Sural Nerve Conduction Velocity Research Articles

Electrophysiological Study of the Tibial Nerve Across the Tarsal Tunnel in Distal Symmetric Diabetic Polyneuropathy.

The aim of the study was to demonstrate abnormalities of motor conduction of the tibial nerve across the tarsal tunnel in type 2 diabetes. One hundred twenty-four consecutive patients (mean age = 66.6 yrs, 62.1% male) with distal symmetric diabetic polyneuropathy clinically diagnosed were prospectively enrolled. Nerve conduction studies of deep peroneal, tibial, superficial peroneal, medial plantar, and sural nerves and standard needle electromyography in the lower limbs were performed. Demographic, anthropometric, and clinical findings were collected. Motor conduction velocity of the tibial nerve across tarsal tunnel was slowed in 60.5% of patients; another 4% showed conduction block across tarsal tunnel without reduction of motor conduction velocity. Overall percentage of abnormalities across tarsal tunnel (64.5%) exceeds that of the sensory conduction velocities of proximal sural and superficial peroneal nerves. Abnormal tibial motor conduction velocity across tarsal tunnel represents the most common abnormality among all motor nerve conduction study parameters and significantly correlates with hemoglobin level, diabetic neuropathic index score, and diabetic complications frequency. Tibial conduction abnormalities across tarsal tunnel are the most sensitive motor parameter in distal symmetric diabetic polyneuropathy, second only to conduction abnormalities of sensory/mixed distal nerves of the feet. The use of nerve conduction studies across tarsal tunnel of the tibial nerve may be useful in the electrophysiological protocol to confirm the diagnosis of distal symmetric diabetic polyneuropathy.

The silent occurrence of cerebral small vessel disease in nonelderly patients with type 2 diabetes mellitus.

The prevalence of cerebral small vessel disease (SVD) increases in elderly patients with type 2 diabetes (T2DM), exacerbating cognitive decline. However, the prevalence and the severity of SVD in dementia-free nonelderly T2DM patients were largely unknown. Our primary aim is to investigate SVD in such patients, with a specific focus on the correlation between SVD and diabetic peripheral sensorimotor polyneuropathy (DSP). We recruited 180 young and middle-aged subjects without cognitive impairment (106 with T2DM, 74 controls). Signs of cerebral SVD on magnetic resonance image were investigated, and the overall SVD burden was evaluated by a combined score. Patients with T2DM underwent further detailed DSP assessment. Regression models were used to investigate the association of SVD with the presence of T2DM, and the associations of the prevalence and severity of SVD and DSP were also explored in patients with T2DM. The prevalence of microbleeds and overall burden of SVD were significantly higher in T2DM patients than in the controls. Further, the presence of DSP related to an increased risk of SVD after adjustment in diabetic group. Moreover, Toronto Clinical Scoring System values were positively associated with the increased SVD scores, and bilateral sural sensory nerve conduction velocities were negatively associated with increasingly severity of SVD scores. The current findings extended the increasing prevalence of SVD to dementia-free nonelderly patients with T2DM, suggesting that the time for cognitive screening and prevention might be moved forward in T2DM patients, especially for those with DSP.

Greater small nerve fibre damage in the skin and cornea of type 1 diabetic patients with painful compared to painless diabetic neuropathy

Damage to small nociceptive fibres may contribute to painful diabetic neuropathy. We aimed to compare large and small nerve fibre measurements together with skin biopsy and corneal confocal microscopy in patients with type 1 diabetes and painful or painless diabetic neuropathy. We have assessed the McGill pain questionnaire, neuropathy disability score, vibration perception threshold, warm and cold sensation thresholds, electrophysiology, corneal confocal microscopy and skin biopsy in participants with type 1 diabetes and painful (n=41) or painless (n=50) diabetic neuropathy and control subjects (n=50). The duration of diabetes, body mass index, glycated haemoglobin (HbA1c), blood pressure and lipid profile did not differ between subjects with painful and painless neuropathy. Neuropathy disability score and vibration perception threshold were higher and sural nerve conduction velocity was lower, but sural nerve amplitude, peroneal nerve amplitude and conduction velocity and cold and warm sensation thresholds did not differ between patients with painful compared to painless diabetic neuropathy. However, intraepidermal nerve fibre density, corneal nerve fibre density, corneal nerve branch density and corneal nerve fibre length were significantly lower in subjects with painful compared to painless diabetic neuropathy. There is evidence of more severe neuropathy, particularly small fibre damage in the skin and cornea, of patients with painful compared to painless diabetic neuropathy.

Association of insulin resistance and serum advance glycation end product with nerve conduction velocity in type Pre-diabetics

Background – Studies have shown that insulin resistance contributes to the development of peripheral neuropathy. However, there is very limited data about the association of insulin resistance with nerve conduction velocity in prediabetics. Objective - To establish any existing association of Insulin resistance (IR) and serum advance glycation end products (AGE) with nerve conduction velocity in prediabetics. Method - Hundred subjects (diagnosed as per 2010 ADA guidelines) between 40 to 65 years of age and ninety controls (age, gender matched) were enrolled for the study. Insulin resistance was determined by Homeostatic model assessment for insulin resistance (HOMA-IR) using the following formula: plasma insulin (μIU/mL) ×plasma glucose (mg/dL)/405. The serum levels of AGEs was determined using commercially available ELISA kits. Nerve conduction studies were performed on right Tibial nerve and right Sural in lower limb, with surface recording, using the standardized technique.Result- : There was a significant reduction in NCV of bilateral peroneal nerve (p<0.001) and sural nerve (p<0.001) in prediabetics as compared to controls. Serum AGE levels were found significantly elevated in prediabetic group. In univariate analysis AGE was seen to be significantly associated with insulin resistance (P < 0.001, r = 0.281). A significant negative association was obtained between HOMA-IR and Nerve conduction velocity of peroneal & sural nerve. HOMA-IR was significantly associated with body weight, BMI, WC, and with body fat % (p<0.001).Conclusion- : Insulin resistance delays nerve conduction in motor and sensory nerves in prediabetics and as such nerve conduction study can serve as an important diagnostic modality for early detection of diabetic neuropathy

Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial.

Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN). Patients and methods: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). Results: B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). Conclusions: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Normal neurophysiologic parameters of the sural nerve among adult healthy Sudanese population

Background: Nerve conduction studies (NCSs) are of central importance for the assessment of peripheral nervous system disorders. They help in the diagnosis, extent distribution of neural lesion as well as the prognosis of a disease process. The aim of this study is to establish normative NCS reference data of the sural nerve in Sudanese population for our EMG electrodiagnostic center; and to survey the effects of age, gender, height, weight and temperature on conduction Parameters. Methods: The study was conducted in Elmagzoub Neuroscience Electrodiagnostic Centre; supported by the Faculty of Medicine, National Ribat University, Khartoum, Sudan. NCSs were performed in 210 sural nerves of 105 adult healthy Sudanese subjects using standardized techniques. Results: The Right sural nerve SNAP parameters in the whole subjects were set as (mean ±standard deviation) for onset latency. peak latency, amplitude and conduction velocity. The values were 2.73±0.42 ms, 3.32±0.46 ms, 8.39±3.49 uV and 52.05±8.47 m/s, respectively. The Left sural nerve SNAP parameters in the whole study group were 2.71±0.50 ms, 3.29 ±0.52 ms, 8.54±4.56 uV and 52.66 ±8.95, respectively. Conclusion: The sural sensory nerve conduction parameters compared favorably with the existing literature. Age showed a positive correlation with latencies, and negative correlation with amplitude and velocity. Gender has conspicuous effect on all sural nerve conduction parameters. Height showed an effect on latency and conduction velocity whereas BMI revealed a negative correlation with amplitude and conduction velocity of sural nerve.

Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy

Accurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress to foot ulceration and to power clinical intervention trials. We have undertaken detailed neuropathy phenotyping to assess the longitudinal utility of different measures of neuropathy in patients with diabetes. Nineteen patients with diabetes (age 52.5 ± 14.7 years, duration of diabetes 26.0 ± 13.8 years) and 19 healthy controls underwent assessment of symptoms and signs of neuropathy, quantitative sensory testing, autonomic nerve function, neurophysiology, intra-epidermal nerve fibre density (IENFD) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL). Mean follow-up was 6.5 years. Glycated haemoglobin (p = 0.04), low-density lipoprotein-cholesterol (LDL-C) (p = 0.0009) and urinary albumin creatinine ratio (p < 0.0001) improved. Neuropathy symptom profile (p = 0.03), neuropathy disability score (p = 0.04), vibration perception threshold (p = 0.02), cold perception threshold (p = 0.006), CNFD (p = 0.03), CNBD (p < 0.0001), CNFL (p < 0.0001), IENFD (p = 0.04), sural (p = 0.02) and peroneal motor nerve conduction velocity (p = 0.03) deteriorated significantly. Change (∆) in CNFL correlated with ∆CPT (p = 0.006) and ∆Expiration/Inspiration ratio (p = 0.002) and ∆IENFD correlated with ∆CNFD (p = 0.005), ∆CNBD (p = 0.02) and ∆CNFL (p = 0.01). This study shows worsening of diabetic neuropathy across a range of neuropathy measures, especially CCM, despite an improvement in HbA1c and LDL-C. It further supports the utility of CCM as a rapid, non-invasive surrogate measure of diabetic neuropathy.

A cross-sectional study on nerve conduction velocity in stable chronic obstructive pulmonary disease

Objectives: This study was undertaken with the aim to find out possible presence of subclinical peripheral neuropathy in patients of chronic obstructive pulmonary disease (COPD) and its association with advancing severity of disease. Changes in nerve conduction parameter values in these patients have been presented. Materials and Methods: Median, ulnar, peroneal motor, and sural sensory nerve conduction latency, amplitude, and velocity were recorded in 100 known cases of COPD in the age group of 25–65 years as per the standard protocol. Results: On analysis, statistically significant lowering of sural nerve conduction velocity (P = 0.002) and amplitude (P = 0.003) was found with decreasing FEV1% in the three stages of COPD. Decrease in ulnar sensory conduction amplitude and velocity was also noted but it was not significant. Fall in sural nerve conduction velocity was found to be strongly and positively correlated (P = 0.029, r = 0.444) with decrease in FEV1%. Conclusion: These findings suggest that with increasing severity of disease, airflow limitation enhances polyneuropathy in COPD patients. It is predominantly axonal and mainly involving sensory nerve.

Corneal confocal microscopy compared with quantitative sensory testing and nerve conduction for diagnosing and stratifying the severity of diabetic peripheral neuropathy

IntroductionDiabetic neuropathy can be diagnosed and assessed using a number of techniques including corneal confocal microscopy (CCM).Research design and methodsWe have undertaken quantitative sensory testing, nerve conduction studies and CCM...

Acupuncture for diabetic peripheral neuropathy: study protocol for a randomized, placebo-controlled trial

BackgroundDiabetic peripheral neuropathy (DPN) is the most common chronic complication of diabetes mellitus that has a considerable impact on quality of life, but there are few effective therapeutic strategies. The aim of this trial is to determine the efficacy and safety of manual acupuncture (MA) versus sham acupuncture (SA) for DPN.Methods/designThis is a study protocol for a randomized, placebo-controlled clinical trial. A total of 118 patients with DPN will be recruited and randomly assigned in a 1:1 ratio to either the MA group or SA group. All patients will receive 24 sessions over 12 weeks. Participants will complete the trial by visiting the research center at month 6 for a follow-up assessment. The primary outcome is peroneal motor nerve conduction velocity (peroneal MNCV) at week 12 compared with baseline. Secondary outcomes include peroneal motor nerve action potential amplitude (peroneal MNAP) and latent period (peroneal MNLP), sural sensory nerve conduction velocity (sural SNCV), action potential amplitude (sural SNAP) and latent period (sural SNLP), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2hPG), glycated hemoglobin (HbAlc) at week 12 compared with baseline, Michigan Neuropathy Screening Instrument (MNSI) score and Diabetes Specific Quality of Life scale (DSQL) at week 12 and month 6 compared with baseline. Safety will be assessed during the whole trial. Masking effectiveness will be assessed by patients.DiscussionThis trial may provide high-quality evidence for evaluating the efficacy and safety of MA treatment for DPN compared with SA treatment. Results of this study will be published in peer-reviewed journals.Trial registrationChinese Clinical Trials Registry ChiCTR1800020444. First registered on 29 December 2018, retrospectively registered, http://www.chictr.org.cn/showproj.aspx?Proj=31063.

Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy.

Aim: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). Patients–methods: In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. Results: At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.027, p = 0.031, and p < 0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p < 0.001, p < 0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p < 0.001, p < 0.001, p = 0.031, p < 0.001, and p < 0.001 respectively). Conclusions: The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.

Glycemic Variability and Diabetic Neuropathy in Young Adults With Type 1 Diabetes.

Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes.Methods: Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE).Results: The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction (P = 0.03), abnormal SNAP (P = 0.04) and incidents of definite CAN (P = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN (P = 0.03), abnormal SNAP (P = 0.01), and SNCV (P = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV (P = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN (P < 0.02) and HRV (P < 0.03) in fully adjusted models.Conclusions: No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.

128-OR: The Ipswich Neurodiab Study: A 5-Year Longitudinal Study Examining Natural History of Diabetes Polyneuropathy (DPN)

This longitudinal, case-control study compares the progression of Small and Large Fibre Neuropathy (SFN and LFN respectively) in T1DM and T2DM and examines determinants of progression. T1DM, T2DM and healthy controls (HC) groups each with 50 subjects were evaluated annually (2014-19). Functional SFN was assessed using the LDIFLARE test in the foot and structural SFN in the cornea [corneal nerve fibre density using confocal microscopy (CCMCNFD)]. LFN was assessed using vibration perception threshold (VPT) and sural nerve conduction velocity (SNCV) and amplitude (SNAP). At year 5 DPN was diagnosed if the Neurology Disability score (NDS) was ≥3 (DPN+). Mean (±SD) age and sex distribution at baseline for T1DM was (41.4±15.0 yr; 27 males), T2DM (54.38±9.1; 25m) and HC (40.7±15.1; 24m). T1DM with DPN+ had a significantly greater decline of LDIFLARE size compared to DPN- [0.15 v 0.08 cm2/yr; p=0.001] and of CCMCNFD (0.16v 0.10 fibres/mm2/yr; p=0.005). In contrast in T2DM there was no difference between DPN+ and DPN- groups in LDIFLARE size (0.22v 0.15cm2/yr; p=0.09) and CCMCNFD (0.23v 0.16 fibres/mm2/yr; p=0.06). Decline in small fibre function and structure in T1DM DPN- was no different from HCs. (LDIFLARE - 0.07cm2/yr; CCMCNFD - 0.05 fibres/mm2/yr) in contrast to all other groups. In T1DM, the decline of LDIFLARE size and CCMCNFD correlated only with HbA1c change (p=&amp;lt;0.05). In T2DM they correlated with HbA1c, triglycerides and BP changes (p=&amp;lt;0.05). There was no significant change of LFN indices (VPT, SNCV and SNAP; p=&amp;gt;0.05) over the 5yrs. This - the first longitudinal comparative study of changes in small fibre nerve structure and function in T1DM and T2DM - demonstrates changes in SFN in both groups that are not paralleled by changes in LFN, supporting the concept that SFN precedes LFN in DPN, It further demonstrates important differences in determinants of progression between T1DM and T2DM; the former being related to glycaemic control and the latter to multiple metabolic factors. Disclosure S. Sharma: None. J. Cross: None. P.R. Vas: None. G. Rayman: None.

Genetic ablation of caspase‐2 decreases muscle function in female mice

Caspase‐2, a cysteine aspartate protease, is an important regulator of apoptosis. We have previously shown that caspase‐2 modulates bone homeostasis. Specifically, we found that 2‐month old female and 5‐month old male Casp2−/− mice exhibited significantly reduced bone mass when compared to wild‐type (WT) mice that continued with aging. Bone is intricately linked to muscle mechanics and function; however, the role of caspase‐2 in skeletal muscle is not clear. This study examined the effect of caspase‐2 on muscle mass and function in 6‐mo‐old WT and Casp2−/− C57BL/6 mice of both sexes. Quantitative nuclear magnetic resonance was used to measure whole‐body lean mass and fat mass. Muscle mass was determined by measuring the mass of quadriceps, gastrocnemius and soleus muscles as well as by measuring cross‐sectional area (CSA) of gastrocnemius muscle. Peak isometric torque of ankle plantarflexors (gastrocnemius, soleus, plantaris) was measured in vivo to determine muscle function. We found decreased body weight and lean mass in both male and female Casp2−/− mice. Muscle mass, CSA and function were not significantly different between male WT and Casp2−/− mice when the data was adjusted for total body lean mass. Similarly, muscle mass and CSA were not different between female Casp2−/− and WT mice. However, significant decrement in muscle function (p &lt; 0.0001) was observed in female Casp2−/− mice compared to female WT mice. We confirmed that our findings in female mice were independent of caspase‐2’s effects on sensorimotor function as there was no difference in sciatic or sural nerve conduction velocity between WT and Casp2−/− mice. Together, these findings suggest a gender‐specific role for caspase‐2 in modulating skeletal muscle function.Support or Funding InformationOwens Foundation

TORONTO CLINICAL NEUROPATHY SCORE AND MODIFIED TORONTO CLINICAL NEUROPATHY SCORE DIAGNOSTIC TESTS IN DISTAL DIABETIC SENSORIMOTOR POLYNEUROPATHY PATIENTS

Background: Distal diabetic sensorimotor polyneuropathy is a common complication occurred in diabetes mellituspatients. Even though the number of diabetes mellitus patients has been increasing, the prevalence is still far from its actual numbers due to diagnostic and method criteria. Objectives:We aimed to determine Toronto Clinical Neuropathy (TCN) and modified Toronto clinical neuropathy (mTCN) scores in distal diabetic sensorimotor polyneuropathy patients. Methods: Cross-sectional study was carried out from October 29th, 2014-June 1st, 2015 in 77 diabetes mellitus patients who visited Outpatient Clinic. Polyneuropathy diagnosis was based on TCN and mTCN scores, with gold standard of peroneal and/or sural nerve conduction velocity examination. Results: Area under curvevalue of TCN score was 84.5% (95% CI: 74.7%-94.3%). TCN diagnostic score above 4 had sensitivity, specificity, and accuracy of 96%, 40%, 82%, respectively. On the other hand, TCN diagnostic score above 8 had sensitivity, specificity, accuracy of 72%, 80%, 74%, respectively. The AUC value of mTCN score was 81.9% (95% CI: 71.8%-92.1%). mTCN diagnostic score above 8 had sensitivity, specificity, accuracy of 63%, 75%, 66%, respectively. Conclusion: TNC score above 4 could be used as a screening test, while score above 8 could be used as a diagnostic test for distal DSP.

Troponin T Parallels Structural Nerve Damage in Type 2 Diabetes: A Cross-sectional Study Using Magnetic Resonance Neurography.

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve's fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve's FA (r = -0.52, P < 0.001), with a closer correlation in DN patients (r = -0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = -0.65, P < 0.001) and tibial NCVs (r = -0.44, P = 0.002) and amplitudes (r = -0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.

Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes.

The aim of this study was to evaluate the contribution of small and large fibre neuropathy to erectile dysfunction (ED) in men with type 2 diabetes (T2D). Measures of small and large fibre neuropathy were evaluated in 49 participants with T2D and 20 age-matched controls. ED was present in 59% of participants with T2D. There was no difference in age, duration of diabetes, blood pressure, lipid profile, vibration perception threshold (V) (14.3 ± 7.8 vs 11.2 ± 6.6, P = .429), peroneal (41.4 ± 8.2 vs 44.8 ± 4.4, P = .10) and sural (45.4 ± 5.6 vs 47.1 ± 5.8) nerve conduction velocities (m/s), cold (25.1 ± 3.8 vs 26.2 ± 2.9, P = .815) and warm (43.2 ± 4.0 vs 41.0 ± 3.8) perception thresholds (°C), and deep breathing heart rate variability (18 ± 8 vs 18 ± 8) between participants with and without ED. However, intraepidermal nerve fibre density (no./mm2 ) (4.6 ± 2.8 vs 13.7 ± 2.7, P < .001), corneal nerve fibre density (no./mm2 ) (23.5 ± 6.8 vs 31.3 ± 8.2, P < .001), corneal nerve fibre branch density (no./mm2 ) (55.4 ± 35.3 vs 97.7 ± 46.4, P = .004), corneal nerve fibre length (mm/mm2 ) (17.6 ± 6.8 vs 27.3 ± 6.8, P < .001), and sural (7.7 ± 6.1 vs 14.6 ± 6.7, P = .003) and peroneal (2.5 ± 2.0 vs 4.7 ± 2.0, P = .003) nerve amplitudes were significantly lower in participants with ED compared with those without ED. ED affects almost 2/3 of men with T2D and is associated with small nerve fibre damage but preserved nerve conduction and cardiac autonomic function. Corneal confocal microscopy may serve as a useful non-invasive imaging method to identify small fibre damage in patients with T2D and ED.

1801P - A longitudinal tracking and quantitative assessment of paclitaxel-induced peripheral neurotoxicity

BackgroundAssessment of chemotherapy-induced peripheral neurotoxicity (CIPN) usually depends on subjective grading scales, such as the Common Terminology Criteria for Adverse Events (CTCAE). We previously validated a newly developed point-of-care nerve conduction device (POCD) for the objective and quantitative assessment of CIPN. The present study used this POCD to prospectively track the natural history of paclitaxel (PTX)-related CIPN. MethodsSural nerve amplitude potentials (SNAP, μV), a quantitative measure of axonal degeneration, and sural nerve conduction velocity (SNCV, m/s), a quantitative measure of the degree of demyelination, were evaluated using a portable, automated POCD (DPN-Check®, Neurometrix Inc., Waltham, MA, USA) in patients with breast cancer scheduled to receive 12 cycles of adjuvant or neoadjuvant weekly PTX, at baseline, after every 2 cycles of PTX (on the first day of the 3rd, 5th, 7th, 11th cycles), and within 1 month after the 12th cycle of PTX. The severity of CIPN was also evaluated according to the CTCAE, version 4.0. Results55 patients completed 12 cycles of PTX (median age 51 years, range 32-74; adjuvant/neoadjuvant = 40/15; worst CTCAE G1/G2/G3 = 32/16/7). A total of 49 patients received dose-dense EC (epirubicin + cyclophosphamide) before PTX, and 18 patients with HER2-positive breast cancer received trastuzumab concurrently with PTX. SNAP decreased significantly during each cycle of chemotherapy (repeated ANOVA, P<0.001), whereas there was no significant change in SNCV (Table). The total sum of SNAP (mean±SD) was 91.7±30.6 in G1, 70.5±30.0 in G2, and 41.4±13.1 in G3. The total sum of SNCV (mean±SD) was 393.5±34.0 in G1, 381.4±39.5 in G2, and 370.1±45.3 in G3. The total SNAP differed significantly according to each CTCAE grade (ANOVA, P<0.001), whereas the total SNCV did not.Table1801P Longitudinal tracking of SNAP and SNCV among 55 patients (mean±SD)Tablebaseline3rd5th7th9th11th1 month after 12th cycleSNAP (μV)14.2± 6.312.2± 4.811.9± 4.811.4± 5.710.7± 5.09.5± 4.99.0± 4.8SNCV (m/s)56.6± 4.055.9± 4.956.2± 4.856.2± 4.855.3± 4.455.4± 4.855.4± 4.6 ConclusionsThis POCD demonstrated SNAP-dominant neuropathy in patients who received PTX, suggesting axonal degeneration as a mechanism of CIPN. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureY. Ando: Honoraria (self): Bristol-Myers Squibb Company; Honoraria (self): Sawai Pharmaceutical Co. Ltd.; Research grant / Funding (self): Mochida Pharmaceutical Co.,Ltd.; Honoraria (self), Research grant / Funding (self): Nippon Kayaku Co.,Ltd.; Honoraria (self), Research grant / Funding (self): Taiho Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.

Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy-induced polyneuropathy symptoms and signs.

Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52weeks for comparison. Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.

324-OR: Rapid Corneal Nerve Fibre Loss Predicts Neuropathy Progression in Diabetes: A Longitudinal Multinational Consortium Study

The measurement of corneal nerve fibre length (CNFL) by in vivo corneal confocal microscopy serves as a biomarker for the presence of diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the threshold for abnormal CNFL change, its prevalence in T1D and T2D, and if this biomarker could predict DSP progression. Data from 622 diabetes patients (424 T1D and 198 T2D) and 204 nondiabetic controls were examined as part of a 5-centre multinational consortium study. Patients had at least 1-year of follow-up data and were classified with Rapid CNFL (RCNFL) loss if the change in CNFL was beyond the 5thpercentile of the controls. Controls were 38±20 y, had a median of 3 follow-up visits over a median of 3.0 y, baseline CNFL of 16±4 mm/mm2, and a mean annual change in CNFL of -0.1%[90% CI, -5.9-5.0%]. RCNFL loss was defined by the 5th percentile value of -6% or greater loss. T1D patients were 40±19 y, had a median of 3 visits over a median of 4.4 y, baseline CNFL of 13.5±4.3 mm/mm2 and had a mean annual change in CNFL of -0.8%[90% CI, -14.0-9.9%]. T2D patients were 60±8 y, had a median of 3 visits over a median of 5.3 y, baseline CNFL of 13.8±4.4 mm/mm2 and a mean annual change in CNFL of -0.2%[90% CI, -14.1-14.3%]. Prevalence of RCNFL loss was similar between T1D (64(16.0%)) and T2D (37(19.4%), p=0.31). Baseline CNFL was not different between cases with RCNFL loss (14.3±4.2 mm/mm2) and diabetes controls (13.5±4.3 mm/mm2) (p=0.073). Cases were more likely to have DSP at baseline (47, (47%) vs. 144, (30%), p=0.001). During follow-up, CNFL decreased in cases (-3.5 mm/mm2[-5.7, -1.5] vs. 0.59 mm/mm2 [-1.3, 2.4], p&amp;gt;0.001). Cases showed DSP progression measured by changes in sural nerve conduction velocity (0.0 m/s [-1.2, 2.4] vs. 0.2 m/s [-1.1, 5.0]. p=0.027) and peroneal conduction velocity (-1.1 m/s [-3.6, 0.9] vs. -0.6 [-2.8, 1.5], p=0.001) compared to diabetes controls. Rapid CNFL loss occurs in over 16% of diabetes patients and appears to predict those at highest risk for DSP progression. Disclosure E.J.H. Lewis: Board Member; Spouse/Partner; Nutarniq Corp. Employee; Self; Nutarniq Corp. L. Lovblom: None. M. Ferdousi: None. M. Jeziorska: None. D. Pacaud: Other Relationship; Self; Novo Nordisk A/S, Sandoz, TOLMAR. N. Pritchard: None. R.M. Shtein: None. N. Efron: None. M. Tavakoli: None. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alexion Pharmaceuticals, Inc., Alnylam, CSL Behring. Consultant; Self; Pfizer Inc. Research Support; Self; Baxter, Biogen, Grifols, UCB, Inc. R.A. Malik: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. Funding National Institutes of Health (1DP3DK104386-01)