Clinical Parkinsonism Related Disorders最新文献

Objective

To assess the incidence of Impulse control and related behavioral disorders (ICRD) in Chinese Idiopathic Parkinson Disease (IPD) patients treated with different dopamine agonists (DA), and their clinical characteristics and associated risk factors.

Methods

This was an observational cohort study based on clinical interviews and medical records of IPD patients treated with DA for >6 months in three hospitals in Hong Kong. The short version of Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP-S) was used to screen for ICRD. ICRD incidence among different DA, clinical characteristics and risk factors were examined.

Results

Incidence of ICRD was analyzed in 311 patients taking their first, single DA. 43 patients (13.8 %) developed ICRD. The mean duration of IPD was 8.5 ± 5.6 years and median HY stage was 2.5. Bromocriptine and rotigotine users had lower ICRD incidence rate. Both pramipexole [adjusted HR 7.28 (2.46–21.54), p < 0.001] and ropinirole [adjusted HR 6.53 (2.67–15.99), p < 0.001] were independently associated with higher risk of ICRD compared to bromocriptine in multivariate analysis. Similarly, pramipexole and ropinirole appeared to carry higher risk compared to rotigotine but did not reach statistical significance. Male [adjusted HR 2.24 (1.07–4.72), p = 0.033], younger IPD onset [adjusted HR 2.99 (1.44–6.19) for onset < 50 year, p = 0.003] and history of psychiatric disorders [adjusted HR 2.80 (1.39–5.62), p = 0.004] were other independent risk factors.

Conclusion

Bromocriptine and probably rotigotine carried a lower ICRD risk compared to pramipexole and ropinirole.

Introduction

Given the unique natural history of GBA-related Parkinson’s disease (GBA-PD) and the potential for novel treatments in this population, genetic testing prioritization for the identification of GBA-PD patients is crucial for prognostication, individualizing treatment, and stratification for clinical trials. Assessing the predictive value of certain clinical traits for the GBA-variant carrier status will help target genetic testing in clinical settings where cost and access limit its availability.

Methods

In-depth clinical characterization through standardized rating scales for motor and non-motor symptoms and self-reported binomial information of a cohort of subjects with PD (n = 100) from our center and from the larger cohort of the Parkinson’s Progression Marker Initiative (PPMI) was utilized to evaluate the predictive values of clinical traits for GBA variant carrier status. The model was cross-validated across the two cohorts.

Results

Leveraging non-motor symptoms of PD, we established successful discrimination of GBA variants in the PPMI cohort and study cohort (AUC 0.897 and 0.738, respectively). The PPMI cohort model successfully generalized to the study cohort data using both MDS-UPDRS scores and binomial data (AUC 0.740 and 0.734, respectively) while the study cohort model did not.

Conclusions

We assessed the predictive value of non-motor symptoms of PD for identifying GBA carrier status in the general PD population. These data can be used to determine a simple, clinically oriented model using either the MDS-UPDRS or subjective symptom reporting from patients. Our results can inform patient counseling about the expected carrier risk and test prioritization for the expected identification of GBA variants.

Introduction

Parkinson’s disease (PD) is associated with increased mortality risk (MR), reflecting progression of motor and nonmotor symptoms. PD psychosis (PDP), a common nonmotor symptom, increases with prolonged disease and elevates the MR of PD even further. Pimavanserin is the only FDA–approved treatment for PDP. This review summarizes real-world evidence around the MR of patients with PDP treated with pimavanserin versus off-label atypical antipsychotics.

Methods

A PubMed search was conducted using the following search terms: pimavanserin AND antipsychotic AND mortality AND Parkinson’s disease AND psychosis. Inclusion criteria specified the entry of retrospective, observational, and open-label studies comparing pimavanserin to atypical antipsychotics or untreated controls.

Results

A total of 10 of the 32 articles met inclusion criteria. Among five comparisons of pimavanserin with atypical antipsychotics, two were large (n = 21,719; n = 21,975), representative, Medicare-database studies, which demonstrated comparable or lower all-cause pimavanserin MR. Among three pimavanserin versus control studies, two reported lower or comparable pimavanserin MR and one, long-term care study reported higher MR for pimavanserin versus non-pimavanserin treated patients with unknown PDP status. Two open-label extensions reported pimavanserin mortality rates of 6.45 and 18.8 deaths per 100 patient-years, which are comparable to, or lower than, mortality rates for PD, PDP, and other atypical antipsychotics. Most studies (70 %; 7 of 10) demonstrated pimavanserin’s MR was lower than or similar to other atypical antipsychotics or untreated controls.

Conclusions

Pimavanserin did not increase the MR in PDP. Pimavanserin’s MR appears to be comparable to or lower than other atypical antipsychotics prescribed for PDP, including quetiapine.

Introduction

This study evaluated constipation, including reduced bowel movement frequency and difficult defecation, in patients with isolated rapid eye movement sleep behavior disorder (IRBD), which is prodromal Parkinson’s disease (PD) or dementia with Lewy bodies (DLB) in middle-aged and older adults.

Methods

We used a validated Japanese version of the Constipation Assessment Scale (CAS-J) to evaluate bowel habits over 1 month in 117 men aged 50–86 years and 34 women aged 56–86 years with video-polysomnography-confirmed IRBD and 22 controls. Furthermore, we performed a longitudinal assessment of outcomes at follow-up visits.

Results

The CAS-J score was higher in the 22 IRBD patients than in 22 age- and gender-matched paired controls. In 151 IRBD patients, the CAS-J score was higher for women than for men. At baseline, the CAS-J score was similar between patients who developed PD and DLB, but the three IRBD patients who developed multiple system atrophy had a low CAS-J score. Those with constipation (CAS-J score ≥ 2) converted to PD or DLB in a significantly shorter time duration (i.e., time frame for phenoconversion) than those with CAS-J score < 2 (log-rank test, p < 0.001). When adjusted for age and gender, Cox hazards analysis revealed that the CAS-J score significantly predicted phenoconversion to PD or DLB (hazard ratio: 5.9, 95 % confidence interval: 1.8–19.1, p = 0.003).

Conclusions

Constipation, i.e., reduced bowel movement frequency and difficult defecation, was common in middle-aged and elderly patients with IRBD, and CAS-J score predicted phenoconversion to PD or DLB.

Infections are important treatable causes of secondary movement disorders (MD) that can have heterogeneous presentations. According to various studies, infection-related movement disorders (IRMD) account for around 10–20% of secondary MD. Certain infections have a predilection for causing various MD, and some MD phenomenologies, such as acute cerebellar ataxia and opsoclonus-myoclonus-ataxia syndromes (OMAS), suggest a strong possibility of an underlying infectious cause. The underlying pathophysiology is multifaceted, including direct neuronal damage due to neurotropism, granulomas, abscesses causing structural damage, and inflammatory and autoimmune responses triggered by infections. Understanding the prevalence, spectrum, and pattern of these IRMD and common infections that are responsible helps in early diagnosis, and instituting appropriate, timely treatment, thereby improving the overall prognosis and avoiding unnecessary investigations. In this review, we aim to provide a brief overview of common infections associated with MD, common clinical presentations of IRMD, their underlying pathophysiology, and overall approach to their treatment, with a focus on specific treatments of prevalent and treatable IRMD.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare neurological emergency that shares clinical features with neuroleptic malignant syndrome. It is usually due to sudden deprivation of dopaminergic treatment, although there are cases related to failure of the deep brain stimulation system.