Clinical features of autopsy-confirmed multiple system atrophy in the Mayo Clinic Florida brain bank.

Background: Multiple system atrophy (MSA) presents with various combinations of autonomic dysfunction, parkinsonism, and cerebellar ataxia. Although clinical diagnostic criteria have been widely used, the sensitivity and specificity are suboptimal. This study aims to provide evidence supporting the revision of the current diagnostic criteria for MSA.

Urine levels of the polyglutamine ataxin-3 protein are elevated in patients with spinocerebellar ataxia type 3.

Introduction: Accumulation of polyglutamine (polyQ) ataxin-3 (ATXN3) contributes to the pathobiology of spinocerebellar ataxia type 3 (SCA3). Recently, we showed that polyQ ATXN3 is elevated in the plasma and cerebrospinal fluid (CSF) of SCA3 patients, and has the potential to serve as a biological marker for this disease [1]. Based on these findings, we investigated whether polyQ ATXN3 can also be detected in urine samples from SCA3 patients.

Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials.

A movement disorder specialist gets a taste of his own medicine.

We present a case in which a movement disorder neurologist developed two different hyperkinetic movements due to corticospinal tract hyperexcitability, which resolved completely with surgical removal of an epidural spinal canal tumor. The first-hand description of these movements creates a unique opportunity for enhanced insight into these complex movement phenomena.

Association of MAPT subhaplotypes with clinical and demographic features in Parkinson's disease.

Objective: To determine whether distinct microtubule-associated protein tau MAPT H1 subhaplotypes are associated with clinical and demographic features in Parkinson's disease.

Methods: A retrospective cohort study included 855 unrelated Caucasian patients with Parkinson's disease who were seen by Movement Disorder specialists at the Mayo Clinic Florida between 1998 and 2016. The primary outcome measures were specific demographic and clinical features of Parkinson's disease, including age at onset, disease progression, survival, motor signs, dementia, dystonia, dyskinesia, autonomic dysfunction, impulse control disorder, psychiatric features, REM sleep behavior disorder, restless legs syndrome, and Parkinson's disease subtype.

Spinocerebellar ataxia type 6 family with phenotypic overlap with Multiple System Atrophy.

Aim Of The Study: Multiple system atrophy (MSA) and spinocerebellar ataxia (SCA) share similar symptomatology. We describe a rare occurrence of familial MSA that proved to be SCA6 upon genetic analysis.

Materials And Methods: Eighty MSA patients were enrolled in our study; blood samples were collected and genetic screening of the familial case for known SCA loci was performed.

Myoclonus: An Electrophysiological Diagnosis.

Background: Many different movement disorders have similar "jerk-like" phenomenology and can be misconstrued as myoclonus. Different types of myoclonus also share similar phenomenological characteristics that can be difficult to distinguish solely based on clinical exam. However, they have distinctive physiologic characteristics that can help refine categorization of jerk-like movements.

Subtypes of dementia with Lewy bodies are associated with α-synuclein and tau distribution.

Objective: To determine whether Lewy body disease subgroups have different clinical profiles.

Methods: Participants had dementia, autopsy-confirmed transitional or diffuse Lewy body disease (TLBD or DLBD) (n = 244), or Alzheimer disease (AD) (n = 210), and were seen at least twice (mean follow-up 6.2 ± 3.

Sudor Anglicus: an epidemic targeting the autonomic nervous system.

Renaissance England witnessed a series of brief epidemics of a rapid and often fatal illness, the predominant feature of which was a disturbance of the autonomic nervous system. Profuse sweating was both an emblematic and ominous sign of this Sudor Anglicus. Its story is medically fascinating as well as historically noteworthy.

Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling.

Background: The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype.

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once.

Functional Analysis of the SIM1 Variant p.G715V in 2 Patients With Obesity.

Context: Single-minded homologue 1 (SIM1) is a transcription factor with several physiological and developmental functions. Haploinsufficiency of SIM1 is associated with early-onset obesity with or without Prader-Willi-like (PWL) features and may exhibit incomplete penetrance.

Case Description: Next-generation sequencing was performed for 2 male patients with obesity, including 1 man presenting with intellectual disability (ID), body mass index (BMI) of 47.

Progressive supranuclear palsy is not associated with neurogenic orthostatic hypotension.

Objective: To evaluate the pattern and severity of autonomic dysfunction in autopsy-confirmed progressive supranuclear palsy (PSP) compared to α-synuclein pathology.

Methods: Autopsy-confirmed cases of 14 patients with PSP, 18 with multiple system atrophy (MSA), and 24 with Lewy body disease (LBD) with antemortem autonomic testing were reviewed retrospectively. All patients underwent comprehensive clinical evaluations by a movement disorder specialist, formal autonomic testing, and postmortem examinations at Mayo Clinic.

Vocal Fold "Paralysis": An Early Sign in Multiple System Atrophy.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by a cerebellar syndrome, autonomic dysfunction, and extrapyramidal signs. Extrapyramidal signs may manifest as parkinsonism as well as dystonia, which is the involuntary contraction of a muscle(s) resulting in an abnormal posture. MSA belongs to a family of diseases known as α-synucleinopathies which are associated with dream enactment reflecting REM sleep behavior disorder (RBD).

A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls.

Association of MAPT Subhaplotypes With Risk of Progressive Supranuclear Palsy and Severity of Tau Pathology.

Importance: The association between the microtubule-associated protein tau (MAPT) H1 haplotype and the risk of progressive supranuclear palsy (PSP) has been well documented. However, the specific H1 subhaplotypes that drive the association have not been evaluated in large studies, nor have they been studied in relation to neuropathologic severity of disease.

Objective: To comprehensively evaluate the associations of MAPT haplotypes with the risk of PSP and the severity of tau pathology using a large series of neuropathologically confirmed PSP cases.

ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans.

Background: Rare coding variants ABI3_rs616338-T and PLCG2_rs72824905-G were identified as risk or protective factors, respectively, for Alzheimer's disease (AD).

Methods: We tested the association of these variants with five neurodegenerative diseases in Caucasian case-control cohorts: 2742 AD, 231 progressive supranuclear palsy (PSP), 838 Parkinson's disease (PD), 306 dementia with Lewy bodies (DLB) and 150 multiple system atrophy (MSA) vs. 3351 controls; and in an African-American AD case-control cohort (181 AD, 331 controls).

ε4 is associated with severity of Lewy body pathology independent of Alzheimer pathology.

Objective: To evaluate whether ε4 is associated with severity of Lewy body (LB) pathology, independently of Alzheimer disease (AD) pathology.

Methods: Six hundred fifty-two autopsy-confirmed LB disease (LBD) cases and 660 clinical controls were genotyped for . In case-control analysis, LBD cases were classified into 9 different groups according to severity of both LB pathology (brainstem, transitional, diffuse) and AD pathology (low, moderate, high) to assess associations between ε4 and risk of different neuropathologically defined LBD subgroups in comparison to controls.

Association study between multiple system atrophy and TREM2 p.R47H.

Objective: The triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not been well studied in relation to the risk of multiple system atrophy (MSA); the aim of this study was to evaluate the association between the TREM2 p.R47H variant and the risk of MSA.

Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype.

Corticobasal degeneration (CBD) is a clinically heterogeneous tauopathy, which has overlapping clinicopathologic and genetic characteristics with progressive supranuclear palsy (PSP). This study aimed to elucidate whether transactive response DNA-binding protein of 43 kDa (TDP-43) pathology contributes to clinicopathologic heterogeneity of CBD. Paraffin-embedded sections of the midbrain, pons, subthalamic nucleus, and basal forebrain from 187 autopsy-confirmed CBD cases were screened with immunohistochemistry for phospho-TDP-43.