Movement Disorders Clinical Practice最新文献

Background: Depression is common in Parkinson's disease (PD) but is underrecognized clinically. Although systematic screening is a recommended strategy to improve depression recognition in primary care practice, it has not been widely used in PD care.

Methods: The 15-item Geriatric Depression Scale (GDS-15) was implemented at 5 movement disorders clinics to screen PD patients. Sites developed processes suited to their clinical workflow. Qualitative interviews with clinicians and patients provided information on feasibility, acceptability, and perceived utility.

Results: Prior to implementation, depression screening was recorded in 12% using a formal instrument; 64% were screened informally by clinical interview, and no screening was recorded in 24%. Of 1406 patients seen for follow-up care during the implementation period, 88% were screened, 59% using the GDS-15 (self-administered in 51% and interviewer administered in 8%), a nearly 5-fold increase in formal screening. Lack of clinician or staff time and inability to provide the GDS-15 to the patient ahead of the visit were the most commonly cited reasons for lack of screening using the GDS-15; 378 (45%) patients completing the GDS-15 screened positive for depression, and 137 were enrolled for a 12-month prospective follow-up. Mean GDS-15 scores improved from 8.8 to 7.0 (P < 0.0001) and the 39-item Parkinson's Disease Questionnaire emotional subscore from 42.2 to 36.7 (P = 0.0007).

Conclusions: Depression screening in PD using a formal instrument can be achieved at much higher levels than is currently practiced, but there are barriers to implementing this in clinical practice. An individual site-specific process is necessary to optimize screening rates.

Background: The GCH1 gene encodes the enzyme guanosine triphosphate cyclohydrolase I (GTPCH), which catalyzes the rate-limiting step in the biosynthesis of tetrahydrobiopterin (BH4), a critical cofactor in the production of monoamine neurotransmitters. Autosomal dominant GTPCH (adGTPCH) deficiency is the most common cause of dopa-responsive dystonia (DRD), whereas the recessive form (arGTPCH) is an ultrarare and poorly characterized disorder with earlier and more complex presentation that may disrupt neurodevelopmental processes. Here, we delineated the phenotypic spectrum of ARGTPCHD and investigated the predictive value of biochemical and genetic correlates for disease outcome.

Objectives: The aim was to study 4 new cases of arGTPCH deficiency and systematically review patients reported in the literature.

Methods: Clinical, biochemical, and genetic data and treatment response of 45 patients are presented.

Results: Three phenotypes were outlined: (1) early-infantile encephalopathic phenotype with profound disability (24 of 45 patients), (2) dystonia-parkinsonism phenotype with infantile/early-childhood onset of developmental stagnation/regression preceding the emergence of movement disorder (7 of 45), and (3) late-onset DRD phenotype (14 of 45). All 3 phenotypes were responsive to pharmacological treatment, which for the first 2 must be initiated early to prevent disabling neurodevelopmental outcomes. A gradient of BH4 defect and genetic variant severity characterizes the 3 clinical subgroups. Hyperphenylalaninemia was not observed in the second and third groups and was associated with a higher likelihood of intellectual disability.

Conclusions: The clinical spectrum of arGTPCH deficiency is a continuum from early-onset encephalopathies to classical DRD. Genotype and biochemical alterations may allow early diagnosis and predict clinical severity. Early treatment remains critical, especially for the most severe patients.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, primarily because of the impairment of dopaminergic neurons. Long-term use of levodopa, the standard PD treatment, often results in fluctuating therapeutic effects and dyskinesia, necessitating alternative therapies.

Objectives: This review aims to synthesize current insights and clinical experiences with foslevodopa-foscarbidopa, focusing on its pharmacokinetics, efficacy, and safety profile, to evaluate its potential in transforming PD therapy.

Methods: A systematic literature search was conducted up to November 2023 using databases PubMed, Web of Science, and Cochrane Library. The search yielded eight eligible articles, including pharmacological studies, case reports, observational studies, and controlled trials. No language restrictions were applied.

Results: Foslevodopa and foscarbidopa, as prodrugs of levodopa and carbidopa, exhibited excellent chemical stability and solubility, facilitating continuous subcutaneous infusion. Clinical trials demonstrated that these prodrugs maintain stable levodopa levels, thereby addressing the limitations of oral levodopa therapy. Phase 1 and 3 studies indicated significant improvements in motor function and quality of life in advanced PD patients. However, a higher incidence of treatment-emergent adverse events, mainly infusion site reactions, was observed compared to oral therapies.

Conclusions: Foslevodopa-foscarbidopa emerges as a promising alternative for advanced PD treatment, offering sustained symptom control. Its efficacy in managing motor fluctuations and dyskinesia makes it a viable option in the PD therapeutic spectrum. Future research should focus on long-term safety, economic impact, and broader accessibility. Foslevodopa-foscarbidopa is now commercially distributed in many countries in Europe and in Japan.

Background: Although performance rating scales, spiral drawing, water pouring, and accelerometry are commonly used to assess tremor severity, the extent to which their results correlate with impairment in activities of daily living (ADL) remains unclear.

Objective: The aim was to identify the most effective predictors of ADL in essential tremor (ET).

Methods: Forty ET patients were examined using The Essential Tremor Rating Assessment Scale (TETRAS), spiral drawing, volume of water spilled, and accelerometric tremor power. Root-mean-square error, R², and F-test were calculated for models predicting TETRAS ADL subscore.

Results: TETRAS Performance Subscale explained the variability in TETRAS ADL with an R² value of 0.686. Models incorporating spiral rating and accelerometric tremor power (R² = 0.731) and water spillage volume (R² = 0.756) were not statistically superior.

Conclusions: TETRAS performance subscore predicted nearly 70% ADL impairment in ET patients. Incorporating the spiral rating, accelerometric tremor power, and water pouring test did not enhance ADL estimation.

Background: Essential tremor (ET) is a chronic, progressive neurological disease that affects an estimated 7 million individuals in the United States (ie, 2.2% of the entire U.S. population). Despite its high prevalence, there are a few published studies on patterns of prescription medication use among patients.

Objective: The aim was to examine prescription drug medication use among ET patients.

Methods: This is a cross-sectional study of ET patients, age ≥40, with at least 1 prescription medication fill using the Optum's de-identified Clinformatics Data Mart Database from 2018 through 2019. We examined patterns of fills of key agents used to treat ET.

Results: The final sample comprised 36,839 ET patients in the United States; 89% had at least 1 prescription drug claim over a 2-year period, indicating that 9 of 10 ET patients take a medication to treat their disease. For each of the 3 most frequently prescribed medications, only a modest fraction (1/5 to 1/4) of patients were taking that medication. Adherence to these agents was 52% to 61%. A high percentage of patients had fills for more than 1 of the main agents we studied.

Conclusion: These data illustrate a need for medication in the ET population. There is only 1 FDA-approved medication to treat ET, propranolol, and less than 25% of ET patients used this drug during our study period. At the same time, no single agent was utilized by more than one quarter of ET patients, adherence was low, and use of multiple agents was common. For such a common disease, the pharmacotherapeutic landscape is impoverished.

Background: The occurrence of tics is the main basis for the diagnosis of Gilles de la Tourette syndrome (GTS). Video-based tic assessments are time consuming.

Objective: The aim was to assess the potential of automated video-based tic detection for discriminating between videos of adults with GTS and healthy control (HC) participants.

Methods: The quantity and temporal structure of automatically detected tics/extra movements in videos from adults with GTS (107 videos from 42 participants) and matched HCs were used to classify videos using cross-validated logistic regression.

Results: Videos were classified with high accuracy both from the quantity of tics (balanced accuracy of 87.9%) and the number of tic clusters (90.2%). Logistic regression prediction probability provides a graded measure of diagnostic confidence. Expert review of about 25% of lower-confidence predictions could ensure an overall classification accuracy above 95%.

Conclusions: Automated video-based methods have a great potential to support quantitative assessment and clinical decision-making in tic disorders.