Dysfunction of peripheral somatic and autonomic nervous system in patients with severe forms of Crohn's disease on biological therapy with TNFα inhibitors-A single center study.

OBJECTIVE: Crohn's disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy. MATERIAL AND METHODS: A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy. RESULTS: Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn's Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test). CONCLUSIONS: This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.

Anorectal dysfunction in multiple sclerosis patients: A pilot study on the effect of an individualized rehabilitation approach.

BACKGROUND: Anorectal dysfunction (ARD), especially bowel incontinence, frequently compromises the quality of life in multiple sclerosis (MS) patients. The effect of rehabilitation procedures has not been clearly established. OBJECTIVE: To determine the effect of an individualized rehabilitation approach on bowel incontinence and anorectal pressures. METHODS: MS patients with ARD underwent 6-months of individually targeted biofeedback rehabilitation. High resolution anorectal manometry (HRAM) and St. Mark's Fecal Incontinence Scores (SMIS) were completed prior to rehabilitation, after 10 weeks of supervised physiotherapy, and after 3 months of self-treatment. RESULTS: Ten patients (50%) completed the study. Repeated measures analysis of variance (ANOVA) demonstrated significant improvement in the SMIS questionnaire over time [14.00 baseline vs. 9.70 after supervised physiotherapy vs. 9.30 after self-treatment (p = 0.005)]. No significant improvements over time were noted in any HRAM readings: maximal pressure [49.85 mmHg baseline vs. 57.60 after supervised physiotherapy vs. 60.88 after self-treatment (p = 0.58)], pressure endurance [36.41 vs. 46.89 vs. 49.95 (p = 0.53)], resting pressure [55.83, vs 52.69 vs. 51.84 (p = 0.704)], or area under the curve [230.0 vs. 520.8 vs. 501.9 (p = 0.16)]. CONCLUSIONS: The proposed individualized rehabilitation program supports a positive overall effect on anorectal dysfunction in MS patients.

Thermal quantitative sensory testing as a screening tool for cardiac autonomic neuropathy in patients with diabetes mellitus.

INTRODUCTION: Electrophysiological diagnosis of cardiac autonomic neuropathy (CAN) is based on the evaluation of cardiovascular autonomic reflex tests (CARTs). CARTs are relatively time consuming and must be performed under standardized conditions. This study aimed to determine whether thermal quantitative sensory testing (TQST) can be used as a screening tool to identify patients with diabetes at a higher risk of CAN. METHODS: Eighty-five patients with diabetes and 49 healthy controls were included in the study. Neurological examination, CARTs, TQST, biochemical analyses, and neuropathy symptom questionnaires were performed. RESULTS: CAN was diagnosed in 46 patients with diabetes (54%). CAN-positive patients with diabetes had significantly higher warm detection thresholds (WDT) and significantly lower cold detection thresholds (CDT) in all tested regions (thenar, tibia, and the dorsum of the foot). CDT on the dorsum < 21.8°C in combination with CDT on the tibia < 23.15°C showed the best diagnostic ability in CAN prediction, with 97.4 % specificity, 60.9% sensitivity, 96.6% positive predictive value, and 67.3% negative predictive value. CONCLUSION: TQST can be used as a screening tool for CAN before CART.

Higher Total Insulin Dose Has Positive Effect on Corneal Nerve Fibers in DM1 Patients.

Purpose: Neuropathies are among the most common long-term complications of diabetes mellitus (DM) and good glycemic control is essential in prevention of this complication. DM patients with similar mean glucose levels or HbA1c levels often exhibit differences in glucose variability. We tested for possible associations between parameters of glycemia compensation and corneal sub-basal nerve fiber status. Methods: The study included 20 patients with DM type 1 treated using an intensified insulin regimen. The corneas of both eyes were examined using in vivo corneal confocal microscopy. Corneal nerve fiber density (NFD), nerve fiber length (NFL), and nerve branch density (NBD) were evaluated. Possible associations between parameters of glycemia compensation (HbA1c, glycemia SD, and insulin dose), and other clinical factors were analyzed. Results: NBD was the highest in those with higher glycemic variability (P = 0.023). HbA1c had a negligible effect on corneal nerve parameters. NFD, NFL, and NBD were statistically significantly higher in those with higher total insulin per kilogram (P = 0.02, P = 0.01, and P = 0.012, respectively). Among other factors, a positive correlation between free thyroxine (fT4) levels and NFD and NBD was also found (P = 0.041 and P = 0.015, respectively). Conclusions: Total insulin dose per kilogram may be an important factor influencing nerve fiber status and needs to be considered in future studies of diabetic neuropathy pathophysiology and its progression. Also, more attention must be paid to other possible factors when elucidating the development of diabetic complications.

Cardiac autonomic neuropathy may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus.

AIMS: Cardiac autonomic neuropathy (CAN) is a frequent and severe complication of type 1 diabetes mellitus (T1DM). CAN diagnosis is associated with increased cardiovascular morbidity and mortality, often due to progressive atherosclerosis. Carotid intima media thickness (CIMT) is a surrogate marker of the atherosclerosis. The aim of our study was to evaluate the relationship between CIMT and CAN in T1DM patients. METHODS: Total of 49 T1DM patients and 45 healthy controls were examined for CAN presence and CIMT. CAN was diagnosed based on the results of Ewing test battery and spectral analysis of heart rate variability. CIMT was measured by two-dimensional ultrasound. Biochemical, anthropometric and anamnestic risk markers of atherosclerosis were evaluated. We used logistic types of generalized additive models (GAM) for statistical analysis. RESULTS: CAN was detected in 22 out of 49 T1DM patients (45%). All 45 healthy controls had normal cardiovascular autonomic tests results. CIMT was significantly positively associated with T1DM diagnosis (p=0.0251), CAN diagnosis (p=0.007), age (p<0.0001), BMI (p=0.0435) and systolic blood pressure (p=0.0098). CAN effect on CIMT interacted with the effect of T1DM. The combination of both factors significantly increased CIMT more than the sum of the individual T1DM and CAN status. CONCLUSIONS: CAN is significantly associated with higher CIMT in T1DM patients. CAN may play a role in pathogenesis of atherosclerosis in type 1 diabetes mellitus.