To provide a concise, clinically oriented update on advanced therapies for Parkinson’s disease. Subcutaneous infusion of foscarbidopa/foslevodopa and apomorphine reduce OFF time and improve “good ON time”, though infusion site reactions remain of some concern. Image-guided programming may shorten programming time while matching motor outcomes; while adaptive/closed-loop deep brain stimulation using local field potential signals may improve symptoms and quality of life with a lower energy use. Remote programming accelerates clinical benefit and expands access. Approved magnetic resonance guided high intensity focused ultrasound targets now include the ventralis intermediate nucleus of the thalamus, the globus pallidus pars interna and, recently, the pallidothalamic tract; while research investigates the subthalamic nucleus, each target with distinct benefits and adverse event profiles. Early studies using magnetic resonance guided low intensity focused ultrasound show safe, transient blood brain barrier opening. First-in-human stem cells-derived dopaminergic grafts show safety and graft functioning. The advanced therapeutic landscape for Parkinson’s disease has evolved through innovations in established and novel therapies. Future priorities for the field include standardized biomarkers and protocols for adaptive deep brain stimulation, long-term evaluation of high intensity focused ultrasound outcomes, and rigorously controlled trials of low intensity focused ultrasound and cell-based therapies designed to assess disease-modifying potential.

Background: Biomarkers of abnormal alpha-synuclein (asyn) that can be obtained with minimal invasiveness are needed. Promising data on dermal serine-129-phosphorylated alpha-synuclein (dermal-ps129-asyn) have emerged but accuracy for aggregated asyn in cerebrospinal fluid (CSF) has not been examined. Objective: Determine sensitivity and specificity of dermal-ps129-asyn for neuronal asyn measured with cerebrospinal fluid asyn seed amplification assay (CSFasynSAA). Methods: Cross-sectional observational study; 50 individuals with positive or negative CSFasynSAA underwent 3 skin biopsies for blinded assessment of phospho-serine-129 asyn in nerve terminals. Sensitivity and specificity versus CSFasynSAA were calculated. Results: Among 50 participants, 30/38 CSFasynSAA+ were dermal-ps129-asyn+; 6/12 CSFasynSAA- were dermal-ps129-asyn-, yielding sensitivity of 79% and specificity of 50%. Conclusion: Dermal-ps129-asyn has low specificity for CSF asyn SAA in this small sample. This precludes its use as a marker of CSF neuronal asyn aggregates. Future studies are needed to determine optimal methods to assess asyn aggregates in central and peripheral compartments. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This study was funded by The Michael J. Fox Foundation for Parkinson's Research, Grant ID: 026366/026110. PPMI is a public-private partnership funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including 4D Pharma, Abbvie, AcureX, Allergan, Amathus Therapeutics, Aligning Science Across Parkinson's, AskBio, Avid Radiopharmaceuticals, BIAL, BioArctic, Biogen, Biohaven, BioLegend, BlueRock Therapeutics, Bristol-Myers Squibb, Calico Labs, Capsida Biotherapeutics, Celgene, Cerevel Therapeutics, Coave Therapeutics, DaCapo Brainscience, Denali, Edmond J. Safra Foundation, Eli Lilly, Gain Therapeutics, GE HealthCare, Genentech, GSK, Golub Capital, Handl Therapeutics, Insitro, Jazz Pharmaceuticals, Johnson & Johnson Innovative Medicine, Lundbeck, Merck, Meso Scale Discovery, Mission Therapeutics, Neurocrine Biosciences, Neuron23, Neuropore, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi, Servier, Sun Pharma Advanced Research Company, Takeda, Teva, UCB, Vanqua Bio, Verily, Voyager Therapeutics, the Weston Family Foundation and Yumanity Therapeutics. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data were obtained on 25-August, 2025 from the PPMI database (www.ppmi-info.org/access-data-specimens/download-data), RRID:SCR_006431. Analyses, conducted by PPMI Statistics Core, used actual dates, a restricted (not publicly available) data element. PPMI Data Access Committee approved use of CSFasynSAA and DaTscan results. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data were obtained on 25-August, 2025 from the PPMI database (www.ppmi-info.org/access-data-specimens/download-data), RRID:SCR_006431. Analyses, conducted by PPMI Statistics Core, used actual dates, a restricted (not publicly available) data element. PPMI Data Access Committee approved use of CSFasynSAA and DaTscan results.

Purpose of Review Essential tremor (ET) is a very common condition that significantly impacts quality of life. Current medical treatments are quite limited, and while surgical treatments like deep brain stimulation (DBS) can be very effective, they come with their own limitations as well as procedural risks. This article reviews updates on recent advances and future directions in the treatment of ET. Recent Findings A new generation of pharmacologic agents specifically designed for ET is in clinical trials. Advances in DBS technology continue to improve this therapy. MRI-guided focused ultrasound (MRgFUS) is now an approved noninvasive ablative treatment for ET that is effective and shows potential for continuing improvement. The first peripheral stimulation device for ET has also now been approved. Summary This article reviews updates on the treatment of ET, encompassing pharmacologic agents in clinical trials, DBS, MRgFUS, and noninvasive stimulation therapies. Recent treatment advances and future directions of development show a great deal of promise for ET therapeutics.

Objective: To explore utilization of anticholinergic medications using the Parkinson Foundation Quality Improvement Initiative (PF-QII) registry. Background: Recent publications have highlighted the association between anticholinergic medication use and increased rates of dementia diagnoses. However, despite accumulating data on the negative cognitive impact of anticholinergics, these medications remain part of the treatment armamentarium in Parkinson’s disease (PD). Design/Methods: Data were collected from the PF-QII registry, an international multi-center prospective study of PD care and outcomes at expert centers. Frequency of anticholinergic use in the cohort was analyzed, and characteristics of anticholinergic users and non-users were compared. Utilization rates of anticholinergics in patients with and without cognitive dysfunction were compared. Additionally, frequency of hospitalizations and ER visits (HER) was compared between anticholinergic users and non-users. Results: 201 (3.4%) out of 5,949 patients were on anticholinergics at baseline visit. Compared to non-users, anticholinergic users tended to be younger (64.5±9.0 vs, 68.2±9.1, p Conclusions: Although there has been a decline in overall utilization of anticholinergics in the PD population, there remains persistent use of anticholinergics in patients with cognitive dysfunction. We additionally found that anticholinergic users performed worse on a cognitive task despite being younger than non-users. This highlights the need for greater education to improve clinicians’ prescribing practices for anticholinergics, given their potential for negative impact on cognition. Disclosure: Dr. Shetty has nothing to disclose. Dr. Dubaz has nothing to disclose. Dr. Yu has nothing to disclose. Dr. Gao has nothing to disclose. Dr. Simuni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acadia, Adamas, Teva, UCB Pharma, AbbVie, Anavex, Allergan, Acorda, NeuroDerm, PhotoPharmics, Revance, Sanofi, Sunovion, Voyager, US World Meds, and the Michael J. Fox Foundation. Dr. Simuni has received research support from Biogen, Roche, NeuroDerm, Sanofi, NINDS, the Michael J. Fox Foundation, and the Parkinson Foundation.

Tuesday, April 28April 14, 2020Free AccessPF-QII Analysis of Deep Brain Stimulation versus Levodopa-carbidopa Intestinal Gel: Real-world Differences in Patient Characteristics and Quality of Life Outcomes. (958)Neil Shetty, Cindy Zadikoff, Samuel Wu, Yue Wu, and Tanya SimuniAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.958 Letters to the Editor