White Matter Abnormalities Track Disease Progression in Multiple System Atrophy.

Background: White matter (WM) abnormalities have been implicated in clinically relevant functional decline in multiple system atrophy (MSA).

Objective: To identify the WM and gray matter (GM) abnormalities in MSA and assess the utility of longitudinal structural and diffusion changes as surrogate markers for tracking disease progression in MSA.

Methods: Twenty-seven participants with early MSA [15 with clinically predominant cerebellar (MSA-C) and 12 with clinically predominant parkinsonian features (MSA-P)] and 14 controls were enrolled as a part of our prospective, longitudinal study of synucleinopathies.

Quantitative assessment of painful diabetic peripheral neuropathy after high-frequency spinal cord stimulation: a pilot study.

Objective: Randomized trials have demonstrated efficacy of spinal cord stimulation (SCS) for treatment of painful diabetic neuropathy (PDN). Preliminary data suggested that treatment of PDN with high-frequency SCS resulted in improvements on neurological examination. The purpose of the present study was to explore whether patients with PDN treated with high-frequency SCS would have improvements in lower-extremity peripheral nerve function.

Neurofilament light chain in spinal fluid and plasma in multiple system atrophy: a prospective, longitudinal biomarker study.

Purpose: There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to cerebrospinal fluid (NfL-c) as a diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression.

Neurofilament Light Chain in Spinal Fluid and Plasma in Multiple System Atrophy - A Prospective, Longitudinal Biomarker Study.

Purpose There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to CSF (NfL-c) as diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression.

Imaging biomarkers for early multiple system atrophy.

Objective: To systematically evaluate structural MRI and diffusion MRI features for cross-sectional discrimination and tracking of longitudinal disease progression in early multiple system atrophy (MSA).

Methods: In a prospective, longitudinal study of synucleinopathies with imaging on 14 controls and 29 MSA patients recruited at an early disease stage (15 predominant cerebellar ataxia subtype or MSA-C and 14 predominant parkinsonism subtype or MSA-P), we computed regional morphometric and diffusion MRI features. We identified morphometric features by ranking them based on their ability to distinguish MSA-C from controls and MSA-P from controls and evaluated diffusion changes in these regions.

Translation and linguistic validation of the Composite Autonomic Symptom Score COMPASS 31 in Danish.

Introduction: The Composite Autonomic Symptom Score (COMPASS 31) is a validated self-assessment questionnaire quantifying the severity and distribution of autonomic symptoms across six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor functions) by scoring 31 clinically selected questions. The aim of this study was to translate into Danish and validate the Danish version of COMPASS 31.

Methods: The original (US) English version of the COMPASS 31 questionnaire was translated into Danish via forward/backward translation and validated in accordance with a protocol set forth by the Autonomic Group at the Mayo Clinic.

Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF.

Alpha-Synuclein Oligomers and Neurofilament Light Chain Predict Phenoconversion of Pure Autonomic Failure.

Objective: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NfL) in cerebrospinal fluid (CSF) of patients with pure autonomic failure (PAF) as markers of future phenoconversion to multiple system atrophy (MSA).

Methods: Well-characterized patients with PAF (n = 32) were enrolled between June 2016 and February 2019 at Mayo Clinic Rochester and followed prospectively with annual visits to determine future phenoconversion to MSA, Parkinson's disease (PD), or dementia with Lewy bodies (DLB). ELISA was utilized to measure NfL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF collected at baseline.

Alpha-Synuclein Oligomers and Neurofilament Light Chain in Spinal Fluid Differentiate Multiple System Atrophy from Lewy Body Synucleinopathies.

Objective: To explore the role of alpha-synuclein (αSyn) oligomers and neurofilament light chain (NFL) in cerebrospinal fluid (CSF) as markers of early multiple system atrophy (MSA) and to contrast findings with Lewy body synucleinopathies.

Methods: In a discovery cohort of well-characterized early MSA patients (n = 24) and matched healthy controls (CON, n = 14), we utilized enzyme-linked immunosorbent assay to measure NFL and protein misfolding cyclic amplification (PMCA) to detect αSyn oligomers in CSF. We confirmed findings in a separate prospectively enrolled cohort of patients with early MSA (n = 38), Parkinson disease (PD, n = 16), and dementia with Lewy bodies (DLB, n = 13), and CON subjects (n = 15).

Elimination of spurious absent sweat response in QSWEAT recordings.

Introduction: Forearm QSWEAT recordings are occasionally absent in females, likely due to high skin resistance.

Methods: We identified consecutive subjects with no sudomotor abnormalities but absent/markedly reduced QSWEAT forearm volume, and repeated QSWEAT at the same site after gentle abrasion.

Results: QSWEAT volumes were absent for 4 subjects and markedly reduced for the other 4 (median 0.

Sex and gender influence symptom manifestation and survival in multiple system atrophy.

To evaluate the influence of sex and gender on clinical characteristics and survival in multiple system atrophy (MSA), we reviewed MSA patients with autonomic testing 1998-2012. Of 685 patients, 52% were male. Median survival overall was 7.

The Orthostatic Discriminant and Severity Scale (ODSS): an assessment of orthostatic intolerance.

Purpose: To assess the ability of the Orthostatic Discriminant and Severity Scale (ODSS) to distinguish symptoms of orthostatic intolerance from non-orthostatic symptoms.

Methods: Clinical evaluations and questionnaire responses were collected in 73 healthy controls and 132 patients referred to the Autonomic Disorders Clinic from September 1, 2016, through April 30, 2018, for queries regarding autonomic dysfunction. A receiver operating characteristic (ROC) curve analysis was used to interpret sensitivity and specificity and to determine cutoff scores for symptom assessment.

Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure.

Objective: To assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity.

Patients And Methods: We searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab-seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated.

Initial validation of symptom scores derived from the orthostatic discriminant and severity scale.

Objective: To develop a scale to quantify and discriminate orthostatic from non-orthostatic symptoms. In the current study, we present validation and reliability of orthostatic and non-orthostatic symptom scores taken from the orthostatic discriminate and severity scale (ODSS).

Methods: Validity and reliability were assessed in participants with and without orthostatic intolerance.

Anhidrosis in multiple system atrophy involves pre- and postganglionic sudomotor dysfunction.

Background: The objective of this study was to characterize the degree, pattern, lesion site, and temporal evolution of sudomotor dysfunction in multiple system atrophy (MSA) and to evaluate differences by parkinsonian (MSA-parkinsonism) and cerebellar (MSA-cerebellar) subtypes.

Methods: All cases of MSA evaluated at Mayo Clinic Rochester between 2005 and 2010 with postganglionic sudomotor testing and thermoregulatory sweat test were reviewed. Pattern and lesion site (preganglionic, postganglionic, or mixed) were determined based on thermoregulatory sweat test and postganglionic sudomotor testing.

Clinical features and autonomic testing predict survival in multiple system atrophy.

Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication.

Symptoms of Autonomic Dysfunction in Human Immunodeficiency Virus.

This retrospective study evaluated the frequencies of symptoms associated with autonomic dysfunction in human immunodeficiency virus (HIV)-infected patients on stable combined antiretroviral therapy. Patients infected with HIV reported higher frequencies of dysautonomia symptoms compared with HIV-negative patients, particularly in the autonomic domains related to urinary, sleep, gastroparesis, secretomotor, pupillomotor, and male sexual dysfunction.

A Double-Blinded Randomized Trial to Compare the Effectiveness of Minimally Invasive Procedures Using Patient-Reported Outcomes.

Background: The Institute of Medicine has included the comparison of minimally invasive surgical techniques in its research agenda. This study seeks to evaluate a model for the comparison of minimally invasive procedures using patient-reported outcomes.

Study Design: A double-blinded randomized controlled trial (NCT01489436) was conducted.

Natural history of multiple system atrophy in the USA: a prospective cohort study.

Background: Multiple system atrophy is a rare, fatal neurodegenerative disorder with symptoms of autonomic failure plus parkinsonism, cerebellar ataxia, or both. We report results of the first prospective natural history study of multiple system atrophy in the USA, and the effects of phenotype and autonomic failure on prognosis.

Methods: We recruited participants with probable multiple system atrophy-of either the parkinsonism subtype (MSA-P) or the cerebellar ataxia subtype (MSA-C)-at 12 neurology centres in the USA specialising in movement or autonomic disorders.

Effects of patient-controlled abdominal compression on standing systolic blood pressure in adults with orthostatic hypotension.

Objective: To assess the effects of patient-controlled abdominal compression on postural changes in systolic blood pressure (SBP) associated with orthostatic hypotension (OH). Secondary variables included subject assessments of their preferences and the ease-of-use.

Design: Randomized crossover trial.

Autonomic system and amyotrophic lateral sclerosis.

Introduction: The aim of this study is to characterize autonomic impairment in motor neuron disease.

Methods: Neurological evaluations and autonomic testing were analyzed retrospectively in 132 patients: 86 classic amyotrophic lateral sclerosis (ALS), 36 lower motor neuron (LMN), and 10 upper motor neuron (UMN) predominant disease.

Results: One-third of patients were symptomatic; urinary urgency and constipation were the most frequent symptoms.

Decreased orthostatic adrenergic reactivity in non-dipping postural tachycardia syndrome.

Whether non-dipping - the loss of the physiologic nocturnal drop in blood pressure - among patients with postural tachycardia syndrome (POTS) is secondary to autonomic neuropathy, a hyperadrenergic state, or other factors remains to be determined. In 51 patients with POTS (44 females), we retrospectively analyzed 24-hour ambulatory blood pressure recordings, laboratory indices of autonomic function, orthostatic norepinephrine response, 24-hour natriuresis and peak exercise oxygen consumption. Non-dipping (<10% day-night drop in systolic blood pressure) was found in 55% (n=28).

Comparison of baroreflex sensitivity with a fall and rise in blood pressure induced by the Valsalva manoeuvre.

The baroreflex plays a key role in human BP (blood pressure) regulation. Its efferent limb consists of a vagal and a sympathetic component. The Valsalva manoeuvre is widely used to quantify vagal baroreflex function [BRS_vagal (vagal baroreflex sensitivity)], but most studies have focused on the R-R interval response to BP decrement, even though the subsequent response to an increment in BP is important and different.