Symptoms Of Autonomic Nervous System Dysfunction Research Articles

Natural History of Pediatric Cyclic Vomiting Syndrome: Progression to Dysautonomia.

The clinical features of pediatric cyclic vomiting syndrome (CVS) often evolve over time. Many patients develop a constellation of chronic symptoms that suggest autonomic nervous system (ANS) dysfunction during adolescence. We aimed to determine the proportion of children with CVS who develop chronic rather than episodic symptoms consistent with ANS dysfunction. Retrospective chart review of children ages 0-18 years followed in an outpatient tertiary care CVS center. Patients completed standardized questionnaires at intake and follow-up visits, documenting clinical symptom pattern. Continuous variables are summarized as median [interquartile range (IQR)]. A Mann-Whitney test was used for group comparisons. One hundred subjects were included. A total of 40% developed symptoms of ANS dysfunction (ANS+); 20% were confirmed by comprehensive ANS testing, 11% by orthostatic vital sign abnormalities, and 9% by clinical symptoms. The median (IQR) age at onset of chronic symptoms was 14 (10.02, 15) years. The presence of another disorder of gut-brain interaction ( P = 0.018) and a greater number of comorbidities ( P = 0.031) were more common in the ANS+ group. ANS+ subjects missed more school days ( P = 0.047) and were seen less frequently in the emergency department ( P = 0.023). Many children with CVS (40%) develop symptoms consistent with clinical dysautonomia in adolescence. These patients experience more comorbid conditions and a greater impact on school attendance, possibly representing a worsened quality of life as their disease course transitions to daily symptoms. When symptoms of CVS change over time, therapeutic interventions may need to be adjusted and targeted accordingly.

0397 Autonomic Reflex Testing Confirms Autonomic Disturbances in a Cohort of Patients with Idiopathic Hypersomnia

Abstract Introduction Symptoms suggestive of autonomic nervous system (ANS) dysfunction have been previously described in patients with idiopathic hypersomnia (IH), however, objective ANS reflex testing data has not been reported. We aimed to better quantify symptoms of ANS dysfunction in a cohort of patients with IH through the use of standardized ANS reflex testing. Methods Patients diagnosed with IH based on ICSD-3 criteria using overnight video polysomnography and multiple sleep latency testing (MSLT) were consecutively enrolled in our study, regardless of ANS symptoms. All patients underwent ANS reflex testing, including measures of parasympathetic (heart rate variability with deep breathing and Valsalva ratio) and sympathetic adrenergic function (Valsalva blood pressure response and 10-minute head-up tilt at an angle of 70 degrees) with continuous blood pressure and heart rate monitoring. Eleven patients also underwent measures of sympathetic cholinergic function (quantitative sudomotor axon reflex testing). All medications that affect ANS function were held prior to ANS testing, including wake-promoting medications and sodium oxybate. Results Twenty patients with IH were enrolled. Fifty percent (10/20) were long sleepers (>11hrs). Mean sleep onset latency and number of sleep onset REM periods (SOREMs) on MSLT were 6.9 (± 3.1) mins and 0.2 (± 0.4), respectively. Mean duration of IH symptoms prior to the date of ANS testing was 6.3 (± 8.1) yrs. Eighty-five percent (17/20) of patients had abnormal ANS testing. Of these, 75% (15/20) had sympathetic adrenergic impairment, 64% (7/11) had sympathetic cholinergic impairment, and 5% (1/20) had parasympathetic impairment. Fifty-five percent (11/20) of patients were diagnosed with postural tachycardia syndrome (POTS), 45% (5/11) with small fiber neuropathy, 5% (1/20) with inappropriate sinus tachycardia and 15% (3/20) with neurally-mediated syncope. Seventy percent (14/20) of patients reported orthostatic intolerance regardless of autonomic diagnosis. Conclusion ANS dysfunction was common and severe in our cohort of IH patients, affecting all domains of ANS reflex testing, with more prominent impairment in sympathetic domains. POTS was the most common comorbid diagnosis, and most patients reported orthostatic intolerance. There was no association with IH disease duration, though our sample size was limited. Future studies will focus on ANS testing in larger cohorts of IH patients, specifically on shared pathophysiological mechanisms of hypersomnia and ANS dysfunction. Support (If Any)

Autonomic Nervous System Dysfunction in Primary Sjögren's Syndrome.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease which primarily affects the exocrine glands, but can also affect other organs, including the nervous system. Many studies have reported evidence of autonomic nervous system (ANS) dysfunction in pSS which may contribute to a wide range of symptoms and functional burden. Symptoms of ANS dysfunction are common and widespread among patients with pSS and are associated with other features of the disease, particularly fatigue. Accumulating data on the inter-relationship between the ANS and the immune system via the vagus nerve have been reported. Vagus nerve stimulation (VNS) has also been associated with improvement in fatigue in patients with pSS. Taken together, these data suggest that the ANS may be a potential treatment target for pSS, in particularly those with fatigue being a predominant symptom. Future research to dissect the link between the ANS, immune dysregulation and clinical manifestations in pSS and to evaluate the potential of VNS as a therapy for pSS is warranted.

P.122 - Autonomic nervous system involvement in spinal muscular atrophy type 1, 2 and 3

Spinal muscular atrophy (SMA) is a selective lower motor neuron disease. There are emerging data indicating the involvement of additional systems, such as the autonomic nervous system (ANS), in SMA 1. The main reported symptoms are tremors and sweating with a correlation with the severity of clinical phenotype. We studied 30 patients with type 1, 2 and 3 SMA (n:10 for each group), with a broad age range and followed regularly in a multidisciplinary setting. We evaluated also age- and sex-matched healthy controls. Symptoms of autonomic dysfunction were assessed using the Composite autonomic symptom scale (COMPASS 31) and specific autonomic tests. They comprise of: Head-up tilting (HUT), Valsalva manoeuvre, deep breathing and cold pressure tests and skin sympathetic reflex. Moreover, we tested the plasma and urinary levels of catecholamines and sudomotor dysfunction with the novel Sudoscan technique. A significant number of patients/caregivers (26/30) reported symptoms of ANS dysfunction, mainly with gastrointestinal involvement. Eleven patients could perform a complete HUT test, the other patients were evaluated on reaching the sitting position from supine due to severe lower limbs contractures. All patients with type 1 SMA and most of patients with type 2 SMA experienced orthostatic intolerance symptoms during tilt test. Moreover, we showed high supine level of epinephrine at baseline and no significant rising of norepinephrine after tilt compared to controls. At variance, the dosage of catecholamines on the 24-hour urine protein test did not confirm differences with controls. Only in the less severe patients (8/30), we were able to perform Valsalva manoeuvre, deep breathing and cold pressure tests, showing normal results. Skin sympathetic reflex and Sudoscan test were normal. Our results suggest the novel hypothesis that SMA patients may have an adrenergic hyperactivity, experiencing several symptoms ranging from tremors to orthostatic intolerance. Further studies on larger cohorts are needed to confirm these interesting results.

Linear and nonlinear methods for analyses of cardiovascular variability in bipolar disorders

Heart rate variability (HRV), blood pressure variability (BPV), and the assessment of baroreflex sensitivity are widely accepted methods for analyzing and characterizing cardiovascular regulation and for an enhanced risk evaluation in different diseases. As a result of the complexity of the investigated regulatory systems, univariate analyses do not often provide a convenient description of pathological changes in the cardiovascular regulation. Therefore, the application of a multivariate approach is preferable. We present principal methods of time-domain, frequency-domain, and nonlinear analyses of HRV, BPV as well as methods for coupling and interaction analyses. Changes in autonomic nervous system (ANS) tone are known to accompany various mental disorders. Depressive patients frequently complain of symptoms of ANS dysfunction, such as dry mouth, diarrhea, and insomnia. These clinical observations propose the assumption of altered autonomic dysfunction in these patients. In contrast to these clinical assumptions, inconsistent results have been found in studies of HRV in depressive patients. This work therefore covers a brief review of the literature in respect to bipolar disorder and the rationale to study autonomic changes in such a psychiatric disease. Prospective studies of cardiovascular changes in mania and depression are needed to evaluate a psychopathological state in connection with cardiovascular changes and cardiac morbidity and mortality. These studies should consider BPV, coupling and interaction analyses, the application of nonlinear methods, and a multivariate approach in addition to the traditional analysis of HRV.

Autonomic Nervous System Dysfunction in Parkinson's Disease.

Autonomic nervous system (ANS) dysfunction is common in Parkinson's disease (PD), affects 70% to 80% of patients, and causes significant morbidity and discomfort. Autonomic nervous system dysfunction symptoms in PD include sexual dysfunction, swallowing and gastrointestinal disorders, bowel and bladder abnormalities, sleep disturbances, and derangements of cardiovascular regulation, particularly, orthostatic hypotension. Autonomic nervous system dysfunction in PD may be caused by an underlying degenerative process that affects the autonomic ganglia, brainstem nuclei, and hypothalamic nuclei. Anti-parkinsonian medications can cause or worsen symptoms of ANS dysfunction. The care of a PD patient with ANS dysfunction relies on its recognition and directed treatment, including coordinated care between the neurologist and appropriate subspecialist. Pharmacotherapy may be useful to treat orthostasis, gastrointestinal, urinary, and sexual dysfunction.

Case/control family study of autonomic nervous system dysfunction in idiopathic congenital central hypoventilation syndrome.

Children with idiopathic congenital central hypoventilation syndrome (CCHS) have a complex phenotype consistent with an imbalance of the autonomic nervous system (ANS). Since CCHS may be genetic in origin, we hypothesized that relatives of individuals with CCHS may exhibit symptoms of ANS dysfunction (ANSD), albeit in a milder form. We tested this hypothesis by assessing aspects of ANS function in relatives of CCHS cases vs. relatives of matched controls with a scripted questionnaire. Only those 35 symptoms of ANSD exhibited by > or =5% of the CCHS cases were included in the analysis as the basis for determining ANSD affection status. Two different arbitrary ANSD affection status definitions are presented in detail: any case, control, or relative with positive findings (1) in two or more symptoms, or (2) in two or more systems. The subjects included in the analysis totaled 2,353, including 56 CCHS cases, 56 age-, gender-, and race-matched controls, and their families. Under each of the two arbitrary ANSD affection statuses, CCHS cases and parents of cases were more likely to be affected than controls and parents of controls (P < 0.001 for both comparisons), 16% of the CCHS siblings had the ANSD phenotype with two or more symptoms, compared to 4% of control siblings (P = 0.03). Aunts and uncles of the CCHS cases were also significantly more likely to have two or more ANSD symptoms than were aunts and uncles of the controls (P= 0.009). These results support our hypothesis and also indicate that relatives of the CCHS cases tended to manifest a milder spectrum of ANSD, with fewer systems and/or fewer symptoms than the cases.