Hentz, Joseph G.

Background and Purpose Previous studies have shown a stroke mimic rate of 9%–31%. We aimed to establish the proportion of stroke mimics amongst suspected acute strokes, to clarify the aetiology of stroke mimic and to develop a prediction model to identify stroke mimics. Methods This was a retrospective cohort observational study. Consecutive “stroke alert” patients were identified over nine months in a primary stroke centre. 31 variables were collected. Final diagnosis was defined as “stroke” or “stroke mimic”. Multivariable regression analysis was used to define clinical predictors of stroke mimic. Results 206 patients were reviewed. 22% were classified as stroke mimics. Multivariable scoring did not help in identification of stroke mimics. 99.5% of patients had a neurological diagnosis at final diagnosis. Discussion 22% of patients with suspected acute stroke had a stroke mimic. The aetiology of stroke mimics was varied, with seizure, encephalopathy, syncope and migraine being commonest. Multivariable scoring for identification of stroke mimics is not feasible. 99.5% of patients had a neurological diagnosis. This strengthens the case for the involvement of stroke neurologists/stroke physicians in acute stroke care.

AbstractObjectiveTo assess the predictive potential of the complete response pattern from the University of Pennsylvania Smell Identification Test for the diagnosis of Parkinson's disease.MethodsWe analyzed a large dataset from the Arizona Study of Aging and Neurodegenerative Disorders, a longitudinal clinicopathological study of health and disease in elderly volunteers. Using the complete pattern of responses to all 40 items in each subject's test, we built predictive models of neurodegenerative disease, and we validated these models out of sample by comparing model predictions against postmortem pathological diagnosis.ResultsConsistent with anatomical considerations, we found that the specific test response pattern had additional predictive power compared with a conventional measure – total test score – in Parkinson's disease, but not Alzheimer's disease. We also identified specific test questions that carry the greatest predictive power for disease diagnosis.InterpretationOlfactory ability has typically been assessed with either self‐report or total score on a multiple choice test. We showed that a more accurate clinical diagnosis can be made using the pattern of responses to all the test questions, and validated this against the “gold standard” of pathological diagnosis. Information in the response pattern also suggests specific modifications to the standard test that may optimize predictive power under the typical clinical constraint of limited time. We recommend that future studies retain the individual item responses for each subject, and not just the total score, both to enable more accurate diagnosis and to enable additional future insights.

Background and purpose Mutations in the glucocerebrosidase ( GBA ) gene are known to be a risk factor for Parkinson's disease ( PD ). Data on clinicopathological correlation are limited. The purpose of this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene. Methods Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to identify autopsied PD cases that did or did not have a GBA gene mutation. Clinical and neuropathological data were compared. Results Twelve PD cases had a GBA mutation and 102 did not. The GBA mutation cases died younger (76 vs. 81 years of age) but there was no difference in disease duration or clinical examination findings. No neuropathological differences were found in total or regional semi‐quantitative scores for Lewy‐type synucleinopathy, senile plaques, neurofibrillary tangles, white matter rarefaction or cerebral amyloid angiopathy scores. Conclusions In longitudinally assessed, autopsied PD cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. Due to the small GBA group size, small differences cannot be excluded.

Introduction: This study set out to clarify the differential acute cognitive impact of lorazepam based on varying genetic risk for Alzheimer disease. Methods: Fifty-seven cognitively unimpaired individuals aged 51 to 88, genotyped according to apolipoprotein E (APOE) and translocase of outer mitochondrial membrane (40 homolog) poly-T lengths, completed cognitive testing before, 2.5 and 5 hours after receiving a 1 mg dose of lorazepam. Results: Post-lorazepam, there were significant (P<0.05) declines from baseline in memory, psychomotor processing speed, and executive function. At 2.5 hours, the magnitude of this lorazepam-induced cognitive change was significantly greater in the APOE3/4 group than in the APOE3/3 group for tests of working memory and visuospatial memory/executive function. At 5 hours postchallenge, verbal memory and working memory deficits persisted in the APOE3/4 group compared with the APOE3/3 group. At 5 hours after lorazepam challenge, as compared with the very long/very long group, the short/short group performed slightly worse on a test of working memory (P<0.05), but no other differences were observed among translocase of the outer mitochondrial membrane 40 homolog poly-T variant groups. Discussion: The lorazepam challenge may be unmasking presymptomatic cognitive dysfunction associated with APOE4 carriage.

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. Methods. We used pathological examination results from 44 Parkinson’s disease subjects from our brain bank with various degrees of cognitive decline, who had undergone electroencephalography. Pathological grading for Lewy type synucleinopathy, plaques, tangles, and indications of vascular pathology in subcortical and cortical areas were correlated with the most associated electroencephalographic biomarker with Parkinson’s disease dementia in our laboratory, delta bandpower. Group differences for all spectral electroencephalographic measures were also analyzed between cases with and without pathological criteria for Alzheimer’s disease. Results. Findings revealed significant correlations between delta bandpower with Lewy type synucleinopathy, whereas indications of Alzheimer’s disease or vascular pathology had nonsignificant correlation. The strongest association was with delta bandpower and Lewy type synucleinopathy in the anterior cingulate region. Mean delta bandpower was higher in the group for Parkinson’s disease dementia with Alzheimer’s disease pathology criteria than without. Conclusions. Lewy type synucleinopathy severity appears to be more associated with increased delta bandpower than with Alzheimer’s disease pathology or indications of vascular pathology over all cases. However, the presence of Alzheimer’s pathology may associate with more cortex physiological disruption in a subset of cases.

Abstract Solid organ and stem cell transplant patients and their caregivers report a substantial level of distress. Mindfulness‐based stress reduction has been shown to alleviate distress associated with transplant, but there is limited experience in this population with other mindfulness‐based interventions, or with combined transplant patient and caregiver interventions. We evaluated a novel, 6‐week mindfulness‐based resilience training ( MBRT ) class for transplant patients and their caregivers that incorporates mindfulness practice, yoga, and neuroscience of stress and resilience. Thirty‐one heart, liver, kidney/pancreas, and stem cell transplant patients and 18 caregivers at Mayo Clinic in Arizona participated. Measures of stress, resilience, depression, anxiety, health‐related quality of life, positive and negative affect, and sleep were completed at baseline, 6 weeks, and 3 months postintervention. At 6 weeks and 3 months, patients demonstrated significant ( P <.005) improvements from baseline in measures of perceived stress, depression, anxiety, and negative affect. Quality‐of‐life mental component ( P =.006) and positive affect ( P =.02) also improved at follow‐up. Most participants adhered to the program, were satisfied with class length and frequency, and reported improved well‐being as a result of the class. MBRT holds promise as an intervention to enhance resilience and manage stress for transplant patients and their caregivers.

Background: Conflicting results from studies of Lewy-type α−synucleinopathy (LTS) in colonic biopsies of subjects with Parkinson’s disease (PD) prompted a two-part multicenter assessment. The first assessment, now published (Acta Neuropathol Commun 4 : 35, 2016), examined archived colonic biopsies and found that none of the tested methods was adequately sensitive or specific. Objective: As the amount of nervous tissue in typical colonic biopsies may be insufficient, and the clinical diagnosis of PD not completely accurate, the objective of the current study was to use instead full-thickness sections of sigmoid colon from autopsy-proven PD and normal subjects. Methods: Seven different immunohistochemical (IHC) methods were used, employing five different primary antibodies and four different combinations of epitope exposure and signal development protocols. Specific staining was defined as being restricted to morphological features consistent with neuronal elements. Stained slides from each subject were independently categorized as being positive or negative for LTS, and their density semi-quantitatively graded, by four raters blinded to diagnosis. Results: Agreement and mean diagnostic performance varied markedly between raters. With the two most accurate raters, 5 methods achieved diagnostic accuracies of 70% or greater; one method had 100% accuracy and 100% inter-rater agreement. The submucosa had the highest prevalence of pathological LTS staining, followed by the muscularis and mucosa. Conclusions: The major conclusion of this study is that, when sufficient submucosa and LTS is present, and when specific staining is defined as being consistent with neuronal morphology, adequately-trained raters may reliably distinguish PD colon from control using suitable IHC methods.

ObjectiveTo identify symptoms, common diagnostic findings, pattern of treatments and referrals offered, and their efficacy in a group of patients with idiopathic functional dysphagia in an otolaryngology setting with multiple providers.Study DesignCase series with chart review.SettingTertiary academic center.Subjects and MethodsFollowing Mayo Clinic Institutional Review Board approval, a retrospective chart review was conducted of patients with dysphagia who had a videofluoroscopic swallow study between January 1, 2013, and April 30, 2015. Each patient’s dysphagia symptomology, videofluoroscopic swallow study, flexible laryngoscopy, and medical chart were reviewed to identify the treatment paradigms that were utilized.ResultsSixty‐seven adult patients met the inclusion criteria. Abnormal laryngeal muscle tension was present in 97% of patients. Eighty‐two percent of patients also demonstrated signs of laryngeal hyperresponsiveness. Nonspecific laryngeal inflammation was evident in 52% of patients. Twenty‐seven patients were referred to speech‐language pathology for evaluation. Thirteen patients completed a course of voice therapy directed toward unloading muscle tension. All 13 patients self‐reported resolution of dysphagia symptoms.ConclusionThe study results suggest that laryngeal muscle tension may be a factor in the underlying etiology in patients with idiopathic functional dysphagia. We propose the diagnostic term muscle tension dysphagia to describe a subset of patients with functional dysphagia. Further prospective studies are needed to better evaluate potential gastroesophageal confounders in this group of patients and to identify an effective paradigm for treatment. In our limited series, speech‐language pathology intervention directed toward unloading muscle tension appears effective.

ABSTRACTIntroductionQuantitative EEG features have been identified as surrogates and predictors of cognitive decline/dementia, a common feature of progressive PD. The biochemical correlates for altered quantitative EEG features are unknown. Our primary objective was to test the hypothesis that quantitative EEG measures correlate with cortical levels of phosphorylated α‐synuclein, a modified form of the synaptic protein α‐synuclein, in PD cases, in contrast to other pathology‐associated proteins. A secondary objective was to explore the same correlations among cellular fractions of these proteins.MethodsWe used posterior cingulate cortex autopsy tissue from 44 PD subjects with various degrees of cognitive decline, who had undergone EEG. In this brain region, which is a major hub of the default mode network, biochemical measurements for levels of phosphorylated α‐synuclein, unmodified α‐synuclein, amyloid beta peptide, phosphorylated tau, and key synaptic proteins were analyzed and data correlated with spectral EEG measures.ResultsFindings revealed significant correlations between background rhythm peak frequency and all bandpower values (highest in delta bandpower) with total phosphorylated α‐synuclein, but not any correlation with total α‐synuclein, phosphorylated tau protein, amyloid beta peptide, or synaptic proteins. Certain fractions of synaptosomal‐associated protein 25 showed correlation with some quantitative EEG measures.ConclusionsThese data show an association between increased phosphorylation of α‐synuclein and the abnormal EEG signatures of cognitive decline. Results suggest that quantitative EEG may provide an in vivo approximation of phosphorylated α‐synuclein in PD cortex. This adds to previous evidence that quantitative EEG measures can be considered valid biomarkers of PD cognitive decline. © 2016 International Parkinson and Movement Disorder Society