Neuropathy Score Research Articles

Clinical Features and Rules of Chinese Herbal Medicine in Diabetic Peripheral Neuropathy Patients.

Objective To analyse the clinical features of diabetic peripheral neuropathy (DPN) and employ data mining technology to explore the rules of Chinese herbal medicine (CHM) therapy. Methods The clinical data of 216 patients with DPN and qi-yin deficiency syndrome were obtained, and the clinical features of the patients were assessed by cluster analysis. Relevant information was entered into the clinical diagnosis and treatment collection system, and data mining techniques were used to analyse the drug frequency, core CHM, CHM pair, and so on. Results In this study, glycated haemoglobin (HbA1c) and homocysteine (HCY) were closely related to the pathogenesis of DPN. Overall, 162 patients had typical DPN syndrome characteristics, and we analysed 216 prescriptions, including 182 CHM. The frequencies of prescription of Astragalus membranaceus, Ligusticum wallichii, Poria cocos, and Radix Rehmanniae were greater than 45%. A Bayesian network analysis diagram showed that the 9 most common core CHM included Astragalus membranaceus, Ligusticum wallichii, Poria cocos, atractylodes rhizome, and Salvia miltiorrhiza Bge. According to the association rules of CHM, Radix Ophiopogon is used for Codonopsis pilosula; Astragalus membranaceus and atractylodes rhizome for Rehmannia are also frequently used. Astragalus membranaceus and Cinnamomi Ramulus or Ligusticum wallichii and Moutan bark were highly related to a decreased Michigan Diabetic Neuropathy Score. Conclusion HbA1c and HCY are related risk factors for DPN. Numbness is a typical syndrome characteristic. Astragalus membranaceus is a monarch CHM and is used most frequently.

Cycle Training improves vascular function and neuropathic symptoms in patients with type 2 diabetes and peripheral neuropathy: A randomized controlled trial.

Diabetic peripheral neuropathy (DPN) is associated with peripheral arterial disease and endothelial dysfunction. We investigated the effect of exercise training on the measures of superficial femoral artery (SFA) and neuropathic symptoms in patients with DPN. In a randomized-controlled trial, 31 volunteers with established DPN were randomly assigned to experimental or control groups. Experimental group performed cycling exercise training (50%-70% of heart rate reserve, 30-45min, 3 sessions/week) over 12weeks. Before and 48h after the experimental period a 5-min flow mediated dilation (FMD) response in SFA using Color Doppler Ultrasonography, fasting glucose level, HbA1c and neuropathic score were assessed. FMD% significantly increased in the experimental group (from 3.2±1.1% to 5.7±1.2%) compared to the control condition (P=0.0001). However, no significant alteration occurred in baseline membrane diameter and intima media thickness (P>0.05). We also observed a significant improvement in fasting glucose, HbA1c and Michigan Diabetic Neuropathy Score (MDNS) following exercise intervention (all P<0.05). Linear regression analysis indicated that the change in MDNS was significantly associated with the change in HbA1c (R Square=0.34, standardized coefficients Beta=-0.58, P=.001) and FMD (R Square=0.37, standardized coefficients Beta=0.61, P=.001). This finding may be clinically of considerable importance as metabolic and vascular factors have been indicated to be involved in the development of DPN.

A Comparative Study on the Diagnostic Utility of Corneal Confocal Microscopy and Tear Neuromediator Levels in Diabetic Peripheral Neuropathy

ABSTRACT Aims To determine the utility of corneal confocal microscopy and tear neuromediator analysis in the diagnosis of diabetic peripheral neuropathy (DPN) as a result of type 1 and type 2 diabetes. Methods Seventy individuals with either type 1 diabetes or type 2 diabetes (T1D/T2D) underwent corneal confocal microscopy to assess the corneal nerve morphology. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Motor excitability studies were conducted on the median nerve to assess axonal ion channel function. Based on total neuropathy score (TNS), participants were stratified into DPN (DPN+ve; TNS ≥ 2; T1D, n = 19; T2D, n = 16) and without DPN (DPN–ve; TNS ≤ 1; T1D, n = 19; T2D, n = 16). Areas under the receiver operating characteristic curves (AUCs) were calculated to obtain specificity and sensitivity of the measures to diagnose DPN. Results In T1D, the concentration of substance P and confocal microscopy measures were significantly reduced (P < .010) in DPN+ve. Also, for the nerve excitability measures, mean peak response, percentage of threshold electrotonus at peak and after 90-100 ms, superexcitability and subexcitability were significantly reduced (P < .050) in DPN+ve. In T2D, except for inferior whorl length (P = .190), all other corneal confocal microscopy measures were significantly reduced (P < .010) in DPN+ve, but there was no difference in substance P concentration. For the diagnosis of DPN in T1D, the AUC for inferior whorl length (0.910), mean peak response (0.800) and concentration of substance P (0.770) were high and in T2D, the AUC for corneal nerve fiber length (0.809) and nerve fractal dimension (0.777) were high. Conclusion Corneal confocal microscopy parameters provide a better diagnostic ability to detect DPN in T1D and T2D than nerve excitability measures or concentrations of tear neuromediators. The concentration of substance P could also be useful in diagnosing DPN but for T1D only.

Length-dependent MRI of hereditary neuropathy with liability to pressure palsies.

ObjectiveHereditary neuropathy with liability to pressure palsies (HNPP) is caused by heterozygous deletion of the peripheral myelin protein 22 (PMP22) gene. Patients with HNPP present multifocal, reversible sensory/motor deficits due to increased susceptibility to mechanical pressure. Additionally, age‐dependent axonal degeneration is reported. We hypothesize that length‐dependent axonal loss can be revealed by MRI, irrespective of the multifocal phenotype in HNPP.MethodsNerve and muscle MRI data were acquired in the proximal and distal leg of patients with HNPP (n = 10) and matched controls (n = 7). More specifically, nerve magnetization transfer ratios (MTR) were evaluated to assay proximal‐to‐distal gradients in nerve degeneration, while intramuscular fat percentages (F per) were evaluated to assay muscle fat replacement following denervation. Neurological disabilities were assessed via the Charcot‐Marie‐Tooth neuropathy score (CMTNS) for correlation with MRI.Results F per values were elevated in HNPP proximal muscle (9.8 ± 2.2%, P = 0.01) compared to controls (6.9 ± 1.0%). We observed this same elevation of HNPP distal muscles (10.5 ± 2.5%, P < 0.01) relative to controls (6.3 ± 1.1%). Additionally, the amplitude of the proximal‐to‐distal gradient in F per was more significant in HNPP patients than controls (P < 0.01), suggesting length‐dependent axonal loss. In contrast, nerve MTR values were similar between HNPP subjects (sciatic/tibial nerves = 39.4 ± 2.0/34.2 ± 2.5%) and controls (sciatic/tibial nerves = 37.6 ± 3.8/35.5 ± 1.2%). Proximal muscle F per values were related to CMTNS (r = 0.69, P = 0.03), while distal muscle F per and sciatic/tibial nerve MTR values were not related to disability.InterpretationDespite the multifocal nature of the HNPP phenotype, muscle F per measurements relate to disability and exhibit a proximal‐to‐distal gradient consistent with length‐dependent axonal loss, suggesting that F per may be a viable biomarker of disease progression in HNPP.

Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy

PurposeSevere peripheral neuropathy is a common dose-limiting toxicity of taxane chemotherapy, with no effective treatment. Frozen gloves have shown to reduce the severity of neuropathy in several studies but comes with the incidence of undesired side effects such as cold intolerance and frostbite in extreme cases. A device with thermoregulatory features which can safely deliver tolerable amounts of cooling while ensuring efficacy is required to overcome the deficiencies of frozen gloves. The role of continuous-flow cooling in prevention of neurotoxicity caused by paclitaxel has been previously described. This study hypothesized that cryocompression (addition of dynamic pressure to cooling) may allow for delivery of lower temperatures with similar tolerance and potentially improve efficacy.MethodA proof-of-concept study was conducted in cancer patients receiving taxane chemotherapy. Each subject underwent four-limb cryocompression with each chemotherapy infusion (three hours) for a maximum of 12 cycles. Cryocompression was administered at 16 °C and cyclic pressure (5–15 mmHg). Skin surface temperature and tolerance scores were recorded. Neuropathy was assessed using clinician-graded peripheral sensory neuropathy scores, total neuropathy score (TNS) and nerve conduction studies (NCS) conducted before (NCSpre), after completion (NCSpost) and 3 months post-chemotherapy (NCS3m). Results were retrospectively compared with patients who underwent paclitaxel chemotherapy along with continuous-flow cooling and controls with no hypothermia.ResultsIn total, 13 patients underwent 142 cycles of cryocompression concomitant with chemotherapy. Limb hypothermia was well tolerated, and only 1 out of 13 patients required an intra-cycle temperature increase, with no early termination of cryocompression in any subject. Mean skin temperature reduction of 3.8 ± 1.7 °C was achieved. Cryocompression demonstrated significantly greater skin temperature reductions compared to continuous-flow cooling and control (p < 0.0001). None of the patients experienced severe neuropathy (clinician-assessed neuropathy scores of grade 2 or higher). NCS analysis showed preservation of motor amplitudes at NCS3m in subjects who underwent cryocompression, compared to the controls who showed significant deterioration (NCS3m cryocompression vs. NCS3m control: ankle stimulation: 8.1 ± 21.4%, p = 0.004; below fibula head stimulation: 12.7 ± 25.6%, p = 0.0008; above fibula head stimulation: 9.4 ± 24.3%, p = 0.002). Cryocompression did not significantly affect taxane-induced changes in sensory nerve amplitudes.ConclusionWhen compared to continuous-flow cooling, cryocompression permitted delivery of lower temperatures with similar tolerability. The lower skin surface temperatures achieved potentially lead to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are required to validate these findings.

Personalized Management of Chemotherapy-Induced Peripheral Neuropathy Based on a Patient Reported Outcome: CALGB 40502 (Alliance).

Chemotherapy-induced peripheral neuropathy (henceforth, neuropathy) is often dose limiting and is generally managed by empirical dose modifications. We aimed to (1) identify an early time point that is predictive of future neuropathy using a patient-reported outcome and (2) propose a dose-adjustment algorithm based on simulated data to manage neuropathy. In previous work, a dose-neuropathy model was developed using dosing and patient-reported outcome data from Cancer and Leukemia Group B 40502 (Alliance), a randomized phase III trial of paclitaxel, nanoparticle albumin-bound paclitaxel or ixabepilone as first-line chemotherapy for locally recurrent or metastatic breast cancer. In the current work, an early time point that is predictive of the future severity of neuropathy was identified based on predictive accuracy of the model. Using the early data and model parameters, simulations were conducted to propose a dose-adjustment algorithm for the prospective management of neuropathy in individual patients. The end of the first 3 cycles (12 weeks) was identified as the early time point based on a predictive accuracy of 75% for the neuropathy score after 6 cycles. For paclitaxel, nanoparticle albumin-bound paclitaxel, and ixabepilone, simulations with the proposed dose-adjustment algorithm resulted in 61%, 48%, and 35% fewer patients, respectively, with neuropathy score ≥8 after 6 cycles compared to no dose adjustment. We conclude that early patient-reported outcome data on neuropathy can be used to guide dose adjustments in individual patients that reduce the severity of future neuropathy. Prospective validation of this approach should be undertaken in future studies.

Association of Mean Serum Vitamin B-12 levels in Patients with Type II Diabetes Mellitus patients with and without Metformin therapy.

Objective: To determine mean serum vitamin B12 levels in patients with type II diabetes mellitus using metformin. Study Design: Prospective Cross sectional Study Location and Duration: Department of Medicine, Nishtar Hospital Multan, from March 2018 to September 2019. Methodology: Ninety two patients were involved after getting informed consent. HbA1 c, body mass index and blood pressure and deficiency for vitamin B12 was assessed by using electro-chem-iluminescence immunoassay method. B12 levels were categorized as normal (&gt;220pg/ml), possibly deficient (150 to 220 pg/ml) and definitely deficient (&lt;150pg/ml). Neuropathy was assessed and was classified by using Toronto clinical scoring system by the researcher himself. All the data was subjected to statistical analysis using computer software SPSS version 23. Continuous variables were analyzed by their mean and standard deviation while quantitative variables were analyzed by frequency and percentages. Chi square test was applied and P value less than or equal to 0.05 was taken as significant. Results: Mean Serum B-12 levels were 378.42±161.27 pg/ml and 488.90±147.02 pg/ml in metformin and non-metformin groups, respectively. The difference was statistically significant (p=0.001). The patients who were possibly deficient and definitely deficient were 15 (28.30%) and 5 (9.43%) in metformin group and were significantly more (p=0.006) than non-metformin group i.e. 4 (10.26%) and 0. The mean Toronto Neuropathy Score was statistically different (p&lt;0.001) between metformin group (6.03±1.73) and non-metformin group (4.13±1.75). The patients who had mild neuropathy and moderate neuropathy were 23 (43.39%) and 5 (9.43%) in metformin group, while 6 (15.38%) and 2 (5.13%) in non-metformin group. Statistically, both the groups were significantly different (p=0.005). Conclusion: At the end of this study conclusion can be made that metformin use for type II diabetes mellitus is strongly associated with vitamin B12 deficiency and worsening of already susceptible neuropathy. Keywords: vitamin B12, Type II diabetes mellitus, neuropathy. DOI : 10.7176/JMPB/62-15 Publication date: December 31 st 2019

Corneal nerve fiber loss in diabetes with chronic kidney disease

AimsPatients with chronic kidney disease (CKD) in type 2 diabetes typically manifest with severe peripheral neuropathy. Corneal confocal microscopy is a novel technique that may serve as a marker of nerve injury in peripheral neuropathy. This study examines the changes that occur in corneal nerve morphology as a result of peripheral neuropathy due to renal dysfunction in people with type 2 diabetes. MethodsSixty-two participants (mean age, 62 ± 12 years) with type 2 diabetes and 25 age-matched healthy controls underwent a comprehensive assessment of neuropathy using the total neuropathy score (TNS). The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fiber length, fiber density, branch density, total branch density, nerve fractal dimension, inferior whorl length and inferior whorl nerve fractal dimension were quantified. Based on the eGFR, participants were classified into those with diabetic CKD (eGFR < 60; n = 22) and those without CKD (eGFR ≥ 60; n = 40). ResultsParticipants with diabetic CKD had significantly lower corneal nerve fiber density (P = 0.037), length (P = 0.036) and nerve fractal dimension (P = 0.036) compared to those without CKD. Multiple linear regression analysis revealed that reduced corneal nerve fiber density (ß coefficient = 0.098, P = 0.017), length (ß coefficient = 0.006, P = 0.008) and nerve fractal dimension (ß coefficient = 0.001, P = 0.007) was associated with low eGFR levels when adjusted for age, duration of diabetes and severity of neuropathy. ConclusionCorneal confocal microscopy detects corneal nerve loss in patients with diabetic CKD and reduction in corneal nerve parameters is associated with the decline of kidney function.

Measuring vincristine-induced peripheral neuropathy in children with cancer: validation of the Dutch pediatric\u2013modified Total Neuropathy Score

PurposeThe aims were to evaluate the construct validity and reliability of the Dutch version of the pediatric-modified Total Neuropathy Score (ped-mTNS) for assessing vincristine-induced peripheral neuropathy (VIPN) in Dutch pediatric oncology patients aged 5–18 years.MethodsConstruct validity (primary aim) of the ped-mTNS was determined by testing hypotheses about expected correlation between scores of the ped-mTNS (range: 0–32) and the Common Terminology Criteria for Adverse Events (CTCAE) (range: 0–18) for patients and healthy controls and by comparing patients and controls regarding their total ped-mTNS scores and the proportion of children identified with VIPN. Inter-rater and intra-rater reliability and measurement error (secondary aims) were assessed in a subgroup of study participants.ResultsAmong the 112 children (56 patients and 56 age- and gender-matched healthy controls) evaluated, correlation between CTCAE and ped-mTNS scores was as expected (moderate (r = 0.60)). Moreover, as expected, patients had significantly higher ped-mTNS scores and more frequent symptoms of VIPN compared with controls (both p < .001). Reliability as measured within the intra-rater group (n = 10) (intra-class correlation coefficient (ICCagreement) = 0.64, standard error of measurement (SEMagreement) = 2.92, and smallest detectable change (SDCagreement) = 8.1) and within the inter-rater subgroup (n = 10) (ICCagreement = 0.63, SEMagreement = 3.7, and SDCagreement = 10.26) indicates insufficient reliability.ConclusionThe Dutch version of the ped-mTNS appears to have good construct validity for assessing VIPN in a Dutch pediatric oncology population, whereas reliability appears to be insufficient and measurement error high. To improve standardization of VIPN assessment in children, future research aimed at evaluating and further optimizing the psychometric characteristics of the ped-mTNS is needed.

Neuropathic pain in patients with Charcot-Marie-Tooth type 1A.

Only several studies analyzed the characteristics of neuropathic pain (NeP) more extensively in patients with Charcot-Marie-Tooth type 1A (CMT1A). Therefore, we sought to determine the frequency and features of NeP in CMT1A patients and to assess the association between NeP and sociodemographic and clinical characteristics of patients with CMT1A. Our research included 51 genetically diagnosed CMT1A patients. The International Association for the Study of Pain (IASP) criteria were used for diagnosis of NeP. PainDETECT questionnaire (PD-Q) was used to assess NeP features. The Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale (ONLS) score, and Beck Depression Inventory were also used. NeP was present in 15 (29.4%) patients with CMT1A. The average intensity of pain was 5.7 ± 2.2 out of 10. The most sensitive neuropathic symptoms were numbness, then tingling, and burning sensations, while the most specific symptom was allodynia. Patients with NeP more frequently reported pain in the back (p < 0.01) and the trunk (p < 0.05). Patients with NeP had more pronounced disability of the upper extremities and overall disability, as assessed by the ONLS score (p < 0.05). Depression was more frequent in patients with NeP compared with patients without NeP (66.7 to 13.9%, p < 0.01). NeP was present in almost one-third of the patients with CMT1A and it was moderate on average. Presence of NeP was associated with worse functional disability and depression.

Association of corneal nerve loss with markers of axonal ion channel dysfunction in type 1 diabetes

ObjectiveCorneal confocal microscopy (CCM) has been identified as a non-invasive technique to assess corneal nerve fiber morphology. It is not known how corneal nerve changes relate to measures of peripheral nerve function in diabetic peripheral neuropathy (DPN). The present study investigates the relationship between nerve structure and function in DPN. MethodsFifty participants with type 1 diabetes (T1DM) and 29 healthy controls underwent CCM to assess corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), nerve fractal dimension (CNFrD) and inferior whorl length (IWL). The severity of DPN was assessed as Total Neuropathy Score (TNS). Motor nerve axonal excitability tests were conducted to assess axonal function. ResultsSignificant correlations were noted between CNFD (rho = −0.783; P < 0.01) or superexcitability (rho = 0.435; P < 0.01) and TNS. CNFrD was significantly correlated with peak response to stimulus (r = 0.414; P < 0.01) and superexcitability (r = −0.467; P < 0.01) measurements. ConclusionCorneal nerve loss demonstrates a significant association with axonal ion channel dysfunction in T1DM. SignificanceDetection of altered corneal nerve morphology may lead to the earlier diagnosis of DPN.

Leading RNA Interference Therapeutics Part 1: Silencing Hereditary Transthyretin Amyloidosis, with a Focus on Patisiran.

In 2018, patisiran was the first-ever RNA interference (RNAi)-based drug approved by the US Food and Drug Administration. Now pharmacology textbooks may include a new drug class thatresults in the effect firstdescribed by Fire and Mello 2 decades ago: post-transcriptional gene silencing by a small-interfering RNA (siRNA). Patients with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) present withmutations in the transthyretin (TTR) gene that lead to the formation of amyloid deposits in peripheral nerves and heart. The disease may also affect the eye and central nervous system. The formulation of patisiran comprises the RNAi drug encapsulated into a nanoparticle especially developed to deliver the anti-TTR siRNA into the main TTR producer: the liver. Hepatic cells contain apolipoprotein E receptors that recognize ApoE proteins opsonized in the lipid carrier and internalize the drug by endocytosis. Lipid vesicles are disrupted in the cell cytoplasm, and siRNAs are free to trigger the RNAi-based TTR gene silencing. The silencing processinvolves the binding of siRNA guide strand to 3'-untranslated region sequence of both mutant and wild-type TTR messenger RNA, which culminates in the TTR mRNA cleavage by the RNA-induced silencing complex (RISC)asthe first biochemical drug effect. Patisiran 0.3mg/kg is administered intravenously every 3weeks. Patients require premedication with anti-inflammatory drugs and antagonists of histamine H1 and H2 receptors to prevent infusion-related reactions and may require vitamin A supplementation. Following patisiran treatment, TTR knockdown remained stable for at least 2years. Adverse effects were mild to moderate with unchanged hematological, renal, or hepatic parameters. No drug-related severe adverse effects occurred in a 24-month follow-up phase II open-label extension study.At the recommended dosage of patisiran, Cmax and AUC values (mean ± standard deviation) were 7.15±2.14μg/mL and 184±159μg·h/mL, respectively. The drug showed stability in circulation with > 95% encapsulated in lipid particles. Metabolization occurred by ribonuclease enzymes, with less than 1% excreted unchanged in the urine. Patisiran ameliorated neuropathy impairment according to the modified Neuropathy Impairment Score + 7 analysis of the phase III study. The Norfolk Quality of Life-Diabetic Neuropathy score and gait speed improved in 51% of the patisiran-treated group in 18months. Additionally,the modified body mass index showed positive outcomes. Altogether, the data across phase I-III clinical trials points to patisiran as an effective and safe drug for the treatment of hATTR amyloidosis. It is hoped that real-world data from a larger number of patients treated with patisiran will confirm the effectiveness of this first-approved siRNA-based drug.

A pilot study of oncology massage to treat chemotherapy-induced peripheral neuropathy (CIPN).

111 Background: Short- and long-term toxicity of platinum compounds and taxanes includes development of CIPN. With an increased interest regarding the role of complementary approaches for symptom control, we investigated massage therapy for symptomatic relief of chronic CIPN. Methods: This pilot study evaluated the optimum treatment schedule and initial efficacy of a standardized Swedish massage technique to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, no other history of attributable causes; self-reported neuropathy score ≥3, 0-10 scale; ≥ 6 months since last chemotherapy treatment; age ≥ 18. Patients (pts) were randomized to one of four groups: 1) LE massage 3 times (3X) week for 4 weeks; LE massage 2X week for 6 weeks; 3) head/neck/shoulder (control) massage 3X week for 4 weeks; or 4) control massage 2X week for 6 weeks. Massage completion rate was examined and symptoms of CIPN measured with the Pain Quality Assessment Scale [PQAS (Range: 0-10); subscales of SP (surface pain), DP (deep pain), and PP (paroxysmal pain)] at baseline and at 10 weeks. Results: 71 pts fulfilled inclusion criteria: 77.5% women; 57.7% (breast cancer), and 42.3% (GI cancer); mean age 60.3 y/o (range: 40-77). Average length of time since the end of chemotherapy was &gt; 3 yrs. Mean massage completion rates (max = 12) were 8.9 (SD 4.2) for 3X week and 9.8 (4.0) for 2X week with no statistical differences. There were no statistically significant differences in PQAS scores at follow-up between site-specific massage groups (lower extremity vs controls). Pts who had massage 3X week reported statistically and clinically significantly improved PQAS scores versus those who had massage 2X week (change scores: PQAS-SP: -2.3 vs. -0.6, p = 0.001; PQAS-DP: -2.1 vs. -0.9, p = 0.008; PQAS-PP: -2.3 vs. -1.0, p = 0.025), with sustained improvement in the 3X week group, but minimal change in the 2X week group. Conclusions: We observed sustained reduction in pts with long-term CIPN up to 6 weeks after treatment completion for the more intensive 3X week massage group, regardless of treatment site. A large-scale efficacy trial is warranted to validate the role of oncology massage therapy for CIPN. Clinical trial information: NCT02221700.

Morning blood pressure surge is associated with autonomic neuropathy and peripheral vascular disease in patients with diabetes.

Although vascular and autonomic nervous system have been involved in the regulation of morning surge in blood pressure (MBPS), data on clinical correlates of MBPS in diabetic population are scarce, in particular with regard to diabetic complications. This study was aimed at investigating predictors and correlates of MBPS in diabetes. In a cross-sectional study including 167 patients with diabetes (age 58.5 ± 11.1 years, duration 15.9 ± 12.1 years), clinical variables, diabetic and neuropathic complications, and MBPS (using 24-h ambulatory blood pressure monitoring) were measured. The upper quartile of MBPS (>30.5 mmHg) was associated with higher values of waist circumference (P = 0.027), triglycerides (P = 0.021), and Michigan Diabetic Neuropathy Score (P = 0.042), with lower HDL cholesterol (P = 0.030), and with the presence of cardiovascular autonomic neuropathy (CAN) (P = 0.016) and peripheral vascular disease (PVD) (P < 0.0001). In a logistic regression analysis, PVD (odds ratio: 10.2, P = 0.001), CAN (odds ratio: 6.09, P = 0.016), and diastolic blood pressure (BP) (odds ratio: 1.06, P = 0.022) predicted MBPS upper quartile (r2 = 0.20, P = 0.0005). In a multiple regression analysis, PVD (P = 0.002) and diastolic BP (P = 0.003) were the only determinants of MBPS (r2 = 0.20). MBPS upper quartile was associated with BP dipping (systolic BP day-night reduction > 10%) (P = 0.012), and MBPS was positively related to systolic (rho = 0.41, P < 0.0001) and diastolic BP day-night reduction. In conclusion, metabolic syndrome stigmata, diastolic BP, CAN and PVD are the main predictors of MBPS in the diabetic population. Excessive MBPS and nondipping are not concurrent 24-h BP alterations. Autonomic dysfunction might exert an exacerbating effect on MBPS phenomenon.

Longitudinal 16-year study of dominant intermediate CMT type C neuropathy.

Dominant-intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) is associated with mutations in the YARS gene. The aim of this study is to investigate the long-term natural history of the disease. In a 5-generation DI-CMTC family, we compared data from 2016 to that of 2000 in 13 of 21 original participants. Five women and 8 men were examined. While most symptoms and signs progressed, only gait progression was statistically significant (P = .016). The median CMT Neuropathy Score was 6.08 in 2000 and 11 in 2016 (P = .001). Quality of life (QOL) deteriorated in mobility (P = .008), pain/discomfort (P = .011), and anxiety/depression (P = .014). Median and ulnar compound muscle action potential amplitudes decreased from 9.35 ± 2.90 mV to 6.0 ± 2.9 mV (P = .002), and from 9.24 ± 2.10 mV to 6.06 ± 1.81 mV (P = .004), respectively, whereas motor nerve conduction velocities remained unchanged. DI-CMTC in this family is a slowly progressive disease with axonal degeneration, deteriorating mobility and QOL.

Evaluation of small nerve fiber dysfunction in type 2 diabetes.

To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). Absent IENF was seen in subjects with T2DM (n=10; 21%) and IGT (n=1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r=-.268, P=.013) and Total Neuropathy Score (r=-.219, P=.042). Positive correlations were found between IENFD and sural nerve amplitude (r=.371, P=.001) as well as conduction velocity of both the sural (r=.241, P=.029) and peroneal nerve (r=.258, P=.018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC=0.887). Signs of neuropathy are becoming more prevalent with decreasingIENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.

Fas-mediated apoptosis and peripheral polyneuropathy in type 2 diabetes mellitus

ObjectiveTo evaluate the role of soluble Fas (sFas) and soluble Fas ligand (sFasL) in the pathogenesis of distal symmetrical polyneuropathy (DSPN) in patients with type 2 diabetes mellitus, and to analyze the relationship between these apoptotic markers with clinical parameters and electrophysiologic profile of DSPN, as well as with different diabetic factors among those patients.Patients and methodsThe study included 60 Egyptians with type 2 diabetes mellitus. All patients were evaluated clinically for DSPN by using Michigan Neuropathy Screening Instrument. Electrophysiological diagnosis of DSPN was based on the criteria suggested by the European Standardized Telematic tool to Evaluate Electrodiagnostic Methods group. Diabetic patients were divided into two groups according to the electrophysiological findings: group A included patients with DSPN (N=42), and group B included patients without DSPN (N=18). The severity of DSPN among group A patients was assessed clinically using Toronto Clinical Neuropathy Score and electrophysiologically by the severity score proposed by Hidasi and colleagues. The study also included 30 healthy volunteers as a control group. Serum levels of sFas and sFasL were assessed in all the studied groups.ResultsSerum level of sFas was significantly elevated in diabetic patients with DSPN compared with diabetics without DSPN and nondiabetic control (P=0.029 and 0.000). Receiver operating characteristic (ROC) curve analysis detected that sFas was statistically significant in discriminating between diabetic patients with DSPN from those patients without DSPN with an accuracy of 66%. The cutoff point that has the highest sensitivity (61%) and specificity (62%) was 33.3 ng/ml. Serum level of sFas showed a positive significant correlation with the electrophysiological severity of DSPN (P=0.020). Serum level of sFasL did not show statistically significant difference between all the studied groups.ConclusionFas-mediated apoptosis has an important role in the development of diabetic DSPN and is correlated with its electrophysiological severity.

Nerve size correlates with clinical severity in Charcot-Marie-Tooth disease 1A.

Nerve cross-sectional area (CSA) is larger than normal in Charcot-Marie-Tooth disease 1A (CMT1A), although to a variable extent. We explored whether CSA is correlated with CMT clinical severity measured with neuropathy score version 2 (CMTNS2) and its examination subscore (CMTES2) in CMT1A. We assessed 56 patients with CMT1A (42 families). They underwent nerve conduction study (NCS) and nerve high-resolution ultrasound (HRUS) of the left median, ulnar, and fibular nerves. Univariate analysis showed NCS and HRUS variables to be significantly correlated with CMTNS2 and CMTES2 and with each other. Multivariate analysis showed that ulnar motor nerve conduction velocity (β: -0.19) and fibular compound muscle action potential amplitude (-1.50) significantly influenced CMTNS2 and that median forearm CSA significantly influenced CMTNS2 (β: 5.29) and CMTES2 (4.28). Nerve size is significantly associated with clinical scores in CMT1A, which suggests that it might represent a potential biomarker of CMT damage and progression.

Glycemic Control and Clinico-Electrophysiological Severity of Diabetic Polyneuropathy

Background: Diabetic polyneuropathy (DPN) has a significant positive correlation with poor glycemic&#x0D; control (HbA1c ≥7%). The clinical, biochemical and electrophysiological parameters of DPN in Bangladeshi citizens have not yet been explored elaborately&#x0D; Objective: The purpose of the study was to detect and categorize status of glycemic control of Bangladeshi people and to analyze its impact on clinical severity of DPN using Toronto Clinical Scoring System (TCSS) and electrophysiological severity by modified Michigan diabetic neuropathy score (MDNS).&#x0D; Methodology: This observational study was carried out on diabetic patients having probable DPN by purposive sampling, attending Neurology OPD of Dhaka Medical College Hospital, Dhaka, Bangladesh and Bangladesh Institute of Research &amp; Rehabilitation in Diabetes, Endocrine &amp; Metabolic Disorder (BIRDEM) Hospital, Dhaka, Bangladesh from July 2014 to June 2016. Clinical parameters were recorded and DPN was graded as “no neuropathy”, “mild”, “moderate” and “severe” neuropathy by the Toronto Clinical Scoring System (TCSS). A standard nerve conduction study was performed on each patient and electrophysiological grading according to modified Michigan diabetic neuropathy score (MDNS) was done. Diabetic status of patients was classified into “controlled” (HbA1c &lt;7.0%) and “uncontrolled” (HbA1c ≥7.0%) groups and HbA1c level and the clinical &amp; electrophysiological severity scores were compared and were analyzed.&#x0D; Results: Mean age of the patients was 57.2±9.37 years. 51.0% cases were males and 49% cases were females. The mean HbA1c in the study population was 7.6±0.94% and 56.0% patients had HbA1c≥ 7% .Motor nerve conduction studies revealed that both CMAP amplitudes and MNCV in the ulnar, peroneal and tibial nerves were reduced significantly in patients of uncontrolled (HbA1c≥7%) DM (p&lt;0.001). Sensory nerve conduction studies revealed significant reduction in SNAP amplitudes of median and ulnar sensory and sural nerves in the uncontrolled group (p&lt;0.001). Electrophysiologically, 65.43% patients had mixed sensory-motor neuropathy (p&lt;0.00001). Clinically severe DPN patients were higher (45.2%) within the uncontrolled (HbA1C ≥7%) group (p&lt;0.00001). Similarly, severity in electrophysiological grading was more in patients with uncontrolled DM (48.8%) (p&lt;0.00001).&#x0D; Conclusions: Neuropathic severity, either clinically or electrophysiologically, was associated with higher values of HbA1c.&#x0D; Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 177-184

Peripheral neuropathy in HIV patients on antiretroviral therapy: Does it impact function?

HIV-associated distal sensory polyneuropathy (DSP), with or without neuropathic symptoms, can develop after anti-retroviral therapy (ART). Symptoms frequently involve small fibres but reports on autonomic dysfunction in HIV-DSP are sparse. We studied an HIV-infected cohort after 5 years of ART, and report on the frequency and severity of autonomic symptoms and the impact of DSP on everyday function. This cross-sectional study comprised of participants from a community-based South African HIV-clinic. The Brief Peripheral Neuropathy Screen and reduced Total Neuropathy Score evaluated neuropathic symptoms/signs. DSP was defined as ≥2 symmetrical DSP-signs, and symptomatic DSP when accompanied by neuropathic symptoms. Autonomic symptoms questionnaires, heart rate variability and postural blood pressure changes were assessed. The Lower Extremity Functional Scale (LEFS) was completed. The 67 participants had a median age of 42 years and median ART exposure of 7 years with viral suppression in 84%. Most (81%) met our criteria for DSP and 36% had additional neuropathic symptoms. Autonomic symptoms and signs (above normative values) were present in 15% and more likely in those with symptomatic DSP (P < .001). Participants with DSP, even without symptoms, had lower LEFS scores (P ≤ .039) than those without. HIV-DSP is prevalent and impacts on daily living.