Nocturnal journey of body and mind in Parkinson’s disease: the manifestations, risk factors and their relationship to daytime symptoms. Evidence from the NIGHT-PD study

Abstract

Nocturnal manifestations of Parkinson's disease (PD) are myriad, have diverse etiologies and include motor, sleep, urinary, and neuropsychiatric symptoms which are often associated with daytime somnolence. While most patients perceive these symptoms as troublesome, the recognition of nocturnal problems related to PD is still low in clinical practice. We conducted a survey using semi-structured interviews and self-rated questionnaires of 215 consecutive patients with PD enrolled in three centers in Thailand to determine the prevalence and risk factors of nocturnal disabilities and their relationship to daytime symptoms. We found that 96.6% of patients reported the presence of nocturnal symptoms as determined by the modified version of Parkinson's Disease Sleep Scale (MPDSS). Our survey indicated that the most frequent and distressing symptom was the interruption of sleep to pass urine (56.7%, 4.4 ± 3.9). The severity of symptoms revealed in the MPDSS increased along with the disease duration (p < 0.05) and Hoehn and Yahr stages (p = 0.01). There were similar to findings of the Nocturnal Akinesia Dystonia and Cramp Score (NADCS) where patients with advanced disease had significantly higher NADCS scores than early/moderate disease (p < 0.001). There was a significant correlation of total MPDSS scores with the total scores of the 9-item Wearing-Off Questionnaire (WOQ-9); (r = -0.43, p < 0.05) [motor (r = -0.35, p < 0.05) and nonmotor subscores (r = -0.43, p < 0.05)]; total nonmotor symptoms (NMS) scores (r = -0.55, p < 0.05); Parkinson's Disease Questionnaire-8 Summary Index (PDQ-8 SI) (r = -0.52, p < 0.05); and the total NADCS (r = -0.35, p < 0.05). Multiple regression analysis identified PDQ-8 SI (β = -0.27, p = 0.005) as the most significant predictor of nocturnal manifestations of PD, followed by the nonmotor subscore of WOQ (β = -0.24, p = 0.006), and the NMS item 20 (feeling light-headed, dizzy, or weak when standing from sitting or lying) (β = -0.22, p = 0.003). Our study found that nocturnal symptoms of PD are very common and we suggest that good clinical practice should include a comprehensive review of nighttime manifestations, particularly for those patients who already experience "wearing-off" symptoms.

Capturing nighttime symptoms in Parkinson disease: Technical development and experimental verification of inertial sensors for nocturnal hypokinesia

“…Although the data cannot as yet be generalized, the results of axial nocturnal movements in our pilot study have identified several characteristics of the problems of rolling over among patients with PD, including less frequent turns, smaller turns, and slower turns when compared with matched spouses. These findings reinforce previous observations of nocturnal hypokinesia-mostly conducted in the form of questionnaires and interviewsshowing that impaired bed mobility exists and is likely to contribute to a wide range of nocturnal motor symptoms and NMSs in patients with PD, such as stiffness, rigidity, pain, breathing disorders, nocturia, or even insomnia [5,9,[18][19][35][36][37]. Moreover, a number of recent studies support the negative effects of nocturnal hypokinesia on the overall sleep quality, daytime symptoms, and quality of life of both patients as well as caregivers [5,7,[35][36][37].…”

“…Specific scales, such as the PDSS, the Pittsburgh Sleep Quality Index, and the Scales for Outcomes in PD-Sleep have been developed specifically to evaluate sleep and nocturnal disabilities in PD [20][21][22]. Recently, our group has modified the PDSS to capture more nocturnal symptom domains and provide evidence for the relationship between nocturnal manifestations of PD and daytime wearing-off [5]. With the advances in sensor technology, there is increased interest in the ambulatory assessment of symptoms in PD [23][24][25], but very few studies have been dedicated to the objective monitoring of nocturnal symptoms [26][27].…”

“…Depending on the instruments used to assess nocturnal symptoms, disturbances during the night are reported to be very common among patients with PD. A recent study found that 96.6 percent of patients had at least one nocturnal symptom based on the criteria developed for the modified version of the Parkinson Disease Sleep Scale (PDSS) [5]. Nocturnal symptoms of PD should not be viewed as solely a nighttime problem.…”

Unmet needs in Parkinson's disease: New horizons in a changing landscape

“…Whereas, we once very much focused on 'end-of-dose wearing-off', we now increasingly consider the time taken to ON, which is related to drug absorption and has been reported to be more than twice the duration of wearing-off [56]. Nocturnal hypokinesia and early morning off is often the longest OFF period in the daily treatment cycle [5,57], and delays to ON time and dose failures have been reported to account for >60% of daily OFF time [58]. As such, this provides a rationale for using non-oral therapies such as apomorphine injections or infusion which do not rely on GI absorption to manage motor fluctuations in patients where oral treatments do not provide sufficient control.…”

“…Nocturnal symptoms as well as early morning fluctuations (motor and NMS) remain neglected [5]. To move forward with medical management, it is important to consider new insights that recent research offers and in this review we examine how a better understanding of the disease pathology and progression might inform our daily clinical practice.…”