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Purpose of Review: The most common four neurodegenerative atypical parkinsonian disorders (APDs) are progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). Their formal diagnostic criteria often require subspecialty experience to implement as designed and all require excluding competing diagnoses without clearly specifying how to do that. Validated diagnostic criteria are not available at all for many of the other common APDs, including normal pressure hydrocephalus (NPH), vascular parkinsonism (VP), or drug-induced parkinsonism (DIP). APDs also include conditions of structural, genetic, vascular, toxic/metabolic, infectious, and autoimmune origin. Their differential diagnosis can be challenging early in the course, if the presentation is atypical, or if a rare or non-neurodegenerative condition is present. This review equips community general neurologists to make an early provisional diagnosis before, or in place of, referral to a tertiary center. Early diagnosis would allay diagnostic uncertainty, allow prompt symptomatic management, provide disease-specific information and support resources, avoid further pointless testing and treatments, and create the possibility of trial referral., Recent Findings: We address 64 APDs using one over-arching flow diagram and a series of detailed tables. Most instances of APDs can be diagnosed with a careful history and neurological exam, along with a non-contrast brain MRI. Additional diagnostic tests are rarely needed but are delineated where applicable. Our diagnostic algorithm encourages referral to a tertiary center whenever the general neurologist feels it would be in the patient's best interest. Our algorithm emphasizes that the diagnosis of APDs is an iterative process, refined with the appearance of new diagnostic features, availability of new technology, and advances in scientific understanding of the disorders. Clinicians' proposals for all diagnostic tests for the APDs, including repeat visits, should be discussed with patients and their families to ensure that the potential information to be gained aligns with their larger clinical goals., Summary: We designed this differential diagnostic algorithm for the APDs to enhance general neurologists' diagnostic skills and confidence and to help them address the less common or more ambiguous cases., Competing Interests: M.K. Bruno: no relevant conflict of interest. She does have research funding from Michael J. Fox Foundation; R. Dhall: no relevant conflict of interest. He has received financial support from the following within the last year: Amneal pharmaceuticals, Sage Therapeutics, Neuroderm, Cerevel Therapeutics, Neurocrine, Neuraly, Alexion, Sun Pharma, Praxis Precision Medicines, Parkinson's Foundation, Aeon Biopharma, Abbvie, Pharma Two B, NIH Parent Grant #UL1TR003107 TRI Pilot Grant “Research Benefitting Rural Populations”. Dr. Dhall has received consulting revenues from Mitsubishi Tanabe Pharma America and Best Doctors. Dr. Dhall reports stock ownership (all at <$10,000) in medically related fields for Armata Pharmaceuticals, Compass Pathways, Biogen Idec, Atea Pharmaceuticals, Gilead Sciences, Imara, Inc, and SQZ Biotech; L.S. Honig: consulted for Biogen Eisai, Genentech/Roche, Medscape, and Prevail/Lilly. L.S. Honig has received research funding from Abbvie, Acumen, Alector, Biogen, Bristol-Myer Squibb, Cognition, Eisai, Genentech/Roche, Janssen/Johnson & Johnson, Eli Lilly, Transposon, UCB, and Vaccinex; Z. Mari: no relevant conflict of interest. He is immediate past Chair of the Movement Disorder Society's Telemedicine Study Group, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health Parkinson's Foundation Center of Excellence, Chair of Parkinson Study Group's Motor Features WG, Associate Editor of Parkinsonism & Related Disorders, president-elect for the Clark County Medical Society, which he also is a Trustee; Z. Mari serves on the IAPRD's Congress Site Selection Committee and Website Committee, and the PPMI's Wearable Devices Task Force. Z. Mari has been recipient of institutional grant support from the NIH, PF, MJFF, Biogen, Eli Lilly, AbbVie, Cerevel, and Praxis Precision Medicines; is cofounder and CMO of Neuraly, Inc, and Z NeuroSciences LLC; is shareholder of D&D PharmaTech, NeuroReserve, Neunos Inc, and Sensory Cloud; and has received honoraria for consulting and advisory board service from GB Sciences, GKC, Bial, Supernus, AbbVie, ACADIA, Sunovion. N.R. McFarland: received research support from the NIH-NINDS, Michael J. Fox Foundation, and Parkinson Foundation. He receives royalties from UpToDate and serves on advisory committee for ONO Pharmaceutical. L. Montaser-Kouhsari received consultant fees from Darmyian, Trinity Life Sciences, Guidepoint, and Techspert, has received research support from the NIH (NINDS), and has received Talk honorarium from Cleveland Clinic. A.M. Wills: no relevant conflict of interest. She does have consulting agreements with Genentech, Amylyx, and Ono pharmaceuticals and have research funding from the NIH, Parkinson's Foundation, and CurePSP. L.I. Golbe: consults for AI Therapeutics, Amylyx, Apellis, Aprinoia, Ferrer, IQVIA, Mitochon, Mitsubishi Tanabe, P3Lab, Roche, Switch, UCB and Woolsey. He serves on advisory boards for Amylyx, CurePSP, Roche, Rossy Centre and Springer. He receives royalties from Rutgers University Press, licensing fees from Rutgers University and travel expenses from CurePSP. The rest of the authors report no relevant conflicts of interest. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia., Methods: Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition., Results: Methodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics., Conclusion: The large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia., (© 2020 American Academy of Neurology.)

Objective: To investigate the topographic arrangement and strength of whole-brain white matter (WM) structural connectivity in patients with early-stage drug-naive Parkinson disease (PD)., Methods: We employed a model-free data-driven approach for computing whole-brain WM topologic arrangement and connectivity strength between brain regions by utilizing diffusion MRI of 70 participants with early-stage drug-naive PD and 41 healthy controls. Subsequently, we generated a novel group-specific WM anatomical network by minimizing variance in anatomical connectivity of each group. Global WM connectivity strength and network measures were computed on this group-specific WM anatomical network and were compared between the groups. We tested correlations of these network measures with clinical measures in PD to assess their pathophysiologic relevance., Results: PD-relevant cortical and subcortical regions were identified in the novel PD-specific WM anatomical network. Impaired modular organization accompanied by a correlation of network measures with multiple clinical variables in early PD were revealed. Furthermore, disease duration was negatively correlated with global connectivity strength of the PD-specific WM anatomical network., Conclusion: By minimizing variance in anatomical connectivity, this study found the presence of a novel WM structural connectome in early PD that correlated with clinical symptoms, despite the lack of a priori analytic assumptions. This included the novel finding of increased structural connectivity between known PD-relevant brain regions. The current study provides a framework for further investigation of WM structural changes underlying the clinical and pathologic heterogeneity of PD., (© 2019 American Academy of Neurology.)

Background: We undertook this study to identify patients with Parkinson disease (PD) with no or rare falls who may progress to frequent falling by their next annual follow-up visit., Methods: We analyzed data in the National Parkinson Foundation Quality Improvement Initiative database to identify factors predicting which patients with PD with no or rare falls at the baseline visit will report at least monthly falls at the annual follow-up visit. Multivariable models were constructed using logistic regression. Variables were introduced in 4 blocks: in the 1st block, variables present at or before the baseline visit were entered; in the 2nd, baseline visit assessments; in the 3rd, interventions implemented during baseline visit; and, in the 4th block, changes in comorbidities, living situation, and treatment between visits., Results: Of 3,795 eligible participants, 3,276 (86.3%) reported no or rare falls at baseline visit, and of them, 382 (11.7%) reported at least monthly falls at follow-up visit. Predictors included female sex, <90% diagnostic certainty, motor fluctuations, levodopa treatment, antidepressant treatment, prior deep brain stimulation (DBS), worse quality of life, Hoehn & Yahr stage 2 or 3, worse semantic fluency, and, between visits, addition of amantadine, referral to occupational therapy, social services, or DBS, new diagnoses of cancer or osteoarthritis, and increased emergency visits., Conclusions: This large-scale analysis identified several predictors of progression to falling in PD. Such identifiers may help target patient subgroups for falls prevention intervention. Some factors are modifiable, offering opportunities for developing such interventions.

Objective: To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable., Methods: In a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale. Secondary outcomes included quality of care, caregiver burden, and time and travel savings., Results: A total of 927 individuals indicated interest, 210 were enrolled, and 195 were randomized. Participants had recently seen a specialist (73%) and were largely college-educated (73%) and white (96%). Ninety-five (98% of the intervention group) completed at least one virtual visit, and 91% of 388 virtual visits were completed. Quality of life did not improve in those receiving virtual house calls (0.3 points worse on a 100-point scale; 95% confidence interval [CI] -2.0 to 2.7 points; p = 0.78) nor did quality of care or caregiver burden. Each virtual house call saved patients a median of 88 minutes (95% CI 70-120; p < 0.0001) and 38 miles per visit (95% CI 36-56; p < 0.0001)., Conclusions: Providing remote neurologic care directly into the homes of people with PD was feasible and was neither more nor less efficacious than usual in-person care. Virtual house calls generated great interest and provided substantial convenience., Clinicaltrialsgov Identifier: NCT02038959., Classification of Evidence: This study provides Class III evidence that for patients with PD, virtual house calls from a neurologist are feasible and do not significantly change quality of life compared to in-person visits. The study is rated Class III because it was not possible to mask patients to visit type., (© 2017 American Academy of Neurology.)

Objective: To identify brain regions generating tics in patients with Tourette syndrome using sleep as a baseline., Methods: We used [15O]H2O PET to study nine patients with Tourette syndrome and nine matched control subjects. For patients, conditions included tic release states and sleep stage 2; and for control subjects, rest states and sleep stage 2., Results: Our study showed robust activation of cerebellum, insula, thalamus, and putamen during tic release., Conclusion: The network of structures involved in tics includes the activated regions and motor cortex. The prominent involvement of cerebellum and insula suggest their involvement in tic initiation and execution.