Impact of the COVID-19 pandemic on clinical autonomic practice in Europe A survey of the European Academy of Neurology (EAN) and the European Federation of Autonomic Societies (EFAS).

OBJECTIVE: To investigate the impact of the coronavirus-disease-2019 (COVID-19) pandemic on European clinical autonomic practice. METHODS: Eighty-four neurology-driven or interdisciplinary autonomic centers in 22 European countries were invited to fill in a web-based survey between September and November 2021. RESULTS: Forty-six centers completed the survey (55%). During the first pandemic year, the number of performed tilt-table tests, autonomic outpatient and inpatient visits decreased respectively by 50%, 45% and 53%, and every-third center reported major adverse events due to postponed examinations or visits. The most frequent newly-diagnosed or worsened cardiovascular autonomic disorders after COVID-19 infection included postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension, and recurrent vasovagal syncope, deemed likely related to the infection by ≥50% of the responders. Forty-seven percent of the responders also reported about people with new-onset of orthostatic intolerance, but negative tilt-table findings, and 16% about people with psychogenic pseudosyncope after COVID-19. Most patients were treated non-pharmacologically and symptomatic recovery at follow-up was observed in ≥45% of cases. By contrast, low frequencies of newly-diagnosed cardiovascular autonomic disorders following COVID-19 vaccination were reported, most frequently POTS and recurrent vasovagal syncope, and most of the responders judged a causal association unlikely. Non-pharmacological measures were the preferred treatment choice, with 50-100% recovery rates at follow-up. CONCLUSIONS: Cardiovascular autonomic disorders may develop or worsen following a COVID-19 infection, while the association with COVID-19 vaccines remains controversial. Despite the severe pandemic impact on European clinical autonomic practice, a specialized diagnostic work-up was pivotal to identify non-autonomic disorders in people with post-COVID-19 orthostatic complaints.

A complex interplay between autonomic symptoms and symptoms of depression, anxiety, and stress.

BACKGROUND: We evaluated the influence of symptoms of depression, anxiety, and stress on the results of COMPASS-31 in a large population of people referred to the head-up tilt test (HUTT) and healthy controls (HC). METHODS: Nine hundred fifty-nine consecutive patients referred to HUTT and 518 HC were enrolled. All participants completed Composite Autonomic Symptom Score-31 (COMPASS-31). Stress symptoms were evaluated by Depression, Anxiety, and Stress-21 (DASS-21) questionnaire. We corrected the result of the COMPASS-31 with the independent predictors in order to improve the specificity of the test. RESULTS: In both patients and HC, COMPASS-31 was higher in participants with depression, anxiety, and stress symptoms (all p < 0.001). In a multivariable linear regression analysis, HC was negative, while female sex and symptoms of depression, anxiety, and stress were independent positive predictors of COMPASS-31. In HC, COMPASS-31 had a median of 7.913, and this value differentiated between HC and patients with a high sensitivity of 87% and low specificity of 50%. In order to adjust the value of COMPASS-31 with the parameters that were significant in the multivariable linear regression model, we calculated the new corrected COMAPSS-31 (cCOMPASS-31), which had comparable sensitivity of 77%, but an increased specificity of 73%. CONCLUSION: This study has shown that symptoms of depression, anxiety, and/or stress worsen the perceived severity of autonomic symptoms in people with symptoms of orthostatic intolerance and healthy population. cCOMPASS-31 is a valuable tool that can help clinicians in discerning the true autonomic background of patients' complaints.

The Interconnection between Carotid Intima-Media Thickness and Obesity: Anthropometric, Clinical and Biochemical Correlations.

Background and Objectives: Carotid intima-media thickness (CIMT) and obesity are considered independent determinants of cardio- and cerebrovascular events. The aim of our study was to investigate the effect of obesity on CIMT and to define which traditional cardiovascular risk factors correlate the most with CIMT values in patients with obesity. Materials and Methods: Anthropometric measurements were collected for the whole study group, as well as body composition and blood pressure data, and biochemical blood analyses were also performed. Results: Although our study group was significantly older according to vascular compared with chronological age, the mean CIMT values were lower when compared with the reference values. We found a statistically significant correlation of CIMT with chronological and vascular age, systolic blood pressure, fasting glucose, total cholesterol and triglyceride levels, waist-to-hip ratio, waist circumference, body muscle mass and skeletal muscle mass index. Atherosclerotic Cardiovascular Disease (ASCVD) risk assessment and SCORE (Systematic COronary Risk Evaluation) showed significant positive correlations, but there was only a weak correlation of ASCVD with CIMT. Conclusions: To deduce, since no diagnostic tool currently includes body weight as an individual risk factor, further trials are highly needed to determine if SCORE, SCORE2, ASCVD risk assessment or CIMT would be the most accurate and relevant diagnostic tool for prediction of risk for future CV events in patients with obesity.

Double immune reconstitution therapy: Cladribine after alemtuzumab in the treatment of multiple sclerosis.

BACKGROUND AND PURPOSE: Alemtuzumab, a monoclonal anti-CD52 antibody, and cladribine, a purine nucleoside analogue, are used for the treatment of highly active relapsing-remitting multiple sclerosis (MS). Both are administered as two short yearly courses but possess the ability to induce long-term remission, labeling them as immune reconstitution therapies. Although disease activity after alemtuzumab administration is rare, there are a small number of people with MS who will experience disease activity despite repeated alemtuzumab treatment. METHODS: We report on six patients with MS who experienced disease activity after alemtuzumab and were subsequently treated with cladribine and followed up for up to 2 years. RESULTS: None of the patients experienced relapses during the follow-up period and in all patients Expanded Disability Status Scale values remained unchanged. All patients had lymphopenia at one time point. In patients 1 and 2, at the nadir, the lymphopenia was grade 1, in patient 3 it was grade 2 and in patients 5 and 6 it was grade 3. No infections or malignancies were recorded during the follow-up. CONCLUSION: This report provides a framework for treating people with MS with sequential immune reconstitution therapies.

Sudomotor dysfunction in people with neuromyelitis optica spectrum disorders.

BACKGROUND AND PURPOSE: The aim was to determine the extent of sudomotor dysfunction in people with neuromyelitis optica spectrum disorder (pwNMOSD) and to compare findings with a historical cohort of people with relapsing-remitting multiple sclerosis (pwRRMS). METHODS: Forty-eight pwNMOSD were enrolled from four clinical centers. All participants completed the Composite Autonomic Symptom Score 31 to screen for symptoms of sudomotor dysfunction. Sudomotor function was assessed using the quantitative sudomotor axon reflex test. The results were compared with a historical cohort of 35 pwRRMS matched for age, sex and disease duration. RESULTS: Symptoms of sudomotor dysfunction, defined by a score in the Composite Autonomic Symptom Score 31 secretomotor domain >0, were present in 26 (54%) of pwNMOSD. The quantitative sudomotor axon reflex test confirmed a sudomotor dysfunction in 25 (52.1%) of pwNMOSD; in 14 of them (29.2%) sudomotor dysfunction was moderate or severe. No difference was observed between pwNMOSD and pwRRMS in any of the studied parameters. However, symptomatic sudomotor dysfunction was more frequent in pwNMOSD (n = 8, 22.9%) compared to pwRRMS (n = 1, 3%; p = 0.028). In a multivariable logistic regression analysis, statistically significant predictors for symptomatic sudomotor failure were age and diagnosis of neuromyelitis optica spectrum disorder. CONCLUSIONS: Sudomotor dysfunction is common in pwNMOSD and more often symptomatic compared to pwRRMS.

Clinical autonomic nervous system laboratories in Europe: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies: A joint survey of the European Academy of Neurology and the European Federation of Autonomic Societies.

BACKGROUND AND PURPOSE: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. METHODS: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. RESULTS: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). CONCLUSIONS: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.

Comparison of pain-provoked versus standard 40-min tilt table test for the conformation of vasovagal syncope.

BACKGROUND: Tilt table test represents a valuable diagnostic method in assessing patients with transient loss of consciousness and confirming the diagnosis of vasovagal syncope. However, the test lacks standardization, and various protocols exist in different centers. The aim of this study was to compare the difference in sensitivity and time-to-syncope of tilt table test with a painful stimulus provocation compared to standard test with no provocation. METHODS: This was a prospective study that included consecutive patients diagnosed with vasovagal syncope who were referred for tilt table testing. Patients were randomly assigned to two groups: group 1 with pain provocation after the first 10 min of upright position and group 2 with no provocation with further 30 min of tilt in both groups. RESULTS: In group 1, 66 (78.6%) patients developed syncope while in group 2, 35 (44.3%) patients had syncope (p < 0.001). This represents an increase of 34.3% in TTT sensitivity with the application of painful provocation. According to results of the Cox regression, the hazard for developing syncope after the 10th min of the tilt for group 2 was 0.275 of the hazard of group 1 (95% C.I. 0.170-0.444, p < 0.001). CONCLUSION: Pain provocation is a useful method for increasing sensitivity and shortening the duration of tilt table testing.

Treatment of relapsing multiple sclerosis - recommendations of the Croatian Neurological Society.

Untreated multiple sclerosis (MS) irretrievably leads to severe neurological impairment. In European health care systems, patient access to disease modifying therapies (DMT) is often confined to more advanced stages of the disease because of restrictions in reimbursement. A discrepancy in access to DMTs is evident between West and East European countries. In order to improve access to DMTs for people with MS (pwMS) living in Croatia, the Croatian Neurological Society issued new recommendations for the treatment of relapsing MS. The aim of this article is to present these recommendations. The recommendations for platform therapies are to start DMT as soon as the diagnosis is made. If poor prognostic criteria are present (≥9 T2 or FLAIR lesions on the initial brain and spinal cord magnetic resonance imaging [MRI] or ≥3 T1 lesions with postcontrast enhancement on the initial brain and spinal cord MRI or Expanded Disability Status Scale after treatment of the initial relapse ≥3), high-efficacy DMT should be initiated. If pwMS experience ≥1 relapse or ≥3 new T2 lesions while on platform therapies, they should be switched to high-efficacy DMT. Further efforts should be made to enable early and unrestricted access to high-efficacy DMT with a freedom of choice of an appropriate therapy for expert physicians and pwMS. The improvement of access to DMT achieved by the implementation of national treatment guidelines in Croatia can serve as an example to national neurological societies from other Eastern European countries to persuade payers to enable early and unrestricted treatment of pwMS.

Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis.

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons' excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.

Peripheral nervous system in multiple sclerosis-understanding the involvement via autonomic nervous system.

AIM: The aim of this review is to summarize the clinical and paraclinical findings that demonstrate that multiple sclerosis (MS) affects the peripheral nervous system (PNS) as well as the central nervous system (CNS). Methods: Narrative review. RESULTS: MS is traditionally defined as a chronic demyelinating immune-mediated disease of the CNS. However, there is emerging evidence that MS is a disease that does not solely affect the CNS but can manifest with PNS involvement as well. Several pathology studies have reported on signs of demyelination in the PNS, as well as on structural and functional involvement of the PNS in persons with MS (pwMS). From the functional aspect, several studies have shown autonomic nervous system (ANS) involvement in the form of sudomotor dysfunction measured with quantitative sudomotor axon reflex test (QSART) in different stages of MS, adding to the growing body of evidence that indicate PNS involvement in MS. In this review the clinical, pathological, neurophysiological, and imaging findings that demonstrate that MS affects the PNS as well as the CNS are summarized, with the emphasis on the ANS abnormalities. CONCLUSION: Further large-scale research is needed in order to fully understand the frequency and importance of PNS affection in MS.

Effectiveness and safety of alemtuzumab in the treatment of active relapsing-remitting multiple sclerosis: a multicenter, observational study.

OBJECTIVE: So far, a limited number of real-world evidence studies about the effectiveness and safety of alemtuzumab (ALM) have been published, some of them with a relatively small number of included patients. We aimed to study the efficacy and safety of ALM in real-world clinical practice in two MS centers in Slovenia and Croatia. METHODS: This was a retrospective chart review of 71 consecutive patients with relapsing-remitting MS who were treated with ALM from 2015 till 2018. The following data were collected: gender, age at disease onset, disease duration at ALM initiation, previous disease modifying therapy, number of relapses, active MRI lesions, and EDSS in the year prior to ALM initiation and every year of follow-up. RESULTS: All patients completed the standard dosing schedule and were followed for a mean time of 3.2±1.1 years after the initiation of treatment. Complete data for the 2 years after treatment (relapses, EDSS, and MRI) were available for 48 patients, of which 14 (29.2%) achieved NEDA. Clinical NEDA was achieved in 38 out of 63 participants (60.3%). In year 1, 24 out of 57 (42.1%) patients achieved NEDA. In year 2, 26 out of 41 (63.4%) patients achieved NEDA. Lower EDSS prior to starting ALM was the only independent predictor of NEDA in a multivariable model. Adverse events occurred in 58 participants (84.1%), with no new safety signals identified. CONCLUSION: According to the data from our cohort of early active RRMS patients we conclude ALM efficacy remains high in the real-world clinical practice.

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.

Factors Contributing to the Reduction of Pain during Electromyography and Nerve Conduction Studies.

BACKGROUND: Electromyography (EMG) and nerve conduction studies (NCS) are an unpleasant and sometimes painful examinations. Pain can reduce patient's compliance and have a negative effect on the examination results. Different studies report that music affects pain perception by acting as a distractor, by inducing positive emotional valence or through the concept of convergence of different sensory modalities. The aim of this study was to explore the effect of music and different environmental and sociodemographic factors on pain perception during EMG and NCS. SUBJECTS AND METHODS: Sixty patients with suspected neuromuscular disease were randomized into music and control group. Specific questionnaire assessed sociodemographic characteristics, medical history, examination waiting time, examination extent and biometeorological forecast. The numerical rating scale was used for the evaluation of pain. The examiner evaluated patient's compliance after the examination. RESULTS: NCS was less painful for patients in the music group (p=0.03), as well as for more cooperative patients (p=0.011). For patients who previously underwent EMG/NCS, present NCS was more painful (p=0.001), regardless of the music intervention (p=0.019). EMG was more painful for older patients (p=0.041). Patients with lower level of education reported lower pain during NCS (p=0.026). Gender, financial satisfaction, biometeorological forecast, diabetes, depression or malignant disease, use and dosing of analgesics or antidepressants, symptoms, examination waiting time and the examination extent had no effect on pain perception. CONCLUSIONS: Music significantly decreased the perception of pain associated with NCS, but not the EMG portion of the examination. During EMG pain level was not significantly reduced, but the median of pain was still lower. Generally, the pain level during NCS, unlike the one during EMG, was affected by patients' compliance, level of education and painful predetermination. We propose using music during EMG/NCS because it can make the examination more comfortable for the patient and thus contribute to better quality of this examination.

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.

Association of Autonomic Nervous System Abnormalities on Head-Up Tilt Table Test with Joint Hypermobility.

AIM: The aim of this study was to investigate the association of autonomic nervous system abnormalities on head-up tilt table test (HUTT) with generalized joint hypermobility, expressed by Beighton score (BS). METHODS: This was a prospective study that included 115 consecutive patients (91 females; mean age 34.35 ± 14.11) referred either for the HUTT or testing of the cardiovascular autonomic reflexes together with HUTT. Generalized joint hypermobility was evaluated according to the BS system after which HUTT was performed. Clinically significant BS was considered if ≥4. RESULTS: Fifteen patients (15.1%) had BS ≥4. Results of the HUTT were normal in 58 (50.4%) patients and in 57 (49.6%) patient HUTT was abnormal. Fifteen (13.0%) patients fulfilled criteria for orthostatic hypotension, 30 (26.1%) for reflex syncope and 21 (18.3%) for postural orthostatic tachycardia syndrome. Patients with pathological findings on HUTT had significantly higher BS compared to patients with normal HUTT (median 1 vs. 0, p = 0.001). There was a significant association between participants with BS ≥4 and pathological HUTT (χ[1] = 6.392, p = 0.011). Results of the multivariate regression analysis revealed that increase in the BS is associated with the increased likelihood of HUTT pathology (Exp[B] 1.44, 95% CI 1.084-1.922, p = 0.012), while increase in age is associated with lower risk of HUTT pathology (Exp[B] 0.968, 95% CI 0.939-0.998, p = 0.036). CONCLUSION: There is an association between autonomic nervous system abnormalities on HUTT test and generalized joint hypermobility.

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.