Symptoms Of Neuropathy Research Articles

The prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease in a New Zealand cohort.

To identify the prevalence and clinical features of leflunomide-associated peripheral neuropathy in patients with rheumatic disease over a 42-month observational period between January 1, 2016 and June 30, 2019. A retrospective observational study was conducted using regional prescription data identifying all patients treated with leflunomide for rheumatic diseases in the Southern District Health Board of New Zealand. Medical records were used to identify patients who developed peripheral neuropathy while receiving treatment with leflunomide. Demographic characteristics, co-therapies, and additional risk factors for peripheral neuropathy were also recorded. A total of 482 patients were identified as receiving leflunomide for the treatment of rheumatic during the study period. In total, 23 patients developed leflunomide-induced peripheral neuropathy within the cohort giving a prevalence of 4.7%. Nerve conduction studies (NCS) performed in 18 (78.2%) of these patients confirmed a distal axonal, sensory, or sensorimotor peripheral neuropathy. The majority of patients (n = 22; 95.6%) either improved, stabilized, or resolved on cessation of the drug, with or without medication washout. Adverse symptoms were reported in association with peripheral neuropathy in 15 of the 23 patients (65.2%): these included pain, poor sleep, compromised skin integrity, poor balance, and a Charcot-like arthropathy. Additional treatment was required to manage symptoms of peripheral neuropathy including nine patients (39%) who received pain relief. This study supports the previously reported association between leflunomide treatment and the development of a peripheral neuropathy. However, our findings suggest that this is more common than the previous estimates. In patients with psoriatic arthritis and previous tarsitis, there appeared to be an association with a Charcot's-like arthropathy, a complication not previously noted in the literature.

Harnessing the therapeutic potential of bone marrow-derived stem cells for sciatic nerve regeneration in diabetic neuropathy

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that affects the angiogenesis and myelination of peripheral nerves. In this study, we investigated the potential of mesenchymal stem cells (MSCs) transplantation to improve DPN by enhancing angiogenesis and remyelination in the sciatic nerve of streptozotocin (STZ)-induced diabetic female rats. The purpose of this study was to evaluate the therapeutic potential of mesenchymal stem cells as a possiblity for clinical intervention to alleviate the symptoms of diabetic peripheral neuropathy. We examined whether transplanted mesenchymal stem cells can produce new and restored angiogenesis, as well as promoting myelination. Overall, our findings suggest that MSCs transplantation has neuroprotective effects. This is particularly the case for Schwann cells. Transplantation may stimulate angiogenesis as well as remyelination of the sciatic nerve in experimentally-induced diabetic peripheral neuropathy. Behavioral assays, histological analysis, and molecular techniques were used to assess the effects of MSCs transplantation. Our results demonstrate that in diabetic rats signs of neuropathy were reversed following a single administration of bone marrow-derived MSCs. Morphological and morphometric analysis of the sciatic nerve revealed that diabetic rats displayed structural alterations that were attenuated with MSCs transplantation.Immunostaining analysis showed increased expression of S100 and VEGF in the sciatic nerve following MSCs transplantation. Western blotting analysis also revealed elevated levels of VEGF and CD31 in rats treated with MSCs compared to diabetic rats.

Painful stimulation increases functional connectivity between supplementary motor area and thalamus in patients with small fibre neuropathy.

The lead symptom of small fibre neuropathy (SFN) is neuropathic pain. Recent functional magnetic resonance imaging (fMRI) studies have indicated central changes in SFN patients of different etiologies. However, less is known about brain functional connectivity during acute pain processing in idiopathic SFN. We conducted fMRI with thermal heat pain application (left volar forearm) in 32 idiopathic SFN patients and 31 healthy controls. We performed functional connectivity analyses with right supplementary motor area (SMA), left insula, and left caudate nucleus (CN) as seed regions, respectively. Since pathogenic gain-of-function variants in voltage gated sodium channels (Nav) have been linked to SFN pathophysiology, explorative connectivity analyses were performed in a homogenous subsample of patients carrying rare heterozygous missense variants. For right SMA, we found significantly higher connectivity with the right thalamus in SFN patients compared to controls. This connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. We found significantly reduced connections between right SMA and right middle frontal gyrus in patients with Nav variants. Likewise, connectivity between left CN and right frontal pole was decreased. Aberrant functional connectivity in SFN is in line with previous research on other chronic pain syndromes. Functional connectivity changes may be linked to SFN, highlighting the need to determine if they result from peripheral changes causing abnormal somatosensory processing. This understanding may be crucial for assessing their impact on painful symptoms and therapy response. We found increased functional connectivity between SMA and thalamus during painful stimulation in patients with idiopathic SFN. Connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. Our findings emphasize the importance of investigating functional connectivity changes as a potential feature of SFN.

Knowledge levels of oncology nurses regarding evidence-based practices in the assessment and management of chemotherapy-induced peripheral neuropathy

ObjectiveThe study aimed to determine the level of oncology nurses' knowledge of evidence-based practice for assessing and managing chemotherapy-induced peripheral neuropathy (CIPN). MethodsThis study employed a descriptive and cross-sectional research design. It was carried out with oncology nurses who were working at a university hospital in the Western Region of Turkey and who were members of the Oncology Nursing Association. The sample of the study consisted of 96 nurses who met the inclusion criteria. ResultsThe study sample comprised 94.8% female oncology nurses, 57.3% of whom held an undergraduate degree, and over half (58.5%) of whom were employed as clinical nurses. A majority of nurses (76.0%) indicated that they had not received any training in peripheral neuropathy. 35.4% of the nurses assessed patients receiving neurotoxic chemotherapy for peripheral neuropathy at each visit/each chemotherapy cycle. A total of 43.8% of nurses indicated that they frequently assessed patients for peripheral neuropathy at the conclusion of the treatment protocol. The oncology nurses assessed the patient-reported symptoms of motor neuropathy (58.3%), sensory neuropathy (56.3%), autonomic neuropathy (51.0%), neuropathic pain (55.2%), and co-occurring symptoms (52.1%) on a frequent basis. The nurses reported that they assessed muscle strength (56.3%), gait and balance (58.3%), and quality of life (52.1%) “frequently”. In contrast, they assessed deep tendon reflex (41.7%), neurological tests (36.5%), and social activities (46.8%) “rarely”. ConclusionsThe study findings indicated that oncology nurses require further education and training in evidence-based practices for the assessment and management of CIPN.

Effect of Metformin on Peripheral Nerve Morphology in Type 2 Diabetes: A Cross-Sectional Observational Study.

Diabetic peripheral neuropathy (DPN) affects around 50% of the 500 million people with type 2 diabetes worldwide and is considered disabling and irreversible. The present study was undertaken to assess the effect of metformin on peripheral neuropathy outcomes in type 2 diabetes. 69 type 2 diabetes participants receiving metformin were recruited and underwent clinical assessment, peripheral nerve ultrasound, nerve conduction studies and axonal excitability studies. 318 participants who were not on metformin were also concurrently screened, and 69 were selected as disease controls and matched to the metformin participants for age, sex, diabetes duration, BMI, HbA1c and use of other diabetes therapies. Medical record data over the previous 20 years were analysed for previous metformin use. Mean tibial nerve cross-sectional area (CSA) was lower in the metformin group (metformin 14.1 ∓ 0.7 mm2, non-metformin 16.2 ∓ 0.9mm2, p=0.038), accompanied by reduction in neuropathy symptom severity (p=0.021). Axonal excitability studies demonstrated superior axonal function in the metformin group and mathematical modelling demonstrated that these improvements were mediated by changes in nodal Na+ and K+ conductances. Metformin treatment is associated with superior nerve structure, clinical and neurophysiological measures. Treatment with metformin may be neuroprotective in DPN.

Case Report: Tolosa-Hunt syndrome, a neuroinflammatory origin of painful ophthalmoplegia

Background Tolosa-Hunt syndrome is a rare neuroinflammatory disease that affects the cavernous sinus and superior orbital fissure, resulting in symptoms of neuropathy. Case presentation We report a case of a 35-year-old male patient with no past medical history who presented to the emergency department (ED) complaining of a four-day history of progressively increasing headaches associated with right eye pain and double vision. A physical examination showed findings suggestive of abducens nerve palsy. A computed tomography (CT) scan showed subtle asymmetric thickening of the right cavernous sinus, which prompted further investigation by magnetic resonance imaging (MRI) scan. The MRI scan showed intensely enhanced soft tissue thickening in the right cavernous sinus region, slightly extending to the right orbital apex, which caused enlargement of the cavernous sinus and appeared isointense to the adjacent muscles on T1 and T2. The diagnosis of Tolosa-Hunt syndrome was made after the exclusion of all other possible pathologies. The patient received prednisolone therapy; his symptoms improved, and he was discharged after three days. Two weeks later, the patient presented again to the ED with the same symptoms and was treated symptomatically. Conclusions This case highlights a very rare etiology for painful ophthalmoplegia, which is Tolosa-Hunt syndrome. Thickening of the cavernous sinus on MRI images with a background history of painful ophthalmoplegia and headache should raise clinician’s suspicion towards the disease. In addition, exclusion of other possible causes is very important, as Tolosa-Hunt syndrome is a diagnosis of exclusion.

Acupuncture-related interventions improve chemotherapy-induced peripheral neuropathy: A systematic review and network meta-analysis

BackgroundThe previous effects of acupuncture-related interventions in improving chemotherapy-induced peripheral neuropathy (CIPN) symptoms and quality of life (QoL) remain unclear in terms of pairwise comparisons.AimsThis systematic review and network meta-analysis aimed to determine the hierarchical effects of acupuncture-related interventions on symptoms, pain, and QoL associated with CIPN in cancer patients undergoing chemotherapy.MethodsNine electronic databases were searched, including PubMed, Embase, Cochrane Library, EBSCO, Medline Ovid, Airiti Library, China National Knowledge Infrastructure (CNKI), China Journal full-text database (CJFD), and Wanfang. Medical subject heading terms and text words were used to search for eligible randomized controlled trials published from database inception to May 2023.ResultsA total of 33 studies involving 2,027 participants were included. Pairwise meta-analysis revealed that acupuncture-related interventions were superior to usual care, medication, or dietary supplements in improving CIPN symptoms, CIPN pain, and QoL. Furthermore, network meta-analysis indicated that acupuncture plus electrical stimulation (acupuncture-E) had the greatest overall effect among the various interventions. The surface under the cumulative ranking curve (SUCRA) revealed that acupuncture-E ranked the highest in improving CINP symptoms. Acupuncture alone was most effective in reducing CIPN pain, and acupuncture plus moxibustion (acupuncture-M) ranked highest in enhancing QoL.ConclusionThis finding suggests that acupuncture-related interventions can provide patients with benefits in improving CIPN symptoms, pain, and QoL. In particular, acupuncture-E could be the most effective approach in which the provided evidence offers diverse options for cancer patients and healthcare professionals.Implication for the profession and/or patient careThese findings provide valuable insights into the potential benefits of acupuncture-related interventions for managing symptoms, pain, and QoL associated with CIPN in patients undergoing chemotherapy. Among the various interventions studied, overall, acupuncture-E had the most significant impact and was effective for a minimum duration of 3 weeks. On the other hand, transcutaneous electrical acupoint/nerve stimulation (TEAS) was identified as a noninvasive and feasible alternative for patients who had concerns about needles or the risk of bleeding. It is recommended that TEAS interventions should be carried out for a longer period, preferably lasting 4 weeks, to achieve optimal outcomes.Trial registrationThe study protocol was registered in the International Prospective Register of Systematic Reviews. Registration Number: CRD42022319871.

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

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

A Case Report on the Ayurvedic Management of Diabetic Peripheral Neuropathy

Diabetic neuropathy is one of the most common microvascular complications of diabetes mellitus. It has a significant impact in lowering quality of life (QOL) of diabetic patients. Currently, there is no effective management rather than tight blood sugar control. Hence an effective management for diabetic peripheral neuropathy (DPN) has to be deduced. A 41‑year‑old female patient, who was a known case of diabetes mellitus presenting with the symptoms of diabetic peripheral neuropathy was treated with a combination of Ayurvedic internal as well as external therapies, considering the treatment protocol of Prameha upadrava and Vatarakta chikitsa. The symptoms were assessed before and after treatment using the Toronto Clinical Scoring System. Significant improvement was seen in all the scores after the treatment. This case elicited that DPN can be successfully managed by Ayurvedic treatment.

Daidzein ameliorates peripheral neuropathy in Sprague Dawley rats.

Neuropathy is the most common disorder comprising peripheral nerve damage in diabetic patients. Prolonged hyperglycaemia and oxidative stress cause metabolic imbalance and are the key reasons for the development of diabetic neuropathy. Daidzein, a soy isoflavone possesses potent anti-hyperglycaemic and antioxidant activity. The present study aims to check the protective effect of Daidzein in diabetic neuropathy in rats. The experimental animal model involved induction of diabetes in rats by intraperitoneal injection of streptozotocin (55mg/kg). Following confirmation of diabetes, the diabetic rats were subjected to oral treatment with varying doses of Daidzein (25, 50, and 100mg/kg) and pregabalin (30mg/kg) for a duration of 4weeks, initiated 6weeks after diabetes induction. Results indicated that Daidzein treatment led to a significant reduction in plasma glucose levels and an improvement in body weight among diabetic animals. Moreover, Daidzein demonstrated a positive impact on sensory functions, as evidenced by the effect on tail withdrawal and response latency. Mechanical hyperalgesia and allodynia, common symptoms of diabetic neuropathy, were also significantly reduced with both Daidzein and pregabalin treatment. Notably, nerve conduction velocities exhibited improvement following the administration of Daidzein and pregabalin. Further investigation into the molecular mechanisms revealed that Daidzein treatment resulted in a notable enhancement of antioxidant enzyme levels and a reduction in the overexpression of NOX-4 in the sciatic nerve. This suggests that Daidzein's therapeutic effect is associated with the inhibition of oxidative stress via NOX-4. In summary, the findings of study suggests that, Daidzein treatment significantly attenuated diabetic neuropathy by inhibiting oxidative stress via NOX-4 inhibition.

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

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

Hubungan Neuropati Diabetikum dengan Kualitas Tidur Pada Pengidap DM Tipe 2 di Rumah Sakit Baladhika Husada Jember

Diabetic neuropathy is a complication of type 2 diabetes mellitus which is caused by lesions or nerve dysfunction in the lower extremities due to chronic hyperglycemia through peripheral and central mechanisms which can cause symptoms of tingling, numbness, numbness, pain, burning sensation, etc. sleep, thus affecting the sleep quality of people with type 2 diabetes mellitus. This aim is to analyze the relationship between diabetic neuropathy and sleep quality in people with type 2 diabetes mellitus at the Baladhika Husada Hospital, Jember. This research uses a correlation research design with a Cross-Sectional Study approach with a sample size of 43 respondents taken using the Pusposive Sampling technique. The statistical test results for diabetic neuropathy with sleep quality using the Spearman Rho test showed that the p value was 0.002 and r = 0.456, which means that diabetic neuropathy has a sufficient relationship with sleep quality. There is a negative relationship between diabetic neuropathy and the sleep quality of type 2 diabetes mellitus patients, so it can be said that increasing the severity of diabetic neuropathy will also affect the sleep quality of sufferers. The results of this research can be used as a guide for sufferers of type 2 diabetes mellitus with diabetic neuropathy to increase self-awareness in paying attention to lifestyle, maintaining diet, and routinely controlling medication in health services, in order to reduce the symptoms of diabetic neuropathy so as to improve the quality of sleep of sufferers.

Topical menthol for chemotherapy-induced peripheral neuropathy: a randomised controlled trial in breast cancer

ObjectivesChemotherapy-induced peripheral neuropathy (CIPN) symptom is one of the side effects of paclitaxel in breast cancer patients. This randomised controlled study was conducted to investigate the effect of topical menthol...

Risk factors associated with the severity of overactive bladder among Syrian patients with type 2 diabetes

The prevalence of overactive bladder (OAB) is known to be higher in patients with type 2 diabetes (T2DM). However, few studies have examined specific risk factors contributing to its progression among diabetes mellitus (DM) patients, so this study aimed to investigate the risk factors specific to diabetes mellitus that influence overactive bladder in the Syrian population. This cross-sectional study was conducted at four endocrinology centers in four Syrian provinces: Damascus, Aleppo, Homs, Hama, and Latakia. The study was comprised of patients who had been diagnosed with both T2DM and OAB and had visited these centers from February 2020 to January 2023. The Arabic version of the Overactive Bladder Symptom Score (OABSS) scale was used to categorize the participants based on the severity score into two groups: the mild OAB group and the moderate-severe OAB group. A logistic analysis was conducted to assess the risk factors associated with the OAB among patients with diabetes. Among the 153 patients diagnosed with both DM and OAB, significant distinctions were found between the two groups concerning the severity of overactive bladder, age, duration of diabetes, symptomatic diabetic peripheral neuropathy (DPN), and ankle reflex (P < 0.05). Furthermore, a multivariate analysis revealed that age (OR 1.48, 95% CI 0.89–2.19), duration of diabetes (OR 1.94, 95% CI 0.53–2.23), and symptomatic DPN (OR 2.74, 95% CI 1.39–4.13) independently acted as risk factors for the advancement of OAB. The severity of OAB in Syrian patients with diabetes is closely associated with the severity of DM. Factors such as age, duration of diabetes, and symptomatic DPN are independent predictors of the severity of OAB. Patients who experience symptomatic DPN are at an increased risk of developing OAB.

Noradrenergic cardiac denervation is associated with gait velocity in Parkinson disease: a dual ligand PET study.

Preliminary data suggest that gait abnormalities in Parkinson disease (PD) may be associated with sympathetic cardiac denervation. No kinematic gait studies were performed to confirm this observation. We aimed to correlate spatiotemporal kinematic gait parameters with cardiac sympathetic denervation as determined by cardiac [11C]HED PET in PD. Retrospective database analysis of 27 PD patients with cardiac sympathetic denervation. All patients underwent spatiotemporal kinematic gait assessment (medication 'off' state), cardiac [11C]HED and dopaminergic brain [11C]DTBZ PET scans. We employed a hierarchical regression approach to examine associations between the extent of cardiac denervation, dopaminergic nigrostriatal neurodegeneration, and three gait parameters - velocity, step length and cadence. More extensive cardiac denervation was associated with slower velocity (estimate: -1.034, 95% CI [-1.65, -0.42], p = 0.002), shorter step length (estimate: -0.818, 95% CI [-1.43, -0.21], p = 0.011) and lower cadence (estimate: -0.752, 95% CI [-1.28, -0.23], p = 0.007) explaining alone 30% (Adjusted-R²: 0.297), 20% (Adjusted-R²: 0.202) and 23% (Adjusted-R²: 0.227) of the variability, respecivetly. These associations remained independent of striatal dopaminergic impairment and confounding factors such as age, Hoehn and Yahr (HY) stages, peripheral neuropathy, cognition, and autonomic symptoms. In contrast, striatal dopaminergic denervation was significantly associated with step length (estimate: 0.883, 95% CI [0.29, 1.48], p = 0.005), explaining about 24% of the variability but was dependent of HY stage. More severe cardiac noradrenergic denervation was associated with lower gait velocity, independent of striatal dopaminergic denervation and HY stage, impacting both step length and cadence. These results suggest independent contributions of the peripheral autonomic system degeneration on gait dynsfunction in PD.

Growth Differentiation Factor 15 and Matrix Metalloproteinase 3 in Plasma as Biomarkers for Neuropathy and Nephropathy in Type 1 Diabetes.

Diabetic neuropathy and nephropathy are common complications of type 1 diabetes (T1D). The symptoms are often elusive in the early stages, and available diagnostic methods can be improved using biomarkers. Matrix metalloproteinase 3 (MMP-3) has been identified in the kidneys and is thought to be involved in diabetic nephropathy. Growth differentiation factor 15 (GDF-15) has been suggested to have positive effects in diabetes, but is otherwise associated with adverse effects such as cardiovascular risk, declined kidney function, and neurodegeneration. This study aims to investigate plasma MMP-3 and GDF-15 as systemic biomarkers for diabetic neuropathy and nephropathy in T1D. The study involves patients with childhood-onset T1D (n = 48, age 38 ± 4 years) and a healthy control group (n = 30, age 38 ± 5 years). Neurophysiology tests, evaluations of albuminuria, and measurements of routine biochemical markers were conducted. The neuropathy impairment assessment (NIA) scoring system, where factors such as loss of sensation and weakened reflexes are evaluated, was used to screen for symptoms of neuropathy. MMP-3 and GDF-15 concentrations were determined in heparinized plasma using ELISA kits. In total, 9 patients (19%) had albuminuria, and 25 (52%) had diabetic neuropathy. No significant differences were found in MMP-3 concentrations between the groups. GDF-15 levels were higher in T1D, with median and interquartile range (IQR) of 358 (242) pg/mL in T1D and 295 (59) in controls (p < 0.001). In the merged patient group, a positive correlation was found between MMP-3 and plasma creatinine, a negative correlation was found between MMP-3 and estimated glomerular filtration rate (eGFR; rho = -0.358, p = 0.012), and there was a positive correlation between GDF-15 and NIA (rho = 0.723, p < 0.001) and high-sensitive C-reactive protein (rho = 0.395, p = 0.005). MMP-3 was increased in macroalbuminuria and correlated positively with NIA only in the nine T1D patients with albuminuria (rho = 0.836, p = 0.005). The present study indicates that high MMP-3 is associated with low eGFR, high plasma creatinine, and macroalbuminuria, and that GDF-15 can be a biomarker for diabetic neuropathy in T1D. MMP-3 may be useful as biomarker for neuropathy in T1D with albuminuria.

Preventive Effect of Neuromuscular Training on Chemotherapy-Induced Neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of life. The lack of effective preventive or therapeutic options regarding CIPN often requires changes in cancer therapy, potentially resulting in reduced survival. To determine whether sensorimotor training (SMT) and whole-body vibration (WBV) training reduce symptoms and decrease the onset of CIPN. This prospective multicenter randomized clinical trial (STOP) followed up patients over 5 years at 4 centers in or near Cologne, Germany. Patients undergoing treatment with oxaliplatin or vinca alkaloids were recruited. Participants were recruited from May 2014 to November 2020. Data were last analyzed in June 2021. Participants in the intervention groups performed supervised SMT or WBV training sessions twice a week, each lasting approximately 15 to 30 minutes, concomitant to medical therapy. The primary end point was the incidence of CIPN. Secondary end points included subjective neuropathy symptoms, balance control, physical activity levels, quality of life, and clinical outcome. For cross-stratum evaluations, the Mantel-Haenszel test (MH) was used, and within individual strata, Fisher exact test was used for analysis. A total of 1605 patients were screened, and 1196 patients did not meet all inclusion criteria, with 251 further excluded or declining participation. A total of 158 patients (mean [SD] age, 49.1 [18.0-82.0] years; 93 [58.9%] male) were randomized into 1 of 3 groups: 55 (34.8%) in SMT, 53 (33.5%) in WBV, and 50 (31.6%) in treatment as usual (TAU). The incidence of CIPN in participants was significantly lower in both intervention groups compared to the control group (TAU): (SMT, 12 of 40 [30.0%; 95% CI, 17.9%-42.1%] and WBV, 14 of 34 [41.2%; 95% CI, 27.9%-54.5%] vs TAU, 24 of 34 [70.6%; 95% CI, 58.0%-83.2%]; P = .002 for intention to treat-MH). Patients receiving vinca alkaloids and performing SMT benefited the most. Results were more pronounced in a per-protocol analysis (>75% participation in the intervention) (SMT, 8 of 28 [28.6%; 95% CI, 16.6%-40.5%] and WBV, 9 of 24 [37.5%; 95% CI, 24.4%-50.5%] vs TAU, 22 of 30 [73.3%; 95% CI, 61.6%-85.6%]). Improvements in favor of SMT compared to TAU were found for balance control bipedal with eyes open; bipedal with eyes closed; monopedal, vibration sensitivity, sense of touch, lower leg strength, pain reduction, burning sensation, chemotherapy dose reductions, and mortality. This randomized clinical trial provides initial evidence that neuromuscular training decreases the onset of CIPN. German Clinical Trials Register: DRKS00006088.

CLINICAL-EXPERIMENTAL JUSTIFICATION OF PATHOGENETIC TREATMENT OF DIABETIC DAMAGE OF THE PERIPHERAL NERVOUS SYSTEM

Background. Diabetes mellitus is a chronic endocrinological disease that, in addition to the somatic sphere, affects all departments and levels of the nervous system. At the same time, its prevalence is increasing every year. Most often, neurological manifestations concern the peripheral nervous system in the form of sensory-motor polyneuropathies. Aim: To clinically and experimentally study the effectiveness of the complex scheme of prevention and treatment of diabetic polyneuropathy, which is composed taking into account the pathogenetic mechanisms of the studied pathology. To find out the clinical features of the course of the disease and electrophysiological patterns. Under experimental conditions, to study the dynamics of changes in the indicators of sensitivity (nociception) and motor function of peripheral nerves in case of diabetic nerve damage. Materials and methods. In the work, streptozotocin-induced diabetic polyneuropathy was reproduced in rats in a chronic experiment. The formation of the latter was confirmed by a morphological study of the sciatic and tail nerves with the determination of edema and degeneration of Schwann cells, as well as segmental demyelination and spasm of precapillary arterioles. Nicergoline, alpha-lipoic acid, group B vitamins, NG-nitro-L-arginine were used for therapeutic or preventive purposes in groups of animals. The speed of conduction of excitation along the tail nerve was studied. In addition, the "hot plate" test was used. In the clinical part of the work, 43 patients with diabetic polyneuropathy were examined. In addition to the clinical and neurological examination; assessed the severity of polyneuropathies according to the scale of neuropathy symptoms, as well as stimulation electroneuromyography.The patients were divided into groups: the first received a developed treatment complex, the second received conventional treatment. Results. The obtained data indicate the feasibility of using direct (NG-nitro-L-arginine) and indirect (nicergoline - "Sermion" and LC - "Alpha-lipon") inhibitors of nitric oxide synthesis, as well as the complex of vitamin preparations "Neovitam", taking into account their reparative and antioxidant properties, in the clinic in patients with diabetic polyneuropathy with a therapeutic, and possibly preventive purpose. The positive experimental and clinical effects of the developed DPP prevention and treatment scheme are associated with the development of antioxidant and reparative effects, as well as the restoration of the myelin sheath of peripheral nerves, since demyelination contributes to the development of the clinic of polyneuropathy. Conclusion. Patients with diabetic polyneuropathy who received a complex treatment scheme achieved probable clinical, neurological and neurophysiological improvement. On the basis of experimental research, the probable mechanisms of this kind of improvement due to the restoration of myelin, blood circulation, antioxidant and reparative effects have been proven.

Ultrasound Features of the Peroneal Nerve in Type 2 Diabetes Mellitus

The aim of the work is to study the ultrasound features of the peroneal nerves in people with type 2 diabetes mellitus and compare them with the symptoms of diabetic peripheral neuropathy and the characteristics of diabetes. The study included 67 patients (average age 59,4 ± 9.7 years) with type 2 diabetes mellitus duration least 7 years. All patients underwent standard general clinical and biochemical examinations, insulin and proinflammatory biomarkers blood levels were assessed. Diabetic peripheral neuropathy was diagnosed by assessing pain, tactile and vibration sensitivity. The presence and severity of neuropathic pain were determined on the basis of a DN4 questionnaire and a visual analog scale. All patients underwent ultrasound examination of the peroneal nerves: the cross-sectional area of the nerve, its echogenicity and structure were studied. The results of the study allow us to state in the overwhelming majority of people with a long course of type 2 diabetes mellitus and unsatisfactory glycemic control the presence of significant changes in peripheral nerves according to ultrasound examination (92,5 % of cases), including in the absence of clinical manifestations of diabetic peripheral neuropathy. Among patients with clinical manifestations of diabetic peripheral neuropathy (49,3 %), significant ultrasound changes in the peroneal nerves were more common than in those with no symptoms of this complication and correlated with the prescription of diabetes mellitus, glycated hemoglobin levels, age, manifestations of metabolic syndrome and the presence of other micro- and macrovascular complications. The study results suggest the possibility of wider use of peroneal nerves ultrasound examination for early diagnosis of diabetic peripheral neuropathy, its course prediction and, probably, can be used to improve the principles of choosing therapeutic tactics in patients with type 2 diabetes mellitus.

Autonomic Stimulation Action of EAT (Epipharyngeal Abrasive Therapy) on Chronic Epipharyngitis.

This study investigated the pathogenesis and pathophysiology of chronic epipharyngitis, which presents a variety of symptoms, with a focus on autonomic neuropathy symptoms, and also investigated the literature for information on EAT, which is useful as a treatment method. The mechanism of action of EAT has recently been clarified in terms of its immune system-stimulating and endocrine system-stimulating effects. However, the autonomic nerve-stimulating effects of EAT are still largely unexplained. This study was conducted to collect and integrate previous studies and papers focusing on the autonomic nerve-stimulating effects of EATand to provide insight into the still not fully elucidated autonomic nerve-stimulating effects of EAT on chronic epipharyngitis. The local stimulating effects of zinc chloride and the bleeding and pain effects of EAT are also summarized, suggesting that EAT exerts its therapeutic effects through the interaction of the immune system, the endocrine system, and the autonomic nervous system. It is important to determine which mechanism is predominantly involved in each case of chronic epipharyngitis and to utilize it in treatment. Elucidating the effects of EAT on the autonomic nervous system will be an important guideline in determining the treatment strategy for chronic epipharyngitis.