Autonomic Dysfunction In Multiple Sclerosis Research Articles

Autonomic dysfunction in multiple sclerosis and neuromyelitis optica spectrum disorder

Autonomic dysfunction occurs frequently in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Patients with either condition may present with autonomic symptoms such as bladder, sexual, cardiovascular, thermoregulatory, and gastrointestinal dysfunction, and fatigue, but autonomic symptoms that affect quality of life are underrecognized in clinical practice. The immunopathogenesis of MS has been considered to be associated with autonomic dysfunction. Applying appropriate treatment strategies for autonomic dysfunction is important to improve the quality of life of patients. Here we review autonomic dysfunction and how this is managed in patients with MS and NMOSD.

Cardiovascular autonomic dysfunction in multiple sclerosis-findings and relationships with clinical outcomes and fatigue severity.

This study evaluates cardiovascular autonomic dysfunction (CAD) in multiple sclerosis (MS) and explores if CAD is related to clinical outcomes and fatigue severity. A total of 53 MS patients (30 relapsing-remitting, RRMS; 23 progressive, PMS) and 30 healthy controls were evaluated. TaskForce® Monitor was used to assess impedance cardiography parameters, heart rate (HRV), and blood pressure (BPV) variability during head-up tilt test (HUTT). Expiration/inspiration (E/I) ratio was assessed in response to a deep breathing test. Fatigue severity was evaluated using Chalder Fatigue Scale (CFQ). Compared to controls, PMS patients were characterized by increased sympathetic-parasympathetic ratio at rest (p < 0.01), decreased resting values of parasympathetic parameters (high-frequency HRV, p < 0.05; E/I ratio, p < 0.001), and index of contractility (p < 0.05), whereas RRMS patients showed reduced E/I ratio (p < 0.01). Compared to RRMS group, PMS patients had higher sympathovagal ratio and lower cardiac inotropy parameters (p < 0.05). No intergroup differences were observed for cardiovascular and autonomic function test parameters after HUTT. PMS and low CFQ physical score were identified as independent predictors of sympathetic hyper-reactivity as measured with HRV. Greater disability and male sex were predictors of diastolic BP increase and reduced cardiac inotropy parameters, and older age was predictor of decreased vagal tone (E/I ratio, high-frequency HRV). Cardiovascular autonomic modulation is altered in MS and highly dependent on disease variant, disability level, fatigue severity, and patients' demographics.

Autonomic failure in multiple sclerosis, complication or precursor?

Autonomic nervous system abnormalities are being increasingly recognized as an important aspect of multiple sclerosis (MS) on a clinical, neurophysiological and molecular level. Autonomic dysfunction in MS shows a distinctive pattern: the disease activity (manifested with relapses and MRI activity) is associated with sympathetic nervous system dysfunction, while the disease progression (manifested by increasing neurological disability) is associated with parasympathetic nervous system dysfunction, with highest percentages of involvement seen in advanced progressive MS. Furthermore, in MS, not only that autonomic symptoms are present, but may influence the disease course. A recent study has shown that presence of autonomic symptoms increase the risk of the second relapse after the diagnosis of clinically isolated syndrome by 2.7 folds. On the other hand, there is evidence suggesting that multiple sclerosis (MS) starts years before the first clinical presentation, and this period has become known as the MS prodrome. This period can span for more than a decade and the most well characterized symptom of it lies in the spectrum of autonomic nervous system abnormalities. Autonomic symptoms before the diagnosis increase the risk for the first clinical manifestation of MS, and if they are present at the diagnosis of MS, they increase the likelihood of the second relapse. All this data, emphasize the importance of studying ANS involvement in MS.

Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies.

Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case–control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing–remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

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±17mmHg, p=0.044), lower heart rate (79±9 vs. 88±16 1/min, p=0.041), and lower epinephrine increment (10±22 vs. 30±38pg/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.

Autonomic dysfunction in multiple sclerosis is better detected by heart rate variability and is not correlated with central autonomic network damage

BackgroundMS-associated autonomic dysfunction (AD) in multiple sclerosis (MS) is poorly understood and the best method for its detection unestablished. We compared classical Ewing battery and newer methods as heart rate variability (HRV) and spontaneous baroreflex sensibility (BRS) to detect AD in MS and related them to central autonomic network (CAN) lesions. MethodsWe enrolled 20 relapsing-remitting MS patients, median age of 36 (interquartile range 32–46) years, disease duration of 5.5 (2.2–6.8) years, Expanded Disability Status Scale (EDSS) score of 1.0 (1.0–1.5) and 20 age- and gender-matched healthy controls. We assessed Ewing battery and spontaneous HRV and BRS. CAN involvement was evaluated by magnetic resonance imaging. ResultsHRV showed both parasympathetic and sympathetic significant impairment in MS (p<0.05). From Ewing battery only isometric test was significantly decreased in MS (p=0.006). Disease duration and severity, lesion burden and CAN involvement were not correlated with laboratorial parameters. ConclusionsOur MS cohort had both sympathetic and parasympathetic dysfunction independently from disease duration, neurological deficits and lesion burden or CAN involvement. HRV analysis maybe more useful than classical Ewing battery to screen AD.

Autonomic Dysregulation in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment.

Brainstem dysfunction protects against syncope in multiple sclerosis

BackgroundThe aim of this study was to investigate the correlation between autonomic dysfunction in multiple sclerosis (MS) and brainstem dysfunction evaluated with the vestibular evoked myogenic potentials (VEMP) score and conventional MRI. MethodsForty-five patients with the diagnosis of clinically isolated syndrome (CIS) suggestive of MS were enrolled. VEMP, heart rate, and blood pressure responses to the Valsalva maneuver, heart rate response to deep breathing, and pain provoked head-up tilt table test, as well as brain and spinal cord MRI were performed. ResultsThere was no difference in the VEMP score between patients with and without signs of sympathetic or parasympathetic dysfunction. However, patients with syncope had significantly lower VEMP score compared to patients without syncope (p<0.01). Patients with orthostatic hypotension (OH) showed a trend of higher VEMP score compared to patients without OH (p=0.06). There was no difference in the presence of lesions in the brainstem or cervical spinal cord between patients with or without any of the studied autonomic parameters. The model consisting of a VEMP score of ≤5 and normal MRI of the midbrain and cervical spinal cord has sensitivity and specificity of 83% for the possibility that the patient with MS can develop syncope. ConclusionsPathophysiological mechanisms underlying functional and structural disorders of autonomic nervous system in MS differ significantly. While preserved brainstem function is needed for development of syncope, structural disorders like OH could be associated with brainstem dysfunction.

Autonomic dysfunction in multiple sclerosis.

Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

Autonomic dysfunction in multiple sclerosis: implications for exercise.

Multiple sclerosis (MS), a progressive neurological disease, can result in autonomic dysfunction. Impairments in the autonomic control of cardiovascular and thermoregulatory function during exercise have been observed in MS. Attenuated elevations in blood pressure during exercise in MS patients can negatively impact blood flow to skeletal muscle. Diminished sweating during exercise may impair heat dissipation likely limiting the exercise intensity that can be performed before detrimental core temperatures are reached. Further understanding the physiologic mechanisms of autonomic dysfunction during exercise in MS may lead to the development of novel therapeutic strategies targeted at improving quality of life in individuals with this disease.

Clinical screening of autonomic dysfunction in multiple sclerosis

Multiple sclerosis (MS) can affect the autonomic nervous system. Although exercise may be beneficial for people with MS, those with autonomic dysfunction may have altered heart rate responses to exercise. We investigated the hypothesis that the pattern of increase in heart rate on commencement of a simple cycle test would be different in those participants with MS who had been shown to have autonomic dysfunction on laboratory testing compared with both control participants and MS participants not exhibiting autonomic involvement. A controlled cohort study with a volunteer sample of 31 adults with MS (26 women, 5 men) with a mean age of 46 +/- 8.00 years (32-60 years), a median Expanded Disability Severity Scale of 3 (1-6) and a mean duration since diagnosis of 10.3 years (0.1-39 years). Thirty-one age-matched, non-disabled, sedentary but healthy adults (26 women, 5 men) with a mean age of 45 +/- 9.5 years (24-57) comprised the control group. Autonomic function was evaluated using continuous heart rate and blood pressure responses to rhythmical deep breathing, the Valsalva manoeuvre, passive postural change and a simple cycle test. There were no significant differences in age, height or weight (p < 0.05) between the two groups or on any of the autonomic test results (p < 0.05). Five participants with MS (16%) had abnormal autonomic function on laboratory testing, two of whom demonstrated an abnormal heart rate response to the cycle test. It is suggested that physiotherapists monitor the heart rate response to a dynamic exercise test in people with MS prior to prescribing an exercise programme to ensure patients' safety. Should the response appear delayed or attenuated, referral for more formal autonomic laboratory testing is recommended.

Stroke-Induced Sudden-Autonomic Death

See related article, pages 2425–2431. Stroke is the third leading cause of death.1,2 Fatal outcome has been primarily related to acute or chronic complications of stroke-induced executive deficits, such as muscle weakness, swallowing disorders, respiratory dysfunction with pneumonia, or cardiac complications.3,4 Only during the last 10 or 15 years has there been an increasing interest in and knowledge of associations between cerebral lesions and altered influences of the central autonomic nervous system on cardiovascular and respiratory function.5–7 Oppenheimer et al8–10 suggested a role of the insular cortex in the pathophysiology of sudden death. The group extensively assessed topographically distinct interactions of the left and the right insular cortex with heart rate and blood pressure control.11 There was agreement that insular cortex lesions essentially contribute to clinically relevant alterations of cardiovascular control.8 In this issue of Stroke , Rincon and coworkers present an analysis of associations between ischemic stroke location and fatal cardiac outcome, based on the epidemiological data of the Northern Manhattan Stroke study (NOMAS).12,13 Considering neurological syndromes and neuroimaging findings, the authors analyzed outcome during a 5-year follow-up period. Mortality rates or nonfatal myocardial infarctions, and particularly sudden unexpected or unwitnessed death, were associated with the location of brain infarctions. Apart from age, male gender, the National Institutes of Health Stroke Scale (NIHSS), and a history of coronary artery disease, the authors identified infarct locations in the frontal, parietal, temporal lobe, and …

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.

Autonomic dysfunction in Guillain-Barré syndrome and multiple sclerosis

This review gives an overview of autonomic dysfunction encountered in Guillain-Barré syndrome (GBS) and multiple sclerosis (MS). In GBS, cardiovascular dysregulation is common and may lead to serious bradyarrhythmias that need to be recognised for the early initiation of appropriate therapy. Although standardised autonomic tests were useful for the diagnosis of autonomic failure, they were not able to indicate vagal over-reactivity. In this regard, eyeball pressure testing may correctly identify patients at risk for impending and potentially life-threatening bradyarrhythmias which may easily be administered at the bedside. In MS, cardiovascular autonomic dysfunction is usually of minor clinical importance. However, orthostatic intolerance may be present in approximately 50% of patients and could easily be detected by routine measurements of heart rate and blood pressure during rest and during standing. More subtle alterations may require more sophisticated methods such as autonomic reflex testing or baroreflex stimulation. Several in vitro, animal and clinical studies provide evidence that there are many interactions between the sympathetic nervous system and the immune system giving rise to the hypothesis that autonomic dysfunction in MS may not only be a consequence of the disease, but may in itself affect the course of MS.

Autonomic dysfunction in multiple sclerosis

Multiple sclerosis (MS) is the most frequent chronic neurological disease affecting young persons in developed countries. MS is, however, considered as a secondary cause, of central origin, for autonomic dysfunction. The most common autonomic symptoms in MS are disorders of micturation, impotence, sudomotor and gastrointestinal disturbances, orthostatic intolerance as well as sleep disorders. The majority of the patients suffer at some period of the disease from lower urinary tract symptoms and sexual dysfunction. Awareness and treatment of these conditions is vital to improving health and quality of life in patients with MS. The increased understanding of the pathophysiological mechanisms in autonomic dysfunction in MS, along with technological and pharmaceutical developments has advanced our ability to treat the multiple aspects complicating autonomic failure in MS.

Autonomic Dysfunction in Multiple Sclerosis: Correlation with Disease-Related Parameters

Cardiovascular autonomic functions were investigated in a prospective, controlled study of 22 consecutive relapsing-remitting multiple sclerosis (MS) patients and 22 healthy subjects using 5 simple noninvasive tests and sympathetic skin response testing. Tests included the heart rate response to deep breathing, valsalva maneuver and standing, blood pressure response to standing and sustained hand grip, and were graded according to the Ewing and Clark classification as early, definite or severe impairment. The relationship between autonomic dysfunction and disease-related parameters such as the expanded disability status scale (EDSS) and disease duration was studied. Ninety percent of the patients had symptoms related with autonomic dysfunction, and 45.5 % had abnormal results in cardiovascular autonomic function testing with 4 patients also having abnormal sympathetic skin responses. Statistical analysis indicated that patients with a long disease duration rather than high EDSS carried a risk of autonomic involvement in MS. Both parasympathetic and sympathetic functions were impaired and this could have been easily overlooked by a standard EDSS follow-up. In this regard, autonomic function testing seems necessary in order to detect subclinical changes in MS patients and should be considered in outcome measures.

Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability

Autonomic dysfunction in multiple sclerosis is related to disease activity and progression of disability

Autonomic dysfunction in multiple sclerosis: cervical spinal cord atrophy correlates.

Autonomic dysfunction has rarely been studied in patients suffering from multiple sclerosis (MS). Some hypotheses have concerned the pathophysiology, especially with regard to a possible spinal cord origin. However, there have been no previous studies on autonomic dysfunction in MS and spinal cord lesions. This study assessed the frequency of autonomic dysfunction (AD) in MS and the correlation to spinal cord magnetic resonance imaging (MRI) findings. We prospectively studied 75 MS patients (25 with relapsing-remitting forms, 25 with secondary progressive forms and 25 with primary progressive forms). We performed sympathetic skin response, R-R interval variability and orthostatic hypotension testing. Spinal cord MRI was performed to detect demyelinating lesions (sagittal and axial plane) or spinal cord atrophy. Clinical and laboratory evidence of AD was found in 84% and 56% of MS patients, respectively. The correlation of the latter with disability was evaluated using the Extended Disability Status Scale. AD was more frequent in primary progressive MS than in the other two forms. AD was correlated with spinal cord cross-sectional area reduction but not with spinal cord hyperintensities. This study confirms that the frequency of AD in MS, especially in primary progressive forms, has until now been underestimated. Furthermore, AD appears to be more closely related to axonal loss, as demonstrated by spinal cord atrophy, than to demyelinating lesions.

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.

Cardiovascular autonomic dysfunction in multiple sclerosis is likely related to brainstem lesions

Impairment of cardiovascular autonomic reflexes has been described in multiple sclerosis (MS), and believed reflecting dysfunction of reflex pathways located within the central nervous system. A battery of cardiovascular autonomic tests were performed in 40 patients with definite MS: R-R interval variation test, deep breathing, Valsalva manoeuvre, blood pressure and heart rate responses to standing, sustained handgrip. The results were evaluated by Bayesian analysis, a pattern recognition technique. The patients had also magnetic resonance imaging (MRI) of brain and in 19 subjects of cervical spinal cord. Deep breathing test and sustained handgrip test produced most frequently abnormal results (17.5% and 40%, respectively). However, only 4 patients (10%) had two or more tests abnormal, with a very variable pattern. Evaluation by Bayesian analysis revealed 7 patients (17.5%) with definite autonomic dysfunction. A correlation was found between the confidence level obtained by Bayesian analysis, as index of autonomic function, and the Kurtzke brainstem FS score ( r = 0.43, P < 0.01). There was a significant association between presence of autonomic dysfunction and clinical ( P < 0.02) and MRI ( P < 0.005) evidence of brainstem lesions.