Autonomic Nervous System Response to Stressors in Newly Diagnosed Patients with Multiple Sclerosis.

Autonomic dysfunction is commonly detected in patients with multiple sclerosis (MS). However, data evaluating autonomic nervous system function in early MS are limited. Present study investigates response to two different stressors in newly diagnosed MS patients, looking for the signs of autonomic dysfunction at the beginning of the disease. We examined 19 MS patients and 19 age, sex, and body mass index matched healthy controls. MS patients were newly diagnosed, untreated, and with low expanded disability status scale (EDSS) values [median 1.0 (interquartile range 1.0-1.5)]. Two stressors were used to evaluate the response of autonomic nervous system: Stroop word-color interference mental stress test and orthostasis. Plasma levels of epinephrine and norepinephrine, blood pressure (BP), and heart rate variability (HRV) parameters were evaluated. At the end of Stroop test MS patients had lower systolic BP (121 ± 15 vs. 132 ± 17 mmHg, p = 0.044), lower heart rate (79 ± 9 vs. 88 ± 16 1/min, p = 0.041), and lower epinephrine increment (10 ± 22 vs. 30 ± 38 pg/ml; p = 0.049) compared to healthy controls. Norepinephrine response was unaffected in MS, however, with lower norepinephrine levels during the test (p = 0.036). HRV parameters were similar in both groups. No differences in BP, heart rate, catecholamines, and HRV parameters between groups during orthostatic testing were found. We found slightly diminished sympathetic response to mental stress test, but unchanged response to orthostasis, in newly diagnosed untreated MS patients. The results suggest that autonomic dysfunction in MS is connected with more developed disease.

Hyperinsulinemia in newly diagnosed patients with multiple sclerosis.

There are limited data regarding glucose metabolism dysregulation in multiple sclerosis (MS). Present study investigates glucose and insulin response during oral glucose tolerance test (oGTT) in MS patients. We examined 19 MS patients and 19 age, sex and body mass index (BMI) matched healthy controls. MS patients were newly diagnosed, untreated and with low Expanded Disability Status Scale (EDSS) score (1.1 ± 0.7). Plasma glucose, lactate, insulin and GLP-1 during oGTT, and fasting adipokines, lipid and inflammatory parameters were analyzed. Insulin sensitivity indices (ISI) were calculated. MS patients had comparable fasting (5.2 ± 0.3 vs. 5.0 ± 0.4 mmol/l, p = 0.05) and post-load glucose concentrations as controls. Insulin response to oral glucose load in MS was increased (p = 0.022). Insulin sensitivity was lower in MS compared to controls [ISI(Matsuda) 6.95 ± 3.44 vs. 10.60 ± 4.81, p = 0.011 and ISI(Cederholm) 49.9 ± 15.3 vs. 61.3 ± 16.3, p = 0.032]. We did not find any difference in lactate, GLP-1, total, HDL and LDL cholesterol, triglycerides, interleukin 6, tumor necrosis factor, C-reactive protein, resistin, leptin, adiponectin levels between groups. We found decreased insulin sensitivity with postprandial hyperinsulinemia in MS patients, which seems not to be related to chronic inflammation or physical inactivity. The role of hyperinsulinemia in CNS function impairment should be further investigated.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients.