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.

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.

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).

Autonomic dysfunction and phenoconversion in idiopathic REM sleep behavior disorder.

Background: REM sleep behavior disorder (RBD) is a common finding among patients with synucleinopathies. We aimed to determine the degree of autonomic dysfunction in patients presenting with idiopathic RBD (iRBD), and the predictive value of autonomic dysfunction for phenoconversion to a defined neurodegenerative disease.

Methods: We searched our electronic medical record for patients diagnosed with iRBD who also underwent standardized autonomic function testing within 6 months of iRBD diagnosis, and who had clinical follow-up of at least 3 years following iRBD diagnosis.

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.

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.

Determination of vagal baroreflex sensitivity in normal subjects.

Introduction: The Valsalva maneuver (VM) is used widely to quantify the sensitivity of the vagal baroreflex loop (vagal baroreflex sensitivity, BRS_v), but most studies have focused on the heart rate (HR) response to blood pressure (BP) decrement (BRS_v↓), even though the subsequent response to an increment in BP after the VM (BRS_v↑) is important and different.

Methods: We evaluated recordings of HR and BP in 187 normal subjects during the VM and determined both BRS_v↑, as determined by relating HR to the BP increase after phase III and BRS_v↓.

Results: BRS_v↑ was related inversely to age.

The role of autonomic testing in the differentiation of Parkinson's disease from multiple system atrophy.

Differentiation of idiopathic Parkinson's disease (PD) from multiple system atrophy (MSA) can be difficult. Methods devised to help distinguish the two disorders include standardized autonomic testing and cardiac imaging with iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. MSA patients had more severe adrenergic and overall autonomic dysfunction when compared to control and PD patients.

Autopsy confirmed multiple system atrophy cases: Mayo experience and role of autonomic function tests.

Background: Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterised by autonomic failure, manifested as orthostatic hypotension or urogenital dysfunction, with combinations of parkinsonism that is poorly responsive to levodopa, cerebellar ataxia and corticospinal dysfunction. Published autopsy confirmed cases have provided reasonable neurological characterisation but have lacked adequate autonomic function testing.

Objectives: To retrospectively evaluate if the autonomic characterisation of MSA is accurate in autopsy confirmed MSA and if consensus criteria are validated by autopsy confirmation.

Prospective differentiation of multiple system atrophy from Parkinson disease, with and without autonomic failure.

Objective: To report preliminary results of a prospective ongoing study of multiple system atrophy (MSA) and Parkinson disease (PD), with a large subset of patients with PD with autonomic failure (25%), to evaluate autonomic indices that distinguish MSA from PD.

Methods: We used consensus criteria, detailed autonomic studies (Composite Autonomic Symptom Scale, Composite Autonomic Scoring Scale, thermoregulatory sweat test, and plasma catecholamines), and functional scales (Unified MSA Rating Scale [UMSARS] I-IV and Hoehn-Yahr grading) on a prospective, repeated, and ongoing basis.

Results: We report the results of a study on 52 patients with MSA (mean [SD], age, 61.

Patterns of neuropathy and autonomic failure in patients with amyloidosis.

Objective: To define the clinical patterns of peripheral neuropathy and autonomic testing abnormalities in patients with amyloidosis.

Patients And Methods: A retrospective chart review was conducted of 65 patients who had biopsy-proven amyloidosis and autonomic function testing between January 1, 1985, and December 31, 1997, at Mayo Clinic's site in Rochester, MN. Patients were required to have neurologic evaluation, autonomic reflex screening, and tissue confirmation of amyloidosis.

Effect of position on valsalva maneuver: supine versus 20 degree position.

Blood pressure changes in response to the Valsalva maneuver (VM), which reflect the integrity of the baroreflex that regulates blood pressure. Performing this maneuver in the standard supine position often prevents adequate venous preload reduction, resulting in a rise rather than a fall in blood pressure, the "flat-top" Valsalva response. We determined whether performing the VM at a 20 degree angle of head-up tilt (20 degrees ) improves preload reduction, thereby reducing the frequency of flat-top responses, improving reflex vasoconstriction, and increasing the Valsalva ratio.

Pilot study of pyridostigmine in constipated patients with autonomic neuropathy.

Background: The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response.

Methods: In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.

Effects of linearly polarized 0.6-1.6 microM irradiation on stellate ganglion function in normal subjects and people with complex regional pain (CRPS I).

Background And Objectives: Stellate ganglion blocks are an effective but invasive treatment of upper extremity pain. Linearly polarized red and near-infrared (IR) light is promoted as a safe alternative to this procedure, but its effects are poorly established. This study was designed to assess the physiological effects of this latter approach and to quantitate its benefits in people with upper extremity pain due to Complex Regional Pain Syndrome I (CRPS I, RSD).