Movement Disorders Clinical Practice最新文献

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a well-established treatment for Parkinson's Disease (PD). However, the long-term trajectory of Quality of Life (QoL) following STN-DBS remains underexplored.

Objectives: We aimed to conduct a systematic review and meta-analysis to assess QoL trends up to five years after STN-DBS.

Methods: We systematically searched PubMed, Embase, and Cochrane databases from inception to August 2024 for studies involving PD patients treated with bilateral STN-DBS, evaluating QoL using the Parkinson's Disease Questionnaire (PDQ), with a minimum follow-up of 12 months post-surgery. Continuous outcomes were pooled using standardized mean differences (SMD), and statistical analyses were conducted using R version 4.3.2.

Results: Out of 4106 screened articles, 42 studies with a total of 2767 patients were included in the meta-analysis. QoL improvements were observed up to 36 months post-surgery (SMD 0.83; 95% CI 0.29 to 1.37), followed by a decline to pre-operative levels at 60 months (SMD -0.06; 95% CI -0.26 to 0.15). Subdomain analysis at 60 months revealed significant deterioration in cognitive function and communication. Meta-regression indicated that QoL improvements were independent of clinical and sociodemographic factors such as age, sex, and disease duration; however, there was a correlation with mean baseline PDQ (P = 0.01).

Conclusions: This meta-analysis provides long-term QoL trends following STN-DBS, highlighting a further need to explore the factors driving the decline in QoL and develop strategies to mitigate this deterioration.

Background: Mutations in the ATP13A2 gene have been implicated in various neurodegenerative disorders, including Kufor-Rakeb syndrome (KRS), neuronal ceroid lipofuscinosis (NCL), hereditary spastic paraplegia (HSP), and amyotrophic lateral sclerosis (ALS). This report presents two Iranian families with ATP13A2 variants exhibiting atypical features of KRS.

Cases: We highlight four patients from two consanguineous Iranian families with mutations in the ATP13A2 gene presenting with variable features of motor neuron disease as well as juvenile-onset parkinsonism, and cognitive decline. The onset of symptoms ranged from 11 to 29 years, with initial manifestations including gait disturbance, postural instability, and cognitive impairment. As the disease progressed, patients developed a range of neurological signs, such as dystonia, spasticity, and dysarthria.

Conclusion: This report expands the phenotypic spectrum of ATP13A2-related disorders, highlighting the potential overlap of symptoms associated with KRS, ALS, and HSP.

Background: The lived experience of Parkinson's disease (PD) includes motor and non-motor symptoms. There is a need to capture the earliest patient experiences in a sensitive and reliable manner for the successful development of interventions that may delay clinical progression in PD.

Objective: Our aim was to synthesize published literature about patient-reported symptoms in prodromal and early motor stages of PD and develop a conceptual framework of the earliest lived experiences in PD.

Methods: We conducted a scoping review of the published literature in MEDLINE, EMBASE, SCOPUS, and CINAHL databases and abstracted patient-reported symptoms from included studies reporting on prodromal or early motor stages of PD populations.

Results: We included 59 articles with data from 64 cohorts (prodromal PD: n = 20/64; 31%, early motor PD: n = 44/64, 69%). Overall, the 10 most frequent symptoms (of 85 standardized reported symptoms [SRSs]) were non-motor. SRSs were grouped into symptom domains (behavioral, cognition, dysautonomia, motor, sensory, sleep, and others) and functional domains (activities of daily living, communication, sexual, and social impairment). The Movement Disorder Society sponsored revision of the Unified Parkinson's Disease Rating Scale parts Ib and II (n = 13/64, 20%) and ad hoc questionnaires (n = 12/64, 19%) were the most frequently used measurement tools.

Conclusion: At prodromal and early motor stages of PD, individuals report symptoms of a diverse range of motor and non-motor domains and higher-level functional domains. There is a need to capture the full spectrum of this lived experience in a new patient-reported clinical outcome measure for clinical trials in the earliest clinical stages of PD.

Background: Dopaminergic neuron depletion in the substantia nigra (SN) and the pathological aggregation of α-synuclein are the neuropathological hallmarks of Parkinson's disease (PD).

Objectives: This study aimed to investigate the association between the polygenic risk score for PD (PD-PRS) and transcranial sonography (TCS)-measured SN hyperechogenicity to enhance the accuracy of PD susceptibility prediction.

Methods: PD-PRSs were calculated for over 41,000 Estonian Biobank participants age 55+ years without a PD diagnosis. Participants in the highest and lowest PD-PRS percentiles (n = 222) underwent TCS measurements and Sniffin' sticks olfactory testing. A multivariable logistic regression model was used to examine the associations between PD-PRS, risk and prodromal markers, and SN hyperechogenicity.

Results: Data from 204 participants with TCS measurements were analyzed, including 107 individuals in the high-risk PD-PRS group and 97 in the low-risk PD-PRS group. Incorporating PD-PRS group assignment improved the explained variance in SN hyperechogenicity from 17.2% to 31.9%. Participants in the low-risk PD-PRS group had 0.16 times lower odds (95% confidence interval (CI) = 0.07-0.35, P < 0.001) of developing SN hyperechogenicity compared to high-risk PD-PRS individuals. Each unit increase in the Sniffin' sticks olfactory test score was significantly associated with reduced odds of SN hyperechogenicity (adjusted odds ratio = 0.60, 95% CI = 0.47-0.78, P = 0.002).

Conclusions: Our findings indicate that TCS-measured SN hyperechogenicity is associated with PD-PRS and olfactory impairment. This combined assessment may improve early diagnosis of prodromal PD by pinpointing individuals at increased risk.

Background: The treatment of levodopa-induced dyskinesia in Parkinson's disease (PD) is a largely unmet need.

Objectives: Mesdopetam is a novel small molecule dopamine D3 receptor antagonist aimed for the treatment of levodopa-induced dyskinesia. This was a phase 2b study dose finding study to investigate efficacy and safety of 2.5 mg, 5 mg and 7,5 mg b.i.d. in a randomized controlled trial.

Methods: PD patients with ≥2 hours of troublesome dyskinesia were randomized to placebo or mesdopetam twice daily for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in ON time without troublesome dyskinesia (Good ON-time) as recorded with home diaries. Secondary efficacy endpoints assessing ON phase dyskinesia were the modified UDysRS (sum of parts 1, 3 and 4) and MDS-UPDRS part 4.2.

Results: Groups did not differ in change from baseline to end of study in Good ON-time. Several secondary assessments for ON phase dyskinesia such as the modified UDysRS showed clinically relevant and statistically significant improvements for the 2.5 and 7.5 mg doses. OFF time showed dose dependent decrease with highest efficacy for the 7.5 mg dose. The adverse event profile was similar to placebo.

Conclusions: In this study mesdopetam failed to increase Good ON-time as compared to placebo. However, a statistically significant and clinically meaningful improvement in the prespecified secondary efficacy endpoint UDysRS warrants further investigation. Results from this dose finding study suggest 7.5 mg b.i.d. to be the preferred dose for further study.