Cardiovascular autonomic function in multiple sclerosis

The autonomic nervous function of the cardiovascular system was investigated by non-invasive methods in 30 multiple sclerosis patients between 20 and 50 years of age. The results were compared to those of 30 healthy controls in the same age group. Minor abnormalities of parasympathetic and sympathetic function occurred. Heart rate variation at deep breathing was reduced and more than half of the patients had abnormal responses during an orthostatic procedure, mainly as an increased rise in heart rate. Decreased rise in blood pressure at sustained handgrip was also demonstrated. The abnormalities correlated poorly with other clinical signs and symptoms in the patients.     

Cardiovascular autonomic dysregulation and fatigue in multiple sclerosis.

Both cardiovascular disturbances and fatigue are frequent in multiple sclerosis (MS). We investigated their relationship in 84 MS patients (mean age 39.9 +/- 8.9 years) using five established autonomic tests and three different fatigue questionnaires. 64.2% of the patients were categorised as being fatigued Fatigue perception was weakly related to EDSS. Moderate cardiovascular disturbances were found in 16.6% of the patients, and 10.7% had severe cardiovascular autonomic abnormalities. Cardiovascular dysfunction was slightly related to age and to EDSS. In 19.4% of all patients signs of autonomic failure and fatigue were co-existent Using correlation analysis, we found only weakly significant correlation coefficients between some single autonomic test parameters and fatigue scores, which were confounded by age effects. The analysis of dichotomised data revealed slightly significant differences in fatigue experience between patients with and without abnormalities regarding the handgrip test and the Valsalva reaction. Thus, autonomic disturbances might contribute to fatigue symptoms in a MS subgroup, but the overall influence of the autonomic cardiovascular regulation towards fatigue experience seems to be of minor relevance.     

Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance

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. Received: 18 September 1998 Received in revised form: 28 December 1998 Accepted: 3 January 1999     

Cardiac autonomic function in patients with early multiple sclerosis

Clinical Autonomic Research - Cardiac autonomic dysfunction has been reported in patients with long-standing multiple sclerosis (MS); however, data in early disease are limited. The present study...     

Cardiac autonomic function during sleep and wakefulness in multiple sclerosis

Some studies in multiple sclerosis (MS) patients have shown evidence of autonomic dysfunction involving the cardiovascular system. However, the findings in these studies have not been completely consistent. The discrepancy may be related to the limits of the traditional autonomic tests during wakefulness. In our study, after the investigation of the cardiovascular reflexes during wakefulness, heart rate (HR) variations were considered during sleep in order to avoid the limits of cooperation and the emotional state of the patient. We evaluated tonic (vagal activity) HR modifications in relation to the deepening of sleep, as well as phasic (sympathetic activity) HR modifications in relation to spontaneous body movements during sleep, in 25 MS patients and 25 age-matched controls. No difference was found between the two groups in autonomic function during wakefulness. A reduced parasympathetic activity was observed in MS subjects during both rapid eye movement (REM) and non-REM sleep, while no difference was found in sympathetic function between patients and controls. No significant correlation was found between cardiac autonomic data during sleep and MRI lesion load in the infratentorial areas and, in particular, of the brain stem. The findings of our study suggest that autonomic nervous system evaluation during sleep could show impairment earlier than the traditional autonomic tests during wakefulness.     

Cardiovascular dysfunction in multiple sclerosis

Cardiovascular dysfunction (CD) in multiple sclerosis (MS) is related to involvement of reflex pathways in the brainstem. The battery of CD tests was applied to a group of 40 healthy subjects and 40 patients with MS, divided in 2 subgroups according to the expanded disability status scale (EDSS). The tests included: 1) postural blood pressure changes, 2) postural heart rate changes, 3) heart rate changes on inspiration/forced expiration and 4) ECG R-R interval measurement on the Valsalva maneuver. Both groups were subjected to the functional independence scale (FIM). Imaging studies were reviewed and autonomic dysfunction at other levels was explored. The results showed a statistically significant difference (P < 0.05) in all tests when comparing patients to controls. Tests 1 and 4 had the highest significance, with findings of more severe involvement in patients with a higher EDSS and lower FIM. A correlation was also found between CD and brainstem lesions on MRI (P < 0.01). A significant number of MS patients had evidence of CD. Test 1 may be considered a simple marker, in daily clinical practice, to detect subclinical CD. Subclinical CD is a cause of disability in this group of patients.     

Subclinical autonomic disturbances in multiple sclerosis

We compared results from non-invasive autonomic testing [sympathetic skin responses (SSR), heart beat variation during deep breathing, and orthostatic manoeuvre with transcranial Doppler monitoring in 22 patients] with motor and somatosensory evoked potentials (MEP and SEP) in 30 unselected patients with multiple sclerosis. We found a similarly high yield of pathological results for SSR, MEP and SEP (66.7%, 65.5%, and 69%, respectively). When analysed for each limb (n = 120), SSR were highly correlated with MEP and SEP (for bothP < 0.001). Heart beat variation was reduced in only 3 patients. In 4 of 22 patients orthostatic manoeuvre induced a pathological decrease in cerebral blood flow velocity despite normal systemic blood pressure being maintained. We conclude that SSR may be a useful additional diagnostic tool in patients with multiple sclerosis. Cerebral dysautoregulation is a rather frequent finding, although its significance is not known.     

Measurement of autonomic dysregulation in multiple sclerosis

OBJECTIVE: Patients with definite multiple sclerosis (MS) were tested for autonomic nervous system (ANS) dysfunction using clinical symptomatology criteria and non-invasive laboratory testing. Exactly 45.45% of patients exhibited subjective symptoms of autonomic dysfunction and 42.42% of patients had abnormal laboratory tests results. METHODS: The sympathetic ANS tests were abnormal in 30.3% of MS patients and the parasympathetic ANS tests were abnormal in 18.18% of MS patients. The most sensitive test for the presence of autonomic dysfunction was the sympathetic skin response. CONCLUSION: Autonomic dysfunction was often subclinical and we conclude that it is preferable to combine several tests for a more thorough and accurate evaluation of the ANS impairment in MS.     

Cardiovascular autonomic function in lateral medullary infarction

Even though the medulla contains the baroreceptor regulatory centers, few studies have focused on the autonomic dysfunction of lateral medullary infarction (LMI). Therefore, cardiac parasympathetic and sympathetic functions were compared in LMI patients and age-matched controls. We prospectively recruited 25 LMI patients who had ipsilateral Horner’s sign and cardiac autonomic function testing without a history of diabetes, cardiac disease, or previous stroke. Parasympathetic function tests included beat-to-beat heart rate variation during deep breathing, 30:15 heart rate ratio testing while standing, and the valsalva ratio. Sympathetic function tests included blood pressure during active standing and sustained handgrip. The composite autonomic score (CAS) was measured as a total of 10 points; parasympathetic dysfunction was designated as ≥3 points in the parasympathetic subscores and sympathetic dysfunction as ≥2 points in the sympathetic subscores. Multiple regression analysis was performed to predict parasympathetic or sympathetic dysfunction. The mean age and stroke risk factors of the study population were not significantly different between the LMI group (n = 25) and control group (n = 29). However, cardiac autonomic functions were significantly different in the groups: parasympathetic dysfunction (14 vs. 4 patients, p = 0.011) and sympathetic dysfunction (3 vs. 13 patients, p = 0.008). In univariate analysis, male-gender (p = 0.011), right-side involvement (p = 0.035) and ventral involvement (p = 0.007) were significantly associated with parasympathetic dysfunction (CAS subscore ≥3). In multivariable analysis, the ventral involvement remained to be the independent predictor for parasympathetic dysfunction (OR 16.0; 95 % CI 2.2–118.3, p = 0.007). This study suggests that LMI patients are susceptible to cardiac parasympathetic dysfunction, especially in the ventral medulla.     

Physiological assessment of aspects of autonomic function in patients with secondary progressive multiple sclerosis

A detailed non-invasive study of systemic and regional haemodynamic responses to a range of autonomic tests which assess sympathetic and parasympathetic pathways (mental arithmetic, cutaneous cold, isometric exercise, deep breathing, Valsalva manoeuvre and head-up tilt) were performed in ten patients with secondary progressive multiple sclerosis and ten age- and sex-matched healthy normal subjects (controls). Blood pressure rose in controls during the pressor tests and was maintained during tilt. In six out of ten patients with multiple sclerosis blood pressure was unchanged during one or more of the three pressor tests, but was maintained in all during tilt. In the controls, superior mesenteric artery blood flow fell during pressor tests and head-up tilt. In multiple sclerosis patients, superior mesenteric artery blood flow did not change during pressor tests but fell during tilt. Cardiac index rose during isometric exercise and fell during head-up tilt in controls. Forearm blood flow rose during mental arithmetic in the controls only, but fell during tilt in both groups. Individual analysis indicated that of the ten multiple sclerosis patients, four had responses during the pressor tests similar to controls. Responses to deep breathing and to the Valsava manoeuvre in controls and multiple sclerosis patients were similar. We conclude that some patients with an aggressive and disabling form of multiple sclerosis have selective autonomic dysfunction, in particular involving pressor responses, despite the lack of postural hypotension. The autonomic abnormality is likely to involve central autonomic interconnections rather than afferent or sympathetic efferent pathways. Further clarification of the nature, site and progression of these lesions is needed. Detection of these abnormalities, which may be clinically silent, may help in the prognostic and diagnostic evaluation of patients with multiple sclerosis.     

Tests of autonomic dysfunction in patients with multiple sclerosis

Autonomic dysfunction is frequent in patients with multiple sclerosis (MS). The sympathetic skin response (SSR) and the R-R interval variation (RRIV) are simple electrophysiologic tests for the assessment of central and peripheral autonomic disturbances. Both tests were performed in 60 patients with clinically definite MS and 30 controls. The SSR was recorded simultaneously from both upper and both lower limbs. In all volunteers normal responses were recorded from the four limbs, but 39 patients (65%) showed abnormal responses in at least one limb. The reduction in amplitude of the response was correlated with patients' EDSS. In individual limbs, the SSR amplitude correlated with weakness, spasticity and cerebellar dysfunction, but was not sufficiently related to the deep sensory loss. The RRIV was abnormal in 48 MS patients (80%), as compared to the controls, but showed no significant relationship either to the EDSS or to the SSR. The sensitivity of SSR and RRIV is high and comparable with that of visual and somatosensory evoked potentials.     

Thyroid function in multiple sclerosis

Thyroid function was studied in 112 MS patients and 175 controls on the basis of T3, T4, T.B.G. and T.S.H. radioimmunoassays. In 33 MS patients the T.R.H. stimulation test was employed additionally. The MS patients had significantly increased T4 levels whereas T3 and T.S.H. were found to be significantly lower. No differences were found in the T.R.H.-stimulated T.S.H. response. The changes in thyroid function parameters were similar in different courses of MS and did not correlate with the degree of clinical disability. The results suggest that in MS the T4/T3 conversion might be reduced as seen in acute or chronic diseases.     

Endocrine function in multiple sclerosis

In 31 patients with multiple sclerosis (MS) the endocrine functions of the hypothalamus, the pituitary and several peripheral endocrine glands were assessed with a combined pituitary test; 3/31 patients had an endocrine disease: one primary hypothyroidism, one primary amenorrhea and one primary male hypogonadism. We found no patient with endocrine disease of the hypothalamus, the pituitary or the adrenals. However, the poststimulatory secretion of cortisol, growth hormone or thyroid-stimulating hormone was impaired in 7/31 patients, suggesting a possible preclinical endocrine insufficiency in these patients.     

Disseminated abnormalities of cardiovascular autonomic functions in multiple sclerosis

To determine whether patients with MS had abnormalities of autonomic cardiovascular functions, we evaluated 22 MS patients and 20 control subjects with a battery of six standardized tests. The two groups differed on three tests: heart rate and blood pressure responses to standing, and the cold-face test. One-half of the MS patients had abnormalities on two or more tests, but individual patients showed diverse abnormality patterns. Abnormalities of neural cardiovascular regulation are frequent in MS patients and show a heterogeneous pattern, consistent with scattered plaques.     

Pupillary function in multiple sclerosis

Eighteen MS patients with visual acuity of 20/30 or better and without recent visual complaints, and 14 age- and sex-matched controls were studied by TV pupillography. The response amplitude and the maximum rate of pupillary constriction or dilation of the light, dark, accommodation and ciliospinal reflexes were unchanged. The latency of the pupillary light response (PLR), however, was prolonged and closely related to walking performance (R = 0.76; p less than 0.001). No relationship was established between PLR latency and previous history of optic neuritis or latency of the VEP. It is concluded that MS patients with preserved visual acuity have only discrete autonomic pupillary disturbances and that the PLR delay is related to disease progression.     

Difficulties in the diagnosis of autonomic dysfunction in multiple sclerosis

Autonomic function was assessed in 24 patients with multiple sclerosis using a questionnaire, cardiovascular reflex tests and sympathetic skin responses. Most patients had some degree of dysautonomia.