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Objective Multiple system atrophy (MSA) is characterized by urinary dysfunction, yet the influence of sex and gender on urinary symptoms and treatment is unclear. We sought to characterize sex and gender differences in the symptomatology, evaluation, and management of urinary dysfunction in patients with MSA.Methods Patients with MSA evaluated at our institution were reviewed and stratified by sex.Results While the prevalence of urinary symptoms was similar in male and female patients, incontinence was more common in females. Despite this, males and females underwent postvoid residual (PVR) measurement at similar rates. While catheterization rates were similar when PVR was measured, males were more than twice as likely to be catheterized than females in the absence of PVR measurement.Conclusion Urinary symptoms are common in MSA, but their presentation differs between males and females. The difference in catheterization rates may be driven by a gender disparity in referrals for PVR, which can guide treatment.

INTRODUCTION: Multiple system atrophy (MSA) typically presents with parkinsonism, ataxia and/or autonomic dysfunction. Occasionally, clinically atypical (ca-MSA) cases masquerade as progressive supranuclear palsy (PSP). We aimed to investigate whether different neuroimaging modalities could facilitate differentiation and whether histopathologic characteristics could explain the atypical presentation. METHODS: We identified 3 neuropathologically-defined ca-MSA patients with clinically diagnosed PSP who underwent various antemortem brain imaging: MRI and PET imaging using (11)C-Pittsburgh compound B, (18)F-flortaucipir, and (18)F-fluorodeoxyglucose. We compared clinical features, brainstem planimetry, and radiotracer standardized uptake value ratios in ca-MSA to 10 autopsy-confirmed PSP patients and 10 healthy controls (imaging only). We also compared histologic count of neuronal loss, iron deposition and α-synuclein-immunoreactive glial cytoplasmic inclusion burden to 10 autopsy-confirmed MSA-parkinsonism (MSA-P) cases. RESULTS: Ca-MSA had better PSP Saccadic Impairment Scale scores (p=0.003) and more frequent good levodopa response (p=0.061) than PSP. Ca-MSA showed higher midbrain-to-pons ratio and lower Magnetic Resonance Parkinsonism Index than PSP (each, p=0.036) and exhibited lower glucose metabolism in the putamen and globus pallidus versus PSP (p=0.017) and controls (p=0.007). These same regions showed higher flortaucipir uptake in ca-MSA than PSP (p=0.007 for putamen, p=0.049 for pallidum) and controls (p=0.012). Lower flortaucipir retention was observed in the subthalamic nucleus versus PSP (p=0.007). The putamen-to-subthalamic ratio distinguished ca-MSA from PSP. No histopathological differences were observed for ca-MSA versus typical MSA-P. CONCLUSION: Severity of saccadic impairment, levodopa responsiveness, MRI planimetric measurements, and different patterns of fluorodeoxyglucose and flortaucipir uptake can help improve antemortem differentiation of MSA masquerading as PSP from true PSP.

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. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0–10) was 7 (interquartile range, 6–7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722–1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

The course of patients with multiple system atrophy (MSA) who undergo deep brain stimulation (DBS) is unclear. In a retrospective review of 1,496 patients with MSA evaluated at our institutions from 1998–2021, 12 patients underwent DBS; 9 had a diagnosis of Parkinson’s disease at the time of surgery. Nine patients reported initial improvement in at least one symptom and 7 experienced overall worsening following DBS. All patients had at least one red flag sign or symptom suggesting atypical parkinsonism prior to surgery. Considering overall poor outcomes of DBS in MSA, we recommend careful consideration of red flags in patient selection.

Risk of sudden death in multiple system atrophy (MSA) is greatest during sleep with unknown mechanisms. We compared nocturnal pulse event frequency in 46 MSA patients and age-/sex-matched controls undergoing overnight pulse oximetry. Nocturnal oxyhemoglobin desaturation indices and pulse event indices (PEIs) were recorded, and relationships between pulse oximetry variables and survival were analyzed. MSA patients had lower PEI (3.1 ± 5.3 vs. 12.8 ± 10.8, p 0.001) despite greater hypoxic burden and similar frequency of respiratory events. Nocturnal pulse events were not associated with severity of daytime autonomic failure. Two MSA patients had suspected sudden death, both with severely reduced PEI. MSA patients have fewer nocturnal pulse events compared with controls, despite similar respiratory event frequency, suggesting abnormal cardiac responses to sleep-disordered breathing. Whether this contributes to sudden death in MSA requires further study. ANN NEUROL 2022.

The stories of early women physicians in the field of neurology are seldom discussed. Understanding the history behind women in neurology can inform our current practice and uncover the possible origins of gender disparities in academic neurology. Utilizing annual section/department reports and other primary sources, we describe the first women trainees and staff who broke gender barriers to train and work in the Mayo Clinic Department of Neurology. The department was founded in 1913 when Walter Shelden became its first consultant. It was not until the 1950s that a woman completed her neurology training and went on to practice neurology. Throughout the early years of the training program, there were no women on staff, as it was not until the 1970s when the first women were hired as consultants.

Purpose Post-COVID-19 syndrome is a poorly understood aspect of the current pandemic, with clinical features that overlap with symptoms of autonomic/small fiber dysfunction. An early systematic analysis of autonomic dysfunction following COVID-19 is lacking and may provide initial insights into the spectrum of this condition. Methods We conducted a retrospective review of all patients with confirmed history of COVID-19 infection referred for autonomic testing for symptoms concerning for para-/postinfectious autonomic dysfunction at Mayo Clinic Rochester or Jacksonville between March 2020 and January 2021. Results We identified 27 patients fulfilling the search criteria. Symptoms developed between 0 and 122 days following the acute infection and included lightheadedness (93%), orthostatic headache (22%), syncope (11%), hyperhidrosis (11%), and burning pain (11%). Sudomotor function was abnormal in 36%, cardiovagal function in 27%, and cardiovascular adrenergic function in 7%. The most common clinical scenario was orthostatic symptoms without tachycardia or hypotension (41%); 22% of patients fulfilled the criteria for postural tachycardia syndrome (POTS), and 11% had borderline findings to support orthostatic intolerance. One patient each was diagnosed with autoimmune autonomic ganglionopathy, inappropriate sinus tachycardia, vasodepressor syncope, cough/vasovagal syncope, exacerbation of preexisting orthostatic hypotension, exacerbation of sensory and autonomic neuropathy, and exacerbation of small fiber neuropathy. Conclusion Abnormalities on autonomic testing were seen in the majority of patients but were mild in most cases. The most common finding was orthostatic intolerance, often without objective hemodynamic abnormalities on testing. Unmasking/exacerbation of preexisting conditions was seen. The temporal association between infection and autonomic symptoms implies a causal relationship, which however cannot be proven by this study.

Multiple system atrophy (MSA) is a neurodegenerative disorder primarily characterized by autonomic failure plus parkinsonism or cerebellar ataxia. The diagnosis may be challenging and is usually made at a tertiary care center. The long-term management issues are equally challenging and frequently require collaboration with the patient's local care providers. Whereas there is currently no cure for MSA, treatment focuses on the most problematic symptoms experienced by the patient. Autonomic symptoms may include severe orthostatic hypotension with syncope, urinary symptoms culminating in incontinence, constipation, anhidrosis, and erectile dysfunction. Motor symptoms include parkinsonism, cerebellar ataxia, and falls. Although certain motor symptoms may respond partially to medications, some of these medications may exacerbate autonomic problems. In this manuscript, we seek to bridge the gap between tertiary care providers and the patient's local care providers to provide multidisciplinary care to the MSA patient. Patients are often best served by management of their chronic and evolving complex problems with a team approach involving their primary care providers and subspecialists. Treatment guidelines typically list myriad therapeutic options without clarifying the most efficacious and simplest treatment strategies. Herein, we provide a guideline based on what has worked in our MSA clinic, a clinic designed to provide care throughout the disease course with subspecialty integration with the goal of empowering a partnership with the patient's home primary care providers.

ObjectiveTo determine predicting factors and frequency of phenoconversion from pure autonomic failure (PAF) into a synucleinopathy with motor or cognitive involvement of multiple system atrophy (MSA), Parkinson disease (PD), or dementia with Lewy bodies (DLB).MethodsWe performed a retrospective review of all patients with PAF from 2001 to 2011 evaluated at Mayo Clinic, Rochester. Clinical follow-up and patient telephone calls were used to assess for development of symptoms and diagnosis of MSA, PD, or DLB. Clinical and laboratory variables were extracted with factors predictive of evolution assessed using group comparison, odds ratio, and logistical regression.ResultsAmong 275 patients with PAF at presentation, 67 (24%) phenoconverted to a synucleinopathy with motor or cognitive involvement; 34 met criteria for MSA, while 33 met criteria for PD or DLB. Age at onset was younger in MSA phenoconverters. Clinical features at presentation influenced phenoconversion: severe bladder symptoms were more common in MSA phenoconverters; subtle motor signs were more frequent in MSA and PD/DLB phenoconverters. MSA phenoconverters were more likely to have higher supine norepinephrine levels and preganglionic pattern of anhidrosis. Presentation variables predicting MSA phenoconversion included subtle motor signs, supine norepinephrine levels, severe bladder symptoms, and dream enactment behavior. Presentation variables predictive of PD/DLB phenoconversion included subtle motor signs, dream enactment behavior, and constipation.ConclusionsOur findings suggest that at least a quarter of patients with PAF phenoconvert to MSA, PD, or DLB. Presentation features determine patients at risk for evolution with specific patterns indicative of phenoconversion to MSA vs PD/DLB.Classification of evidence:This study provides Class II evidence that several presentation variables including subtle motor signs, severe bladder symptoms, and dream enactment behavior are associated with an increased risk of developing a synucleinopathy with motor or cognitive involvement.

Blood pressure (BP) plays an important role in white matter integrity. We sought to determine the role of intra-individual BP changes on white matter and evaluate the impact on gait speed and imbalance by sex. We identified 990 eligible participants in the population-based Mayo Clinic Study of Aging and analyzed fractional anisotropy (FA) in white matter regions. Using structural equation models (SEM), we assessed the effect of BP slope on corticospinal tract (CST) FA and downstream effects on gait speed and imbalance after age and sex effects. Of 990 participants, 438 (44%) were female with mean age of 76 years. In linear models predicting CST FA, a greater change in BP slope (0.0004; p = 0.026) and female sex (0.017; plt; 0.001) were significant predictors of lower CST FA. SEMs showed that older age, female sex, and higher BP slope predicted lower CST FA, and lower CST FA predicted worse downstream motor control. Therefore, intra-individual BP slope and variability impact corticospinal tract microstructural properties of white matter with females having increased susceptibility to damage.

Women currently make up 45.9% of neurology residents and fellows1 although little is known about the individual women who broke gender barriers to train as neurologists. Grace Elizabeth “Betty” Clements (1918-1965) was the first woman trainee at the Mayo Clinic to practice neurology and later became a founder of the Barrow Neurological Institute. Prior to paving the way for future women trainees in neurology, she served as a Women Airforce Service Pilot (WASP) including flying atomic bomb planning missions during World War II. Following the war, her path to medicine included volunteering in the American Red Cross in the Philippines where she treated patients with Hansen’s disease (leprosy). Clements returned to her home state to complete medical school at the University of Nebraska before seeking neurologic training at the Mayo Clinic in 1954. Following additional training at Queen Square, she became a founder of the Barrow Neurological Institute in Phoenix, Arizona. Many early women in neurology have remarkable backgrounds that have equipped them for their career in medicine which Clements exemplifies.

Hyperkinetic movement disorders are characterized by an excess of movement. This chapter outlines the classification, causes, and treatment of chorea, tic disorders, and dystonia. The term chorea refers to dancelike irregular, arrhythmic, rapid, involuntary movements that appear to flow between muscle groups. Athetosis, a slower and twisting dystonialike movement, may be superimposed with chorea, leading to choreoathetosis. Ballism is a form of high-amplitude and proximal chorea that has the appearance of flailing movement.

ObjectiveTo describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester.MethodsWe performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests).ResultsA total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group (p < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period.ConclusionsABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.