Primary Progressive Apraxia of Speech Caused by TDP-43: A Case Report.

Objectives: To introduce the first case in which primary progressive apraxia of speech (PPAOS) is associated with TAR DNA-binding protein 43 (TDP-43) instead of 4-repeat tau.

Methods: This patient was identified through a postmortem autopsy. Following an initial diagnostic evaluation, he participated in 3 annual research visits during which speech, language, cognitive, and neurologic assessments were administered.

Parkinson's disease progression is multifaceted: Evidence for the underlying benchmarks.

Long-term Parkinson's disease (PD) progression is not a homogeneous process and manifests in diverse ways over the lifetime. Recognition of progression benchmarks and their substrates is important for treatment and addressing the expectations of patients, as well as for PD research planning.

40-Year Incidence of Early-Onset Parkinson's Disease in Southeast Minnesota.

Background: Parkinson's disease (PD) most commonly surfaces at middle age. An earlier onset is named early-onset Parkinson's disease (EOPD), but the exact definition is a matter of ongoing scientific debate.

Objective: To investigate 40-year EOPD incidence trends in a population-based cohort of parkinsonism in Olmsted County, Minnesota.

Tenascin-R Autoimmunity: Isolated Tremor Reversed with Immunotherapy.

Autoimmune movement disorders are increasingly recognized, but isolated tremor is extremely rare. We describe a 70-year-old male with rapidly progressive, severe postural and intention tremor and weight loss. His cerebrospinal fluid was inflammatory and harbored a neural tissue-restricted antibody.

Levodopa, homocysteine and Parkinson's disease: What's the problem?

Elevated circulating homocysteine levels have been associated with cognitive impairment and cardio-cerebro-vascular events. Levodopa treatment of Parkinson's disease tends to further elevate circulating homocysteine levels due to the metabolism of levodopa via catechol-O-methyltransferase (COMT). COMT co-factors are vitamins B12, B6 and folic acid.

Lifelong constipation in Parkinson's disease and other clinically defined alpha-synucleinopathies: A population-based study in Southeast Minnesota.

Introduction: Epidemiological studies show correlations between constipation and development of Parkinson's disease (PD); however, few studies have explored the association between constipation and dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and multiple system atrophy (MSA). We sought to explore the lifelong association of constipation and PD, DLB, PDD, and MSA (α-Synucleinopathies), compared to age- and sex-matched controls.

Methods: Using the Rochester Epidemiology Project (REP), we established an incident cohort of clinically defined α-synucleinopathies.

CBP-HSF2 structural and functional interplay in Rubinstein-Taybi neurodevelopmental disorder.

Patients carrying autosomal dominant mutations in the histone/lysine acetyl transferases CBP or EP300 develop a neurodevelopmental disorder: Rubinstein-Taybi syndrome (RSTS). The biological pathways underlying these neurodevelopmental defects remain elusive. Here, we unravel the contribution of a stress-responsive pathway to RSTS.

Utility of routine surface electrophysiology to screen for functional tremor prior to surgical treatment of essential tremor.

Background: Patients with functional tremor may be clinically misdiagnosed as "medication-refractory" essential tremor (ET) and referred for surgical treatment. Electrophysiology can screen for functional tremor and avoid inappropriate surgery.

Objective: To report the utility of surface electrophysiology (SEMG) to screen for functional tremor in patients referred for ET surgery.

Tau-PET and multimodal imaging in clinically atypical multiple system atrophy masquerading as progressive supranuclear palsy.

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.

Histologic lesion type correlates of magnetic resonance imaging biomarkers in four-repeat tauopathies.

Primary four-repeat tauopathies are characterized by depositions of the four-repeat isoform of the microtubule binding protein, tau. The two most common sporadic four-repeat tauopathies are progressive supranuclear palsy and corticobasal degeneration. Because tau PET tracers exhibit poor binding affinity to four-repeat pathology, determining how well MRI findings relate to underlying pathology is critical to evaluating their utility as surrogate markers to aid in diagnosis and as outcome measures for clinical trials.

Cancer cells use self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress.

Genotoxic therapy such as radiation serves as a frontline cancer treatment, yet acquired resistance that leads to tumor reoccurrence is frequent. We found that cancer cells maintain viability during irradiation by reversibly increasing genome-wide DNA breaks, thereby limiting premature mitotic progression. We identify caspase-activated DNase (CAD) as the nuclease inflicting these de novo DNA lesions at defined loci, which are in proximity to chromatin-modifying CCCTC-binding factor (CTCF) sites.

Speech-induced action myoclonus.

Background: Speech-induced action myoclonus may occur as a component of a generalized myoclonus syndrome. However, it may also present in isolation, or with a paucity of other findings, and be diagnostically challenging.

Objectives: To report a retrospective case series of restricted speech-induced action myoclonus.

Does limited EMG denervation in early primary lateral sclerosis predict amyotrophic lateral sclerosis?

: We assessed whether a cohort of patients with primary lateral sclerosis (PLS) and limited electromyography (EMG) motor unit denervation changes evolve into amyotrophic lateral sclerosis (ALS) with prolonged follow-up. : We initially ascertained all PLS patients diagnosed at Mayo Clinic-Rochester (1990-2016). Of 64 total cases, 43 had normal EMGs ("pure" PLS) during the first 4 years after symptom onset and were the focus of a prior publication, documenting absence of evolution to ALS.

Brainstem Biomarkers of Clinical Variant and Pathology in Progressive Supranuclear Palsy.

Background: Magnetic resonance brainstem measurements are useful structural biomarkers in the Richardson's syndrome variant of progressive supranuclear palsy (PSP). However, it is unclear how these biomarkers differ across the phenotypic spectrum of PSP and how they relate to underlying pathology.

Objective: The aim of this study was to compare brainstem imaging measures across clinical variants of PSP and determine sensitivity and specificity based on pathologically diagnosed cases.

Gray and White Matter Correlates of Dysphagia in Progressive Supranuclear Palsy.

Background: Dysphagia is a common symptom of progressive supranuclear palsy often leading to aspiration pneumonia and death.

Objective: The aim of this study was to examine how impairments of the oral and pharyngeal phases of the swallow and airway incursion during liquid swallows relate to gray and white matter integrity.

Methods: Thirty-eight participants with progressive supranuclear palsy underwent videofluorographic swallowing assessment and structural and diffusion tensor head magnetic resonance imaging.

Diffusion tensor imaging analysis in three progressive supranuclear palsy variants.

Background: Clinical variants of progressive supranuclear palsy (PSP) include the classic Richardson's syndrome (PSP-RS), as well as cortical presentations such as PSP-speech/language (PSP-SL) and subcortical presentations such as PSP-parkinsonism (PSP-P). Patterns of white matter tract degeneration underlying these variants, and the degree to which white matter patterns could differentiate these variants, is unclear.

Methods: Forty-nine PSP patients (28 PSP-RS, 12 PSP-P, and 9 PSP-SL) were recruited by the Neurodegenerative Research Group and underwent diffusion tensor imaging.

My Treatment Approach to Multiple System Atrophy.

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.

Natural History of "Pure" Primary Lateral Sclerosis.

Objective: To assess whether primary lateral sclerosis (PLS), classified as pure when the EMG is normal, converts to amyotrophic lateral sclerosis (ALS) after longitudinal follow-up.

Methods: Retrospective chart review was performed of patients with pure PLS at Mayo Clinic in Rochester, MN (1990-2016). Inclusion criteria required a normal EMG during the first 4 years of symptoms.

Common Myths and Misconceptions That Sidetrack Parkinson Disease Treatment, to the Detriment of Patients.

Parkinson disease symptoms become apparent when there has been substantial loss of brain dopamine. That is the consequence of the slow progression of the Lewy body neurodegenerative process. Replenishment of brain dopamine with levodopa therapy dates back approximately a half century and continues to be the most efficacious symptomatic treatment.

PSP-like syndrome after aortic surgery in adults (Mokri syndrome).

Background: A rare progressive supranuclear palsy-like syndrome seemingly triggered by aortic surgery was first described in 2004. This largest case series to date describes the features of this syndrome.

Methods: We searched the Mayo Clinic electronic medical records using the advanced cohort explorer search engine for patients evaluated for neurologic symptoms after cardiac-aortic surgery in the past 30 years.

Infections or Sepsis Preceding Clinically Diagnosed α-Synucleinopathies: A Case-Control Study.

Background: Several studies have proposed a role for infections to induce an inflammatory response triggering Parkinson's disease. This remains controversial and the influence of severe infections on other α-synucleinopathies (Dementia with Lewy Bodies, Parkinson's disease dementia, and Multiple System Atrophy) has not been adequately investigated.

Objectives: To assess the association between hospitalization-required infections or sepsis and risk of clinically diagnosed α-synucleinopathies.

Levodopa-induced dyskinesia in dementia with Lewy bodies and Parkinson disease with dementia.

Objective: To investigate the frequency of levodopa-induced dyskinesia in dementia with Lewy bodies (DLBs) and Parkinson disease with dementia (PDD) and compare these frequencies with patients with incident Parkinson disease (PD) through a population-based cohort study.

Methods: We identified all patients with DLB, PDD, and PD without dementia in a 1991-2010 population-based parkinsonism-incident cohort, in Olmsted County, Minnesota. We abstracted information about levodopa-induced dyskinesia.

Traumatic brain injury preceding clinically diagnosed α-synucleinopathies: A case-control study.

Objective: To determine the association between traumatic brain injury (TBI) and any clinically diagnosed α-synucleinopathy including Parkinson disease (PD), dementia with Lewy bodies (DLB), PD dementia (PDD), and multiple system atrophy (MSA).

Methods: Using the medical records-linkage system of the Rochester Epidemiology Project, we identified incident cases of α-synucleinopathies in Olmsted County, Minnesota, from 1991 to 2010, matching by age (±1 year) at symptom onset and sex to controls. We reviewed records of cases and controls to detect TBI prior to clinical-motor onset of any α-synucleinopathies.