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Introduction/aims: In Guillain-Barré syndrome (GBS), patients with dysautonomia demonstrate sympathetic overactivity (SO). This study assessed the role of prazosin (α 1 -blocker) in the management of SO., Methods: This cohort study was conducted from January 2022 to September 2023. Thirty-two GBS patients with SO received prazosin (2.5-10 mg three times a day) (prazosin group). For comparison, we included historical controls that included 33 GBS patients having SO with similar baseline characteristics, including median age and disability, who did not receive prazosin, from a GBS registry of patients admitted during February 2018-December 2021. The primary endpoint was days to resolution of SO. Secondary endpoints were daily fluctuations in the systolic (SBP) and diastolic blood pressure (DBP), duration of hospital stay, in-hospital mortality, and disability at 3 months., Results: The median ages of both the treatment and the control groups were 36 (IQR 25-49) years and 43 (66.2%) were males. The demographic and clinical parameters were comparable. Prazosin resulted in significantly earlier normalization of SO compared to the control group (median 15 vs. 20 days; p = .01). The mean fluctuations in the SBP and DBP at 15 days were significantly lower in the prazosin group. However, the duration of hospital stay and good recovery at 3 months were comparable. Three patients developed hypotension, while two patients died (ventilator-associated pneumonia) in the prazosin group., Discussion: This study provides new evidence supporting the role of prazosin in SO, and needs randomized trials to confirm our findings., (© 2024 Wiley Periodicals LLC.)

Background: After COVID-19 infection, 10-20% of patients suffer from varying symptoms lasting more than 12 weeks (Long COVID, LC). Exercise intolerance and fatigue are common in LC. The aim was to measure the maximal exercise capacity of the LC patients with these symptoms and to analyze whether this capacity was related to heart rate (HR) responses at rest and during exercise and recovery, to find out possible sympathetic overactivity, dysautonomia or chronotropic incompetence., Methods: Cardiopulmonary exercise test was conducted on 101 LC patients, who were admitted to exercise testing. The majority of them (86%) had been treated at home during their acute COVID-19 infection. Peak oxygen uptake (VO2peak), maximal power during the last 4 min of exercise (Wlast4), HRs, and other exercise test variables were compared between those with or without subjective exercise intolerance, fatigue, or both., Results: The measurements were performed in mean 12.7 months (SD 5.75) after COVID-19 infection in patients with exercise intolerance (group EI, 19 patients), fatigue (group F, 31 patients), their combination (group EI + F, 37 patients), or neither (group N, 14 patients). Exercise capacity was, in the mean, normal in all symptom groups and did not significantly differ among them. HRs were higher in group EI + F than in group N at maximum exercise (169/min vs. 158/min, p = 0.034) and 10 min after exercise (104/min vs. 87/min, p = 0.028). Independent of symptoms, 12 patients filled the criteria of dysautonomia associated with slightly decreased Wlast4 (73% vs. 91% of sex, age, height, and weight-based reference values p = 0.017) and 13 filled the criteria of chronotropic incompetence with the lowest Wlast4 (63% vs. 93%, p < 0.001), VO2peak (70% vs. 94%, p < 0.001), the lowest increase of systolic blood pressure (50 mmHg vs. 67 mmHg, p = 0.001), and the greatest prevalence of slight ECG-findings (p = 0.017) compared to patients without these features. The highest prevalence of chronotropic incompetence was seen in the group N (p = 0.022)., Conclusions: This study on LC patients with different symptoms showed that cardiopulmonary exercise capacity was in mean normal, with increased sympathetic activity in most patients. However, we identified subgroups with dysautonomia or chronotropic incompetence with a lowered exercise capacity as measured by Wlast4 or VO2peak. Subjective exercise intolerance and fatigue poorly foresaw the level of exercise capacity. The results could be used to plan the rehabilitation from LC and for selection of the patients suitable for it., (© 2024. The Author(s).)

Background and Purpose: Olfactory dysfunction or dysautonomia is one of the earliest prodromal nonmotor symptoms of Parkinson's disease (PD). We aimed to investigate whether PD patients with dysautonomia and hyposmia at the de novo stage present different prognoses regarding PD dementia (PDD) conversion, motor complication development, and change in levodopa-equivalent doses (LED)., Methods: In this retrograde cohort study, we included 105 patients with newly diagnosed PD patients who underwent cross-cultural smell identification test (CC-SIT), autonomic function tests (AFT), and dopamine transporter (DAT) scan at the de novo stage. PD patients were divided into Hyposmia + /Dysautonomia + (H + /D +) and Hyposmia - /Dysautonomia - (H - /D -) groups depending on the result of AFT and CC-SIT. Baseline clinical, cognitive, imaging characteristics, longitudinal risks of PDD development and motor complication occurrence, and longitudinal LED changes were compared between the two groups., Results: When compared with the H - /D - group, the H + /D + group showed lower standardized uptake value ratios in all subregions, lower asymmetry index, and steeper ventral - dorsal gradient in the DAT scan. The H + /D + group exhibited poorer performance in frontal/executive function and a higher risk of PDD development. The risk of motor complications including levodopa-induced dyskinesia, wearing off, and freezing of gait, was comparable between the two groups. The analysis of longitudinal changes in LED using a linear mixed model showed that the increase of LED in the H + /D + group was more rapid., Conclusions: Our results suggest that PD patients with dysautonomia and hyposmia at the de novo stage show a higher risk of PD dementia conversion and rapid progression of motor symptoms., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Dysautonomia has been associated with paraneoplastic neurological syndrome (PNS)-related mortality in anti-Hu PNS, but its frequency and spectrum remain ill-defined. We describe anti-Hu patients with dysautonomia, estimate its frequency, and compare them to patients without dysautonomia., Methods: Patients with anti-Hu antibodies diagnosed in the study centre (1990-2022) were retrospectively reviewed; those with autonomic signs and symptoms were identified., Results: Among 477 anti-Hu patients, 126 (26%) had dysautonomia (the only PNS manifestation in 7/126, 6%); gastrointestinal (82/126, 65%), cardiovascular (64/126, 51%), urogenital (24/126, 19%), pupillomotor/secretomotor (each, 11/126, 9%), and central hypoventilation (10/126, 8%). Patients with isolated CNS involvement less frequently had gastrointestinal dysautonomia than those with peripheral (alone or combined with CNS) involvement (7/23, 30% vs. 31/44, 70% vs. 37/52, 71%; P = 0.002); while more frequently central hypoventilation (7/23, 30% vs. 1/44, 2.3% vs. 2/52, 4%; P < 0.001) and/or cardiovascular alterations (18/23, 78% vs. 20/44, 45% vs. 26/52, 50%; P = 0.055). Median [95% CI] overall survival was not significantly different between patients with (37 [17; 91] months) or without dysautonomia (28 [22; 39] months; P = 0.78). Cardiovascular dysautonomia (HR: 1.57, 95% CI [1.05; 2.36]; P = 0.030) and central hypoventilation (HR: 3.51, 95% CI [1.54; 8.01]; P = 0.003) were associated with a higher risk of death, and secretomotor dysautonomia a lower risk (HR: 0.28, 95% CI [0.09; 0.89]; P = 0.032). Patients with cardiovascular dysautonomia dying ≤ 1 year from clinical onset had severe CNS (21/27, 78%), frequently brainstem (13/27, 48%), involvement., Discussion: Anti-Hu PNS dysautonomia is rarely isolated, frequently gastrointestinal, cardiovascular and urogenital. CNS dysfunction, particularly brainstem, associates with lethal cardiovascular alterations and central hypoventilation, while peripheral involvement preferentially associates with gastrointestinal or secretomotor dysautonomia, being the latest more indolent., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Maintaining cerebral perfusion in the early stages of recovery after stroke is paramount. Autoregulatory function may be impaired during this period leaving cerebral perfusion directly reliant on intravascular volume and blood pressure (BP) with increased risk for expanding cerebral infarction during periods of low BP and hemorrhagic transformation during BP elevations. We suspected that dysautonomia is common during the acute period related to both pre-existing vascular risk factors and potentially independent of such conditions. Thus, we sought to understand the state of the science specific to dysautonomia and acute stroke. The scoping review search included multiple databases and key terms related to acute stroke and dysautonomia. The team employed a rigorous review process to identify, evaluate, and summarize relevant literature. We additionally summarized common clinical approaches used to detect dysautonomia at the bedside. The purpose of this scoping review is to understand the state of the science for the identification, treatment, and impact of dysautonomia on acute stroke patient outcomes. There is a high prevalence of dysautonomia among persons with stroke, though there is significant variability in the type of measures and definitions used to diagnose dysautonomia. While dysautonomia appears to be associated with poor functional outcome and post-stroke complications, there is a paucity of high-quality evidence, and generalizability is limited by heterogenous approaches to these studies. There is a need to establish common definitions, standard measurement tools, and a roadmap for incorporating these measures into clinical practice so that larger studies can be conducted., (© 2024. Fondazione Società Italiana di Neurologia.)

Objective: Coronavirus disease (COVID-19) is a respiratory disease caused by SARS-CoV-2, which complicates the functioning of multiple systems, including the autonomic nervous system (ANS), causing dysautonomia. Investigation of dysautonomia and its association with exposure to COVID-19 is limited in healthy people. Therefore, the study aimed to investigate the relationship between ANS dysautonomia and coronavirus exposure and compare the ANS function between exposed and non-exposed to COVID-19., Subjects and Methods: The study involved 141 participants, with a mean age of 18-24.5 years, 83% male (49.6% exposed to COVID-19). The ANS was measured using a composite autonomic symptom scale (COMPASS-31) questionnaire and heart rate variability (HRV) using photoplethysmography. Exposure to COVID-19 was investigated using two national health-status tracking and COVID-19 exposure applications, "Sehhaty" and "Twakkalna"., Results: A significantly inverse weak correlation between COMPASS-31 scores and COVID-19 exposure (r=-0.2, p=0.04). No significant association was found between HRV and COVID-19 exposure. COMPASS-31 scores for the exposed group (median=15, n=70) were significantly higher than those for the non-exposed group (median=12, n=71), U=1,913.5, p=0.03. Height (r=-0.4, p=0.002) and gender (r=0.3, p=0.001) were moderately correlated with COMPASS-31 among the exposed group., Conclusions: These findings indicated that exposure to COVID-19 was associated with poorer ANS scores measured via COMPASS-31. Additionally, exposure to COVID-19 resulted in higher dysautonomia symptoms than non-exposed. Height and gender differences contribute to the severity of dysautonomia among exposed people.

Early in the pandemic, clinicians recognized an overlap between Long COVID symptoms and dysautonomia, suggesting autonomic nervous system (ANS) dysfunction. Our clinical experience at Johns Hopkins with primary dysautonomia suggested heritability of sympathetic dysfunction, manifesting primarily as hyperhidrosis and as other dysautonomia symptoms. Whole exome sequencing revealed mutations in genes regulating electrical signaling in the nervous system, thus providing a genetic basis for the sympathetic overdrive observed. We hypothesize that dysautonomia in Long COVID requires two molecular hits: a genetic vulnerability to prime the ANS and a SARS-CoV-2 infection, as an immune trigger, to further disrupt ANS function resulting in increased sympathetic activity. Indeed, Long COVID patients show signs of chronic inflammation and autoimmunity. We have translated this two-hit concept to the clinic using ion channel inhibitors to target genetic susceptibility and immunomodulators to treat inflammation. This multi-hit hypothesis shows promise for managing Long COVID and merits further study., (© 2024 The American Clinical and Climatological Association.)

Aim of the Study: To assess and compare autonomic nervous system (ANS) dysfunction, especially cardiovascular dysautonomia, in Parkinson's Disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and healthy controls., Clinical Rationale for the Study: Assessment of ANS can be useful in differential diagnosis. Dysautonomia affects quality of life and can lead to potentially life-threatening complications. There is very little literature data regarding dysautonomia in PSP in relation to other parkinsonian syndromes. This study expands the knowledge about ANS dysfunction in parkinsonisms, especially PSP., Material and Methods: Patients with PD, MSA and PSP were prospectively recruited to our study. Demographic data and information about clinical and neuropsychological assessment, medication and comorbidities was collected. SCOPA-AUT questionnaire, 5-minute tilt test, and 5-minute heart rate variability (HRV) analysis in time and frequency domains were used to assess ANS. Analysis was also performed in patients with PSP-RS and PSP-P phenotypes, and in a subgroup with eliminated confounding factors, including age and disease duration., Results: 76 PD, 25 PSP, and 12 MSA patients, and 20 controls, were included. Symptoms of dysautonomia revealed by a SCOPA-AUT questionnaire were present in all groups of patients. Urinary dysfunction was more pronounced in atypical parkinsonisms, and cardiovascular symptoms in α-synucleinopathies. HRV was disrupted in all groups of patients. However, when PSP-P and PSP-RS phenotypes were considered, HRV was diminished in PSP-RS, but there were no differences in HRV parameters between PSP-P and controls. Neurogenic orthostatic hypotension was present in 25% of PD and 58% of MSA patients, but it was absent in PSP patients and the control group. 13 PD and nine PSP patients and 16 controls were included in subanalysis. This revealed that PSP, but not PD, patients had significantly more symptoms of dysautonomia and lower HRV indices compared to controls, and that orthostatic hypotension was even more common in PD than in controls., Conclusions and Clinical Implications: Our study suggests that dysautonomia is common in PD, MSA and PSP, even though it has different profiles in the different diseases. NOH is present in PD and MSA, but not in PSP.

There is accumulating evidence of autonomic dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction. This study aimed to explore the autonomic responses through an orthostatic test and analysis of the peripheral skin temperature variations and vascular endothelium state in ME/CFS patients. Sixty-seven adult female ME/CFS patients and 48 healthy controls were enrolled. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Postural changes in blood pressure, heart rate, and wrist temperature were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-h profile of peripheral temperature and activity. Circulating endothelial biomarkers were measured as indicators of endothelial functioning. Results showed that ME/CFS patients presented higher blood pressure and heart rate values than healthy controls in the supine and standing position ( p < 0.05 for both), and also a higher amplitude of the activity rhythm ( p < 0.01). Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME/CFS ( p < 0.05). In ME/CFS, ET-1 levels were associated with the stability of the temperature rhythm ( p < 0.01), and also with the self-reported questionnaires ( p < 0.001). This suggests that ME/CFS patients exhibited modifications in circadian rhythm and hemodynamic measures, which are associated with endothelial biomarkers (ET-1 and VCAM-1). Future investigation in this area is needed to assess dysautonomia and vascular tone abnormalities, which may provide potential therapeutic targets for ME/CFS.

Context: About one-third of diabetic patients suffer from neuropathic pain, which is poorly responsive to analgesic therapy and associated with greater autonomic dysfunction. Previous research on diabetic neuropathy mainly links pain and autonomic dysfunction to peripheral nerve degeneration resulting from systemic metabolic disturbances, but maladaptive plasticity in the central pain and autonomic systems following peripheral nerve injury has been relatively ignored., Objective: This study aimed to investigate how the brain is affected in painful diabetic neuropathy (PDN), in terms of altered structural connectivity (SC) of the thalamus and hypothalamus that are key regions modulating nociceptive and autonomic responses., Methods: We recruited 25 PDN and 13 painless (PLDN) diabetic neuropathy patients, and 27 healthy adults as controls. The SC of the thalamus and hypothalamus with limbic regions mediating nociceptive and autonomic responses was assessed using diffusion tractography., Results: The PDN patients had significantly lower thalamic and hypothalamic SC of the right amygdala compared with the PLDN and control groups. In addition, lower thalamic SC of the insula was associated with more severe peripheral nerve degeneration, and lower hypothalamic SC of the anterior cingulate cortex was associated with greater autonomic dysfunction manifested by decreased heart rate variability., Conclusion: Our findings indicate that alterations in brain structural connectivity could be a form of maladaptive plasticity after peripheral nerve injury, and also demonstrate a pathophysiological association between disconnection of the limbic circuitry and pain and autonomic dysfunction in diabetes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To determine whether functional impairments and autonomic symptoms are correlated in young people with developmental and epileptic encephalopathies (DEEs)., Method: Cross-sectional, online surveys (2018-2020) of parents recruited from family groups obtained information on several aspects of children's conditions including functional abilities (mobility, hand use, eating, and communication), 18 autonomic symptoms in six groups (cardiac, respiratory, sweating, temperature, gastrointestinal, and other), and parental stress. Bivariate and multivariable logistic regression analyses examined associations of dysautonomias with functional impairment, adjusted for type of DEE and age., Results: Of 313 participants with full information on function and dysautonomias, 156 (50%) were females. The median age was 8 years (interquartile range 4-12y); 255 (81%) participants had symptoms in at least one autonomic symptom group; 283 (90%) had impairment in at least one functional domain. The number of functional impairment domains and of autonomic symptom groups varied significantly across DEE groups (both p<0.001). The number of functional impairment domains and of autonomic symptom groups were correlated (Spearman's r=0.35, p<0.001) on bivariate and multivariable analysis adjusted for DEE group and age. Parental stress was also independently correlated with dysautonomias (p<0.001)., Interpretation: Parent-reported dysautonomias are common in children with DEEs. They correlate with extent of functional impairment and may contribute to caregiver stress. What this paper adds Dysautonomic symptoms are common in young people with developmental and epileptic encephalopathies (DEEs). Burden of dysautonomias is strongly correlated with burden of functional impairments. Aspects of dysautonomic function may provide biomarkers of DEE disease severity., (© 2021 Mac Keith Press.)

Dysautonomia is a recognized manifestation in patients with joint hypermobility (JH) disorders. Symptoms can be highly debilitating and commonly include physical deconditioning and poor aerobic fitness. In this study, the prevalence of dysautonomia, range of associated symptoms, patient-reported physical activity levels, and echocardiographic features were assessed retrospectively in a cohort of 144 patients (94% female) with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Echocardiographic parameters of left ventricular size and function were compared between patients with and without dysautonomia as well as to reported values from healthy controls. Dysautonomia was identified in 65% of female and 44% of male subjects and was associated with a high burden of symptomatology, most commonly exercise intolerance (78%). Exercise capacity was limited by dysautonomia, often postural symptoms, in half of all patients. We observed a reduction in physical activity following the onset or significant flare of hEDS/HSD, most strikingly noting the proportion of dysautonomic patients with sedentary lifestyle, which increased from 44% to 85%. JH-related dysautonomia was associated with smaller cardiac chamber sizes, consistent with the previous reports in positional orthostatic tachycardia syndrome. Dysautonomia is prevalent in patients with hEDS/HSD, and exercise intolerance is a key feature and leads to drastic decline in physical activity. Unfavorable cardiac geometry may underlie dysautonomia symptoms and may be due to cardiac atrophy in the setting of aerobic deconditioning., (© 2021 Wiley Periodicals LLC.)

Wilson disease (WD) is a rare genetic condition that results from a build-up of copper in the body. It requires life-long treatment and is mainly characterized by hepatic and neurological features. Copper accumulation has been reported to be related to the occurrence of heart disease, although little is known regarding this association. We have conducted a systematic review of the literature to document the association between WD and cardiac involvement. Thirty-two articles were retained. We also described three cases of sudden death. Cardiac manifestations in WD include cardiomyopathy (mainly left ventricular (LV) remodeling, hypertrophy, and LV diastolic dysfunction, and less frequently LV systolic dysfunction), increased levels of troponin, and/or brain natriuretic peptide, electrocardiogram (ECG) abnormalities, and rhythm or conduction abnormalities, which can be life-threatening. Dysautonomia has also been reported. The mechanism of cardiac damage in WD has not been elucidated. It may be the result of copper accumulation in the heart, and/or it could be due to a toxic effect of copper, resulting in the release of free oxygen radicals. Patients with signs and/or symptoms of cardiac involvement or who have cardiovascular risk factors should be examined by a cardiologist in addition to being assessed by their interdisciplinary treating team. Furthermore, ECG, cardiac biomarkers, echocardiography, and 24-hours or more of Holter monitoring at the diagnosis and/or during the follow-up of patients with WD need to be evaluated. Cardiac magnetic resonance imaging, although not always available, could also be a useful diagnostic tool, allowing assessment of the risk of ventricular arrhythmias and further guidance of the cardiac workup., (© 2021 SSIEM.)

Increasing numbers of COVID-19 patients, continue to experience symptoms months after recovering from mild cases of COVID-19. Amongst these symptoms, several are related to neurological manifestations, including fatigue, anosmia, hypogeusia, headaches and hypoxia. However, the involvement of the autonomic nervous system, expressed by a dysautonomia, which can aggregate all these neurological symptoms has not been prominently reported. Here, we hypothesize that dysautonomia, could occur in secondary COVID-19 infection, also referred to as "long COVID" infection. 39 participants were included from December 2020 to January 2021 for assessment by the Department of physical medicine to enhance their physical capabilities: 12 participants with COVID-19 diagnosis and fatigue, 15 participants with COVID-19 diagnosis without fatigue and 12 control participants without COVID-19 diagnosis and without fatigue. Heart rate variability (HRV) during a change in position is commonly measured to diagnose autonomic dysregulation. In this cohort, to reflect HRV, parasympathetic/sympathetic balance was estimated using the NOL index, a multiparameter artificial intelligence-driven index calculated from extracted physiological signals by the PMD-200 pain monitoring system. Repeated-measures mixed-models testing group effect were performed to analyze NOL index changes over time between groups. A significant NOL index dissociation over time between long COVID-19 participants with fatigue and control participants was observed (p = 0.046). A trend towards significant NOL index dissociation over time was observed between long COVID-19 participants without fatigue and control participants (p = 0.109). No difference over time was observed between the two groups of long COVID-19 participants (p = 0.904). Long COVID-19 participants with fatigue may exhibit a dysautonomia characterized by dysregulation of the HRV, that is reflected by the NOL index measurements, compared to control participants. Dysautonomia may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia. Trial registration: The study was approved by the Foch IRB: IRB00012437 (Approval Number: 20-12-02) on December 16, 2020.

Abstract: We present a case of chronic, progressive proximal weakness with dysautonomia and hyporeflexia/areflexia ultimately diagnosed with Lambert-Eaton myasthenic syndrome. An approach to neuroanatomical localization is discussed leading to the appropriate selection of electrodiagnostic studies. The electrophysiologic triad of Lambert-Eaton myasthenic syndrome is demonstrated with diffusely reduced motor amplitudes, decrement with low-frequency repetitive nerve stimulation, and increment of motor amplitudes after maximum voluntary contraction. Subsequent serologic testing for P/Q-type voltage-gated calcium channel antibodies are markedly elevated. We highlight the clinical features and pitfalls of examining a patient with Lambert-Eaton myasthenic syndrome when suspecting this challenging diagnosis. The neurophysiological underpinning of the electrodiagnostic results is explained, and the diagnostic utility of single-fiber electromyography is briefly discussed., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Cardiac and respiratory involvement constitutes serious complications of Duchenne muscular dystrophy (DMD). We hypothesized that obstructive sleep apnea syndrome (OSAS) may play a role in cardiac autonomic dysfunction in DMD. We sought to assess the presence of cardiac autonomic function in patients with DMD by analyzing heart rate variability (HRV) during polysomnography (PSG)., Methods: In a prospective study, all participants had whole-night PSG recorded and scored according to American Academy of Sleep Medicine guidelines. HRV analysis was performed on electrocardiography recordings from PSG recordings., Results: Twelve consecutive males with DMD (mean age 9.0 ± 3.1 years, mean BMI 20.6 ± 4.8 kg/m2) and eight age-matched healthy males were enrolled. On clinical evaluation, 58% of patients with DMD had at least one symptom related to OSAS, such as snoring, witnessed apnea, or restless sleep. None of the controls had OSAS-related complaints. By PSG none of the controls had OSAS, while 42% of patients with DMD had OSAS (p = 0.004). Average R-R duration and mean percentage of successive R-R intervals > 50 ms values were significantly lower in patients with DMD than those in controls (p < 0.006). In patients with DMD and OSAS, LF/HF (low/high-frequency) ratio was significantly increased in NREM sleep compared with those in controls (p = 0.005). Higher apnea-hypopnea index and lower oxygen saturation showed significant correlations with higher LF power and LF/HF ratio (p < 0.001)., Conclusion: Cardiac autonomic dysfunction is present in DMD, being more pronounced in the presence of OSAS.

Autoimmune gastrointestinal dysmotility (AGID), an idiopathic or paraneoplastic phenomenon, is a clinical form of limited autoimmune dysautonomia. The symptoms of AGID and gastrointestinal manifestations in patients with autoimmune rheumatic diseases are overlapping. Antineuronal autoantibodies are often detected in patients with AGID. Autoantibodies play a key role in GI dysmotility; however, whether they cause neuronal destruction is unknown. Hence, the connection between the presence of these autoantibodies and the specific interference in synaptic transmission in the plexus ganglia of the enteric nervous system has to be determined. The treatment options for AGID are not well-defined. However, theoretically, immunomodulatory therapies have been shown to be effective and are therefore used as the first line of treatment. Nonetheless, diverse combined immunomodulatory therapies should be considered for intractable cases of AGID. We recommend comprehensive autoimmune evaluation and cancer screening for clinical diagnosis of AGID. Univocal diagnostic criteria, treatment protocols, and outcome definitions for AGID are required for prompt diagnosis and treatment and appropriate management of immunotherapy, which will circumvent the need for surgeries and improve patient outcome. In conclusion, AGID, a disease at the interface of clinical immunology and neurogastroenterology, requires further investigations and warrants cooperation among specialists, especially clinical immunologists, gastroenterologists, and neurologists.

Objective: We aimed to test whether patients who died of sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation., Methods: We conducted a retrospective, observational, case-control study of a group of patients who died of SUDEP and controls who were matched to the patients for epilepsy type, drug resistance, sex, age at EEG recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and HR variability (HRV) at rest and during and after hyperventilation performed during the patient's last EEG recording before SUDEP. In each group, changes over time in HRV indexes were analyzed with linear mixed models., Results: Twenty patients were included in each group. In the control group, the HR increased and the root mean square of successive RR-interval differences (RMSSD) decreased during the hyperventilation and then returned to the baseline values. In the SUDEP group, however, the HR and RMSSD did not change significantly during or after hyperventilation. A difference in HR between the end of the hyperventilation and 4 minutes after its end discriminated well between patients with SUDEP and control patients (area under the receiver operating characteristic curve 0.870, sensitivity 85%, specificity 75%)., Conclusion: Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in HR on hyperventilation might be predictive of the risk of SUDEP and could be used to select patients at risk of SUDEP for inclusion in trials assessing protective measures., (© 2021 American Academy of Neurology.)

Objective: Patients with acquired autonomic dysfunction may have antibodies specific to the ganglionic nicotinic acetylcholine receptor (gAChR). However, the clinical features of children and adolescents with acquired autonomic dysfunction (AAD) remain unclear. This study aimed to determine the clinical features of pediatric patients with acquired autonomic dysfunction., Methods: This study retrospectively examined a series of patients of AAD with serum gAChR antibodies who were referred to our laboratory for antibody testing between January 2012 and April 2019. The study included 200 patients (<20 years, 20 cases; ≥20 years, 175 cases) with clinical features of AAD., Results: Upon comparing pediatric and adult patients, we found that antecedent infection and autonomic symptoms at onset with gastrointestinal symptoms occurred more frequently in children with AAD. We confirmed that four children (20.0%) met the diagnostic criteria for postural orthostatic tachycardia syndrome (POTS). A significantly higher number of children than adults had POTS (P = 0.002). In addition, upper GI dysfunction was more prevalent in children than in adults (P = 0.042). In particular, nausea and vomiting occurred in 60.0% of children with AAD and in 21.1% of adults (P < 0.001). The frequency of paralytic ileus was significantly higher in children with AAD (20.0%) relative to adults (6.3%) (P = 0.030). Regarding extra-autonomic manifestations, encephalopathy was more frequent in children (15.0%) than in adults (1.1%) (P < 0.001)., Interpretation: Pediatric AAD patients have their own clinical characteristics, and these features may be unique to children and adolescents., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality., Methods: A total of 581 hospitalized patients with confirmed SARS-CoV-2 infection, neurologic involvement, and brain imaging were compared to hospitalized non-neurologic patients with coronavirus disease 2019 (COVID-19). Four patterns of neurologic manifestations were identified: acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, preexisting comorbidities, vital signs, laboratory values, and pattern of neurologic manifestations. Significant predictors were incorporated into a disease severity score. Patients with neurologic manifestations were matched with patients of the same age and disease severity to assess the risk of death., Results: A total of 4,711 patients with confirmed SARS-CoV-2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurologic issues of sufficient concern to warrant neuroimaging. These patients were compared to 1,743 non-neurologic patients with COVID-19 matched for age and disease severity admitted during the same period. Patients with altered mentation (n = 258, p = 0.04, odds ratio [OR] 1.39, confidence interval [CI] 1.04-1.86) or radiologically confirmed stroke (n = 55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age- and severity-matched controls., Conclusions: The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Achalasia is a disease characterized by the inability to relax the esophageal sphincter due to a degeneration of the parasympathetic ganglion cells located in the wall of the thoracic esophagus. Achalasia has been associated with extraesophageal dysmotility, suggesting alterations of the autonomic nervous system (ANS) that extend beyond the esophagus. The purpose of the present contribution is to investigate whether achalasia may be interpreted as the esophageal manifestation of a more generalized disturbance of the ANS which includes alterations of heart rate and/or blood pressure. Therefore simultaneous non-invasive records of the heart inter-beat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) of 14 patients (9 female, 5 male) with achalasia were compared with the records of 34 rigorously screened healthy control subjects (17 female, 17 male) in three different conditions: supine, standing up, and controlled breathing at 0.1 Hz, using a variety of measures in the time and spectral domains. Significant differences in heart rate variability (HRV) and blood pressure variability (BPV) were observed which seem to be due to cardiovagal damage to the heart, i.e., a failure of the ANS, as expected according to our hypothesis. This non-invasive methodology can be employed as an auxiliary clinical protocol to study etiology and evolution of achalasia, and other pathologies that damage ANS., Competing Interests: The authors have declared that no competing interests exist.

Monoclonal gammopathy is encountered quite frequently in the general population. This type of hematologic abnormality may be mild, referred to as monoclonal gammopathy of undetermined significance or related to different types of hematologic malignancies. The association of a peripheral neuropathy with monoclonal gammopathy is also fairly common, and hemopathy may be discovered in an investigation of peripheral neuropathy. In such a situation, it is essential to determine the exact nature of the hematologic process in order not to miss a malignant disease and thus initiate the appropriate treatment (in conjunction with hematologists and oncologists). In this respect, nerve biopsy (discussed on a case-by-case basis) is of great value in the management of such patients. We therefore propose to present the objectives and main interests of nerve biopsy in this situation., (© 2020 American Academy of Neurology.)

The autonomic nervous system controls cardiovascular function. Autonomic dysfunction or dysautonomia is commonly encountered in several diseases like Parkinson's disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a chemical that changes into the neurotoxin MPP+, which causes catecholamine depletion. We aimed to study the effects of citicoline on cardiovascular function in MPTP-treated albino rats. Twenty-four male albino rats were divided into four groups (6 rats/group): negative control received intraperitoneal (i.p.) saline injection for five consecutive days, a positive control (Citicoline group) received citicoline (250 mg/kg) by oral gavage for consecutive 20 days, MPTP treated with MPTP-HCL (30 mg/kg, i.p.) for five consecutive days, MPTP + citicoline treated with MPTP-HCL (30 mg/kg, i.p.) for five consecutive days followed by treatment with oral doses of citicoline (250 mg/kg) for 20 days. Cardiovascular functions evaluated through recording electrocardiogram (ECG), echocardiography, measuring arterial blood pressure and assessment of aortic rings vascular reactivity. Biochemical measurements on cardiac tissue for tyrosine hydroxylase, norepinephrine, glucose transporter 1 (GLUT1), insulin receptor substrate 1 (IRS1), peroxisome proliferator-activated receptor γ co-activator-1 (PPAR-γ co-activator-1) (PGC-1), phosphatase and tensin homolog-induced kinase 1 (PINK1), carnitine palmitoyltransferase I (CPT1), uncoupling protein 2 (UCP2) and adenosine monophosphate-activated protein kinase alpha 2 (AMPKα2). Citicoline increased cardiac norepinephrine and tyrosine hydroxylase and improved markers related to ROS scavenger, mitochondrial permeability, calcium homeostasis on the cellular level, metabolic homeostasis, and mitochondrial biogenesis. We conclude that citicoline improved cardiovascular dysautonomia and that was reflected on cardiac contractility, electrical activity, blood pressure, and vascular reactivity.

Objective: Autonomic dysfunction occurs in approximately two-thirds of Guillain-Barré syndrome (GBS) patients in the acute phase of the disease. Although improving over time, subclinical autonomic involvement may be present for 3-8 years after the GBS episode. The aim of this study was to determine the frequency of self-reported autonomic disorders in GBS patients three and six months after disease onset compared to healthy controls (HCs)., Methods: Our study included adult patients diagnosed with GBS from May 2017 until May 2018 in seven healthcare centers (67.6 % with demyelinating and 13.6 % with axonal syubtype). Functional disability was assessed by the Guillain-Barré syndrome disability scale (GDS). Each subject filled in the Serbian version of the SCOPA-Aut questionnaire. Using GDS and SCOPA-Aut, patients were tested at month 3 (M3) (n = 71) and month 6 (M6) (n = 70) from symptom onset., Results: Dysautonomia was more common in patients with GBS compared to HCs at M3 (p < 0.01), while there was no difference at M6 (p > 0.05). Among autonomic disorders, constipation, complications to pass stool, and orthostatic hypotension were the most frequently reported. Patients with axonal variants had worse total SCOPA-Aut scores at M3 in comparison to AIDP patients (11.7 ± 10.1 vs. 6.1 ± 5.1, p < 0.05). GDS score correlated with the total SCOPA-Aut score., Conclusion: Autonomic symptoms are common in GBS patients during the recovery phase. They are more pronounced in patients with axonal forms of GBS and those with a higher degree of functional disability., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Disruptions of brain-gut axis have been implicated in the progression of a variety of gastrointestinal (GI) disorders and central nervous system (CNS) diseases and injuries, including traumatic brain injury (TBI). TBI is a chronic disease process characterized by persistent secondary injury processes which can be exacerbated by subsequent challenges. Enteric pathogen infection during chronic TBI worsened cortical lesion volume; however, the pathophysiological mechanisms underlying the damaging effects of enteric challenge during chronic TBI remain unknown. This preclinical study examined the effect of intestinal inflammation during chronic TBI on associated neurobehavioral and neuropathological outcomes, systemic inflammation, and dysautonomia., Methods: Dextran sodium sulfate (DSS) was administered to adult male C57BL/6NCrl mice 28 days following craniotomy (Sham) or TBI for 7 days to induce intestinal inflammation, followed by a return to normal drinking water for an additional 7 to 28 days for recovery; uninjured animals (Naïve) served as an additional control group. Behavioral testing was carried out prior to, during, and following DSS administration to assess changes in motor and cognitive function, social behavior, and mood. Electrocardiography was performed to examine autonomic balance. Brains were collected for histological and molecular analyses of injury lesion, neurodegeneration, and neuroinflammation. Blood, colons, spleens, mesenteric lymph nodes (mLNs), and thymus were collected for morphometric analyses and/or immune characterization by flow cytometry., Results: Intestinal inflammation 28 days after craniotomy or TBI persistently induced, or exacerbated, respectively, deficits in fine motor coordination, cognition, social behavior, and anxiety-like behavior. Behavioral changes were associated with an induction, or exacerbation, of hippocampal neuronal cell loss and microglial activation in Sham and TBI mice administered DSS, respectively. Acute DSS administration resulted in a sustained systemic immune response with increases in myeloid cells in blood and spleen, as well as myeloid cells and lymphocytes in mesenteric lymph nodes. Dysautonomia was also induced in Sham and TBI mice administered DSS, with increased sympathetic tone beginning during DSS administration and persisting through the first recovery week., Conclusion: Intestinal inflammation during chronic experimental TBI causes a sustained systemic immune response and altered autonomic balance that are associated with microglial activation, increased neurodegeneration, and persistent neurological deficits.

Objective: To analyse autoantibody status in a well-defined European multicentre cohort of patients with epilepsy of unknown aetiology and to validate the recently proposed Antibody Prevalence in Epilepsy (APE2) and Response to ImmunoTherapy in Epilepsy (RITE2) scores., Methods: We retrospectively collected clinical and paraclinical data of 92 patients referred to the Neurology Units of Verona and Salzburg between January 2014 and July 2019 with new-onset epilepsy, status epilepticus or chronic epilepsy of unknown aetiology. Fixed and live cell-based assays, tissue-based assays, immunoblot, and live rat hippocampal cell cultures were performed in paired serum/cerebrospinal fluid (CSF) to detect antineuronal and antiglial antibodies. The APE2 and RITE2 scores were then calculated and compared with clinical and laboratory data., Results: Autoantibodies were detected in 29/92 patients (31.5%), with multiple positivity observed in 6/29 cases. The APE2 score (median 5, range 1-15) significantly correlated with antibody positivity (p=0.014), especially for the presence of neuropsychiatric symptoms (p<0.01), movement disorders (p<0.01), dysautonomia (p=0.03), faciobrachial dyskinesias (p=0.03) and cancer history (p<0.01). Status epilepticus was significantly more frequent in antibody-negative patients (p<0.01). Among the items of the RITE2 score, early initiation of immunotherapy correlated with a good treatment response (p=0.001), whereas a cancer history was significantly more common among non-responders (p<0.01). Persistence of neuropsychiatric symptoms and seizures correlated with antiepileptic maintenance after at least 1 year., Conclusions: This is the first study that independently validates the APE2 and RITE2 scores and includes the largest cohort of patients whose paired serum and CSF samples have been tested for autoantibodies possibly associated with autoimmune epilepsy., Competing Interests: Competing interests: SB, RD, GC, FM, GZ, TZ, MT, GV, MC, FarR, LDT, CZ, GTM, FS, FrR, ET, SalM and RH: report no disclosures. SF received support for attending scientific meetings by Shire, Sanofi Genzyme and Euroimmun. SarM received support for attending scientific meetings by Merck and Euroimmun and received speaker honoraria from Biogen., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Cognitive impairment may be correlated with cardiovascular dysautonomia, including blood pressure (BP) dysregulation, in Parkinson's disease (PD), but the association between these factors in dementia with Lewy bodies (DLB) is uncertain. This study aimed to clarify whether cardiovascular dysautonomia had an influence on cognitive function in Lewy body disease or not., Methods: Ninty-nine patients with de novo PD (n = 75) and DLB (n = 24) were evaluated using the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, orthostatic hypotension (OH), supine hypertension (SH), postprandial hypotension (PPH), nocturnal BP fall in 24-h ambulatory blood pressure monitoring (ABPM) and constipation were estimated. Associations of these factors with cognitive and executive dysfunction were examined., Results: In DLB, MIBG uptake was reduced and OH, PPH and SH were severely disturbed, compared to PD. The nocturnal BP fall in ABPM was lower in DLB, and the failure of nocturnal BP fall in PD was associated with MMSE, after adjustment for other clinical features. FAB was significantly associated nocturnal BP fall, age and SH in PD, but no significant correlations among factors were found for DLB., Conclusion: The significant association between nocturnal BP dysregulation and cognitive or executive decline in PD might be due to impaired microvascular circulation or invasion of α-synuclein in the CNS. The lack of a correlation of BP insufficiency with cognitive impairment in DLB suggests initial involvement of Lewy body pathology in the neocortex, regardless of Lewy body invasion of the autonomic nervous system.

To propose a new test to evaluate the autonomic nervous system in patients with syncope: Multimodal Monitoring for Diagnosis of Dysautonomia (MMDD). We included 21 patients with syncope (16 female, 6 male, mean age 43.5 years) and 21 with no-syncope subjects (15 female, 7 male, mean age 45.1 years) to perform a test of nine 2-min stages: four while resting and four during active testing of autonomic response. Transcranial-Doppler, electrocardiogram, and photoplethysmography blood pressure pulse-to-pulse monitoring, allow registering six variables from the Middle Cerebral Artery and four from the Cardiovascular System. We analyze each variable's mean differences in each stage and its change when they pass from one stage to another with the T and Z tests. To understand the significance of the change, we use a logistic regression model for a certain subgroup of variables. Since we have a small dataset, we use the bootstrap technique to infer the general behavior that characterizes a syncope. Our data confirm differences between syncope and non-syncope patients during MMDD stress stages 2, 4, 6 and 8. Bootstrap and multivariate logistic regression allow us to identify which sets of variables in each of these stages of the MMDD are sufficiently sensitive to recognizing syncope. MMDD protocol can recognize a syncope patient with some confidence by detecting subtle changes in the autonomic nervous system. This protocol encourages us to continue to study the effectiveness of MMDD protocol allowing a new approach to future research.

Purpose: The aim of this study was to investigate the association between autonomic dysfunction and striatal dopamine depletion or metabolic changes in de novo Parkinson disease (PD)., Methods: Based on the Composite Autonomic Severity Score (CASS), patients with de novo PD were classified into PD with (PD-AUT+) and without autonomic dysfunction (PD-AUT-) groups. We compared the dopamine transporter (DAT) availability in the striatum by quantitatively measuring F-FP-CIT PET between both groups. We also assessed the association between DAT availability and the CASS. In addition, we compared regional uptake in early-phase images of F-FP-CIT PET as well as cortical thickness between the PD-AUT+ and PD-AUT- groups., Results: The PD-AUT+ group had significantly lower DAT availability in all striatal subregions than did the PD-AUT- group. The total CASS was significantly correlated with DAT availability in all striatal subregions. In addition, the subscores of the adrenergic component were correlated with DAT availability in all striatal subregions. The subscores of the cardiovagal component were negatively correlated with DAT availability in the caudate and ventral striatum. In early-phase F-FP-CIT PET, the PD-AUT+ group exhibited decreased regional perfusion in the parieto-occipital areas and increased regional perfusion in the pallidothalamic, pontocerebellar, inferior frontal, and primary motor areas compared with the PD-AUT- group. There were no regions of different cortical thickness between the PD groups., Conclusions: The present study revealed that autonomic dysfunction is closely linked to striatal dopamine depletion and prominent PD-related perfusion patterns in de novo PD, suggesting a greater pathological burden in patients with dysautonomia.

Familial history of hypertension is associated with autonomic dysfunction and increase in blood pressure (BP). However, an active lifestyle has been found to improve a number of health outcomes and reduce all-cause mortality. The aim of the present study was to investigate the effects of an active lifestyle on hemodynamics, heart rate variability (HRV) and oxidative stress markers in offspring of hypertensive parents. One hundred twenty-seven subjects were assigned into four groups: sedentary offspring of normotensives (S-ON) or hypertensives (S-OH); and physically active offspring of normotensives (A-ON) or hypertensives (A-OH). Diastolic BP and heart rate were reduced in the physically active groups when compared to S-OH group. A-ON and A-OH groups presented increased values of RR total variance when compared to the sedentary ones (A-ON: 4,912 ± 538 vs. S-ON: 2,354 ± 159; A-OH: 3,112 ± 236 vs. S-OH: 2,232 ± 241 ms 2 ). Cardiac sympato-vagal balance (LF/HF), systemic hydrogen peroxide and superoxide anion were markedly increased in S-OH group when compared to all other studied groups. Additionally, important correlations were observed between LF/HF with diastolic BP (r = 0.30) and hydrogen peroxide (r = 0.41). Thus, our findings seem to confirm an early autonomic dysfunction in offspring of hypertensive parents, which was associated with a systemic increase in reactive oxygen species and blood pressure. However, our most important finding lies in the attenuation of such disorders in offspring of physically active hypertensives, thus emphasizing the importance of a physically active lifestyle in the prevention of early disorders that may be associated with onset of hypertension.

Alzheimer's disease is the most common neurodegenerative disorder, and its prevalence increases with age. Although there is a large amount of scientific literature focusing on Alzheimer's disease cardinal cognitive features, autonomic nervous system dysfunction remains understudied despite being common in the elderly. In this article, we reviewed the evidence for autonomic nervous system involvement in Alzheimer's disease. We identified four major potential causes for dysautonomia in Alzheimer's disease, out of which two are well-studied (comorbidities and medication) and two are rather hypothetical (Alzheimer's pathology and brain co-pathology). Although there appears to be some evidence linking Alzheimer's disease pathology to autonomic nervous system dysfunction, there is an important gap between two types of studies; histopathologic studies do not address dysautonomia manifestations, whereas clinical studies do not employ histopathologic diagnostic confirmation. Moreover, brain co-pathology is emerging as an important confounding factor. Therefore, we consider the correlation between dysautonomia and Alzheimer's disease to be an open question that needs further study. Nevertheless, given its impact on morbidity and mortality, we emphasize the importance of assessing autonomic dysfunction in patients with Alzheimer clinical syndrome.

KIF1A-related disorders (KRD) were first described in 2011 and the phenotypic spectrum has subsequently expanded to encompass a range of central and peripheral nervous system involvement. Here we present a case series demonstrating the range of clinical, neurophysiological, and radiological features which may occur in childhood-onset KRD. We report on all the children and young people seen at a single large tertiary centre. Data were collected through a retrospective case-notes review. Twelve individuals from 10 families were identified. Eight different mutations were present, including four novel mutations. Two patients displayed a very severe phenotype including congenital contractures, severe spasticity and/or dystonia, dysautonomia, severe sensorimotor polyneuropathy and optic atrophy, significant white matter changes on brain MRI, respiratory insufficiency, and complete lack of neurodevelopmental progress. The remaining 10 patients represented a spectrum of severity with common features including a movement disorder with spasticity and/or dystonia, subtle features of dysautonomia, sensory axonal neuropathy, varying degrees of optic atrophy and of learning and/or behavioural difficulties, and subtle or absent-but sometimes progressive-changes in white matter on MRI. Epilepsy was common among the more severely affected children. This case series demonstrates that KRD comprise a range of neurological disorders, with both the milder and the more severe forms combining central and peripheral (including autonomic) nervous system deficits., (© 2020 Peripheral Nerve Society.)

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.

Angina is a type of chest pain, experienced by patients with ischemic heart diseases. Cardiac autonomic modulation as assessed by heart rate variability and baroreflex sensitivity is found reduced in ischemic heart disease patients. Marked reduction in heart rate variability and baroreflex sensitivity in ischemic heart disease patients is found associated with sudden cardiac death. We report a case of a 35-year-old man who presented with angina for the last few months. Thorough investigations showed no evidence of any cardiac or other systemic diseases. However, his cardiovascular autonomic modulation (as assessed by heart rate variability) and spontaneous baroreflex sensitivity were markedly reduced. The patient had sudden death within 6 months of follow-up. Reportedly, no other specific abnormalities were found before death. This case report suggests that patients presenting with typical chest pain as angina may have severe dysautonomia and risk of sudden death even in the absence of cardiovascular or any other known end-organ diseases.

Background: Heart rate variability (HRV) decreases in Parkinson's disease (PD) and it can be considered a marker for cardiovascular dysautonomia. The purpose of this pilot study is to evaluate long-term time-domain analysis of HRV of PD patients and compare the results with those of matched healthy individuals., Methods: Idiopathic PD patients without comorbidity impairing HRV, and age-matched healthy individuals were recruited in a pilot study. A long-term time domain analysis of HRV using 24-h ambulatory ECG was performed., Results: Overall, 18 PD patients fulfilling inclusion criteria completed the evaluation (mean age was 55.6 ± 8.8, disease duration: 5.0 ± 4.7). Mean SCOPA-AUT score was 10.1 ± 7.3. Patients were on Hoehn & Yahr stage 1-2 and mean Levodopa Equivalent Dose (LED) was 311 ± 239.9. Mean of the 5-min standard deviation (SD) of R-R intervals distribution (SDNN) for all 5 min segments of the entire recording (ISDNN) was significantly lower in patients compared to controls. ISDNN was significantly different between Parkinson's disease patients and healthy controls., Conclusions: In our population characterized by mild to moderate disease severity, time-domain assessment of HRV seemed to be a potential tool to characterize cardiovascular dysautonomia. Decrease of ISDNN in PD may reflect an autonomic derangement extending all day and night long.

Background: Guillain-Barré syndrome (GBS), when severe, involves the autonomic nervous system; our objective was to assess the spectrum and predictors of dysautonomia, and how it may impact functional outcomes., Methods: A retrospective review of patients admitted to the Mayo Clinic in Rochester, MN between January 1, 2000, and December 31, 2017, with GBS and dysautonomia was performed. Demographics, comorbidities, parameters of dysautonomia, clinical course, GBS disability score, and Erasmus GBS Outcome Score (EGOS) at discharge were recorded., Results: One hundred eighty seven patients were included with 71 (38%) noted to have at least one manifestation of dysautonomia. There are 72% of patients with a demyelinating form of GBS and 36% of patients with demyelination had dysautonomia. Ileus (42%), hypertension (39%), hypotension (37%), fever (29%), tachycardia or bradycardia (27%), and urinary retention (24%) were the most common features. Quadriparesis, bulbar and neck flexor weakness, and mechanical ventilation were associated with autonomic dysfunction. Patients with dysautonomia more commonly had cardiogenic complications, syndrome of inappropriate antidiuretic hormone, posterior reversible encephalopathy syndrome, and higher GBS disability score and EGOS. Mortality was 6% in patients with dysautonomia versus 2% in the entire cohort (P = 0.02)., Conclusions: Dysautonomia in GBS is a manifestation of more severe involvement of the peripheral nervous system. Accordingly, mortality and functional outcomes are worse. There is a need to investigate if more aggressive treatment is warranted in this category of GBS.

Purpose: Autonomic dysfunction is a known consequence of chronic and excessive alcohol consumption. The aim of this systematic review was to characterise this phenomenon, describe the frequency at which it occurs and to explore the best management strategies., Methods: A systematic, computer-based search was conducted using the PubMed database. All studies identified by the search were evaluated independently by at least three authors. For inclusion, studies had to report human subjects consuming ethanol in excess. Case reports and non-original studies were excluded from this review., Results: A total of 55 studies were included in this review. According to cardiovascular reflex tests, 16-73% of chronic alcohol abusers suffer from autonomic dysfunction. The most commonly occurring symptom is erectile dysfunction, whilst other features such as postural dizziness are rare. The most important risk factor for this condition is total lifetime dose of ethanol, although there is mixed evidence supporting the role of other risk factors. The only management strategy currently explored in the literature is abstinence, which appears to lead to significant improvement in autonomic investigations., Conclusion: Current literature includes studies of highly heterogeneous populations, consuming differing volumes of alcohol over variable periods of time and utilising a number of different autonomic test batteries and criteria to diagnose autonomic dysfunction. Therefore, further research using homogeneous methods for measuring autonomic dysfunction in the field is needed. Despite this limitation, our review demonstrated that autonomic dysfunction is very common among alcohol abusers.

Background: Cognitive impairment and cardiovascular dysautonomia are two major non-motor features of Parkinson's disease (PD). They have been investigated separately and extensively, but their interactive outcomes have rarely been studied., Objective: The purpose of this study was to examine the association between central atrophy and cognition and to assess the influence of cardiovascular lability on this association in PD patients., Methods: Out of 151 early PD patients, 47 subjects were ultimately enrolled according to our selection criteria. Their cognitive status was examined by comprehensive neuropsychological tests assessing five domains of cognition. Supine and orthostatic blood pressures were recorded during head-up tilt tests, and orthostatic mean arterial pressure change was calculated. Every patient underwent brain magnetic resonance imaging, and intercaudate nucleus ratio was obtained as a central atrophy surrogate marker. The associations and interactions between central atrophy, cognition, and blood pressure variability were analyzed., Results: Among 47 subjects, 20 (42.6%) had orthostatic hypotension. Attention/working memory, executive function, and delayed recall were inversely associated with central atrophy (r = -0.332, p = 0.028; r = -0.314, p = 0.038; r = -0.399, p = 0.024; respectively). In a multiple regression model, only attention/working memory was independently associated with central atrophy when modulated by orthostatic mean arterial pressure change (p < 0.05)., Conclusion: This study revealed that cardiovascular dysautonomia interacted with the inverse association between cerebral atrophy and cognition, and it reinforced its relationship. Interaction between these two non-motor features should be kept in mind in clinical practice, particularly in PD patients with co-morbid vascular factors.

Introduction: dysautonomic dysfunction and cognitive impairment represent the most disabling non-motor features of Parkinson's Disease (PD). Recent evidences suggest the association between Orthostatic Hypotension (OH) and PD-Dementia. However, little is known on the interactions between cardiovascular dysautonomia and Mild Cognitive Impairment (MCI). We aimed to evaluate the association between cardiovascular dysautonomia and MCI in patients with PD., Methods: non-demented PD patients belonging to the PACOS cohort underwent a comprehensive instrumental neurovegetative assessment including the study of both parasympathetic and sympathetic function (30:15 ratio, Expiratory-Inspiratory ratio [E-I] and presence of Orthostatic Hypotension [OH]). Diagnosis of MCI was made according to the MDS criteria level II., Results: we enrolled 185 PD patients of whom 102 (55.1%) were men, mean age was 64.6 ± 9.7 years, mean disease duration of 5.6 ± 5.5 years with a mean UPDRS-ME score of 31.7 ± 10.9. MCI was diagnosed in 79 (42.7%) patients. OH was recorded in 52 (28.1%) patients, altered 30:15 ratio was recorded in 39 (24.1%) patients and an altered E-I ratio was found in 24 (19.1%) patients. Presence of MCI was associated with an altered 30:15 ratio (adjOR 2.83; 95%CI 1.25-6.40) but not with an altered E-I ratio, while OH was associated only with the amnestic MCI subgroup (OR 2.43; 95% CI 1.05-5.06)., Conclusion: in our study sample, MCI was mainly associated with parasympathetic dysfunction in PD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Guillain-Barré syndrome (GBS) is an inflammatory polyradiculoneuritis. Our aim in this study was to describe the clinical characteristics and the long-term sequelae of GBS in a French pediatric population., Methods: In this multicenter, retrospective study we evaluated clinical signs, radiological examinations, laboratory tests, treatments, and outcomes., Results: One hundred ten children were included in this investigation. These children presented with walking difficulties, muscle weakness, and cranial nerve impairment. Electrodiagnostic testing revealed 70% with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and 16% with acute motor axonal neuropathy (AMAN). One hundred children received immunoglobulins. At follow-up, 77% were cured, whereas 9% had sequelae, associated with an axonal form (P < .01) and a short interval between symptom onset and hospitalization (P < .01). The need for intubation was correlated with peripheral facial paralysis (P < .01) and dysautonomia (P < .01)., Discussion: Although AIDP and AMAN present in a similar way, the axonal form is associated with a worse outcome., (© 2019 Wiley Periodicals, Inc.)

Objectives: Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system., Methods: The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four-hour ambulatory blood pressure variability (BPV) was calculated and the participants were evaluated for orthostatic hypotension and supine hypertension. Serum levels of vitamin D, VDBP and VDR were measured., Results: The mean serum vitamin D level was significantly lower in MS patients than in controls (p = 0.044); however there was no significant difference in terms of VDR and VDBP levels between the groups. Supine hypertension and orthostatic hypotension were significant and the 24-hour systolic BPV was significantly decreased in patients with MS (p < 0.05) compared to controls. No correlation was found between vitamin D, VDBP and VDR with supine hypertension, orthostatic hypotension and systolic BPV values (p > 0.05). Also, there was a negative correlation between VDBP and the EDSS (p = 0.039, r = -0.406)., Conclusion: There was no correlation between orthostatic hypotension, supine hypertension and systolic BPV values and serum vitamin D, VDBP and VDR in MS patients. Future prospective studies with large number of patients may help us to better understand the relationship between vitamin D and the autonomic nervous system.

Objectives: Autonomic nervous system dysfunction after ischemic stroke predisposes to cardiovascular complications. We aimed to investigate cardiac autonomic activity in ischemic stroke patients using heart rate variability analysis, illustrating the sympathovagal balance at different sympathetic and parasympathetic activation tests., Patients and Methods: We studied the dynamics of the linear and non-linear heart rate variability parameters in 31 left and 40 right middle cerebral artery ischemic stroke patients in rest condition and during autonomic activation tests (handgrip, standing, deep breathing and Valsalva maneuver). Data were compared with 30 age- and sex-matched healthy controls., Results: We found different responses after autonomic activation tests in stroke patients depending on the cortical lateralization of the ischemic lesion. In resting state, left hemisphere stroke patients presented enhanced parasympathetic modulation of the heart rate (higher values for RMSSD, pNN50, HF and SD1, p < 0.05), comparing to right hemisphere stroke patients. This second group displayed a reduced cardiac parasympathetic control in resting state and during autonomic activation tests (handgrip and standing tests) compared to the left hemisphere stroke group and controls. Non-linear parameters SD1 and DFA α1 showed a decrease of variability and complexity of the heart rate in right hemisphere stroke patients, ameliorated during vagal activation tests., Conclusion: To prevent possible complications with vital risk, assessment of cardiovascular autonomic activity becomes a necessary stage in stroke patient management, facilitating immediate implementation of preventive and therapeutic strategies. Heart rate variability analysis in resting state and during autonomic activation tests allows identifying patients prone to sympathetic hyperactivity. New therapeutic perspectives for stroke management may emerge founded on the modulation of the autonomic nervous system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Study Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to loss of motor neurons. However, the autonomic nervous system (ANS) can also be involved. The aim of this research was to assess the sleep macro- and microstructure, the cardiac ANS during sleep, and the relationships between sleep, autonomic features, and clinical parameters in a cohort of ALS patients., Methods: Forty-two consecutive ALS patients underwent clinical evaluation and full-night video-polysomnography. Only 31 patients met inclusion criteria (absence of comorbidities, intake of cardioactive drugs, or recording artifacts) and were selected for assessment of sleep parameters, including cyclic alternating pattern (CAP) and heart rate variability (HRV). Subjective sleep quality and daytime vigilance were also assessed using specific questionnaires., Results: Although sleep was subjectively perceived as satisfactory, compared with age- and sex-matched healthy controls, ALS patients showed significant sleep alteration: decreased total sleep time and sleep efficiency, increased nocturnal awakenings, inverted stage 1 (N1)/stage 3 (N3) ratio, reduced REM sleep, and decreased CAP rate, the latter supported by lower amounts of A phases with an inverted A1/A3 ratio. Moreover, a significant reduction in HRV parameters was observed during all sleep stages, indicative of impaired autonomic oscillations., Conclusion: Our results indicate that sleep is significantly disrupted in ALS patients despite its subjective perception. Moreover, electroencephalogram activity and autonomic functions are less reactive, as shown by a decreased CAP rate and a reduction in HRV features, reflecting an unbalanced autonomic modulation., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Dysautonomia and headache are 2 common diagnoses within pediatric neurology; in the case of dysautonomia, a lack of consideration may lead to misdiagnosis. Despite being common conditions, there is a lot to learn about each individually as well as collectively. Many of the symptoms between headache and dysautonomia patients overlap making the diagnosis difficult. Migraine patients often exhibit symptoms of dysautonomia, namely postural orthostatic tachycardia syndrome (POTS); yet these symptoms are overlooked or lumped in as a part of their migraine diagnosis. The distinction or coexistence between dysautonomia and headache is identified through a thorough history, a full exam, and an open mind. This is crucial for the treatment and outcomes of these patients. Struggles arise when critical treatment differences are overlooked because dysautonomia is not considered. In this review, we will look at the epidemiology of dysautonomia and headache with focus on POTS and migraine. We will then compare the clinical features of both conditions as well as some hypothesized pathophysiology overlaps. We will conclude by summarizing the diagnostic approach and multitiered treatment options for POTS and migraine., (© 2019 American Headache Society.)