Autonomic dysfunction in people with neuromyelitis optica spectrum disorders.

AIMS: To determine the difference in autonomic symptom burden measured with the Composite Autonomic System Score-31 (COMPASS-31) and presence of objective dysautonomia in people with neuromyelitis optica spectrum disorders (pwNMOSD) compared to people with multiple sclerosis (pwMS). DESIGN/METHODS: Twenty pwNMOSD and 20 pwMS, matched for age, sex, and disease duration, were enrolled. All patients completed the COMPASS-31. The quantification of cardiovascular autonomic dysfunction (CAD) was made using the two indices of the Composite Autonomic Scoring Scale (CASS): adrenergic index (AI) and cardiovagal index (CI). RESULTS: In all pwNMOSD, COMPASS-31 was >0. Sympathetic dysfunction was present in 8 (40%), parasympathetic dysfunction in 10 (50%), and orthostatic hypotension in 6 (30%) pwNMOSD. This group of patients had higher frequency and level on the pupillomotor domain of the COMPASS-31 compared to pwMS (p = 0.048 and p = 0.006, respectively). A binary logistic regression model showed that drop in diastolic blood pressure (dBP) during tilt-table test and normal function of autonomic nervous system, defined as AI = 0 and CI = 0, were independent predictors of pwNMOSD (p = 0.042 and p = 0.029, respectively). If CAD was present, it was significantly worse in pwNMOSD compared to pwMS (p = 0.003). CONCLUSION: Significant proportion of pwNMOSD experience dysautonomia, which seems to be different from dysautonomia observed in pwMS.

The association between the adrenergic hyperactivity and blood pressure values in people with multiple sclerosis.

OBJECTIVES: To evaluate the evolution of adrenergic baroreflex sensitivity (BRSa) over 2-year follow-up and to investigate the effect of baseline BRSa indices on blood pressure values after 2 years in people with multiple sclerosis (pwMS). METHODS: The following data were analysed at baseline and after 2 years: BRSa measured with BRSa1, α-BRSa and ß-BRSa, supine and tilted levels of epinephrine and norepinephrine, supine and tilted systolic and diastolic blood pressure levels. RESULTS: Compared to baseline values, there was no change in α-BRSa (6.96 ± 2.56 vs. 6.64 ± 2.24, p = 0.379) at month 24. α-BRSa at month 24 positively correlated with tilted levels of norepinephrine at month 24 (rp = 0.357, p = 0.005). Univariable linear regression analysis revealed that α-BRSa at baseline predicts the value of tilted systolic and diastolic blood pressure at month 24 (B = 2.724, 95% CI 1.357-4.091, p < 0.001 and B = 1.489, 95% CI 0.459-2.519, p = 0.005). CONCLUSION: This study provides further evidence for possible role of α-BRSa as a marker of adrenergic hyperactivity in pwMS. These results may explain increased risk for cardiovascular diseases in pwMS.

The incidence of postural orthostatic tachycardia syndrome in the population of Zagreb, Croatia.

AIM: To estimate the incidence of postural orthostatic tachycardia syndrome (POTS) in the population of Zagreb, Croatia, and to determine the patients' demographic and clinical characteristics. METHODS: From 2012-2017, we identified patients with POTS by a retrospective analysis of medical records at University Hospital Center Zagreb. Crude incidence rates were directly standardized by age according to the European and World Standard Population. RESULTS: Out of 385 patients with suspected POTS, 23 had a definitive POTS diagnosis. The annual incidence ranged from 3.3 to 14.8 per 1000000 for both sexes combined. The highest incidence rates were in the age groups 18-29 and 30-39 years, with female predominance. The mean age at diagnosis was 30.7 years (standard deviation ±9.2, range 18-52). The median duration of symptoms at diagnosis was 7.5 months (range 3-180 months). Regarding associated comorbidities, two patients had chronic gastritis and one patient had each of the following: epilepsy, prior subarachnoid hemorrhage, anxiety, mitral insufficiency, obstructive sleep apnea, hypothyreosis, and irritable bowel syndrome. In patients not fulfilling the criteria for POTS, the most common alternative diagnoses were autonomic dysfunction due to multiple sclerosis in 22, anxiety disorder in 17, epilepsy in 16, and orthostatic tachycardia due to deconditioning in 13 patients. CONCLUSION: The data obtained in this study can be used to optimize disease surveillance in population, comprehensive assessment of disease burden, and organization of health care services.

Autonomic symptom burden is an independent contributor to multiple sclerosis related fatigue.

OBJECTIVES: To investigate a possible association between autonomic dysfunction and fatigue in people with multiple sclerosis. METHODS: In 70 people with multiple sclerosis early in the disease course (51 females, mean age 33.8 ± 9.1), quantitative sudomotor axon reflex tests, cardiovascular reflex tests (heart rate and blood pressure responses to the Valsalva maneuver and heart rate response to deep breathing), and the tilt table test were performed. Participants completed the Composite Autonomic Symptom Score 31, the Modified Fatigue Impact Scale, and the Epworth Sleepiness Scale, as well as the Beck Depression Inventory. Cutoff scores of ≥ 38 or ≥ 45 on the Modified Fatigue Impact Scale were used to stratify patients into a fatigued subgroup (N = 17 or N = 9, respectively). RESULTS: We found clear associations between fatigue and scores in subjective tests of the autonomic nervous system: fatigued patients scored significantly worse on Composite Autonomic Symptom Score 31, and there was a strong correlation between the Modified Fatigue Impact Scale and the Composite Autonomic Symptom Score 31 (rs = 0.607, p < 0.001). On the other hand, we found only modest associations between fatigue and scores in objective tests of the autonomic nervous system: there was a clear trend for lower sweating outputs at all measured sites, which reached statistical significance for the distal leg and foot. We found weak correlations between the Modified Fatigue Impact Scale and the Valsalva ratio (rs = - 0.306, p = 0.011), as well as between the Modified Fatigue Impact Scale and quantitative sudomotor axon reflex tests of the forearm, proximal, and distal lower leg (rs = - 0.379, p = 0.003; rs = - 0.356, p = 0.005; and rs = - 0.345, p = 0.006, respectively). A multiple regression model showed that the Composite Autonomic Symptom Score 31, Beck Depression Inventory, and Epworth Sleepiness Scale were independent predictors of fatigue (p = 0.005, p = 0.019, and p = 0.010, respectively). CONCLUSION: These results suggest that-even early in the course of the disease-people with multiple sclerosis suffer from objective and subjective impairments of the autonomic nervous system. The results also point to an association between autonomic nervous system impairment and multiple sclerosis related fatigue.

Performance of the COMPASS-31 questionnaire with regard to autonomic nervous system testing results and medication use: a prospective study in a real-life setting.

The aim of this study was to investigate the performance of the Composite Autonomic System Score-31 (COMPASS-31) questionnaire in a real-life setting in consecutive patients referred to the laboratory for objective testing of the autonomic nervous system (ANS), with the hypothesis that COMPASS-31 results differ depending on medications and findings of the tilt table test results. One hundred seventy-one consecutive patients (125 females, mean age 41.5 ± 19.3) referred for testing of the ANS were enrolled. Before testing, all patients completed the recently validated Croatian version of COMPASS-31. The following data were systematically collected for all patients: age, sex, diagnoses, and medications. Results of COMPASS-31 were significantly higher in patients taking medications with a known influence on the ANS (p < 0.001). Patients with postural orthostatic tachycardia had significantly higher orthostatic intolerance and vasomotor domains of COMPASS-31 (p = 0.048 and p = 0.022, respectively). Patients with a cardiovagal score ≥ 1 had a significantly higher vasomotor domain of COMPASS-31 compared to patients with normal results of ANS tests (p = 0.030). These findings suggest the COMPASS-31 might be a valuable screening tool for autonomic dysfunctions, as it is associated with impaired ANS tests, but usage of medications that modify the ANS should always be taken into account.

Postprandial hypotension in neurological disorders: systematic review and meta-analysis.

PURPOSE: Postprandial hypotension (PPH) has been associated with increased risk of syncope, falls, stroke, angina and mortality. As the majority of patients with PPH are asymptomatic, the diagnosis is often overlooked. The aim of this study was to perform a systematic review and meta-analysis of available scientific evidence on the likelihood of PPH in neurological diseases. METHODS: A systematic review of the literature (PubMed library, Cochrane Database for Systematic Reviews and Cochrane Central Register of Controlled Trials for results up to January 2017) identified 327 studies, of which 11 reported the frequency of PPH in patients with neurological diseases compared to healthy controls. These 11 studies were on patients with Parkinson's disease (PD; n = 6 studies), multiple system atrophy (MSA; n = 1), Alzheimer's disease (AD; n = 1) and diabetic neuropathy (DN; n = 2). RESULTS: The meta-analysis revealed that patients with neurological diseases had a significantly higher frequency of PPH than healthy controls [147/289 patients vs. 41/217 controls; odd ratio (OR) 5.23, 95% confidence interval (CI) 2.90-9.45, p < 0.00001]. For each of the four diseases, the respective patients had a significantly higher frequency of PPH than healthy controls (PD: 107/201 patients vs. 32/136 controls; OR 3.49, 95% CI 2.09-5.83, p < 0.0001; MSA: 19/27 patients vs. 0/24 controls; OR 89.55, 95% CI 2.65-3030.33, p = 0.01; AD: 7/10 patients vs. 6/23 controls; OR 6.61, 95% CI 1.28-34.14, p = 0.02; DN: 14/51 patients vs. 3/34 controls; OR 4.83, 95%CI 1.20-19.41, p = 0.03). CONCLUSION: The likelihood of having PPH is higher in patients with neurological diseases than in healthy controls. These findings should prompt further research focusing on the epidemiology and pathophysiology of PPH in different neurological diseases.

Postural Orthostatic Tachycardia Predicts Early Conversion to Multiple Sclerosis after Clinically Isolated Syndrome.

BACKGROUND/AIMS: There have been suggestions that interactions exist between the autonomic nervous system (ANS) and the immune system functions in multiple sclerosis (MS). We aimed to evaluate the ANS dysfunction, more specifically postural orthostatic tachycardia syndrome (POTS), as a possible predictor of conversion to MS in patients with clinically isolated syndrome (CIS). METHODS: In this observational, prospective, longitudinal study, 84 patients were enrolled (56 females, mean age 32.9 ± 8.9 years). Disease activity during a 6-month period was monitored (relapses and/or MRI disease activity indicated by new T2 or T1 enhancing lesions), and the following predictors analyzed: age, Expanded Disability Status Scale, MRI midbrain, pontine or medulla oblongata lesions, and POTS on the head up tilt test. RESULTS: POTS was identified in 8 (9.5%) patients. Of 84 patients, 62 (73.8%) completed the 6-month follow-up, and 28 (45.2%) patients converted to MS. Results of the multivariate regression analysis revealed age (10-year increase) and POTS as significant predictors of early conversion to MS (OR 2.34, 95% CI 1.15-4.78, p = 0.019 and OR 12.40, 95% CI 1.13-136.62, p = 0.040). The logistic model was statistically significant, χ2 (6) = 13.885, p = 0.031. CONCLUSION: POTS may be an indicator of a more active disease course in CIS patients and possibly be used as a prognostic factor.

Clinical Neurophysiology of Multiple Sclerosis.

Different neurophysiological methods such as evoked potentials (EP), testing of the autonomic nervous system (ANS) or polysomnography have the potential to detect clinically silent lesions or to confirm the existence of an association between a clinical symptom and multiple sclerosis (MS); previously undetected by MRI. Therefore, in the most recent MRI criteria for the diagnosis of MS (MAGNIMS consensus guidelines), neurophysiological confirmation of optic nerve dysfunction (slowed conduction on visual EP), support dissemination in space and, in patients without concurrent visual symptoms, dissemination in time. In this chapter we will review the existing evidence regarding the role of different neurophysiological tests (specifically the role of EPs, autonomic nervous system testing and sleep testing in MS) in the diagnosis and management of MS.

Validation and cross-cultural adaptation of the COMPASS-31 in Croatian and Serbian patients with multiple sclerosis.

AIM: To validate and cross-culturally adapt Croatian and Serbian versions of composite autonomic symptom score-31 (COMPASS-31) for the detection of dysautonomia in patients with multiple sclerosis (MS). METHODS: A total of 179 patients, 67 with clinically isolated syndrome (CIS) and 112 with MS, completed the COMPASS-31 at two MS centers in Zagreb and Belgrade between April 1 and October 31, 2016. Demographic and clinical data including age, gender, MS phenotypes, and the Expanded Disability Status Scale (EDSS) score were collected. RESULTS: The Cronbach's alpha coefficient of COMPASS-31 total score was 0.844 for the Croatian MS sample and 0.779 for the Serbian MS sample. A joint analysis yielded Cronbach's alpha coefficients ranging from 0.394 to 0.796, with values in four domains higher than 0.700. In Croatian and Serbian samples and the total study sample, the Cronbach's alpha coefficient of COMPASS-31 was 0.785. Reproducibility measured by intra-class correlation coefficient (ICC) was acceptable (ICC=0.795). With regard to the clinical validity, significant correlation was found between EDSS and the COMPASS-31 total score (P<0.001). Furthermore, significant differences between MS phenotypes were detected for bladder and gastrointestinal domains and for the COMPASS-31 total score (PP<0.001, P=0.005, and P=0.027, respectively). Finally, significant differences between MS phenotypes in patients with score >0, which implies the existence of at least one of the symptoms investigated in each domain, were detected for secretomotor and bladder domains (P=0.015 and PP<0.001, respectively). CONCLUSION: COMPASS-31 represents a valid and acceptable self-assessment instrument for the detection of dysautonomia in MS patients.

Sympathetic cardiovascular and sudomotor functions are frequently affected in early multiple sclerosis.

OBJECTIVE: The aim of this study was to determine the prevalence of autonomic dysfunction using the composite autonomic scoring scale (CASS) and heart rate variability (HRV) in patients with clinically isolated syndrome (CIS) and to correlate autonomic dysfunction with other measures of MS disease activity. METHODS: CASS, HRV and plasma catecholamines during supine and tilted phase were performed in 104 CIS patients. MRI findings were analyzed for total number of lesions and the presence of brainstem and cervical spinal cord lesions. RESULTS: Autonomic dysfunction (CASS >1) was present in 59.8 % of patients, parasympathetic dysfunction in 5 %, sympathetic in 42.6 % and sudomotor in 32.7 % of patients. Patients with autonomic dysfunction on CASS had lower level of norepinephrine in the supine position compared to patients without autonomic dysfunction (1.06 ± 0.53 vs. 1.37 ± 0.86, p = 0.048). The CASS score showed positive correlation with s-HF (r = 0.226, p = 0.031), s-SDNN (r = 0.221, p = 0.035), t-HF (r = 0.225, p = 0.032), and t-HFnu (r = 0.216, p = 0.04), and a negative correlation with t-LF/HF (r = -0.218, p = 0.038). More patients with MRI brainstem lesions had a positive adrenergic index (p = 0.038). Patients with MRI brainstem lesions also had a lower t-SDNN (26.2 ± 14.2 vs. 32 ± 13.3, p = 0.036) and a lower t-LF (median 415.0 vs. 575.5, p = 0.018) compared to patients without these lesions. Patients with adrenergic index ≥1 had a significantly higher standing heart rate compared to patients with an adrenergic index of 0 (96 ± 13.5 vs. 90 ± 12, p = 0.032). CONCLUSION: Autonomic (primarily sympathetic) dysfunction is present in a large proportion of early MS patients and it seems to be related to brainstem involvement.

Tongue somatosensory evoked potentials reflect midbrain involvement in patients with clinically isolated syndrome.

AIM: To test the hypothesis that tSSEP findings reflect clinical and MRI MS lesions, the aim of this study was to investigate tSSEP changes in patients with clinically isolated syndrome (CIS) in relation to clinical and brainstem MRI findings. The second aim was to investigate whether the interpretation of the tSSEP results in the form of the tSSEP score enables better evaluation of the afferent trigeminal pathway involvement than analyzing each tSSEP parameter separately. METHODS: 115 consecutive CIS patients were enrolled from August 1, 2014 until March 1, 2016. Facial sensory symptoms and brainstem MRI (1.5 T) lesions were analyzed. tSSEP testing was performed for each patient from the raw tSSEP data. The tSSEP score was calculated separately for the left and right side (according to the cut-off values for absent response and prolonged latency of the main component, P1 (0=normal response, 1=prolonged latency, 3=absent response) and the two values were summed. RESULTS: There was no difference in the absolute values of the tSSEP variables regarding the presence of clinical symptoms. No association was found between tSSEP abnormalities and clinical symptoms (P=0.544). Brainstem lesions (midbrain and pons) were associated with the absent tSSEP responses (P=0.002 and P=0.005, respectively). tSSEP score was significantly higher in patients with brainstem lesions (P=0.01), especially midbrain (P=0.004) and pontine (P=0.008) lesions. Binary logistic regression showed that tSSEP score had a significant effect on the likelihood that patients have midbrain MR lesions, ?2(1)=6.804, P=0.009; and the model correctly classified 87% of cases. CONCLUSIONS: The consistent finding of this study was the association between tSSEP and midbrain lesions on MRI, indicating that tSSEP evaluates proprioception of the face. This study establishes the value of tSSEP in assessing brainstem function in early multiple sclerosis.

Characteristics and predictors of sexual dysfunction in men with multiple sclerosis.

PURPOSE: To validate and culturally adapt the Sexual Health Inventory for Men (IIEF-5) and the Premature Ejaculation Diagnostic Tool (PEDT), to compare the frequency and severity of erectile dysfunction (ED) and premature ejaculation (PE) in male individuals with MS (mwMS) in comparison with healthy controls (HC) and to investigate predictors of the severity of ED and PE in mwMS. METHODS: 216 consecutive mwMS and 37 HC completed IIEF-5 and PEDT. Additionally, 114 mwMS completed the Modified Fatigue Impact Scale (MFIS), Beck Depression Inventory (BDI-2), Composite Autonomic System Score-31 (COMPASS-31), and the 5-level EQ-5D questionnaire. RESULTS: The test-retest reliability was satisfactory for both questionnaires, with acceptable reliability for both questionnaires. mwMS scored less on IIEF-5 compared to HC (23, IQR 18.25-25 vs 24, IQR 20.25-25, p = 0.028). ED was present in 39.4 % of mwMS and 27.8 % of HC (p = 0.198). Definite PE was present in 12.1 %, and possible PE in 7.8 % of mwMS; and 5.6 % and 11.1 % of HC respectively (p = 0.496). An increase in EDSS was a positive predictor (Exp(B) 1.455, 95 %CI 1.135-1.886, p = 0.003) and the presence of cremasteric reflex was a negative predictor (Exp(B) 0.381, 95 %CI 0.183-0.790, p = 0.010) for the presence of ED. For the PE, disease duration was the only positive predictor in a univariable logistic regression (Exp(B) 1.084, 95 %CI 1.019-1.153, p = 0.070). CONCLUSION: SD is frequent in mwMS with EDSS being a positive and the presence of cremasteric reflex a negative predictor of ED and disease duration a positive predictor of PE symptoms.

How to explore and explain autonomic changes in multiple sclerosis.

Autonomic dysfunction (AD) in people with MS (pwMS) is a frequent finding. This narrative review will present an overview of central neural mechanisms involved in the control of cardiovascular and thermoregulatory systems, and methods of autonomic nervous system testing will be discussed thereafter. Since the need for standardization of autonomic nervous system (ANS) testing, we will focus on the standard battery of tests (blood pressure and heart rate response to Valsalva maneuver and head-up tilt, and heart rate response to deep breathing test plus one of the tests for sudomotor function), which can detect ANS pathology in the majority of pwMS. The review will briefly discuss the other types of AD in pwMS and the use of appropriate tests. While performing ANS testing in pwMS one has to consider the multiple sclerosis phenotypes, disease duration, and its activity, the degree of clinical disability of patients included in the study, and the disease-modifying therapies taken, as these factors may have a great influence on the results of ANS testing. In other words, detailed patient characteristics presentation and patient stratification are beneficial when reporting results of ANS testing in pwMS.

Impact of the autonomic dysfunction on the quality of life in people with NMOSD and MS: An international cross-sectional study.

BACKGROUND: A substantial autonomic nervous system (ANS) dysfunction has been described in multiple sclerosis (MS) and recently, also in neuromyelitis optica spectrum disorder (NMOSD). The prevalence of ANS symptoms contributes to the chronic symptom burden in both diseases. The aim of our study was to assess ANS dysfunction in people with (pw) NMOSD and MS, using the Composite Autonomic Symptom Score-31 (COMPASS-31), and additionally, to evaluate if ANS dysfunction have impact on the quality of life of these patients. METHODS: We conducted cross-sectional study at three national referral neurological clinics in Serbia, Croatia, and Montenegro. A total of 180 consecutive subjects, 80 pwNMOSD and 100 pwMS, followed-up at these clinics, were enrolled in the study. Subjects included in the study completed: the validated versions of the COMPASS-31 and the Multiple Sclerosis Quality of Life-54 (MSQoL-54), and the Beck Depression Inventory (BDI). RESULTS: This study demonstrated that the total COMPASS-31 score > 0.0, implicating the presence of ANS dysfunction, was detected in almost all NMOSD and MS study participants tested (80/80, and 97/100, respectively). Our findings showed that autonomic symptom burden was statistically significantly correlated with decreased quality of life, in both NMOSD and MS cohorts. The independent predictors of the better quality of life in pwNMOSD were lower autonomic burden, particularly the absence of the orthostatic intolerance (p = 0.005), along with lower EDSS and BDI score (p ≤ 0.001). Similarly, in pwMS, independent predictors were EDSS, BDI, orthostatic intolerance, and the total COMPASS-31 (p ≤ 0.001). CONCLUSION: Our study demonstrated that a significant proportion of persons with both NMOSD and MS have considerable dysautonomic symptom burden which is correlated with the decreased quality of life. Further investigations are warranted in order to optimize treatment interventions in MS and NMOSD.

Short- and long-term effects of siponimod on autonomic nervous system in secondary progressive multiple sclerosis.

OBJECTIVES: The aim of this study was to investigate the short- and long-term effects of siponimod on autonomic nervous system (ANS) function, in people with secondary progressive multiple sclerosis (pwSPMS) METHODS: The following ANS tests were performed in 26 pwSPMS: a 10 min supine resting position, Valsalva maneuver, deep breathing test and a 10 min tilt-up table test. Heart rate variability (HRV) was performed for the 10 min in supine resting position (M0) and for a 3 h period after siponimod treatment initiation (M0s1-6). All ANS tests were repeated after at least 6 months of treatment with siponimod (M6). RESULTS: In all 6 intervals after siponimod ingestion (M0s1-6), standard deviation of NN intervals (SDNN) was higher compared to M0. After 6 months of continuous treatment with siponimod, SDNN was significantly lower compared to M0. At M6, Valsalva ratio and respiratory sinus arrhythmia were lower compared to M0 values (1.510±0.338 vs 1.864±0.456, p=0.003 and 7.969±2.865 vs 13.091±4.687, p<0.001, respectively). Cardiovagal index was significantly higher at M6 compared to M0 (1 (range 0-2) vs 0 (range 0-1), p=0.008, respectively). Active Magnetic Resonance Imaging (MRI) one year prior to starting siponimod was a positive predictor of M6 SDNN and Adrenergic Index (AI) at M0 was a negative predictor of M6 SDNN. CONCLUSION: This study has shown an inverse relationship in short- versus long-term effects of siponimod on ANS function. A shift towards parasympathetic predominance was observed during the first three hours after ingestion, while after 6 or more months of continuous treatment with siponimod, a shift towards sympathetic predominance was observed.

Blood pressure variability is altered in secondary progressive multiple sclerosis but not in patients with a clinically isolated syndrome.

OBJECTIVES: To investigate differences in beat-to-beat systolic blood pressure variability (SBPV) in people with secondary progressive MS (pwSPMS), clinically isolated syndrome (pwCIS) and healthy controls (HC). METHODS: This retrospective case-control study included 46 pwSPMS, 46 pwCIS and 44 HC. A semi-automated software made with MATLAB R2019b (The MathWorks, Inc.) was used for the evaluation of SBPV. The frequency domain characteristics observed were the power spectrum in the LF and HF bands and the LF/HF ratio. Data is expressed in absolute power (mmHg2) of LF and HF and ratio (LF/HF) during both supine and tilt-up phases of testing. RESULTS: There were no significant differences in mean systolic (sBP) or diastolic blood pressure (dBP) values during supine and tilt-up phases of testing between groups. During the supine phase of testing LF and LF/HF were significantly lower in the SPMS group (4.17±5.38 and 3.52±2.34, respectively) compared to the CIS (5.42±3.59, p = 0.015 and 5.92±4.63, p = 0.029, respectively) and HC group (6.03±4.55, p = 0.011 and 6.52 ±â€¯5.09, p = 0.010, respectively), while during the tilt-up phase, LF was significantly lower compared to both the CIS and HC group, and HF was significantly lower only compared to the CIS group. CONCLUSION: SBPV is altered in pwSPMS compared to pwCIS and normal controls. Further research in the field of MS related dysautonomia is warranted not only because of its relevance to comorbidities and MS symptoms, but also because of its likely involvement in the pathophysiology of MS.

Autonomic nervous system abnormalities predict cardiovascular changes after initiation of siponimod in secondary progressive multiple sclerosis.

OBJECTIVE: The aim of this study was to identify whether autonomic nervous system (ANS) dysfunction identified prior to treatment initiation can predict siponimod related decrease in heart rate (HR) after treatment initiation. METHODS: In 26 people with secondary progressive multiple sclerosis (SPMS) the following ANS testing protocol was applied: 10-min supine resting position, Valsalva maneuver, deep breathing test, 10 min tilt-up table test, 5-min supine resting period, ingestion of siponimod, followed by 180-min supine resting period recordings. Heart rate variability (HRV) parameters were investigated as possible predictors of decrease in HR (ΔHR) after treatment initiation. RESULTS: After treatment initiation, there was a statistically significant drop in HR (71.1 ± 9.2 to 66.3 ± 8.1, p < 0.001) and elevation of systolic blood pressure (sBP) (113.2 ± 12.4 to 117.1 ± 10.8, p = 0.04). Values of the diastolic BP (dBP) followed similar trend as did sBP, however not reaching statistical significance (72.8 ± 9.6 to 74.9 ± 8.3, p = 0.13). In a multivariable regression model, disease duration and standard deviation of NN intervals (SDNN) were identified as independent predictors for ΔHR, where increase in SDNN and longer disease duration predict smaller ΔHR. CONCLUSION: ANS abnormalities may predict cardiovascular abnormalities associated with treatment initiation with siponimod. SIGNIFICANCE: Results of this study may help mitigate risks associated with siponimod treatment.

Adrenergic hyperactivity: a missing link between multiple sclerosis and cardiovascular comorbidities?

The aim of the study is to investigate differences in non-standard adrenergic baroreflex sensitivity (BRS) indices in patients with different phenotypes of multiple sclerosis (pwMS) and healthy controls (HC). Retrospective analysis of types of systolic blood pressure (BP) curves during Valsalva maneuver (VM) [balanced (BAR), augmented (AAR) and suppressed (SAR) autonomic responses] and adrenergic baroreflex sensitivity (BRSa) measured with BRSa1, α-BRSa and ß-BRSa in patients with clinically isolated syndrome (CIS), relapsing remitting multiple sclerosis (RRMS), progressive multiple sclerosis (PMS) and HC. We also investigated correlations between BRSa1, α-BRSa, ß-BRSa and resting catecholamine levels. pwMS had higher α-BRSa compared to HC (p = 0.02). There was no difference in BRSa1, s and ß-BRSa between patients with CIS, RRMS and PMS. There was no association between pwMS and HC, and the type of sBP curve [χ2 = 4.332, p = 0.114]. pwMS and BAR or AAR had higher supine systolic and diastolic BP compared to pwMS and SAR. There was a significant correlation between α-BRSa and upright systolic BP (rp =0.194, p = 0.017), α-BRSa and norepinephrine (rs =0.228, p = 0.021), and BRSa1 and epinephrine (rs = 0.226, p = 0.040). pwMS and HC exhibit different alpha-adrenergic response to Valsalva maneuver. These results may explain the connection between MS and increased cardiovascular risk.

The Relationship between Autonomic Regulation of Cardiovascular Function and Body Composition.

BACKGROUND: We investigated whether the results of autonomic function tests correlate with body composition and shape in healthy young people. METHODS: We conducted cardiovascular reflex tests (heart rate [HR] and blood pressure [BP] responses to the Valsalva maneuver and HR response to deep breathing) and the tilt table test with 32 subjects (19 males; mean age, 22.1±1.9 years). Participants also completed an anthropometric measurement sequence (weight; height; upper arm, hips, and waist circumference; triceps and subscapular skinfold), bioelectric impedance testing, and hand grip strength measurements. RESULTS: Markers of obesity, other anthropometric measures, functional measures, and the basal metabolic rate (BMR) were significantly positively correlated with systolic BP (SBP) and diastolic BP (DBP) in both the supine and tilted positions. There was a positive correlation between the difference in HR (ΔHR) between the tilt and supine body positions and markers of obesity, the functional marker of dominant handgrip strength, and BMR. Participants with a body mass index (BMI) <25 kg/m2 had significantly lower median values of ΔHR, DBP in the tilt-test, SBP at rest, and SBP in the tilt-test than participants who had a BMI ≥25 kg/m2 (10.55 vs. 21.95 bpm, P=0.003; 77.55 vs. 90.05 mmHg, P=0.045; 113.45 vs. 140.55 mmHg, P=0.013; 117.00 vs. 135.25 mmHg, P=0.006, respectively). Body fat percentage was identified as an independent positive predictor (ß=0.993; 95% confidence interval [CI], 0.070 to 1.916; P=0.036) and body water percentage was an independent negative predictor of tilted SBP (ß=-1.370; 95% CI, -2.634 to 0.106; P=0.035). CONCLUSION: High sympathetic activity, as evaluated by cardiovascular regulation, correlates with a high share of adipose tissue in young healthy persons.