Clinicopathological Heterogeneity of Lewy Body Diseases: The Profound Influence of Comorbid Alzheimer's Disease.

In recent years, proposals have been advanced to redefine or reclassify Lewy body disorders by merging the long-established entities of Parkinson's disease (PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). These proposals reject the International DLB Consortium classification system that has evolved over three decades of consensus collaborations between neurologists, neuropsychologists and neuropathologists. While the Consortium's "one year rule" for separating PD and DLB has been criticized as arbitrary, it has been a pragmatic and effective tool for splitting the continuum between the two entities.

Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology.

Lewy body (LB) disorders, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. By applying data-driven disease progression modelling to regional neuropathological LB density scores from 814 brain donors, we describe three inferred trajectories of LB pathology that were characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression.

Cerebral white matter rarefaction has both neurodegenerative and vascular causes and may primarily be a distal axonopathy.

Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due to cerebral arteriolosclerosis. Renewed attention came with CT and MR brain imaging, and neuropathological studies finding a high rate of CWMR in Alzheimer disease (AD). The relative contributions of cerebrovascular disease and AD to CWMR are still uncertain.

Low clinical sensitivity and unexpectedly high incidence for neuropathologically diagnosed progressive supranuclear palsy.

The objective of this study was to determine the prevalence, incidence, and clinical diagnostic accuracy for neuropathologically diagnosed progressive supranuclear palsy (PSP) with data from a longitudinal clinicopathological study using Rainwater criteria to define neuropathological PSP. Of 954 autopsy cases, 101 met Rainwater criteria for the neuropathologic diagnosis of PSP. Of these, 87 were termed clinicopathological PSP as they also had either dementia or parkinsonism or both.

Olfactory Dysfunction in Incidental Lewy Body Disease and Parkinson's Disease: An Update.

Objective: Measuring olfactory dysfunction shows promise as one of a number of nonmotor biomarkers that can be used to detect clinically manifest and prodromal Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and to differentiate these from nonsynucleinopathies. Using a larger sample size than in our previous study, we evaluated the relationship between olfactory dysfunction based on the University of Pennsylvania Smell Identification Test (UPSIT) to the clinicopathological findings in patients with PD (n=41), patients with incidental Lewy body disease (ILBD) (n=47), and controls with no neurodegenerative disease (n=137).

Design: This study was conducted through the Arizona Study of Aging and Neurodegenerative Disease (AZSAND).

In Patients With Functional Movement Disorders, Is Specialized Physical Therapy Effective in Improving Motor Symptoms?: A Critically Appraised Topic.

Background: Functional movement disorders (FMD, aka psychogenic movement disorders) are very common and frequently chronic and disabling. Despite this, there is a paucity of evidence-based treatment to manage and alleviate these conditions. Specialized physical therapy (PT), involving sequential motor relearning and redirecting attention, has shown promise as a therapeutic intervention for motor symptoms.

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.

Correlation Between the Movement Disorder Society's Unified Parkinson's Disease Rating Scale and Nonmotor Scales in Patients with Parkinson's Disease.

The Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDSUPDRS), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Mayo Sleep Questionnaire, Epworth Sleepiness Scale, and Neuropsychiatric Inventory Questionnaire (NPI-Q) are validated instruments for assessing signs and symptoms of Parkinson's disease (PD). We sought to determine whether responses on the MDS-UPDRS correlate with responses to other scales used in patients with PD. Study subjects were enrolled in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).

Brain Lewy-Type Synucleinopathy Density Is Associated with a Lower Prevalence of Atherosclerotic Cardiovascular Disease Risk Factors in Patients with Parkinson's Disease1.

Background: Some epidemiology studies suggest that atherosclerotic cardiovascular disease (ASCVD) risk factors increase the risk of developing Parkinson's disease (PD). However, conflicting data suggest lower rates of ASCVD in PD.

Objective: The objective of this study is to determine, with data from a longitudinal clinicopathological study, whether ASCVD risk factors are associated with a PD diagnosis and/or increased brain or peripheral load of Lewy-type synucleinopathy (LTS).

Association Between Pathology and Electroencephalographic Activity in Parkinson's Disease.

Introduction: The key mechanisms that connect Parkinson's disease pathology with dementia are unclear. We tested the hypothesis that the quantitative spectral electroencephalographic measure, delta bandpower, correlates with Lewy type synucleinopathy on pathological examination in Parkinson's disease. As a corollary hypothesis, we analyzed whether there would be delta bandpower electroencephalographic differences between Parkinson's disease dementia cases with and without pathological criteria for Alzheimer's disease.

Graph theory network function in Parkinson's disease assessed with electroencephalography.

Objectives: To determine what differences exist in graph theory network measures derived from electroencephalography (EEG), between Parkinson's disease (PD) patients who are cognitively normal (PD-CN) and matched healthy controls; and between PD-CN and PD dementia (PD-D).

Methods: EEG recordings were analyzed via graph theory network analysis to quantify changes in global efficiency and local integration. This included minimal spanning tree analysis.

Longitudinal EEG changes correlate with cognitive measure deterioration in Parkinson's disease.

Background: QEEG could provide physiological biomarkers for changes over time in Parkinson's disease (PD) cognitive decline if they track with longitudinal neuropsychological performance.

Objective: Our aim was to correlate longitudinal changes in frequency domain quantitative electroencephalography (QEEG) measures with change in neuropsychological performance testing in PD.

Methods: 71 PD subjects, not demented at baseline, were studied from the Arizona Study of Aging and Neurodegenerative Disorders cohort.

SMG1 identified as a regulator of Parkinson's disease-associated alpha-synuclein through siRNA screening.

Synucleinopathies are a broad class of neurodegenerative disorders characterized by the presence of intracellular protein aggregates containing α-synuclein protein. The aggregated α-synuclein protein is hyperphosphorylated on serine 129 (S129) compared to the unaggregated form of the protein. While the precise functional consequences of S129 hyperphosphorylation are still being clarified, numerous in vitro and in vivo studies suggest that S129 phosphorylation is an early event in α-synuclein dysfunction and aggregation.

Movement disorders and sleep.

This article summarizes what is currently known about sleep disturbances in several movement disorders including Parkinson disease, essential tremor, parkinsonism, dystonia, Huntington disease, myoclonus, and ataxias. There is an association between movement disorders and sleep. In some cases the prevalence of sleep disorders is much higher in patients with movement disorder, such as rapid eye movement sleep behavior disorder in Parkinson disease.

Incidental Lewy body disease: electrophysiological findings suggesting pre-clinical Lewy body disorders.

Objective: Evaluate electrophysiologic findings in incidental Lewy body disease (ILBD).

Methods: ILBD, Control, and Parkinson's disease (PD) subjects had electrophysiological evaluation within 2 years prior to autopsy. Data analyzed included surface electromyography (EMG) of upper extremity muscles during rest and muscle activation, and electroencephalography (EEG) recording at rest.

Patient versus informant reporting of ICD symptoms in Parkinson's disease using the QUIP: validity and variability.

Questions exist regarding the validity of patient-reporting of psychiatric symptoms in Parkinson's disease (PD). We assessed observer variability and validity in reporting of impulse control disorder (ICD) symptoms in PD by using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP). PD patients and their informants (71 pairs) completed the QUIP to assess four ICDs (compulsive gambling, buying, sexual behavior, and eating) in patients.

Are corticosteroid and antiviral treatments effective for bell palsy? A critically appraised topic.

Background: : Bell palsy is idiopathic peripheral facial weakness that typically resolves without severe clinical sequelae. Treatment with corticosteroids and antiviral drugs is often initiated to improve the likelihood of a favorable outcome.

Objective: : Are corticosteroid and antiviral medications effective in the treatment of Bell palsy?

Methods: : The objective was addressed through the development of a structured critically appraised topic.

Superficial siderosis mimicking amyotrophic lateral sclerosis.

We report a case of superficial siderosis erroneously diagnosed as amyotrophic lateral sclerosis. The patient's symptoms began 18 years prior with unilateral upper extremity weakness, fasciculations, and hyperreflexia. The patient then developed ataxia and hearing loss 15 years after his original symptoms.

Efficacy of rivastigmine for cognitive symptoms in Parkinson disease with dementia.

Background: Impairment of multiple neurotransmitter networks, including acetylcholine, may contribute to the cognitive impairment in patients with Parkinson disease with dementia (PDD). Therefore, cholinesterase inhibitors might improve cognitive function in PDD. On the other hand, enhancing cholinergic function could plausibly worsen features of parkinsonism.

Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease.

As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson's disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results.