Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS), but clinical studies disagree on the frequency and type of abnormalities in autonomic function tests. Orthostatic dizziness (OD) has been reported in up to 49% of patients, but the pathophysiological mechanisms are poorly understood. This study investigated cardiovascular reflex tests and their association with OD in patients with MS in order to examine the hypothesis that the sympathetic nervous system is specifically involved in these patients. Forty patients with clinically active relapsing-remitting (n = 27) and secondary progressive MS (n = 13), aged 35.0+/-8.5 years, were studied by parasympathetic (heart rate responses to the Valsalva maneuver, deep breathing, and active change in posture) and sympathetic function tests (blood pressure responses to active change in posture and sustained handgrip), and by spectral analysis of heart rate variability during rest and during standing. Results were compared to those obtained in 24 healthy volunteers, aged 29.4+/-7.2 years. A standardized questionnaire was used to evaluate symptoms of orthostatic intolerance. Abnormal responses on at least one cardiovascular reflex test were observed in 40% of MS patients, compared to 17% of the control group, with a statistically significant involvement of the sympathetic vasomotor system. Orthostatic intolerance was reported in 50% of patients (controls: 14%, P<0.006). Subgroup comparison of patients with and without OD suggests that orthostatic intolerance results from impaired sympathetic vasoconstriction. These results provide further evidence that the sympathetic nervous system is involved in patients with MS.
"The prevalence of impairments in the autonomic control of cardiovascular function in MS patients from the previous studies has ranged from 7% to 60% when using standard tests, including the Valsalva maneuver, hand grip test, deep breathing, and standing test (Acevedo et al., 2000; Flachenecker et al., 2001, 2003, 1999; Frontoni et al., 1996; Nasseri et al., 1998; Pentland and Ewing, 1987; Sanya et al., 2005; Senaratne et al., 1984; Sterman et al., 1985; Vita et al., 1993). Keller et al. recently reported that direct measures of spontaneous, resting muscle sympathetic nerve activity (MSNA) were reduced in MS patients compared to healthy individuals (Keller et al., 2014). "
[Show abstract][Hide abstract] ABSTRACT: Internal Jugular Veins (IJVs) are the principle outflow pathway for intracranial blood in clinostatism condition. In the seated position, IJVs collapse, while Vertebral Veins (VVs) increase the venous outflow and partially compensate the venous drainage. Spinal Epidural Veins are an additional drainage pathway in the seated position. Colour- Doppler-Sonography (CDS) examination is able to demonstrate IJVs and VVs outflow in different postural and respiratory conditions. The purpose of this study was to evaluate CDS quantification of the cerebral venous outflow (CVF) in healthy subjects and patients with multiple sclerosis (MS).
In a group of 27 healthy adults (13 females and 14 males; mean age 37.8 ± 11.2 years), and 52 patients with MS (32 females and 20 males; mean age 42.6 ± 12.1 years), CVF has been measured in clinostatism and in the seated position as the sum of the flow in IJVs and VVs. The difference between CVF in clinostatism and CVF in the seated position (ΔCVF) has been correlated with patients' status (healthy or MS), and a number of clinical variables in MS patients. Statistical analysis was performed by Fisher's exact test, non-parametric Mann-Whitney U test, ANOVA Kruskal-Wallis test, and correntropy coefficient. The value of ΔCVF was negative in 59.6% of patients with MS and positive in 96.3% of healthy subjects. Negative ΔCVF values were significantly associated with MS (p<0.0001). There was no significant correlation with clinical variables.
Negative ΔCVF has a hemodynamic significance, since it reflects an increased venous return in the seated position. This seems to be a pathologic condition. In MS patients, a vascular dysregulation resulting from involvement of the autonomous nervous system may be supposed. ΔCVF value should be included in the quantitative CDS evaluation of the cerebral venous drainage, in order to identify cerebral venous return abnormalities.
PLoS ONE 09/2011; 6(9):e25012. DOI:10.1371/journal.pone.0025012 · 3.23 Impact Factor
"For instance, the complex generation of autonomic activity patterns for 'flight and fight' or 'resting-state regulation' has not been investigated in more detail. Those patterns are disturbed in diseases of the central nervous system such as Parkinson's disease (Dubow, 2007) or multiple sclerosis (Flachenecker et al., 1999). Furthermore, central autonomic dysfunction has been reported in various psychiatric conditions and, in particular, in patients suffering from anxiety (Yeragani et al., 1998), depression (Agelink et al., 2001; Boettger et al., 2008) and schizophrenia (Boettger et al., 2006; Bär et al., 2007a,b), resulting in the development of tachycardia and increasing the risk of life-threatening arrhythmias. "
[Show abstract][Hide abstract] ABSTRACT: Recent studies applying functional magnetic resonance imaging have focused on the description of cerebral substrates of changes in cardiac function during diverse autonomic maneuvers or stressful cognitive tasks. These studies might be limited by the indistinguishable neuronal activity due to cognitive processes, which are known to influence autonomic function, and the 'baseline' activity in the central autonomic network. We therefore investigated 26 healthy volunteers in the magnetic resonance scanner to simultaneously obtain functional brain images and RR intervals (intervals between ventricular depolarizations) of the high-resolution electrocardiogram. The mean RR interval length within each functional scan was computed, which was finally convolved with the canonical hemodynamic response function to obtain a regressor for the functional time series. The resulting individual contrast image indicated a positive covariation of the blood oxygen level-dependent signal and RR interval length in the ventromedial prefrontal cortex (vmPFC). Furthermore, a reduced mean cross-approximate entropy value was shown for the interaction between the vmPFC and individual RR intervals. This suggests reduced asynchrony between the heart rate and vmPFC activity in contrast to other brain areas. Our findings confirm data obtained in animals describing the vmPFC as an important forebrain structure of the central autonomic network and an influence of the vmPFC in the cortical generation of efferent vagal activity. This finding needs to be investigated in diseases with known suppression of efferent vagal modulation.
European Journal of Neuroscience 12/2009; 30(11):2205-10. DOI:10.1111/j.1460-9568.2009.07008.x · 3.18 Impact Factor
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