ABSTRACT
Objective:To investigate the relationship between excessive daytime sleepiness and freezing of gait in Parkinson′s disease (PD).Methods:A total of 136 participants with PD were consecutively recruited between August 2017 and January 2018 at the Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The patients were divided into freezers with 50 patients and nonfreezers with 86 patients. The clinical characteristics of freezers and nonfreezers in PD patients were assessed. In the longitudinal study, a cohort of nonfreezers with 86 patients at baseline clinical visit for a maximum of 18 months were prospectively followed. The patients were divided into the excessive daytime sleepiness group ( n=14) and the non-excessive daytime sleepiness group ( n=72). Then a Cox regression analysis was performed to further investigate the relationship between excessive daytime sleepiness and freezing of gait in PD, and explore risk factors for freezing of gait. Results:The freezers had significantly worse sleep compared with the nonfreezers. The proportion of patients with excessive daytime sleepiness in freezers was higher than nonfreezers [40% (20/50) vs 16% (14/86), χ2=9.49, P=0.002]. The proportion of freezers in the patients with excessive daytime sleepiness was significantly higher than that in the patients without excessive daytime sleepiness [59% (20/34) vs 29% (30/102), χ2 =9.49, P=0.002]. During a maximum of 18-month follow-up, freezing of gait incidence (6/7) in the excessive daytime sleepiness group was significantly higher than that in the non-excessive daytime sleepiness group [21% (8/39) , χ2 =9.04, P=0.003]. Excessive daytime sleepiness ( HR=8.03, 95% CI 2.58-24.99, P<0.01) and high L-dopa equivalent daily dose ( HR=5.92, 95% CI 1.95-17.93, P=0.002) were significantly associated with an increased hazard of freezing of gait. Conclusion:Excessive daytime sleepiness and high L-dopa equivalent daily dose may be risk factors for the development of freezing of gait in PD in the future.
ABSTRACT
Objective To investigate the clinical features and LRRK2 gene mutation in patients with autosomal dominant familial Parkinson's disease (PD). Methods The clinical features of 16 autosomal dominant familial PD probands were analyzed in terms of age at onset, onset symptoms, UPDRS scores, response to the levodopa treatment and drug-induced dyskinesia. The LRRK2 gene exons 5,13,31,32,35,37,41 and 48 of 16 probands were sequenced after polymerase chain reaction. The novel mutation was further screened in 24D sporadic PD patients and 214 controls using PCR-RFLP for the genotypo frequency analysis. Results Clinically, most of 16 probands had late-onset age. Resting tremor (9patients, 56. 25%,t=0.558,P=0.679)and bradykinesia (9 patients,56.25%,t=0.369,P=0.454)were common onset symptoms followed by rigidity(6 patients,37.50%,t=1.324,P=0.735)and postural instability(5 patients,31.25%,t=2.369,P=0.956).Majority of them had good response to levedopa treatment and rare occurrence of drug-induced dyskinesia. Among the 16 autosomal dominant familial PD probands,6 variants were identified:c.457 T＞C(Leu153Leu),c.1432 G＞T(Asp478Tyr),c.5457 T＞C(Gly1819Gly),c.7153 G＞A(Gly2385Arg),IVS31+28 T＞G and IVS37+162 T＞C. The c.1432G＞T(Asp478Tyr)variant was a novel mutation and it was not detected in 240 sporadic PD patients and 214 controls. The reported mutations associated with the PD, such as Arg1441 Cys/Gly/His, Arg1514Gln, Tyr1699Cys, Ile2012Thr, Gly2019Ser and Ile2020Thr,were not found in our study. Conclusions The autosomal dominant familial PD patients present with classical symptoms of PD and bear the LRRK2 variantsAsp478Tyr and Gly2385Arg.