Publications by authors named "William Ondo"

This review discusses non-pharmacological, non-surgical interventions for action tremor, including essential tremor (ET). We review transcutaneous peripheral nerve stimulation (PNS), a variety of orthotic/mechanical devices, cooling and vibration strategies, and adaptive utensils, most of which are currently available. The PNS section discusses open loop (CALA-Trio) and closed loop systems (Felix™, NeuroAI™ and Motimove® systems).

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Article Synopsis
  • Cervical dystonia (CD) is a common neurological condition, with about one-third of patients also experiencing tremors in their head and hands, complicating diagnosis and treatment.
  • Researchers analyzed data from over 3,100 CD patients across various continents using machine learning to identify clinical features predicting the presence and nature of neck tremor.
  • Key findings revealed that increased severity of CD, longer disease duration, and older age were strong predictors of neck tremor, with notable differences in tremor characteristics based on gender and the involvement of other body parts.
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Study Objectives: To determine any correlation between serum alpha-synuclein (α-syn) concentrations and restless legs syndrome (RLS), and to explore the impact of intravenous iron supplementation on serum α-syn levels.

Methods: We collected clinical data on 113 RLS patients in whom serum α-syn levels were quantified using an ELISA kit and compared to a group of 45 age matched controls. A subset of 9 RLS patients who received intravenous (IV) iron underwent pre- and post-treatment blood sampling to assess α-syn and ferritin response.

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Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed.

Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment.

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Background: Both measured orthostatic hypotension and symptomatic orthostasis are common in PD but their relationship is unclear.

Objective: We aim to determine clinical predictors of both measured orthostatic hypotension and reported symptomatic orthostasis in PD, including the impact of "on"/"off" status and seasons, and to determine the correlation between measured OH and subjective orthostasis.

Methods: We analyzed BP readings, demographic and disease state predictors for both 1.

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The number of large clinical trials of restless legs syndrome (RLS) have decreased in recent years, this coincides with reduced interest in developing and testing novel pharmaceuticals. Therefore, the International Restless Legs Syndrome Study Group (IRLSSG) formed a task force of global experts to examine the causes of these trends and make recommendations to facilitate new clinical trials. In our article, we delve into potential complications linked to the diagnostic definition of RLS, identify subpopulations necessitating more attention, and highlight issues pertaining to endpoints and study frameworks.

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Article Synopsis
  • Restless legs syndrome (RLS) affects nearly 10% of older adults, but many face delays in diagnosis and treatment.
  • A large-scale genetic study identified 164 risk loci for RLS, enhancing our understanding of its genetic basis and showing similarities in genetic predispositions between sexes.
  • Findings suggest potential drug targets, a relationship between RLS and diabetes, and highlight the effectiveness of machine learning in predicting RLS risk using genetic and other data.
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Background: Prior studies have indicated that female individuals outnumber male individuals for certain types of dystonia. Few studies have addressed factors impacting these sex differences or their potential biological mechanisms.

Objectives: To evaluate factors underlying sex differences in the dystonias and explore potential mechanisms for these differences.

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Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABA receptors.

Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET).

Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days.

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Current clinician-rated tardive dyskinesia (TD) symptom scales have not addressed the expanding clinical signs and functional impact of TD. The study objective was to develop and test the reliability of a new integrated instrument. A movement disorder neurologist devised the outline of the rating scale.

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Background: There are several widely used clinical rating scales for documenting the severity and distribution of various types of dystonia.

Objectives: The goal of this study was to evaluate the performance of the most commonly used scales in a large group of adults with the most common types of isolated dystonia.

Methods: Global Dystonia Rating Scale (GDRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) scores were obtained for 3067 participants.

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Background: Dose optimization of sublingual apomorphine (SL-APO), a dopamine agonist for the treatment of OFF episodes in patients with Parkinson's disease (PD), has been performed under clinical supervision in clinical trials. SL-APO may be a candidate for home dosing optimization which would be less burdensome for patients.

Objectives: To evaluate the feasibility and safety of home optimization of SL-APO in patients with PD and OFF episodes.

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Background: Psychosis is a common manifestation of Parkinson's disease (PD), and a major source of caregiver burden, nursing home placement, and mortality. Psychosis symptoms are often not volunteered during the clinic visit because of embarrassment or lack of insight, and there is no validated screening scale. We compare a new self-administered psychosis screening questionnaire against the Parkinson's Disease Psychosis Scale (PDPS) and physician interview as the gold standard assessments.

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Restless legs syndrome (RLS) is responsive to opioid, dopaminergic and iron-based treatments. Receptor blocker studies in RLS patients suggest that the therapeutic efficacy of opioids is specific to the opioid receptor and mediated indirectly through the dopaminergic system. An RLS autopsy study reveals decreases in endogenous opioids, β-endorphin and perhaps Met-enkephalin in the thalamus of RLS patients.

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Importance: Levodopa has a short half-life and a limited window of opportunity for absorption in the proximal small intestine. IPX203 is an oral, extended-release formulation of carbidopa-levodopa developed to address these limitations.

Objective: To assess the efficacy and safety of IPX203 vs immediate-release carbidopa-levodopa in patients with Parkinson disease who are experiencing motor fluctuations.

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Background: Task specific tremor (TST) is a poorly understood entity without any standard treatments, that may subsequently develop tremor during additional tasks, later develop postural/kinetic tremor (essential tremor criteria), and later develop Parkinson's disease. The pathophysiology is not understood as it has features of tremor, dystonia, and parkinsonism.

Objectives: To assess response of TST to apomorphine and thus infer pathophysiology.

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Background: Nausea is common upon initiating dopamine agonists in patients with Parkinson's disease (PD); however, pretreatment with an antiemetic is recommended only when initiating apomorphine formulations.

Objective: Evaluate the need for prophylactic antiemetic use during dose optimization of apomorphine sublingual film (SL-APO).

Methods: A post hoc analysis of a Phase III study evaluated nausea and vomiting treatment-emergent adverse events in patients with PD who underwent SL-APO dose optimization (10-35 mg; 5-mg increments) to achieve a tolerable FULL ON.

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Pimavanserin is the only approved drug for Parkinson's disease psychosis (PDP) and is an increasingly used therapy where available. Clozapine has proven efficacy for PDP but is much less commonly used secondary to frequent blood tests to monitor for agranulocytopenia. We identified 27 patients with PDP (72 ± 7.

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Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS.

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γ-Aminobutyric acid (GABA) is the most prevalent inhibitory CNS neurotransmitter. Activating GABA-A receptors hyperpolarizes cells via Cl influx, which inhibits action potentials. Although the exact pathophysiologies of tremor are incompletely understood, proposed neuroanatomy extensively implicates GABA pathways.

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The purpose of this review is to characterize and compare validated clinical rating scales and transducers that are used in the clinical assessment of tremor disorders. Tremor is an involuntary oscillatory movement of a body part. Tremor can be characterized in terms of amplitude and frequency of oscillation, and these kinematic properties vary randomly and with activities of daily living.

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Stroke-related restless legs syndrome (RLS) is one of stroke-related sleep disorders, which may be due to de novo RLS after stroke onset or an exacerbation of RLS symptoms after incident stroke. To date, the diagnostic rate of stroke-related RLS is low but it has a significant effect on patients' daily life and functional outcome. This review provides an overview of the epidemiology, clinical characteristics, pathophysiology, and impact on functional outcome of stroke-related RLS.

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Article Synopsis
  • Cervical dystonia (CD) is a movement disorder that affects quality of life, and abobotulinumtoxinA (aboBoNT-A) has been studied to assess its efficacy in treating this condition using two different dilutions (500 U/1 mL and 500 U/2 mL).
  • A retrospective analysis of three clinical trials showed that both dilutions resulted in similar significant improvements in patient symptoms, with no increased risk of side effects from the higher dilution.
  • The findings emphasize that both dilutions of aboBoNT-A are equally effective and safe, allowing for flexible treatment options in managing CD.
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