Gastrointestinal symptom burden in diabetic autonomic and peripheral neuropathy - A Danes cohort study.

OBJECTIVE: We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA1C and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately. RESULTS: We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group. CONCLUSIONS: A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.

Baseline prevalence and longitudinal assessment of autonomic dysfunction in early Parkinson's disease.

Autonomic dysfunction (AutD) is common and debilitating in Parkinson's disease (PD). Predictors of AutD are unclear, and data are limited on the biological relevance of AutD in PD. Here, we evaluated the baseline prevalence and 2-year longitudinal assessment of AutD in patients with de novo PD compared with healthy controls (HC). Moreover, we also assessed various variables that could predict longitudinal changes in AutD in early PD. Parkinson's Progression Markers Initiative (PPMI) was utilized to evaluate untreated PD participants at baseline and HC. Autonomic function was assessed using the 25-item Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT) score at baseline and 2 years. Clinical and biological variables were measured for their correlations with AuD for up to 2 years. Two hundred and ninety PD subjects and 170 HC were enrolled and followed for 2 years. SCOPA-AUT mean (SD) scores increased from baseline 8.49 ± 5.23 to 10.12 ± 5.77 at year 2 in PD subjects (p < 0.001) versus from 4.98 ± 3.34 to 5.03 ± 374 in HC (p = 0.496), with a significant difference between the groups (p < 0.001). Among them, 242 PD participants and 151 HC completed the SCOPA-AUT assessment, including sexual function. In the multivariate analysis, a higher baseline SCOPA-AUT score was associated with higher baseline MDS-UPDRS Part I scores (p < 0.001). Moreover, a longitudinal increase in autonomic function severity was associated with the white race (p = 0.010) at baseline. In contrast, there was no association with the CSF biomarkers. MDS-UPDRS Part I score may predict AuD in patients with early PD, which is correlated with nonmotor symptoms and race.

Assessment of comorbid symptoms in pediatric autonomic dysfunction.

PURPOSE: Pediatric patients with autonomic dysfunction and orthostatic intolerance (OI) often present with co-existing symptoms and signs that might or might not directly relate to the autonomic nervous system. Our objective was to identify validated screening instruments to characterize these comorbidities and their impact on youth functioning. METHODS: The Pediatric Assembly of the American Autonomic Society reviewed the current state of practice for identifying symptom comorbidities in youth with OI. The assembly includes physicians, physician-scientists, scientists, advanced practice providers, psychologists, and a statistician with expertise in pediatric disorders of OI. A total of 26 representatives from the various specialties engaged in iterative meetings to: (1) identify and then develop consensus on the symptoms to be assessed, (2) establish committees to review the literature for screening measures by member expertise, and (3) delineate the specific criteria for systematically evaluating the measures and for making measure recommendations by symptom domains. RESULTS: We review the measures evaluated and recommend one measure per system/concern so that assessment results from unrelated clinical centers are comparable. We have created a repository to apprise investigators of validated, vetted assessment tools to enhance comparisons across cohorts of youth with autonomic dysfunction and OI. CONCLUSION: This effort can facilitate collaboration among clinical settings to advance the science and clinical treatment of these youth. This effort is essential to improving management of these vulnerable patients as well as to comparing research findings from different centers.

Electrophysiological assessment of peripheral and central autonomic disorders.

The autonomic nervous system (ANS) coordinates multiple reflex actions which are essential for life. The tests employed to evaluate the ANS provide valuable information of the functional state of these reflex arcs. The ideal test should be simple to perform, noninvasive, reproducible, sensitive, specific, safe, and appropriate for longitudinal studies. The availability of computer-based techniques has facilitated the electrophysiological assessment of ANS-mediated reflexes. The information provided by autonomic testing must be analyzed in combination with the clinical history and physical examination of the patient, allowing for a hypothesis that can be tested. Properly performed and interpreted, ANS testing can be used to confirm the presence of an ANS disturbance and the involved functional pathways, as well as the extent, intensity, and site of injury. This chapter describes the most important electrophysiological tests used to evaluate the ANS control of cardiovascular reflexes and sweat gland activity.

Functional magnetic resonance imaging for the assessment of autonomic dysfunction in patients with antineutrophil cytoplasmic antibody-associated vasculitides.

INTRODUCTION: Nervous system involvement is common in antineutrophil cytoplasmic antibody-associated vasculitides (AAV). While the involvement of the peripheral and central nervous system is well described, it is still unclear how and to what extent the autonomic nervous system (ANS) is affected. Functional magnetic resonance imaging (fMRI) can provide information on both structure and potential damage of the brain, as well as on the function of selected brain centers. OBJECTIVES: The aim of this study was to investigate the ANS dysfunction in AAV patients and its correlation with the results of fMRI performed during the Valsalva maneuver. PATIENTS AND METHODS: A total of 31 patients with AAV and 30 healthy controls were enrolled in the study. Each participant completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire. MRI was performed using a 3T scanner. The participants were asked to perform the Valsalva maneuver according to the fixed protocol, and their airway pressure was monitored. During the maneuver, fMRI data were collected. The generalized least­ squares time series analysis and the region of interest (ROI) analysis were subsequently performed. RESULTS: The patients with AAV had a higher median COMPASS­ 31 score than the controls (12.86 vs 2.99, respectively; P <0.01). Structural MRI investigation did not reveal any significant differences between the groups. The brain centers involved in ANS function were detected during fMRI; however, the ROI analysis showed no differences between the study patients and controls. CONCLUSIONS: The patients with AAV reported symptoms related to the ANS dysfunction; however, no differences with respect to the functioning of the ANS brain centers were demonstrated between these patients and healthy controls in the fMRI study during the Valsalva maneuver.

Assessment of autonomic nervous system dysfunction associated with peripheral neuropathies in the context of clinical neurophysiology practice.

Peripheral neuropathies may involve the small diameter nerve fibers of the autonomic nervous system. In the presence of clinical signs compatible with dysautonomia, it is very difficult to affirm that these signs are really linked to an alteration in postganglionic autonomic innervation, and not to a lesion of the central nervous system or to a direct damage to the tissues and innervated organs. Also, in the context of the investigation of peripheral neuropathies, there is an interest in performing objective and quantitative assessment of distal autonomic innervation. The corresponding autonomic tests are mainly based on the exploration of sudomotor or vasomotor disorders of the limb extremities. In this article, we provide an overview of the various tests available for the study of the autonomic nervous system in clinical practice, including vasomotor reactivity tests, in particular based on laser Doppler techniques, and sudomotor tests, based on axon-reflexes produced by iontophoresis of cholinergic drugs or on the simpler measurement of electrochemical skin conductance by the Sudoscan® device.

Sympathetic and electrochemical skin responses in the assessment of sudomotor function: a comparative study.

OBJECTIVES: The sympathetic skin response (SSR) is a well-established test, whereas the electrochemical skin conductance (ESC) is still under evaluation. Our aim was therefore to assess the diagnostic accuracy of ESC to detect abnormal sudomotor function, using SSR as a reference test. METHODS: A cross sectional observational study was performed of 61 neurological patients assessed for possible sudomotor dysfunction and 50 age-matched healthy controls (HC). Patients with diagnoses of vasovagal syncope (VVS, n=25), Parkinson's disease (PD, n=15), multiple system atrophy (MSA, n=11) and peripheral neuropathies (PN, n=10) were included. Sudomotor function was assessed with SSR and ESC tests in all participants. The absence of SSR in the palms or soles indicates abnormal sudomotor function. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of the ESC. Cardiovascular autonomic (CV-Aut) function was evaluated through the Ewing score, based on the following tests: Heart rate change with deep breathing, Valsalva ratio, 30:15 ratio, blood pressure changes on standing and during isometric exercise. A Ewing score ≥ 2 indicates the presence of CV-Aut dysfunction. RESULTS: Mean SSR amplitudes and ESC values showed differences between HC and patients with MSA or PN (p < 0.05), but not in patients with VVS or PD. Absence of SSR was associated with abnormal ESC (p < 0.05). Patients with abnormal CV-Aut dysfunction had lower ESC (p< 0.05). Palm ESC (P-ESC) and sole ESC (S-ESC) assessment had a sensitivity of 0.91 and 0.95 to predict sudomotor dysfunction, with a specificity of 0.78 and 0.85, respectively. The area under ROC curve was 0.905 and 0.98, respectively. CONCLUSIONS: ESC in palms and soles has a high diagnostic accuracy for sudomotor dysfunction as detected by absent SSR in patients with MSA and PN.

The relationship of masked hypertension with autonomic dysfunction and cardiometabolic parameters: a case-control study.

OBJECTIVE: Masked hypertension (MH) is associated with cardiovascular events and mortality. Data on the association between exaggerated blood pressure response (EBPR) to exercise, heart rate recovery (HRR), which are indicators of autonomic dysfunction, and MH are lacking. This study aimed at evaluating the association between EBPR, HRR, and MH. PATIENTS AND METHODS: Between January 2020 and January 2021, 130 MH (57 male, median age = 52.8 years) and 60 healthy (28 male, median age = 40.8 years) subjects were included in this single-center, case-control, and cross-sectional study. Office blood pressure measurement, 24-hour ambulatory blood pressure monitoring, treadmill test, echocardiography, and specific biochemical parameters were evaluated. RESULTS: The frequency of blunted HRR (73 subjects, 56.2%) and EBPR (40 subjects, 30.8%) were significantly higher in patients with MH (p < 0.001). Patients with MH had higher serum uric acid levels and frequency of hyperlipidemia (p < 0.05). Diameters of the left atrium (LA), aortic root, and ascending aorta were significantly higher in MH patients (p < 0.05). Thirty-two (24.6%) patients with MH had left ventricular hypertrophy and 33 (25.4%) had diastolic dysfunction (p < 0.001). Multivariate analysis identified the presence of blunted HRR as an independent predictor factor of MH as well as smoking, hyperlipidemia, GFR, LA diameter, and aortic root diameter were other independent factors. CONCLUSIONS: The frequency of blunted HRR and EBPR were significantly higher in the MH group compared to the control group, suggesting a close relationship between MH and autonomic dysfunction.

Bedside Assessment of Autonomic Dysfunction in Multiple System Atrophy.

Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder of the adulthood, characterized by autonomic failure, parkinsonian and cerebellar features in various combinations. Distinguishing MSA from common clinical look-alikes such as Parkinson's disease, other atypical parkinsonian disorders or alternative causes of sporadic adult-onset cerebellar ataxia may be difficult, especially at early disease stages. Nonetheless, some simple and cost-effective screening tools help detecting important red flags guiding towards a MSA diagnosis. Here we outline which clinical pearls and bedside tests may disclose autonomic dysfunction in multiple domains, enabling an early MSA diagnosis and, even more importantly, personalized treatment.

Assessment of autonomic dysfunction with the COMPASS-31 and its relationship with disease activity and cardiovascular risks in patients with psoriatic arthritis.

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

Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study.

BACKGROUND AND OBJECTIVES: Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P), with the latter characterized by diffuse anhidrosis in prospective study, including patients in late stage of disease. We aimed to evaluate morphologic and functional postganglionic sudomotor involvement in patients with newly diagnosed MSA-P and PD to identify possible biomarkers that might be of help in differentiating the 2 conditions in the early stage. METHODS: One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At the time of recruitment, questionnaires to assess nonmotor, autonomic, and small fiber symptoms were administered, and patients underwent postganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from the distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies, including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured on confocal images with dedicated software. A follow-up visit 12 months after recruitment was performed to confirm the diagnosis. RESULTS: We recruited 57 patients with PD (M/F 36/21, age 63.5 ± 9.4 years) and 43 patients with MSA-P (M/F 27/16, age 62.3 ± 9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in patients with MSA-P compared to those with PD. Sweating output and intraepidermal, pilomotor, and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in patients with MSA-P. Pilomotor and sudomotor nerve density correlated with sweating function and with nonmotor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers efficiently separated the 2 populations; the receiver operating characteristics curve showed an area under the curve of 0.83. DISCUSSION: Dynamic sweat test and the quantification of cutaneous autonomic nerves proved to be a sensitive morpho-functional approach to assess the postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to differentiate the 2 conditions early. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that postganglionic sudomotor morpho-functional assessment accurately distinguish patients with PD from patients with MSA-P.

Clinical Assessment of Autonomic Function in Fibromyalgia by the Refined and Abbreviated Composite Autonomic Symptom Score (COMPASS 31): A Case-Controlled Study.

BACKGROUND: It has been shown that autonomic dysfunction in fibromyalgia can be assessed by the Composite Autonomic Symptom Score (COMPASS) questionnaire. More recently, a refined and much abbreviated 31-item version of the questionnaire has been developed, the COMPASS 31. OBJECTIVES: First, to determine whether the COMPASS 31 can assess changes in autonomic function in fibromyalgia. Second, to assess whether the COMPASS 31 values in fibromyalgia patients are positively correlated with scores on the Revised Fibromyalgia Impact Questionnaire (FIQR). METHODS: A cross-sectional, case-controlled study was carried out with 25 fibromyalgia patients and 26 healthy controls. RESULTS: The two groups were matched for age, sex and ethnicity, but not for body mass index (BMI). The total mean (standard error) COMPASS 31 for the fibromyalgia patients, 37.2 (1.8), differentiated the patients from the controls (9.5 (1.4); p < 0.00000001). The scores were greater in the fibromyalgia patients across all COMPASS 31 autonomic domains, namely orthostatic intolerance (p < 0.00000001), and vasomotor (p < 0.0001), secretomotor (p < 0.000001), gastrointestinal (p < 0.000001), bladder (p < 0.00001) and pupillomotor functions (p < 0.00000001). The total COMPASS 31 values were positively correlated with FIQR scores (rs = 0.45, p < 0.05). General linear modelling of the COMPASS 31 scores showed that only group status (fibromyalgia or control) was significant (p = 3.4 × 10-16), with age, sex and BMI being non-significant. CONCLUSION: This study confirms that non-pain autonomic dysfunction symptoms occur in fibromyalgia and can be assessed with the COMPASS 31.

Longitudinal Assessment of Autonomic Function during the Acute Phase of Spinal Cord Injury: Use of Low-Frequency Blood Pressure Variability as a Quantitative Measure of Autonomic Function.

High-level spinal cord injury (SCI) can disrupt cardiovascular autonomic function. However, the evolution of cardiovascular autonomic function in the acute phase following injury is unknown. We evaluated the timing, severity, progression, and implications of cardiovascular autonomic injury following acute SCI. We tested 63 individuals with acute traumatic SCI (aged 48 ± 2 years) at five time-points: <2 weeks, and 1, 3, 6-12, and >12 months post-injury. Supine beat-to-beat systolic arterial pressure (SAP) and R-R interval (RRI) were recorded and low-frequency variability (LF SAP and LF RRI) determined. Cross-spectral analyses were used to determine baroreflex function (low frequency) and cardiorespiratory interactions (high frequency). Known electrocardiographic (ECG) markers for arrhythmia and self-reported symptoms of cardiovascular dysfunction were determined. Comparisons were made with historical data from individuals with chronic SCI and able-bodied controls. Most individuals had high-level (74%) motor/sensory incomplete (63%) lesions. All participants had decreased LF SAP at <2 weeks (2.22 ± 0.65 mm Hg2). Autonomic injury was defined as high-level SCI with LF SAP <2 mm Hg2. Two distinct groups emerged by 1 month: autonomically complete SCI with sustained low LF SAP (0.76 ± 0.17 mm Hg2) and autonomically incomplete SCI with increased LF SAP (5.46 ± 1.0 mm Hg2, p < 0.05). Autonomically complete injuries did not recover over time. Cardiovascular symptoms were prevalent and worsened with time, especially in those with autonomically complete lesions, and chronic SCI. Baroreflex function and cardiorespiratory interactions were impaired after SCI. Risk of arrhythmia increased immediately after SCI, and remained elevated throughout the acute phase. Acute SCI is associated with severe cardiovascular dysfunction. LF SAP provides a simple, non-invasive, translatable, quantitative assessment of autonomic function, and is most informative 1 month after injury.

Cardiovascular Autonomic Dysfunction in Spinal Cord Injury: Epidemiology, Diagnosis, and Management.

Spinal cord injury (SCI) disrupts autonomic circuits and impairs synchronistic functioning of the autonomic nervous system, leading to inadequate cardiovascular regulation. Individuals with SCI, particularly at or above the sixth thoracic vertebral level (T6), often have impaired regulation of sympathetic vasoconstriction of the peripheral vasculature and the splanchnic circulation, and diminished control of heart rate and cardiac output. In addition, impaired descending sympathetic control results in changes in circulating levels of plasma catecholamines, which can have a profound effect on cardiovascular function. Although individuals with lesions below T6 often have normal resting blood pressures, there is evidence of increases in resting heart rate and inadequate cardiovascular response to autonomic provocations such as the head-up tilt and cold face tests. This manuscript reviews the prevalence of cardiovascular disorders given the level, duration and severity of SCI, the clinical presentation, diagnostic workup, short- and long-term consequences, and empirical evidence supporting management strategies to treat cardiovascular dysfunction following a SCI.

[Spanish validation of the Autonomic Standards Assessment Form in spinal cord injuries]. / Validación española del cuestionario Autonomic Standards Assessment Form en la lesión medular.

INTRODUCTION AND OBJECTIVES: Autonomic nervous system (ANS) dysfunction in patients with spinal cord injury (SCI) severely impacts morbidity and mortality. However, research initiatives aiming to gain insight into the direct impact of ANS dysfunction on health outcomes in persons with SCI are still lacking. Thus, this study had 2main objectives: 1) to translate into Spanish the revised edition of the International Standards on documentation of remaining Autonomic Function after SCI (ISAFSCI), and 2) to describe the impact of ANS dysfunction in a sample of SCI patients. MATERIAL AND METHODS: Cross-sectional observational pilot study in 51 traumatic SCI patients (> 1 year after injury). Demographic, medical and ISAFSCI data were studied. RESULTS: The Spanish version of the ISAFSCI showed that the most altered systems in the sample were sweating control (above-lesion hyperhidrosis in 33.3%; below-lesion hyperhidrosis in 17.6%; below-lesion hypohidrosis in 21.6%) and temperature control (hyperthermia in 76.5%). In addition, 74.5% of the sample had complete loss of control of the lower urinary tract, and 82.4% had no control of the bowel. Finally, genital arousal was reflex in 47.1% and orgasm and ejaculation were reduced or altered in most of the patients (92.2% and 84.3%, respectively). CONCLUSION: The Spanish version of the ISAFSCI is a useful and practical tool, and can be employed in clinical practice to assess ANS function in patients with SCI. Understanding the role of ANS in persons with SCI is crucial to improve their health status and reduce secondary complications post-SCI, and consequently help to improve the clinical management in these individuals.

Autonomic symptom burden is an independent contributor to multiple sclerosis related fatigue.

OBJECTIVES: To investigate a possible association between autonomic dysfunction and fatigue in people with multiple sclerosis. METHODS: In 70 people with multiple sclerosis early in the disease course (51 females, mean age 33.8 ± 9.1), quantitative sudomotor axon reflex tests, cardiovascular reflex tests (heart rate and blood pressure responses to the Valsalva maneuver and heart rate response to deep breathing), and the tilt table test were performed. Participants completed the Composite Autonomic Symptom Score 31, the Modified Fatigue Impact Scale, and the Epworth Sleepiness Scale, as well as the Beck Depression Inventory. Cutoff scores of ≥ 38 or ≥ 45 on the Modified Fatigue Impact Scale were used to stratify patients into a fatigued subgroup (N = 17 or N = 9, respectively). RESULTS: We found clear associations between fatigue and scores in subjective tests of the autonomic nervous system: fatigued patients scored significantly worse on Composite Autonomic Symptom Score 31, and there was a strong correlation between the Modified Fatigue Impact Scale and the Composite Autonomic Symptom Score 31 (rs = 0.607, p < 0.001). On the other hand, we found only modest associations between fatigue and scores in objective tests of the autonomic nervous system: there was a clear trend for lower sweating outputs at all measured sites, which reached statistical significance for the distal leg and foot. We found weak correlations between the Modified Fatigue Impact Scale and the Valsalva ratio (rs = - 0.306, p = 0.011), as well as between the Modified Fatigue Impact Scale and quantitative sudomotor axon reflex tests of the forearm, proximal, and distal lower leg (rs = - 0.379, p = 0.003; rs = - 0.356, p = 0.005; and rs = - 0.345, p = 0.006, respectively). A multiple regression model showed that the Composite Autonomic Symptom Score 31, Beck Depression Inventory, and Epworth Sleepiness Scale were independent predictors of fatigue (p = 0.005, p = 0.019, and p = 0.010, respectively). CONCLUSION: These results suggest that-even early in the course of the disease-people with multiple sclerosis suffer from objective and subjective impairments of the autonomic nervous system. The results also point to an association between autonomic nervous system impairment and multiple sclerosis related fatigue.

Autonomic function testing in Friedreich's ataxia.

BACKGROUND: Friedreich ataxia (FRDA) is an inherited movement disorder which manifests with progressive gait instability, sensory loss and cardiomyopathy. Peripheral neuropathy is an established feature of FRDA. At neuropathological examination, a depletion of large, myelinated axons is evident, but also unmyelinated fibers are affected which may result in a variety of sensory and autonomic signs and symptoms. Impaired temperature perception, vasomotor disturbances of lower extremities and a high prevalence of urinary symptoms have been documented in FRDA, but data from autonomic function testing in genetically confirmed cases are lacking. METHODS: Genetically confirmed FRDAs were recruited in an outpatient setting. In a screening visit, general and neurological examination, laboratory testing, ECG and echocardiography were performed. Autonomic functions were evaluated by means of systematic questionnaires (SCOPA-Aut, OHQ), skin sympathetic reflex and cardiovascular autonomic function testing (CAFT). For the latter, a comparison with matched healthy controls was performed. RESULTS: 20 patients were recruited and 13 underwent CAFT. Symptoms referred to multiple autonomic domains, particularly bladder function, thermoregulation and sweating were reported. SCOPA-Aut scores were significantly predicted by disease severity. At CAFT, FRDAs did not differ from controls except for increased heart rate at rest and during orthostatic challenge. Two patients had non-neurogenic orthostatic hypotension (14%). Skin sympathetic responses were pathologic in 3 out of 10 patients (of whom 2 aged > 50). CONCLUSIONS: FRDA patients may experience several autonomic symptoms and overall their burden correlates with disease severity. Nonetheless, clinical testing shows no major involvement of sudomotor and cardiovascular autonomic function.

Progressive multiple sclerosis patients have a higher burden of autonomic dysfunction compared to relapsing remitting phenotype.

OBJECTIVE: To determine autonomic dysfunction (AD) differences in patients with relapsing remitting multiple sclerosis (pwRRMS) and progressive MS (pwPMS). METHODS: Composite autonomic scoring scale (CASS) and heart rate variability (HRV) were performed in 40 pwRRMS and 30 pwPMS. RESULTS: pwPMS had a significantly higher sudomotor index and total CASS score compared to pwRRMS (p < 0.001 and p < 0.001, respectively). Disease duration positively correlated with sudomotor index and total CASS (rs = 0.409, p < 0.001 and rs = 0.472, p < 0.001, respectively), while the Expanded Disability Status Scale (EDSS) positively correlated with sudomotor index and total CASS (rs = 0.411, p < 0.001 and rs = 0.402, p = 0.001, respectively) in all patients. Type of multiple sclerosis (pwRRMS or pwPMS) corrected for age, sex and disease duration, was a statistically significant predictor of CASS value (B = 1.215, p = 0.019). Compared to pwRRMS, pwPMS had a significantly lower standard deviation of NN intervals (SDNN), low frequency (LF), and high frequency (HF), during both the supine and tilt-up phases (all p-values <0.006). pwPMS had a significantly lower LF/HF (p = 0.008) during tilt-up. CONCLUSION: There is a significant difference in autonomic function in pwRRMS and pwPMS; with pwPMS having a higher burden of AD, which is particularly evident for sweating dysfunction. SIGNIFICANCE: Further research is needed to establish whether parasympathetic and sudomotor dysfunction may serve as markers of progressive MS.

Incidence of paroxysmal sympathetic hyperactivity following traumatic brain injury using assessment tools.

INTRODUCTION: A consensus statement proposed a diagnostic framework to systematise the identification of paroxysmal sympathetic hyperactivity (PSH) using the PSH-Assessment Measure (PSH-AM). METHODS: This retrospective study identified adult patients with a primary diagnosis of traumatic brain injury and a hospital length of stay >14 days. Based on PSH-AM scores, patients were grouped into 'unlikely', 'possible', or 'probable' PSH. For this study, 'possible' and 'probable' PSH patients were collapsed into a single group (PSH+), and resultant data were compared with 'unlikely' diagnoses (PSH-). PSH-AM data were assessed against clinical diagnoses to establish sensitivity and specificity data. RESULTS: Sixty five patients met inclusion criteria, with 45/65 (69%) categorised as either 'possible' or 'probable' PSH on the PSH-AM. Only 16 of these patients were diagnosed by clinicians. The most common symptoms triggering clinical diagnosis were tachycardia, fever and posturing. Increased respiratory rate, blood pressure or the presence of diaphoresis were not used in diagnosing PSH if the PSH-AM was not utilised. Assuming clinical assessment as the current gold standard, the PSH-AM yielded a sensitivity of 94% and a specificity of 35% when used retrospectively. Patients clinically diagnosed with PSH were discharged 5 days earlier compared to those identified by the PSH-AM. CONCLUSIONS: The recently proposed diagnostic framework may reduce misdiagnosis, length of stay and hospitalisation costs.