Background/Objectives: Primary Familial Brain Calcification is a rare neurodegenerative disorder of adulthood characterized by calcium deposition in the basal ganglia and other brain areas; the main clinical manifestations include movement disorders, mainly parkinsonism. Non-motor symptoms are not well defined in PFBC. This work aims at defining the burden of non-motor symptoms in PFBC. Methods: A clinical, genetic and neuropsychological evaluation of a cohort of PFBC patients, COMPASS-31 scale administration. Results: A total of 50 PFBC patients were recruited; in 25, the genetic test was negative; 10 carried mutations in SLC20A2 gene, 8 in MYORG, 3 in PDGFB, 1 in PDGFRB, 2 in JAM2 (single mutations), and one test is still ongoing. The main motor manifestation was parkinsonism. Headache was reported in 26% of subjects (especially in PDGFB mutation carriers), anxiety or depression in 62%, psychosis or hallucinations in 10-12%, sleep disturbances in 34%; 14% of patients reported hyposmia, 32% constipation, and 34% urinary disturbances. A neuropsychological assessment revealed cognitive involvement in 56% (sparing memory functions, to some extent). The COMPASS-31 mean score was 20.6, with higher sub-scores in orthostatic intolerance and gastrointestinal problems. MYORG patients and subjects with cognitive decline tended to have higher scores and bladder involvement compared to other groups. Conclusions: The presence of non-motor symptoms is frequent in PFBC and should be systematically assessed to better meet patients\' needs.

Introduction Polycystic ovary syndrome (PCOS) is a frequently occurring endocrine condition prevalent in women of reproductive age characterized by chronic anovulation, hyperandrogenism, insulin resistance, and a low-grade inflammatory state. Patients with PCOS are more vulnerable to developing cardiac and metabolic co-morbidities. Sympathetic overactivity is also reported in PCOS patients. Objective This study aimed to assess cardiac autonomic function in PCOS by Heart Rate Variability Analysis, Ewing\'s Test, and Composite Autonomic Symptom Scale-31 (COMPASS-31). Methods Thirty female PCOS patients and 30 age-matched control females were enrolled in the study. Both cases and controls were subdivided into sub-groups based on body mass index (BMI) and waist-to-hip ratio (WHR). The cardiac autonomic functions were assessed by the COMPASS-31 questionnaire, Ewing\'s battery tests, and short-term heart rate variability analysis. Results There was no significant difference in age, BMI, and WHR of both groups. Additionally, cases had a significantly higher low frequency to high frequency (LF/HF) ratio and COMPASS-31 score and also reported more derangement in Ewing\'s battery test, indicating cardiac autonomic dysfunction in PCOS patients. Conclusion Patients with PCOS are more prone to developing cardiac and metabolic co-morbidities. Early assessment of cardiac autonomic function can prevent future complications with timely interventions. Altered autonomic function in PCOS patients can be due to hyperandrogenism and insulin resistance.

OBJECTIVE: Non-motor symptoms, such as sleep disturbances, fatigue, neuropsychiatric manifestations, cognitive impairment, and sensory abnormalities, have been widely reported in patients with idiopathic cervical dystonia (ICD). This study aimed to clarify the autonomic nervous system (ANS) involvement in ICD patients, which is still unclear in the literature.
METHODS: We conducted a pilot case-control study to investigate ANS in twenty ICD patients and twenty age-sex-matched controls. The Composite Autonomic System Scale 31 was used for ANS clinical assessment. The laser Doppler flowmetry quantitative spectral analysis, applied to the skin and recorded from indices, was used to measure at rest, after a parasympathetic activation (six deep breathing) and two sympathetic stimuli (isometric handgrip and mental calculation), the power of high-frequency and low-frequency oscillations, and the low-frequency/high-frequency ratio.
RESULTS: ICD patients manifested higher clinical dysautonomic symptoms than controls (p < 0.05). At rest, a lower high-frequency power band was detected among ICD patients than controls, reaching a statistically significant difference in the age group of ≥ 57-year-olds (p < 0.05). In the latter age group, ICD patients showed a lower low-frequency/high-frequency ratio than controls at rest (p < 0.05) and after mental calculation (p < 0.05). Regardless of age, during handgrip, ICD patients showed (i) lower low-frequency/high-frequency ratio (p < 0.05), (ii) similar increase of the low-frequency oscillatory component compared to controls, and (iii) stable high-frequency oscillatory component, which conversely decreased in controls. No differences between the two groups were detected during deep breathing.
CONCLUSIONS: ICD patients showed ANS dysfunction at clinical and neurophysiological levels, reflecting an abnormal parasympathetic-sympathetic interaction likely related to abnormal neck posture and neurotransmitter alterations.

UNASSIGNED: Peripheral neuropathies with autonomic nervous system involvement are a recognized cause of gastrointestinal dysmotility for a wide spectrum of diseases. Recent advances in wireless motility capsule testing allow improved sampling of regional and whole gut motility to aid in the diagnosis of gastrointestinal motility disorders and may provide additional insight into segment-specific enteric involvement of peripheral neuropathies affecting autonomic nervous system function.
UNASSIGNED: We utilized standardized autonomic nervous system (ANS) reflex assessment and wireless motility capsule testing to evaluate 20 individuals with idiopathic autonomic neuropathy and unexplained gastrointestinal symptoms. Additionally, we examined the relationship between quantifiable autonomic neuropathy and gastrointestinal dysmotility at specific neuroanatomical levels. Symptom profiles were evaluated using the 31-item Composite Autonomic Symptom Score questionnaire (COMPASS-31) and compared to wireless motility capsule data.
UNASSIGNED: We found that transit times were predominately abnormal (delayed) in the foregut (10 of 20; 50%), while contractility abnormalities were far more prominent in the hindgut (17 of 20; 85%), and that motility and symptom patterns, as assessed by the COMPASS-31 GI domain items, generally corresponded. Finally, we also found that there was neuroanatomical overlap in the presence of autonomic reflex abnormalities and WMC-based transit and/or contractility abnormalities.
UNASSIGNED: We found that transit times were predominately abnormal in the foregut and midgut, while contractility abnormalities were far more prominent in the hindgut in individuals with idiopathic autonomic neuropathy. There was a high rate of agreement in segmental wireless motility capsule data with neuroanatomically corresponding standardized ANS function measures (e.g., cardiovagal, sudomotor, adrenergic). Expanded sudomotor testing, including additional neuroanatomical segments, could provide additional indirect assessment of visceral involvement in ANS dysfunction.

UNASSIGNED: To assess the prevalence and burden of autonomic symptoms in migraine, and determine the relationship with migraine frequency.
UNASSIGNED: Autonomic symptoms in migraine have been theorized to occur in the setting of inter-ictal sympathetic hypoactivity and hyper-sensitivity. There is limited data prospectively assessing cranial and extra-cranial autonomic symptoms with a validated instrument, or longitudinal data on the relationship between migraine disease activity and autonomic symptoms.
UNASSIGNED: Patients attending a single tertiary academic center were recruited into a prospective cohort study between September 2020 and June 2022. In addition to standard clinical care, they completed several surveys including the Composite Autonomic Symptom Scale (COMPASS-31) questionnaire, a validated survey of autonomic symptoms.
UNASSIGNED: A total of 43 patients (66.7% female, median age 42, IQR 17) were included in the final analysis. There was a baseline 20 monthly headache days (MHD) (IQR 21.7), and 65.1% of the population had chronic migraine by ICHD-3 criteria. A significantly elevated weighted COMPASS-31 score was reported in 60.5% of respondents (mean 30.3, SD 13.3) at baseline. After 12 months treatment, significant improvements were reported in migraine frequency (median MHD 20-8.7) and disability (median Migraine Disability Assessment Score 67-48), but not in autonomic symptoms (mean score 30.3, SD 11.2).
UNASSIGNED: Autonomic symptoms were frequently reported in patients with migraine. However, they did not correlate with headache frequency or reversion to episodic frequency. Further study is required to elucidate specific approaches and treatments for autonomic symptoms, and further evaluate the underlying pathophysiological mechanisms.

BACKGROUND: Evidence is emerging about an extra-pulmonary involvement of SARS-CoV-2, including the nervous system. Autonomic dysfunction in patients recovering from acute coronavirus disease 2019 (COVID-19) has been recently described. Dysautonomic symptoms have been reported in the acute phase of the disease, but clear evidence is lacking, especially in the non-critical forms of the infection.
OBJECTIVE: The aim of this study is to assess the prevalence of dysautonomia in acute, non-critically ill COVID-19 patients.
METHODS: In this observational, cross-sectional study, we compared 38 non-critically ill patients with acute COVID-19 (COVID + group) to 38 healthy volunteers (COVID - group) in order to assess the prevalence of signs and symptoms of dysautonomia through the administration of the composite autonomic symptom score 31 (COMPASS-31) and an active standing test. Comparisons between groups were performed by means of both univariate and multivariate analyses.
RESULTS: The prevalence of orthostatic hypotension was significantly higher in the COVID + group. Higher total scores of COMPASS-31 were observed in the COVID + group than controls. Significant differences between groups emerged in the secretomotor, orthostatic intolerance, and gastrointestinal COMPASS-31 domains. All these results maintained the statistical significance after the adjustment for concomitant drugs with a known effect on the autonomic nervous system assumed by the study participants, except for the differences in the gastrointestinal domain of COMPASS-31.
CONCLUSIONS: Our results suggest that an autonomic dysfunction could be an early manifestation of COVID-19, even in the contest of mild forms of the infection.

This study aimed to evaluate the autonomic dysfunction as assessed by the Composite Autonomic Symptom Score-31 (COMPASS-31) as well as its relationship with disease activity and cardiovascular risks in patients with psoriatic arthritis (PsA). This cross-sectional observational study involved 118 PsA patients (85 females, mean age 45.6 years) and 64 healthy subjects. Cardiovascular risks were recorded including body mass index (BMI), hypertension (HT), diabetes mellitus (DM), dyslipidemia, metabolic syndrome (MetS), and 10-year Framingham Risk scores (FRS) were calculated. PsA was assessed with regard to disease activity, quality of life, and function. Autonomic dysfunction was evaluated using the COMPASS-31 consisting of six subdivisions including orthostatic, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor functions. The mean disease duration was 63.3 months. The mean total COMPASS-31 score was significantly higher in PsA patients than in controls (24.4 vs 11.1; p < 0.001), as were all sub-domain scores. COMPASS-31 scores were significantly lower in patients with DAPSA-REM and MDA. The COMPASS-31 total score showed significant correlations with scores of pain, global assessment, fatigue, function, quality of life, DAPSA, and BASDAI (p < 0.05).The presence of HT, dyslipidemia, MetS, and abdominal obesity did not significantly affect the total COMPASS-31 and sub-domain scores, except for the secretomotor scores being significantly higher in patients with abdominal obesity and MetS (p < 0.05). COMPASS-31 scores were not significantly different across the FRS risk groups. The symptoms of autonomic dysfunction are prevalent in PsA patients. High disease activity and pain have negative effects on autonomic function, and also functional impairment, fatigue, and poor quality of life are associated with autonomic dysfunction. However, the COMPASS-31 was found to be insufficient to demonstrate a clear relationship between autonomic dysfunction and cardiovascular risk.

The autonomic nervous system (ANS) can be affected by COVID-19, and dysautonomia may be a possible complication in post-COVID individuals. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been suggested to be common after SARS-CoV-2 infection, but other components of ANS function may be also impaired. The Composite Autonomic Symptom Scale 31 (COMPASS-31) questionnaire is a simple and validated tool to assess dysautonomic symptoms. The aim of the present study was to administer the COMPASS-31 questionnaire to a sample of post-COVID patients with and without neurological complaints. Participants were recruited among the post-COVID ambulatory services for follow-up evaluation between 4 weeks and 9 months from COVID-19 symptoms onset. Participants were asked to complete the COMPASS-31 questionnaire referring to the period after COVID-19 disease. Heart rate and blood pressure were manually taken during an active stand test for OH and POTS diagnosis. One-hundred and eighty participants were included in the analysis (70.6% females, 51 ± 13 years), and OH was found in 13.8% of the subjects. Median COMPASS-31 score was 17.6 (6.9-31.4), with the most affected domains being orthostatic intolerance, sudomotor, gastrointestinal and pupillomotor dysfunction. A higher COMPASS-31 score was found in those with neurological symptoms (p < 0.01), due to more severe orthostatic intolerance symptoms (p < 0.01), although gastrointestinal (p < 0.01), urinary (p < 0.01), and pupillomotor (p < 0.01) domains were more represented in the non-neurological symptoms group. This study confirms the importance of monitoring ANS symptoms as a possible complication of COVID-19 disease that may persist in the post-acute period.

Background: There are many methods to diagnose diabetic autonomic neuropathy (DAN); however, often, the various methods do not provide consistent results. Even the two methods recommended by the American Diabetes Association (ADA) guidelines, Ewing\'s test and heart rate variability (HRV), sometimes give conflicting results. The purpose of this study was to evaluate the degree of agreement of the results of the Composite Autonomic Symptom Score 31 (COMPASS-31), skin sympathetic reaction (SSR) test, Ewing\'s test, and HRV in diagnosing DAN. Methods: Patients with type 2 diabetes were recruited and each received the COMPASS-31, SSR, Ewing\'s test, and HRV for the diagnosis of DAN. Patients were categorized as DAN(+) and DAN(-) by each of the tests. Kappa consistency tests were used to evaluate the agreement of diagnosing DAN between any two methods. Spearman\'s correlation test was used to evaluate the correlations of the severity of DAN between any two methods. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic value and the cutoff value of each method. Results: A total of 126 type 2 diabetic patients were included in the study. The percentages of DAN(+) results by HRV, Ewing\'s test, COMPASS-31, and SSR were 61, 40, 35, and 33%, respectively. COMPASS-31 and Ewing\'s test had the best agreement for diagnosing DAN (κ = 0.512, p < 0.001). COMPASS-31 and Ewing\'s test also had the best correlation with respect to the severity of DAN (r = 0.587, p < 0.001). Ewing\'s test and COMPASS-31 had relatively good diagnostic values (AUC = 0.703 and 0.630, respectively) in the ROC analyses. Conclusions: COMPASS-31 and Ewing\'s test exhibit good diagnostic consistency and severity correlation for the diagnosis of DAN. Either test is suitable for the diagnosis of DAN and treatment follow-up.

BACKGROUND: Dysautonomic symptoms (DS) are frequent but often underrecognized in multiple sclerosis (MS) patients, despite the relevant impact on quality of life and physical performance.
OBJECTIVE: To assess frequency and characteristics of DS in our MS population compared with healthy controls (HC). To investigate the relationship between DS and disease characteristics (MS subtype, disease duration, Expanded Disability Status Scale (EDSS), clinical and/or radiological activity, disability progression).
METHODS: Cross-sectional study includes 324 MS patients (mean age 44.9 ± 10.7 years; 66% female) and 190 HC (mean age 40.60 ± 12.83 years; 63% female). DS were assessed using the Italian validated version of the Composite Autonomic Symptom Score-31 (COMPASS-31). Possible confounding factors were considered.
RESULTS: More than 94% of enrolled MS patients reported alterations in ≥ 2 domains of the COMPASS-31 scale (score > 0) and significantly higher COMPASS-31 total and single domain median scores compared with HC, independently from possible confounding factors (orthostatic intolerance: p = 0.001; vasomotor: p = 0.017; secretomotor: p = 0.040; gastrointestinal: p = 0.047; bladder: p < 0.001; pupillomotor: p < 0.001; COMPASS-31 total score: p < 0.001). COMPASS-31 total, secretomotor, gastrointestinal, and bladder domain scores showed weak to moderate correlation with disease duration (Rho = 0.19, p < 0.001; Rho = 0.18, p = 0.01; Rho = 0.25, p = 0.030; Rho = 0.28, p < 0.001, respectively). A moderate correlation between EDSS score, COMPASS-31 total, and bladder domain scores (Rho = 0.32, p < 0.001 and Rho = 0.48, p < 0.001, respectively) was observed. Progressive subtypes showed higher COMPASS-31 total (p = 0.025), gastrointestinal (p = 0.07), and bladder (p < 0.001) domain scores vs relapsing-remitting patients.
CONCLUSIONS: Our findings confirm that MS-related DS are frequent and tend to increase paralleling disease duration and clinical worsening, reaching the highest clinical impact in progressive subtypes.