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.

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.

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.

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.

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.

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.

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.

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.

Evolution of tongue somatosensory evoked potentials in people with multiple sclerosis.

INTRODUCTION: The aim of the present study was to investigate the long-term evolution of tongue somatosensory evoked potentials (tSSEP) in people with multiple sclerosis (pwMS). METHODS: Out of initial 121 participants, after two-year follow-up, the data were available for 74 and after four-year follow-up for 58 pwMS. In all pwMS complete neurological examination, brain MRI, cervical spinal cord MRI (if available) and tSSEP were performed at baseline visit (M0). Complete neurological examination and tSSEP were performed 2 and 4 years later (M24 and M48). tSSEP results were interpreted in the form of ordinal tSSEP score and quantitative tSSEP zscore calculated from the sum of z-transformed tSSEP latencies. RESULTS: Differences in tSSEP scores and tSSEP zscores in three different timepoints showed significant worsening of both scores over time. For the tSSEP score the difference was significant for M0-M24 and M0-M48 visits, but not for M24-M48 visits. For the tSSEP zscore the difference was significant for M0-M48 and M24-M48 visits, but not for M0-M24 visits. The only significant negative predictor found for the tSSEP score improvement was presence of cervical spinal cord lesions on the MRI. A moderate to high correlation was observed between both forms of tSSEP score at all three timepoints. CONCLUSION: This study demonstrates a significant deterioration of trigeminal sensory pathway in MS over time, giving further insight into trigeminal system damage 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.

Persistent postural-perceptual dizziness: Clinical and neurophysiological study.

The aim of this study was to evaluate clinical and neurophysiological characteristics of Persistent postural-perceptual dizziness (PPPD) in a tertiary vertigo clinic. This was a cross-sectional study that included consecutive patients examined in the Vertigo clinic of the University Hospital Center Zagreb, Croatia. The following data were extracted from the electronic hospital records: age, sex, the duration of symptoms, initial trigger event, results of the caloric testing, video head impulse test (vHIT) for all six semicircular canals and ocular and cervical vestibular evoked myogenic potentials (oVEMP and cVEMP). During the study period 147 consecutive patients with dizziness were examined and 28 (19%) were diagnosed with PPPD, 68% of them were women and the mean age was 59.5 ± 15 years. The median duration of symptoms was 23 months. The most common initial event was vestibular neuritis in 39.3% of patients, followed by benign paroxysmal positional vertigo in 10.7% of patients. Caloric testing was performed in 25 patients. It revealed six cases of unilateral canal paresis. vHIT was performed in 24 patients. There were 13 pathological responses with three cases of lateral canal dysfunction, two cases of posterior, one case of anterior and seven cases of multiple canals affection. VEMP was performed in 23 patients. There were five isolated oVEMP pathologies, one isolated cVEMP pathology and 11 findings of a combined oVEMP and cVEMP pathology. This study provides clinical and neurophysiological data on PPPD and indicates the utility of complete neurophysiological assessment of vestibular function in this group of patients.

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.

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.

Effect of Food Intake on Hemodynamic Parameters during the Tilt-Table Test in Patients with Postural Orthostatic Tachycardia Syndrome.

BACKGROUND AND PURPOSE: The aim of this study was to determine the effect of food intake on the heart rate (HR) in postural orthostatic tachycardia syndrome (POTS). METHODS: The following five-phase protocol was applied to 41 subjects who had a sustained HR increment of ≥30 beats/min within 10 min of standing in an initial tilt-table test: 1) 10-min supine phase, 2) 10-min 70°-tilted phase, 3) ingestion of 400 mL of Nutridrink Multi Fibre®, 4) 45-min supine phase, and 5) 10-min 70°-tilted phase. Subjects were divided into four groups: A) difference in HR for standing vs. supine (ΔHR) before the meal of ≥30 beats/min (n=13), B) ΔHR <30 beats/min before the meal but ≥30 beats/min after the meal (n=12), and C) ΔHR <30 beats/min both before and after the meal (n=16). Group D consisted of 10 healthy subjects. RESULTS: Before the meal, ΔHR was significantly higher in group A than in all of the other groups, and in group B than in group D (p<0.001). After the meal, ΔHR was significantly higher in groups A and B (p<0.001 and p<0.0001, respectively). When we pooled patients (according to their symptoms) from group A and B into a POTS group and from group C and D into a non-POTS group, an increase in HR of 25 beats/min before the meal had a sensitivity of 92.0% and a specificity of 80.8%. After the meal, an increase in HR of 30 beats/min had a sensitivity of 96.0% and a specificity of 96.2%. CONCLUSIONS: Food intake can significantly alter the results of the tilt-table test and so should be taken into account when diagnosing POTS.

Autonomic symptom burden can predict disease activity in early multiple sclerosis.

BACKGROUND: We aimed to evaluate the role of autonomic nervous system (ANS) abnormalities on disease activity (relapses and new MRI lesions) and disease progression in people with clinically isolated syndrome (pwCIS). METHODS: Out of 121 consecutive pwCIS, data on disease activity and progression after 2.9 (1.4-4.1) years of follow-up, was available for 94 pwCIS. Baseline characteristics included MRI parameters, Composite Autonomic System Score-31 (COMPASS-31), Composite Autonomic Scoring Scale, and supine and standing levels of epinephrine and norepinephrine. RESULTS: Univariable logistic regression analysis revealed three predictors for occurrence of new relapse, COMPASS-31 > 7.32, total number of T2 lesions > 3 and decreasing supine level of epinephrine. The Kaplan-Meier survival analysis showed that patients with COMPASS-31 > 7.32 have statistically significant lower probability that they will be relapse free (p = 0.013). It has also showed that the relative risk reduction for occurrence of new relapse in participants with COMPASS < 7.32 was 46%. The multivariable regression model confirmed that COMPASS-31 > 7.32 and total number of T2 lesions > 3 increase the likelihood and the increasing supine level of epinephrine reduces the likelihood for a relapse. Finally, results of the Cox regression analysis showed, that after controlling for age, sex, total number of T2 lesions > 3 and supine level of epinephrine, the hazard for occurrence of new relapse for participants with COMPASS-31 > 7.32 is 2.7 times that of participants with COMPASS-31 < 7.32. CONCLUSION: This study provides evidence that ANS is an important contributor to development of disease activity in pwCIS.

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.

Establishing the diagnosis of multiple sclerosis in Croatian patients with clinically isolated syndrome: 2010 versus 2017 McDonald criteria.

AIM: To compare the sensitivity, specificity and accuracy of the 2010 and 2017 revisions of the McDonald criteria in a Croatian cohort of patients with a clinically isolated syndrome (CIS). METHODS: Prospectively collected data from 113 patients were retrospectively analyzed. Sensitivity, specificity and accuracy for both criteria were calculated regarding conversion to clinically definite multiple sclerosis (Poser CDMS) or multiple sclerosis (MS) (defined as fulfilment of clinical or MRI evidence for dissemination in space and the development of a second relapse and/or ≥1 new T2 lesions on the follow-up MRIs) during a two-year follow-up. Survival analysis was performed to estimate the cumulative risk of patients developing Poser CDMS. Binary logistic regression model was used to determine which variables are statistically significant predictors for the conversion to MS. RESULTS: The 2017 revision had higher sensitivity (85 vs. 30% and 85 vs. 41%) and lower specificity (33 vs. 63% and 63 vs. 85%) compared to the 2010 revisions, for conversion to Poser CDMS and MS, respectively. Patients who did not meet the 2017 McDonald criteria had a higher chance of conversion-free survival for Poser CDMS than those who met the 2017 McDonald criteria (p = 0.037). Results of the multivariate regression analysis revealed that patients who at baseline fulfilled 2017 revisions of the McDonald criteria have the increased likelihood of conversion to MS (Exp(B) 9.68, 95%CI 3.62-25.90, p < 0.00001). CONCLUSION: This study provides new information about the application of the 2017 revisions of the McDonald criteria in a Croatian cohort of patients with typical CIS.

Progressive multiple sclerosis patients have a higher burden of autonomic dysfunction compared to relapsing remitting phenotype.

OBJECTIVE: To determine autonomic dysfunction (AD) differences in patients with relapsing remitting multiple sclerosis (pwRRMS) and progressive MS (pwPMS). METHODS: Composite autonomic scoring scale (CASS) and heart rate variability (HRV) were performed in 40 pwRRMS and 30 pwPMS. RESULTS: pwPMS had a significantly higher sudomotor index and total CASS score compared to pwRRMS (p < 0.001 and p < 0.001, respectively). Disease duration positively correlated with sudomotor index and total CASS (rs = 0.409, p < 0.001 and rs = 0.472, p < 0.001, respectively), while the Expanded Disability Status Scale (EDSS) positively correlated with sudomotor index and total CASS (rs = 0.411, p < 0.001 and rs = 0.402, p = 0.001, respectively) in all patients. Type of multiple sclerosis (pwRRMS or pwPMS) corrected for age, sex and disease duration, was a statistically significant predictor of CASS value (B = 1.215, p = 0.019). Compared to pwRRMS, pwPMS had a significantly lower standard deviation of NN intervals (SDNN), low frequency (LF), and high frequency (HF), during both the supine and tilt-up phases (all p-values <0.006). pwPMS had a significantly lower LF/HF (p = 0.008) during tilt-up. CONCLUSION: There is a significant difference in autonomic function in pwRRMS and pwPMS; with pwPMS having a higher burden of AD, which is particularly evident for sweating dysfunction. SIGNIFICANCE: Further research is needed to establish whether parasympathetic and sudomotor dysfunction may serve as markers of progressive MS.

Relationship Between Sensory Dysfunction and Walking Speed in Patients With Clinically Isolated Syndrome.

PURPOSE: The aim of this study was to investigate a relationship between sensory dysfunction examined with somatosensory-evoked potentials of the posterior tibial nerve (tSSEP) and walking speed in patients with clinically isolated syndrome. METHODS: In 120 patients (mean age 32.2 ± 8.7 years, 84 females), Expanded Disability Status Scale (EDSS), timed 25-foot walk test (T25FW), brain and spinal cord MRI, and tSSEP were performed. P40 latencies and N22a-P40 interlatencies were analyzed, and the z-score for each latency was calculated and combined into total tSSEP z-score. RESULTS: T25FW significantly correlated with total tSSEP z-score (rs = 0.211; P = 0.021). When looking at each component of the tSSEP separately, T25FW significantly correlated with z-scores of P40 wave latencies (rs = 0.223; P = 0.014) and N22a-P40 interlatencies (rs = 0.241; P = 0.008) of the left side. There were no significant correlations with N22a wave latencies. Patients who presented with transverse myelitis (N = 41) and patients who had spinal cord lesions on MRI (N = 53) had significantly higher total tSSEP z-score compared with other patients (0.07 vs. -0.28, P = 0.019 and -0.02 vs. -0.38 P = 0.023; respectively). Somatosensory-evoked potentials of the posterior tibial nerve z-score corrected for age, sex, cervical spinal cord MRI lesions, and total number of supratentorial T2 lesions was a statistically significant predictor for T25FW (B = 0.267, P = 0.023). CONCLUSIONS: Spinal somatosensory dysfunction is one of the factors associated with reduction in walking speed in early patients with multiple sclerosis. Somatosensory-evoked potentials of the posterior tibial nerve may potentially be useful in identifying patients at higher risk for the development of walking impairment in the future.