (4.5%), moderate as many as 5 people (22.7%), mild as many as 16 people (72.7%). Based on the Chi Square test, it was found that there was a significant association between the waist hip ratio and the severity of diabetic peripheral neuropathy in type 2 DM patients with p&lt;0.01. Conclusion: There is a statistically significant association between waist hip ratio and the severity of diabetic neuropathy in type 2 DM with p &lt; 0.01.

Evaluation of methodologies for indirect comparison of eplontersen and vutrisiran for the treatment of hereditary transthyretin-mediated amyloidosis with polyneuropathy (P12-4.005)

<h3>Objective:</h3> To investigate comparative efficacy and safety of eplontersen and vutrisiran in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy (ATTRv-PN). <h3>Background:</h3> ATTRv-PN is a rare, autosomal dominant disease caused by mutations in the gene encoding transthyretin (TTR) protein, resulting in accumulation of ATTR amyloid in multiple tissues including the peripheral nervous system. TTR silencers developed and in development to treat ATTRv-PN include vutrisiran (recently approved by the FDA and EMA), and eplontersen, which met its co-primary endpoints and demonstrated an overall favourable safety profile in a planned Week 35 interim analysis of the phase III NEURO-TTRansform trial (NCT04136184). The eplontersen and vutrisiran trials both used an external placebo arm from earlier trials. No head-to-head studies have been conducted for eplontersen and vutrisiran to date. Therefore, the feasibility and implications of indirect treatment comparisons (ITCs) should be evaluated. ATTRv-PN exhibits substantial clinical heterogeneity, which challenges traditional ITC methods. Additional challenges relate to the trial designs, including the use of external placebo comparators. Different ITC approaches will be evaluated to assess the impact of these factors on the ability to compare efficacy and safety of eplontersen and vutrisiran. <h3>Design/Methods:</h3> In addition to a naïve comparison, population-adjusted methods that attempt to account for heterogeneity and differences in trial designs were evaluated, including matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC). Whilst MAIC may fail to match characteristics demonstrating substantial heterogeneity, this is not an issue for STC. However, unlike MAIC, STC can falter when dealing with non-linear outcomes. Efficacy will be assessed based on the Modified Neuropathy Impairment +7 and Norfolk Quality of Life-Diabetic Neuropathy scores, and safety will also be assessed. <h3>Results:</h3> Results will become available ahead of AAN2023. <h3>Conclusions:</h3> This ITC feasibility assessment supports interpretation of comparative efficacy and safety analyses, which is important for decision-making by clinicians, payers and researchers. <b>Disclosure:</b> Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Karam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Karam has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Karam has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuroderm. Julian D. Gillmore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam Pharmaceuticals. Julian D. Gillmore has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intellia. Julian D. Gillmore has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AstraZenica. Julian D. Gillmore has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BridgeBio. Julian D. Gillmore has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Mrs. Chen has received personal compensation for serving as an employee of AstraZeneca. Mrs. Chen has stock in AstraZeneca. Miss Jenkins has nothing to disclose. Dr. Hale has received research support from Cancer Research UK. Dr. Taylor has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NIH France. Dr. Chen has received personal compensation for serving as an employee of AstraZeneca. Dr. Chen has stock in AstraZeneca. Nicholas Viney has received personal compensation for serving as an employee of Ionis Pharmaceuticals Inc.. Nicholas Viney has stock in Ionis Pharmaceuticals. Nicholas Viney has received intellectual property interests from a discovery or technology relating to health care. Dr. Schneider has received personal compensation for serving as an employee of ionis pharmaceuticals.