Serotonin Transporter Imaging in Multiple System Atrophy and Parkinson's Disease.

BACKGROUND: Both Parkinson's disease (PD) and multiple system atrophy (MSA) exhibit degeneration of brainstem serotoninergic nuclei, affecting multiple subcortical and cortical serotoninergic projections. In MSA, medullary serotoninergic neuron pathology is well documented, but serotonin system changes throughout the rest of the brain are less well characterized. OBJECTIVES: To use serotonin transporter [11 C]3-amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile positron emission tomography (PET) to compare serotoninergic innervation in patients with MSA and PD. METHODS: We performed serotonin transporter PET imaging in 18 patients with MSA, 23 patients with PD, and 16 healthy controls to explore differences in brainstem, subcortical, and cortical regions of interest. RESULTS: Patients with MSA showed lower serotonin transporter distribution volume ratios compared with patients with PD in the medulla, raphe pontis, ventral striatum, limbic cortex, and thalamic regions, but no differences in the dorsal striatal, ventral anterior cingulate, or total cortical regions. Controls showed greater cortical serotonin transporter binding compared with PD or MSA groups but lower serotonin transporter binding in the striatum and other relevant basal ganglia regions. There were no regional differences in binding between patients with MSA-parkinsonian subtype (n = 8) and patients with MSA-cerebellar subtype (n = 10). Serotonin transporter distribution volume ratios in multiple different regions of interest showed an inverse correlation with the severity of Movement Disorders Society Unified Parkinson's Disease Rating Scale motor score in patients with MSA but not patients with PD. CONCLUSIONS: Brainstem and some forebrain subcortical region serotoninergic deficits are more severe in MSA compared with PD and show an MSA-specific correlation with the severity of motor impairments. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Differential cholinergic systems' changes in progressive supranuclear palsy versus Parkinson's disease: an exploratory analysis.

Prior studies indicate more severe brainstem cholinergic deficits in Progressive Supranuclear Palsy (PSP) compared to Parkinson's disease (PD), but the extent and topography of subcortical deficits remains poorly understood. The objective of this study is to investigate differential cholinergic systems changes in progressive supranuclear palsy (PSP, n = 8) versus Parkinson's disease (PD, n = 107) and older controls (n = 19) using vesicular acetylcholine transporter [18F]-fluoroethoxybenzovesamicol (FEOBV) positron emission tomography (PET). A whole-brain voxel-based PET analysis using Statistical Parametric Mapping (SPM) software (SPM12) for inter-group comparisons using parametric [18F]-FEOBV DVR images. Voxel-based analyses showed lower FEOBV binding in the tectum, metathalamus, epithalamus, pulvinar, bilateral frontal opercula, anterior insulae, superior temporal pole, anterior cingulum, some striatal subregions, lower brainstem, and cerebellum in PSP versus PD (p < 0.05; false discovery rate-corrected). More severe and diffuse reductions were present in PSP vs controls. Higher frequency of midbrain cholinergic losses was seen in PSP compared to the PD participants using 5th percentile normative cut-off values (χ2 = 4.12, p < 0.05). When compared to PD, these findings suggested disease-specific cholinergic vulnerability in the tectum, striatal cholinergic interneurons, and projections from the pedunculopontine nucleus, medial vestibular nucleus, and the cholinergic forebrain in PSP.

Isolated REM sleep behavior disorder in North American older adults in an integrated health care system.

STUDY OBJECTIVE: Identifying individuals with isolated rapid eye movement sleep behavioral disorder (iRBD) is an important clinical research priority for future synucleinopathy trials. Nevertheless, little is known about the breadth of clinical settings where diagnoses of iRBD are initially made. METHODS: We conducted a retrospective cohort study using the electronic medical record system at the University of Michigan to identify patients aged ≥ 60 years with new diagnoses of iRBD between 2015 and 2020. We focused specifically on patients receiving primary care at the University of Michigan so that we might use the university's electronic medical record system to capture the full scope of their multispecialty care interactions and diagnoses in this integrated health care system. We used International Classification of Diseases, Ninth Revision and Tenth Revision, diagnosis codes to identify the time of initial clinical diagnosis. RESULTS: We found that 62/105 (59.0%) diagnoses were made by a sleep specialist, 9 (8.6%) by neurologists, and 30 (29.5%) by generalists or primary care (29.5%) providers. In addition, 67/105 (63.8%) diagnoses were made in the context of having available polysomnography results, while the remainder was made on the basis of clinical symptoms alone. The prognostic implications of iRBD were documented in 40/105 (38.1%) encounter notes and were more likely to occur in sleep clinic settings (chi-square = 12.74; P < .001) than in other contexts. CONCLUSIONS: Initial iRBD diagnoses occur in varied clinical settings in an integrated health care system and are often made without a confirmatory polysomnogram. Documented prognostic counseling is seen most often in sleep medicine clinics. Synucleinopathy prevention trials may be best designed around a sleep clinic-focused recruitment approach. CITATION: Havis I, Coates T, Wyant KJ, Spears CC, Garwood M, Kotagal V. Isolated REM sleep behavior disorder in North American older adults in an integrated health care system. J Clin Sleep Med. 2022;18(9):2173-2178.

An Unusual Case of Essential Tremor Deep Brain Stimulation: Where is the Lead?

Clinical Vignette: A 73-year-old female with essential tremor (ET) underwent bilateral thalamic ventralis intermedius (Vim) deep brain stimulation (DBS) surgery. The leads provided tremor benefit, but the location was suboptimal and contributed to stimulation-induced hemichorea. Clinical Dilemma: Can patients with ET derive benefit when stimulating outside the Vim? What do we know about stimulation-induced hemichorea in the setting of ET? Clinical Solution: Lead localization combined with advanced programming strategies can be employed to troubleshoot DBS in settings when benefits are observed along with adverse effects. Gap in Knowledge: Sparse information exists about DBS when applied to neuroanatomic regions outside the Vim for the management of ET. Subthalamic nucleus DBS-induced chorea has been reported in multiple movement disorders, but not in ET.

Causes and outcomes of hospitalization in Lewy body dementia: A retrospective cohort study.

INTRODUCTION: Understanding hospitalization in Lewy body dementia (LBD) is a known knowledge gap. We aimed to identify common causes, medication profiles, complications, and outcomes of hospitalization in LBD. METHODS: A retrospective cohort study investigated details of academic medical center hospitalizations over a two-year period for patients with LBD. Data collected included demographics, home medications, pre-hospital living status, reason for admission, admission service, inpatient medications, complications, and discharge status. Non-parametric statistics assessed associations between variables and length of stay. Odds of a change in living situation based on admission variables was calculated. RESULTS: The study included 178 hospitalizations (117 individuals). Neuropsychiatric symptoms were the most common admission reason (40%), followed by falls (24%) and infection (23%). Patients were usually admitted to medicine services; neurology or psychiatric consultations occurred less than 40% of the time. Antipsychotics were administered during 38% of hospitalizations. Use of antipsychotics other than quetiapine or clozapine was associated with longer length of stay and increased odds of discharge to a higher level of care. One-third of hospitalizations resulted in transition to a higher level of care; 15% ended in hospice care or death. CONCLUSION: The most common reasons for hospitalization in LBD are potentially modifiable. Opportunities for improved care include increased involvement of neurological and psychiatric services, delirium prevention strategies, and reduced antipsychotic use. Clinicians should counsel patients and families that hospitalizations in LBD can be associated with end of life. Research is needed to identify strategies to prevent hospitalization and optimal standards for inpatient care. FUNDING: Lewy body dementia research at the University of Florida is supported by the University of Florida Dorothy Mangurian Headquarters for Lewy Body Dementia and the Raymond E. Kassar Research Fund for Lewy Body Dementia.