Autonomic Symptom Profile Research Articles

Where Is the Core of the Volcano? The Undetermined Origin of Primary Restless Legs Syndrome

ABSTRACTAn association between small fiber neuropathy and primary Restless Legs Syndrome (RLS) is suggested since both of them share common characteristics. Our aim was to investigate the existence of autonomic neuropathy on the basis of autonomic tests. The patients and the age-matched controls were evaluated with Neuropathy Symptom Profile and Autonomic Symptom Profile, nerve conduction studies (NCS), and autonomic tests. Patients suffered from neuropathic and autonomic complaints obviously. There was no significant difference for NCS, heart rate variability tests, and sympathetic skin responses (SSRs) among patients and controls. Since both the NCSs and the autonomic tests were within normal, the complaints were considered to be the consequences of the problem in sensory integration due to the dysfunction of the caudal diencephalic A11 group, rather than a neuropathic process. The cardiac autonomic imbalance possibly emerges as a consequence of arousal periods prior to or during the Periodic Leg Movements (PLM) episodes during sleep, but not due to autonomic neuropathy.

Impaired Gastric Emptying in Primary Sjögren’s Syndrome

To investigate the prevalence of impaired gastric emptying (IGE) and its relation to autonomic nervous dysfunction (AD), functional bowel syndrome, and inflammatory and serological variables in patients with primary Sjögren's syndrome (pSS). Twenty-eight patients with pSS according to the American-European Consensus Criteria were included in the study. Gastric emptying was evaluated by the octanoate breath test from which half-time (t(half)) and lag-time (t(lag)) were determined and compared with the results from 50 healthy controls. Autonomic nervous function was evaluated by 5 objective autonomic reflex tests (ART) and by the Autonomic Symptom Profile (ASP) questionnaire evaluating AD symptoms. These results were compared with previously investigated healthy ART controls and population-based ASP controls. Patients were also assessed regarding symptoms of functional bowel syndrome. The t(half) and the t(lag) were significantly prolonged in patients compared to controls. Forty-three percent of patients with pSS presented signs of IGE and 29% fulfilled the criteria for gastroparesis. Significant correlations were found between t(lag) and increased levels of IgG (p = 0.02) and erythrocyte sedimentation rate (ESR; p = 0.01). In addition, rheumatoid factor (RF) seropositives showed objective signs of IGE to a greater extent than RF seronegatives. No associations between IGE, ART variables, ASP variables, or gastrointestinal symptoms were found. IGE was common in pSS. Associations with inflammatory and serological features of pSS could imply immunological mechanisms behind the IGE. Objective signs of IGE were not associated with objective signs or subjective symptoms of AD or functional bowel syndrome.

Autonomic neuropathy in Fabry disease: a prospective study using the Autonomic Symptom Profile and cardiovascular autonomic function tests

BackgroundFabry patients have symptoms and signs compatible with autonomic dysfunction. These symptoms and signs are considered to be due to impairment of the peripheral nervous system, but findings indicative of autonomic neuropathy in other diseases, such as orthostatic intolerance and male sexual dysfunction, are infrequently reported in Fabry disease. The aim of our study was to investigate autonomic symptoms and cardiovascular autonomic function in a large cohort of male and female Fabry patients.MethodsForty-eight Fabry patients (15 male, 30 treated with enzyme replacement therapy) and 48 sex- and age-matched controls completed a questionnaire on autonomic symptoms (the Autonomic Symptom Profile). Thirty-six Fabry patients underwent cardiovascular function tests.ResultsThe Autonomic Symptom Profile revealed a significantly higher sum score in Fabry patients than in healthy control subjects (22 versus 12), but a relatively low score compared to patients with proven autonomic neuropathy. Fabry patients scored worse than healthy controls in the orthostatic intolerance domain. Scores in the male sexual dysfunction domain were comparable between healthy controls and male Fabry patients. The cardiovascular autonomic function tests revealed only mild abnormalities in seven patients. None of these seven patients showed more than one abnormal test result. Enzyme replacement therapy was not associated with less severe disease, lower ASP scores or less frequent abnormal cardiovascular function test results.ConclusionsMale sexual function and autonomic control of the cardiovascular system are nearly normal in Fabry patients, which cast doubt on the general accepted assumption that autonomic neuropathy is the main cause of symptoms and signs compatible with autonomic dysfunction in Fabry disease. Possibly, end-organ damage plays a key role in the development of symptoms and signs in Fabry patients. An exceptional kind of autonomic neuropathy is another but less likely explanation.

Autonomic nervous dysfunction development in patients with primary Sjogren's syndrome: a follow-up study

To investigate autonomic dysfunction (AD) development in patients with primary SS (pSS) and the associations between AD and clinical, inflammatory and serological features of pSS. Twenty-seven patients with pSS, who had previously been evaluated for AD, were included in the study. The patients were studied at baseline and at follow-up by objective autonomic reflex tests (ARTs) and by the autonomic symptom profile (ASP) questionnaire, evaluating AD symptoms. The median follow-up time was 5 years for the ART and 4 years for the ASP variables. The results were compared with previously investigated healthy ART controls and population-based ASP controls. Fatigue, anxiety and depression were assessed by the profile of fatigue and by the Hospital Anxiety and Depression scale. Three of five ART variables as well as the ASP total score were significantly abnormal both at baseline and at follow-up in pSS patients in comparison with controls. When comparing ART and ASP results in pSS patients between baseline and follow-up, only the lowest diastolic blood pressure (lDBP) ratio significantly deteriorated during the follow-up period. The ART and ASP variables were not significantly correlated. However, the ASP total score significantly correlated with measurements of fatigue, anxiety and depression. Both objective signs and subjective symptoms of parasympathetic and sympathetic dysfunction were seen in pSS patients, both at baseline and at follow-up. During follow-up, only the lDBP ratio was found to significantly deteriorate. AD symptoms were significantly associated with fatigue, anxiety and depression.

Versión española del test perfil de síntomas autonómicos

The Autonomic Symptom Profile (ASP) is a self-administered questionnaire that has been validated in English to assess autonomic symptoms and to differentiate between patients and healthy subjects according to said symptoms. Our group has studied its application in Spanish. After translating the English version into Spanish and then back-translating it, the reliability and validity of criteria in the Spanish version of the ASP test were evaluated in a sample of 50 subjects (27 controls and 23 patients). All the patients with symptoms of autonomic dysfunction were studied by means of the Ewing and Clarke battery. The reliability of the Spanish version of the ASP was high and an interclass correlation coefficient of 0.93 was obtained. A score of 47 or over in the test yields a sensitivity of 73.9% and a specificity of 100% for the detection of autonomic dysfunction. Furthermore, the score in the Spanish version of the ASP test showed statistically significant differences between the group of patients and the control group. The Spanish version of the ASP is reliable and makes it possible to distinguish between patients with autonomic dysfunction and control subjects. As far as we are aware, this is the first test to evaluate the symptoms of the autonomic nervous system in a global manner and in Spanish.

Experiencia de dos años en una consulta específica de sistema nervioso autónomo

Despite the high incidence and prevalence of pathologies affecting the autonomic nervous system (ANS), this part of neurology has received very little specific attention in clinical care in our country.To present the experience we have gained over a two-year period in an ANS-specific service.Our patients were referred to the ANS service by other colleagues, most of whom were neurologists, between April 2006 and April 2008, after proposing a set of eligibility and exclusion criteria. Clinical history, examination and general analysis were performed for all patients. The following tests were also carried out on an individualised basis: Ewing-Clarke test, the Spanish version of the autonomic symptom profile test, tilt table test, holter heart monitor, urodynamic study and reflex sympathetic test, among other complementary studies.Thirty-four first visits and 62 successive visits were registered. The most frequent diagnoses were neurologically mediated syncopes and diabetic autonomic neuropathies, but other less prevalent conditions were also diagnosed. The most cost-effective complementary tests were the Ewing-Clarke test and the autonomic symptom profile test. Apart from benzodiazepines, the most commonly prescribed pharmacological treatments were paroxetine and pyridostigmine.As expected, neurologically mediated syncopes and diabetic neuropathies with an autonomic component are the most frequent pathologies in an ANS service. Nevertheless, their diagnosis and individualised treatment, together with that of other less prevalent autonomic pathologies, may require specific attention. To our knowledge, this is the first service of its kind in our country.

Recurrent urinary tract infections and bladder dysfunction in systemic lupus erythematosus

To assess bladder function in systemic lupus erythematosus (SLE) patients with recurrent urinary tract infections (UTIs). A convenience sample of consecutive patients with SLE (American College of Rheumatology criteria), with recurrent UTIs (>/=3 events in the preceding 12 months), without history of central nervous system involvement, urolithiasis or preceding tuberculosis were studied. Disease activity (SLEDAI-2K), damage (SDI), lower urinary tract symptoms [Pelvic pain and Urgency/Frequency (PUF) and the Interstitial Cystitis Symptom and Problem Index (ICSPI) scales] and Autonomic Symptom Profile (ASP) were assessed. All patients underwent urological examination and urodynamic assessment with cystometry, uroflow, micturition and urethral pressure profile. Ten patients (nine women) were included. The majority of the patients reported urinary symptoms: urgency (n = 8), frequency (n = 8), nocturia (n = 9) and pain (n = 10). The patients had a mean (SD) ICSPI score of 18.4 (9.8), PUF score of 17.4 (5.3) and ASP weighted score of 31.7 (16.1). Abnormal urodynamics findings were identified in seven of the 10 patients, including small bladder capacity (two patients), reduced bladder sensation (four patients), subnormal urinary flow rate (one patient) and a significant amount of residual urine (two patients). The urodynamics findings suggest that bladder dysfunction could be one of the mechanisms involved on the occurrence of recurrent UTIs in patients with SLE. These findings have potential implications for the proper assessment and management of SLE patients with recurrent UTIs. Further studies are needed to corroborate our results.

Assessment of autonomic symptoms in diabetics: the Swedish version of the Autonomic Symptom Profile

Autonomic dysfunction (AD) is a complication of diabetes and may be associated with troubling symptoms and increased mortality. Commonly, AD is detected by objective physiological tests and only recently, a validated self-completed English questionnaire assessing AD symptoms, the Autonomic Symptom Profile (ASP), was developed. The aims of this study were to translate the ASP into Swedish and evaluate its reliability and validity. Forward and back translations were performed. Thirty-one patients with type I diabetes, 200 population-based controls and two AD experts participated in the study. Test-retest reliability was evaluated by letting 25 patients to fill in the ASP twice. Content validity was evaluated by two Swedish AD experts and construct validity was evaluated by studying associations between the ASP total score and five objective autonomic nervous function test variables. Finally, discriminant validity was evaluated by studying differences in the ASP total and domain scores between patients and controls. The translation was accepted without changes. Test-retest reliability and content validity of the Swedish ASP were considered good. The construct validity was considered acceptable with two significant associations between the ASP total score and the autonomic nervous function test variables. In addition, discriminant validity was considered acceptable with regard to the ASP total score as well as the sexual dysfunction, sleep disorder and vasomotor dysfunction domain scores significantly differing between patients and controls. The Swedish version of the ASP was considered a reliable and valid instrument for the study of AD symptoms in patients with type I diabetes.

Autonomic nervous symptoms in primary Sjogren's; syndrome

Objective signs of autonomic dysfunction (AD) have been reported in patients with primary SS (pSS) while the presence of associated symptoms has not been systematically studied. Therefore, the aims of this study were (i) to assess the presence and severity of various AD symptoms in pSS patients and (ii) to relate AD symptoms to other clinical features of pSS. Thirty-eight pSS patients and 200 population-based controls were studied for presence and severity of AD symptoms using the Autonomic Symptom Profile (ASP), a validated self-completed questionnaire evaluating various AD symptoms. In addition, patients were investigated by three different objective autonomic nervous function tests. pSS patients scored significantly higher in the parasympathetic [secretomotor disorder, urinary disorder, gastroparesis (females only) and pupillomotor disorder] as well as sympathetic (orthostatic intolerance and vasomotor disorder) ASP domains compared with controls. Consequently, the standardized ASP total score was significantly increased in pSS patients [1.77 (0.57, 3.15) vs - 0.21 (-0.82, 0.72); P = 0.00] and 45% of pSS patients had an ASP total score >/=2 s.d. Furthermore, the autonomic nervous function tests showed signs of objective parasympathetic and sympathetic dysfunction as well. However, the ASP domain and total scores showed limited associations with the objective autonomic nervous function test parameters as well as clinical and serological factors of pSS. pSS patients showed subjective and objective signs of both a parasympathetic and a sympathetic dysfunction. However, AD symptoms showed limited associations with objective autonomic nervous function as well as other clinical features of the disease.

Autonomic Symptoms and Diabetic Neuropathy

The prevalence of autonomic symptoms and deficits in certain systems is known, but a comprehensive autonomic symptom profile in diabetes is not available. We aimed to estimate this using a laboratory evaluation of autonomic function and a validated self-report measure of autonomic symptoms in patients and matched control subjects from the population-based Rochester Diabetic Neuropathy Study. Participants included 231 patients with diabetes (type 1, n=83; type 2, n=148) and 245 healthy age-matched control subjects. We assessed symptoms using a validated self-report instrument (Autonomic Symptom Profile) and evaluated the severity and distribution of autonomic deficits (cardiovagal, sudomotor, adrenergic) with the objective, laboratory-based Composite Autonomic Severity Score (CASS). Autonomic symptoms were present more commonly in type 1 than in type 2 diabetes, with symptoms of orthostatic intolerance, secretomotor, urinary control, diarrhea, and sleep disturbance and pupillomotor, vasomotor, and erectile dysfunction significantly increased over healthy control subjects in type 2 diabetic patients. The prevalence of autonomic impairment was 54% in type 1 and 73% in type 2 diabetic patients. Severity of autonomic failure was mild overall (mean CASS 2.3; maximum 10), with orthostatic hypotension occurring in 8.4 and 7.4% of type 1 and 2 diabetic patients, respectively. Fourteen percent of patients had a CASS > or =5, indicating moderate to severe generalized autonomic failure. The correlation of symptoms with autonomic deficits (CASS) was better in type 1 than type 2 diabetic subjects and was weak overall. These findings indicate that autonomic symptoms and deficits are common in diabetes, but mild in severity, and that the correlation between symptom scores and deficits is overall weak in mild diabetic neuropathy, emphasizing the need to separately evaluate autonomic symptoms.

Quality of Life in Patients With Postural Tachycardia Syndrome

To quantify quality of life and identify demographic and clinical correlates of functioning in a well-characterized sample of patients with postural tachycardia syndrome (POTS). Prospective patients were those seen at the Mayo Clinic Autonomic Disorders Laboratory from September 2000 to June 2001. Neurologists made diagnoses of POTS according to established criteria. Patients completed a questionnaire packet that included measures of quality of life (36-Item Short-Form Health Survey [SF-36]) and symptom severity (Autonomic Symptom Profile). Additional clinical information was abstracted from medical records. Ninety-four patients (89% female; mean age, 34.2 years) were enrolled in the study. Patients with POTS reported impairment across multiple domains on the SF-36. Physical functioning, role functioning, bodily pain, general health, vitality, and social functioning were all significantly impaired compared with a healthy population (P<.01 for all) and similar to that reported by patients with other chronic, disabling conditions. Hierarchical regression analyses revealed that symptom severity (beta = -.36, P<.001) and disability status (beta = -36, P<.001) were independent predictors of SF-36 physical component scores, with the full model accounting for 54% of the variance (P<.001). None of the variables examined accounted for a significant amount of the variance in SF-36 mental component scores. Patients with POTS experience clear limitations across multiple domains of quality of life, including physical, social, and role functioning. Treatment should address the multiple and varied impairments experienced by these patients and may require a multidisciplinary approach. Future research must further delineate factors, both disease related and psychosocial, that predict functioning and adjustment in this population.

Postural Tachycardia Syndrome: Clinical Features and Follow-up Study

To define the clinical features and outcome of postural tachycardia syndrome (POTS). In this cross-sectional study of the autonomic symptom profile, inclusion criteria were orthostatic heart rate increment of 30 beats/min or greater, orthostatic symptoms, completion of a standardized autonomic test battery, and follow-up of 18 months or longer. We used 2 instruments. The first part was a structured and validated autonomic symptom profile (108 patients). The second part was a structured questionnaire focused on autonomic status on prospective follow-up (40 patients) (mean +/- SD follow-up, 67+/-52 months). Most patients had frequent, persistent, and at least moderately severe symptoms for less than 5 years. The following orthostatic symptoms occurred in more than 75% of subjects: light-headedness or dizziness, lower extremity or diffuse weakness, disequilibrium, tachycardia, and shakiness. Nonorthostatic symptoms included dry eyes or mouth, gastrointestinal complaints of bloating, early satiety, nausea, pain, and alternating diarrhea and constipation. Half of the patients reported an antecedent illness presumed to be of viral origin. On follow-up, 80 % of patients were improved, 60% were functionally normal, and 90% were able to return to work. Patients who had an antecedent event appeared to do better than those with spontaneous POTS. Salt supplementation and beta-blockers were the most efficacious therapies. In the majority of patients, POTS is self-resolving, especially in those with a triggering event.

The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms.

To develop a new specific instrument called the Autonomic Symptom Profile to measure autonomic symptoms and test its validity. Measuring symptoms is important in the evaluation of quality of life outcomes. There is no validated, self-completed questionnaire on the symptoms of patients with autonomic disorders. The questionnaire is 169 items concerning different aspects of autonomic symptoms. The Composite Autonomic Symptom Scale (COMPASS) with item-weighting was established; higher scores indicate more or worse symptoms. Autonomic function tests were performed to generate the Composite Autonomic Scoring Scale (CASS) and to quantify autonomic deficits. We compared the results of the COMPASS with the CASS derived from the Autonomic Reflex Screen to evaluate validity. The instrument was tested in 41 healthy controls (mean age 46.6 years), 33 patients with nonautonomic peripheral neuropathies (mean age 59.5 years), and 39 patients with autonomic failure (mean age 61.1 years). COMPASS scores correlated well with the CASS, demonstrating an acceptable level of content and criterion validity. The mean (+/-SD) overall COMPASS score was 9.8 (+/-9) in controls, 25.9 (+/-17.9) in the patients with nonautonomic peripheral neuropathies, and 52.3 (+/-24.2) in the autonomic failure group. Scores of symptoms of orthostatic intolerance and secretomotor dysfunction best predicted the CASS on multiple stepwise regression analysis. We describe a questionnaire that measures autonomic symptoms and present evidence for its validity. The instrument shows promise in assessing autonomic symptoms in clinical trials and epidemiologic studies.

Autonomic failure in Guamanian neurodegenerative disease

Autonomic impairment is minor in idiopathic amyotrophic lateral sclerosis (ALS) and Alzheimer's-type dementia (D) and is usually not marked in Parkinson's disease. The autonomic status of Guamanian parkinsonism (P), ALS, and parkinsonism-dementia complex (PDC) is essentially unknown. We therefore evaluated the autonomic nervous system in Guamanian D, ALS, P, and PDC. Cardiovagal, adrenergic, and postganglionic sudomotor functions were quantitated in 16 patients and 14 paired household controls. Patients comprised PDC (N = 11), D (N = 2), P (N = 2), and ALS (N = 1). Autonomic deficit was expressed on a composite autonomic scoring scale (CASS) and its subsets that corrects for the effects of age and gender. CASS severity was rated from 0 to 10 and the maximal subset scores were 3, 3, and 4 for postganglionic sudomotor, cardiovagal, and adrenergic deficits, respectively. CASS scores for mild, moderate, and severe autonomic failure are 1 to 3, 4 to 6, and 7 to 10, respectively. Symptoms were scored by an Autonomic Symptom Profile (ASP). The affected patients were older than and had a sex distribution different from paired controls (64.2 +/- 8.0 versus 53.1 +/- 13.5; p < 0.01; male/female = 9/7 versus 2/12; p = 0.045). CASS scores were markedly increased over paired controls (6.2 +/- 2.3 versus 1.9 +/- 1.3; p < 0.001), and involvement was generalized by system. There were deficits in sudomotor, cardiovagal, and adrenergic function. Orthostatic hypotension occurred in 6 of 16 patients and 2 of 14 paired controls. Guamanian patients had more autonomic dysfunction than non-Guamanian Parkinson's disease. ASP scores were higher in patients than controls and regressed with CASS. These differences persisted when corrected for the confounding effects of age, gender, and diabetes. We conclude that Guamanian patients have autonomic failure to a greater extent than non-Guamanian Parkinson's disease or ALS. This autonomic failure suggests multisystem autonomic involvement similar to but less severe than in multiple system atrophy.

Motor Neurone Disease

<h3>Objective</h3> To investigate the prevalence of impaired gastric emptying (IGE) and its relation to autonomic nervous dysfunction (AD), functional bowel syndrome, and inflammatory and serological variables in patients with primary Sjögren’s syndrome (pSS). <h3>Methods</h3> Twenty-eight patients with pSS according to the American-European Consensus Criteria were included in the study. Gastric emptying was evaluated by the octanoate breath test from which half-time (t_half) and lag-time (t_lag) were determined and compared with the results from 50 healthy controls. Autonomic nervous function was evaluated by 5 objective autonomic reflex tests (ART) and by the Autonomic Symptom Profile (ASP) questionnaire evaluating AD symptoms. These results were compared with previously investigated healthy ART controls and population-based ASP controls. Patients were also assessed regarding symptoms of functional bowel syndrome. <h3>Results</h3> The t_half and the t_lag were significantly prolonged in patients compared to controls. Forty-three percent of patients with pSS presented signs of IGE and 29% fulfilled the criteria for gastroparesis. Significant correlations were found between t_lag and increased levels of IgG (p = 0.02) and erythrocyte sedimentation rate (ESR; p = 0.01). In addition, rheumatoid factor (RF) seropositives showed objective signs of IGE to a greater extent than RF seronegatives. No associations between IGE, ART variables, ASP variables, or gastrointestinal symptoms were found. <h3>Conclusion</h3> IGE was common in pSS. Associations with inflammatory and serological features of pSS could imply immunological mechanisms behind the IGE. Objective signs of IGE were not associated with objective signs or subjective symptoms of AD or functional bowel syndrome.