Neurodegenerative Diseases最新文献

Background: Sativex (USAN: nabiximols [NAB]) oromucosal spray is indicated for treatment of multiple sclerosis (MS) patients with moderate to severe spasticity and inadequate response to other antispasticity medications who demonstrate clinically significant improvement during an initial trial of therapy. This narrative review investigated the efficacy and effectiveness of NAB oromucosal spray for moderate to severe MS spasticity by examining spasticity 0-10 numerical rating scale (NRS) data from interventional and observational studies which featured a 4-week trial period as per the European Union-approved label.

Summary: Across both study types, clinically relevant and statistically significant reductions in mean MS spasticity 0-10 NRS scores were measured soon after treatment start and were maintained in the mid- to long term in treatment responders. Initial responder rates (≥20% NRS improvement from baseline at week 4) ranged from 47.6% to 81.4%, tending lower in the randomized clinical trials setting. Clinically relevant responder rates (≥30% NRS improvement from baseline at week 12) were similar between study types (range 30-41%) except for one outlier (74% in an observational study). Two open studies reported treatment continuation for ≥18 months in approximately half of patients who initiated treatment. In most longer term studies, symptomatic improvement in MS spasticity was maintained at mean daily dosages of about 6-7 sprays/day. Safety was consistent with the known profile of NAB.

Key messages: Experimental and observational studies of NAB oromucosal spray recorded similar findings. About half to two-thirds of MS patients who begin treatment will perceive initial symptomatic relief of spasticity within the 4-week trial period. About 40% of patients who initiate treatment will reach the ≥30% NRS improvement threshold at 3 months, comprising the majority of patients who continue long-term treatment. A trial of therapy with NAB is useful to identify patients most likely to gain longer term improvement in spasticity symptoms and discontinue those with insufficient benefit.

Background: Patients with Parkinson's disease (PD) regularly report an increased desire for food or beverages with high sugar content.

Objective: The aim of this study was to verify the hypothesis of an increased intake of fast-acting carbohydrates in PD patients.

Methods: This study investigated the consumption of high-sugar content food products in 221 PD patients compared with 184 healthy controls using a self-administered questionnaire.

Results: Male PD patients reported a significantly more often high consumption of chocolate (p = 0.005) and other sweets (p < 0.001) than healthy controls. Moreover, PD patients with a high intake of these products showed a significantly longer disease duration (p = 0.002).

Conclusion: Our study confirmed changes in intake of fast-acting carbohydrates derived from sweets in PD. Future studies should address the observed association with disease progression to understand underlying pathophysiological mechanisms leading to this behavioral change.

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS.

Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal syndrome (CBS) patients, and 31 controls. We also compared the values in depressed and nondepressed patients.

Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 μg/L, in MSA 13.6 μg/L vs. 24.3 μg/L in controls; p = 0.0008 in PD, p = 0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBS compared to the control group (median in PSP 22.7 μg/L, in CBS 18.7 μg/L vs. 24.3 μg/L in controls; p = 1 in both PSP and CBS). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, p < 0.0001).

Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD; however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD and MSA) than in tauopathies (PSP and CBS).

Introduction: Autonomic dysfunction has been reported as one of nonmotor manifestations of both presymptomatic and manifest Huntington's disease (HD). The aim of our study was to evaluate heart rate variability (HRV) during wake and sleep in a cohort of patients with manifest HD.

Methods: Thirty consecutive patients with manifest HD were enrolled, 14 men and 16 women, mean age 57.3 ± 12.2 years. All patients underwent full-night attended video polysomnography. HRV was analyzed during wake, NREM sleep, and REM sleep, in time and frequency domain. Results were compared with a control group of healthy volunteers matched for age and sex.

Results: During wake, HD patients presented significantly higher mean heart rate than controls (72.4 ± 9.6 vs. 58.1 ± 7.3 bpm; p < 0.001). During NREM sleep, HD patients showed higher mean heart rate (65.6 ± 11.1 vs. 48.8 ± 4.6 bpm; p < 0.001) and greater low frequency (LF) component of HRV (52.9 ± 22.6 vs. 35.5 ± 17.3 n.u.; p = 0.004). During REM sleep, we observed lower standard deviation of the RR interval in HD subjects (3.4 ± 2.2 vs. 3.7 ± 1.3 ms; p = 0.015).

Conclusion: Our results show that HD patients have higher heart rate than controls, during wake and NREM, but not during REM sleep. Among HRV parameters, the most relevant difference regarded the LF component, which reflects, at least partially, the ortho-sympathetic output. Our results confirm the involvement of autonomic nervous system in HD and demonstrate that it is evident during both wake and sleep.

Introduction: There is growing interest in using patient-reported outcomes as end points in clinical trials, such as the progressive supranuclear palsy quality of life (PSP-QoL) scale. However, this tool has not been widely validated and its correlation with validated motor scales has not been explored. To evaluate the potential utility of using PSP-QoL as an outcome, it is important to examine its relationship with a standard scale used to evaluate neurologic parameters, such as the PSP Rating Scale.

Methods: PSP-QoL and PSP Rating Scale scores were gathered from 60 clinically diagnosed PSP patients, including patients with Richardson syndrome PSP (PSP-RS, n = 43) and those with non-RS PSP variants (n = 17). Linear regression analysis adjusted for age, sex, and disease duration was used to evaluate the cross-sectional relationship between the total and subscale scores of the 2 instruments.

Results: Among 60 PSP patients, there was a significant correlation between total PSP-QoL and PSP Rating Scale scores. The physical and mentation subscales of each instrument also demonstrated significant correlations. Comparisons among PSP subtypes indicated that worsening PSP-QoL Total and Physical subscale scores correlated with worsening PSP Rating Scale gait subscale scores more strongly for the non-RS PSP variants than for PSP-RS.

Discussion: There is a significant association between the total scores and many of the subscale scores of the PSP-QoL and the PSP Rating Scale. Additionally, the relationship between these measures may differ for PSP-RS and non-RS variants. These findings suggest that the PSP-QoL may be useful in clinical trials as a patient-reported outcome measure. Large prospective multicenter studies utilizing the PSP-QoL are necessary to examine its relationship to disease evolution and changes in the PSP Rating Scale.

Background: Parkinson's disease (PD) is one of the most common neurological disorders, of insidious onset, with major motor symptomatology including bradykinesia, rest tremor, rigidity, and postural disturbances. Virtual reality (VR) and motor imagery (MI) are among the more innovative techniques for the rehabilitation of patients with PD which promote motor learning both through explicit and implicit processes. This study is unique in that it will examine the combined effects of VR and MI on motor function, balance and activities of daily living (ADLs) in patients with PD.

Objective: The aim of this work is to investigate the effects of VR with MI techniques in addition to routine physical therapy on motor function, balance, and ADLs in patients with PD.

Methods: This is a two-armed parallel design, single-blinded (assessor blinded), single-centered, randomized controlled trial, and the study protocol is based on SPIRIT guidelines. Thirty-four patients with PD (Modified Hoehn and Yahr stages I-III) will be randomly allocated with a 1:1 ratio into Group A (control group) and Group B (treatment group). Group A will be given routine physical therapy in 40-min sessions and 20 min of walking and cycling with a short period of rest, every alternate day (3 days per week) for 12 weeks, while for Group B routine physical therapy protocols along with VR and MI will be used in 60-min sessions, every alternate day (3 days per week) for 12 weeks. The primary outcome measures are as follows: (i) the Unified PD Rating Scale (UPDRS; part III), (ii) the Berg Balance Scale (BBS), and the Activities-Specific Balance Confidence Scale (ABC). The secondary outcome measure is the UPDRS (part II). Assessments will be recorded at baseline, the sixth and twelfth weeks of therapy, and 1 month after the discontinuation of therapy. Clinical Study Registration: This randomized controlled prospective study was registered with the Iranian Registry of clinical trials (IRCT20200221046567N1) on April 1, 2020 (https://www.irct.ir/trial/46073).