Mastering nocturnal jigsaws in Parkinson's disease: a dusk-to-dawn review of night-time symptoms.

Finding out about night-time symptoms from Parkinson's disease (PD) patients can be a challenge as many patients and their carers cannot recall many symptoms that occur during the night, resulting in an under-recognition or a large variability of responses from clinical interviews and scales. Moreover, technology-based assessments for most night-time symptoms are still not universally available for use in a patient's home environment. Therefore, most physicians rely on their clinical acumen to capture these night-time symptoms based on pieces of patients' history, bedpartner's reports, clinical features, associated symptoms or conditions. To capture more night-time symptoms, the authors identified common nocturnal symptoms based on how they manifest from dusk to dawn with selected features relevant to PD. While some symptoms occur in healthy individuals, in PD patients, they may impact differently. The authors intend this narrative review to provide a practical guide on how these common night-time symptoms manifest and highlight pertinent issues by focusing on prevalence, clinical symptomatology, and specific relationships to PD. It is also important to recognise that PD-specific sleep disturbances increase with advancing disease with additional contributions from ageing, comorbidities, and medication side effects. However, the relative contribution of each factor to individual symptom may be different in individual patient, necessitating clinical expertise for individual interpretation. While there are debatable issues in certain areas, they underlie the complexity of night-time symptoms. Understanding night-time symptoms in PD is like re-arranging jigsaw pieces of clinical information to create, but never complete, a picture for physicians to instigate appropriate management.

Too little or too much nocturnal movements in Parkinson's disease: A practical guide to managing the unseen.

Nocturnal and sleep-related motor disorders in people with Parkinson's disease (PD) have a wide spectrum of manifestations and present a complex clinical picture. Problems can arise due to impaired movement ability (hypokinesias), e.g. nocturnal hypokinesia or early-morning akinesia, or to excessive movement (hyperkinesias), e.g. end-of-the-day dyskinesia, parasomnias, periodic limb movement during sleep and restless legs syndrome. These disorders can have a significant negative impact on the sleep, daytime functional ability, and overall quality of life of individuals with PD and their carers. The debilitating motor issues are often accompanied by a combination of non-motor symptoms, including pain and cramping, which add to the overall burden. Importantly, nocturnal motor disorders encompass a broader timeline than just the period of sleep, often starting in the evening, as well as occurring throughout the night and on awakening, and are not just limited to problems of insomnia or sleep fragmentation. Diagnosis can be challenging as, in many cases, the 'gold standard' assessment method is video polysomnography, which may not be available in all settings. Various validated questionnaires are available to support evaluation, and alternative approaches, using wearable sensors and digital technology, are now being developed to facilitate early diagnosis and monitoring. This review sets out the parameters of what can be considered normal nocturnal movement and describes the clinical manifestations, usual clinical or objective assessment methods, and evidence for optimal management strategies for the common nocturnal motor disorders that neurologists will encounter in people with PD in their clinical practice.

Impaired night-time mobility in patients with Parkinson's disease: a systematic review.

Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most common nocturnal symptoms of Parkinson's disease (PD) and may lead to extreme pain and even death; it also increases the burden on the patients' caregivers. In this systematic review, we included 19 studies involving a total of 1,407 patients with PD to observe the causes, assessment methods, and treatment options for IBM. We conclude that the extent of IBM is positively correlated with the severity of symptoms such as disease duration, dyskinesia and decreased sleep quality in patients with PD, and the evidence implies that IBM may be able to serve as a prodromal feature in the development of PD. IBM probably results from low nocturnal dopamine concentrations, reduced function of the spinal tract, torque problems in the muscles, and aging. Therefore, treatment is mostly based on continuously increasing the patient's nocturnal dopamine concentration, while deep brain stimulation (DBS) also has a mitigating effect on IBM. Both scales and sensors are commonly used to measure the severity of IBM, the wearable device monitoring and scales being updated makes measurements easier and more accurate. The future of the advancement in this field lies in the use of more family-oriented devices (such as smart phones or watches and bracelets, etc.) to monitor IBM's symptoms and select the appropriate therapeutic treatment according to the severity of the symptoms to relieve patients' suffering.

Investigation of Nocturnal Hypokinesia and Health-Related Quality of Life in Parkinsonian Patients with the Korean Version of the Nocturnal Hypokinesia Questionnaire.

OBJECTIVE: To assess nocturnal hypokinesia using the Korean version of the Nocturnal Hypokinesia Questionnaire (NHQ-K) in Parkinson's disease (PD) patients across disease stages. METHODS: We developed the NHQ-K and performed questionnaire-based interviews with 108 PD patients from three referral hospitals. Clinical associations of nocturnal hypokinesia and its impact on health-related quality of life (HRQoL) were also analyzed. RESULTS: The NHQ-K showed acceptable internal consistency (0.83) and interrater reliability (0.95). Nocturnal hypokinesia significantly affected HRQoL in PD patients at both the early and advanced stages (adjusted p < 0.001). Increased severity of nocturnal hypokinesia was associated with dyskinesias, off-period disability, apathy, and anxious mood in PD patients (adjusted p < 0.01) after controlling for disease severity and medication dose. CONCLUSION: The NHQ-K is useful for screening nocturnal hypokinesia in PD patients. Given the high impact of nocturnal hypokinesia on HRQoL, comprehensive management of nocturnal disability is needed for PD patients.

Evaluation of nocturnal hypokinesia in Parkinson's disease using a novel patient/proxy questionnaire and correlations with objective monitoring.

BACKGROUND: Nocturnal hypokinesia is a decreased ability to perform sufficient axial rotation and/or trunk flexion to turn in or get out of bed. Currently, there are no validated questionnaires specifically to assess nocturnal hypokinesia in PD patients. OBJECTIVE: To develop and validate a questionnaire to assess PD patients' problems associated with turning or getting out of bed. METHODS: The nocturnal hypokinesia questionnaire (NHQ) consists of 10 items, completed independently by patients and their caregivers. For validation, 76 patient-caregiver pairs completed the questionnaire and validity, agreement levels, and internal consistency assessed. In addition, 76 healthy couples served as controls. The NHQ and Modified Parkinson's Disease Sleep Scale (PDSS-2) were compared and 25 random patients-caregiver pairs were also assessed with objective night-time monitoring. RESULTS: Patient and caregiver scores showed a high level of agreement (Intra-class correlation: 0.84) with high internal consistency (KR-20 coefficient of 0.73 for patients and 0.69 for caregivers). No significant difference between the mean total NHQ scores as rated by patients and caregivers was observed. Mean NHQ scores from patients and caregivers were significantly higher than healthy controls (p < 0.001). Moderate correlations were found between the NHQ and PDSS-2 (r = 0.32, p = 0.004), and with objective monitoring (Number of turns: r = -0.41, p = 0.04, Degree of turn: r = -0.44, p = 0.02). CONCLUSION: The NHQ is a reliable instrument to identify symptoms of nocturnal hypokinesia amongst PD patients. Strong patient-caregiver agreement supports the use of proxy evaluation by caregivers when patient's information is unobtainable.

Analysis of nocturnal hypokinesia and sleep quality in Parkinson's disease.

Nocturnal hypokinesia/akinesia and sleep disorder are believed to be common in Parkinson's disease (PD), but are often underestimated. To date, only a few studies have focused on nocturnal symptoms related to motor function and sleep quality in PD patients, and the assessments were based mainly on the subjective descriptions of the patients. In this study, we assessed the relationships between motor symptoms and sleep quality in 29 PD patients (17 PD patients reporting impaired bed mobility (IBM) and 12 patients without IBM). All the participants were monitored using multisite inertial sensors and polysomnography in sleep-monitoring rooms for whole night. Compared with PD-IBM patients, PD+IBM patients tended to have fewer turning-over episodes and smaller degree turns. Meanwhile, PD+IBM patients had worse Pittsburgh Sleep Quality Index (PSQI) and Parkinson's Disease Sleep Scale (PDSS) scores, and less total sleep time (TST) than PD-IBM patients. Spearman correlation analyses found that the number of turning-over events showed negative correlations with disease duration (r = -0.378, P < 0.05) and Unified Parkinson's Disease Rating Scale (UPDRS) axial scores (r = -0.370, P < 0.05). Moreover, TST (r = 0.505, p < 0.05) and sleep efficiency (SE) (r = 0.473, p < 0.05) positively correlated with the number of turns in bed. Multivariate linear regression analyses showed that UPDRS axial scores and the number of turns were significantly associated with TST (both p < 0.05). In conclusion, the number of turns in bed and UPDRS axial scores were two significant factors affecting sleep quality. Multisite inertial sensors can be used to quantitatively evaluate nocturnal motor functions in PD patients.

Getting a good night sleep? The importance of recognizing and treating nocturnal hypokinesia in Parkinson's disease.

When Parkinson's disease (PD) patients are asked about the quality of their sleep, their answers are dominated by difficulties associated with impaired mobility in bed, medically referred to as nocturnal hypokinesia. Nocturnal hypokinesia is symptomatic from the mid-stage of the disease, affecting up to 70% of PD patients, and contributes to poor sleep quality, and increased carer burden. Here we explore four areas of nocturnal hypokinesia that are relevant to clinical practice, namely: manifestations and definition; clinical assessment and objective monitoring; etiologies and contributing factors; and evidence-based therapeutic approaches. In addition, we provide an operational definition of what constitutes nocturnal hypokinesia and outline different methods of assessment, ranging from clinical interviews and rating scales to objective night-time monitoring with inertial sensors. Optimal management of nocturnal hypokinesia in PD begins with recognizing its manifestation by inquiring about cardinal symptoms and contributing factors from, not only patients, but also carers, followed by formal assessment, and the application of individualized evidence-based treatment. Night-time dopaminergic treatment is the primary therapy; however, careful clinical judgment is required to balance the benefits with the potential adverse events related to nocturnal dopaminergic stimulation. Future studies are needed to explore the practicality of home-based objective assessment of nocturnal hypokinesia, new therapeutic options not limited to dopaminergic medications, and non-pharmacologic approaches, including training on compensatory strategies and bedroom adaptations.

Impaired bed mobility: quantitative torque analysis with axial inertial sensors.

Difficulty in turning in bed is rated as the most troublesome night-time symptom among Parkinson's disease (PD) patients. AIM: To develop a practical objective method for home assessment of a patient's ability to turn in bed. METHODS: Nocturnal parameters and torque of self-turning in bed from 17 PD couples were assessed and compared using a wearable axial sensor for two nights in their homes. RESULTS: The torque of axial rotation which indicates the ability of PD patients to turn in bed was significantly less than their spouses (p < 0.001). Significant correlations were observed between the torque of turning in bed and total unified Parkinson's Disease Rating Scale score (r = 0.71; p = 0.001), and total Nocturnal Akinesia Dystonia and Cramp score (r = 0.634; p = 0.006). CONCLUSION: Our study confirms a decreased ability in turning in PD.

Time for a strategy in night-time dopaminergic therapy? An objective sensor-based analysis of nocturnal hypokinesia and sleeping positions in Parkinson's disease.

BACKGROUND: Nocturnal hypokinesia is a common night-time symptom in patients with Parkinson's disease (PD). However, there is still little understanding of the nature, and variations of severity of this symptom. OBJECTIVES: To evaluate the severity of nocturnal hypokinesia and sleep positions in PD patients using multisite wearable sensors. METHODS: Nocturnal parameters and sleep positions in 18 PD couples were assessed and compared using wearable sensors (limbs and trunk) for one night in their homes. Nocturnal parameters included number, velocity, acceleration, degree, limb movements and the number of times they got out of bed. RESULTS: PD patients had significantly fewer episodes of turns in bed than their spouses (p=0.043), which was associated with significantly slower speed (p=0.005), acceleration (p=0.005) and fewer degrees (p=0.017). When we split the night into the first and second half, significant findings were mainly demonstrated in the second half of the night, including significantly fewer turns (p=0.02) with smaller degrees (p=0.017), slower speed (p=0.005) and acceleration (p=0.007). No significant differences in these parameters were shown in the first half of the night except for smaller degrees of turn in bed in PD patients (p=0.028) and slower acceleration (p=0.037). In addition, PD patients spent significantly more time in a supine position compared to their spouses (p=0.031) with significantly less time in a prone position (p=0.041). CONCLUSION: Nocturnal hypokinesia gets worse as the night progresses. Treatment of nocturnal hypokinesia should aim at providing a continuous dopaminergic delivery that can achieve a sustained therapeutic level of dopamine throughout the night.

Evaluating the Efficacy of Nocturnal Continuous Subcutaneous Apomorphine Infusion in Sleep Disorders in Advanced Parkinson's Disease: The APO-NIGHT Study.

BACKGROUND: There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). OBJECTIVE: Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. METHODS: We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. RESULTS: NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales (p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. CONCLUSION: This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy.

Quantitative demonstration of the efficacy of night-time apomorphine infusion to treat nocturnal hypokinesia in Parkinson's disease using wearable sensors.

BACKGROUND: Nocturnal hypokinesia/akinesia is one of the common night-time symptoms in patients with Parkinson's disease (PD), negatively affecting quality of life of patients and caregivers. The recognition of this problem and treatment options are limited in clinical practice. OBJECTIVES: To evaluate the efficacy of nocturnal apomorphine infusion, using a wearable sensor, in patients who are already on daytime continuous subcutaneous apomorphine infusion and still suffer from nocturnal hypokinesia. METHODS: Nocturnal parameters in 10 PD patients before and during nocturnal infusion were assessed over two nights at their homes, using a wearable sensor (trunk). Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, and number of times they got out of bed. Correlations with validated clinical rating scales were performed. RESULTS: Following nocturnal apomorphine infusion (34.8 ± 6.5 mg per night), there were significant improvements in the number of turns in bed (p = 0.027), turning velocity (p = 0.046), and the degree of turning (p = 0.028) in PD patients. Significant improvements of Modified Parkinson's Disease Sleep Scale (p = 0.005), the axial score of Unified Parkinson's Disease Rating Scale (p = 0.013), and Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.014) were also observed. CONCLUSION: Our study was able to demonstrate quantitatively the efficacy of nocturnal apomorphine infusion in PD patients with nocturnal hypokinesia and demonstrated the feasibility of using wearable sensors to yield objective and quantifiable outcomes in a clinical trial setting. More studies are needed to determine the long-term efficacy of this treatment in a large prospective cohort of PD patients.

Sensor-based evaluation and treatment of nocturnal hypokinesia in Parkinson's disease: An evidence-based review.

The manifestations of nocturnal movements in Parkinson's disease (PD) are protean, with major disabilities related to nocturnal hypokinesia. While it can be assessed by clinical interviews and screening instruments, these are often inaccurate and prone to recall bias. In light of advances in sensor technology, we explored the use of sensors in the study of nocturnal hypokinesia, by performing a systematic review of the professional literature on this topic. Evidence suggests that nocturnal hypokinesia exists even in patients in the early stages, and PD patients turned significantly less and with much slower speed and acceleration than controls, partly related to low nocturnal dopamine level. We conducted another systematic review to evaluate the evidence of the efficacy of dopaminergic agents in the treatment of nocturnal hypokinesia. Several lines of evidence support the use of long-acting drugs or by continuous administration of short-acting agents to control symptoms. Sensor parameters could be considered as one of the important objective outcomes in future clinical trials investigating potential drugs to treat nocturnal hypokinesia. Physicians should be aware of this technology as it can aid the clinical assessment of nocturnal hypokinesia and enhance the quality of patient care. In addition, the use of sensors currently is being considered for various aspects of research on early diagnosis, treatment, and rehabilitation of PD patients.

How well do Parkinson's disease patients turn in bed? Quantitative analysis of nocturnal hypokinesia using multisite wearable inertial sensors.

BACKGROUND: Nocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone. OBJECTIVES: To quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores. METHODS: Nocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy. RESULTS: PD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale-Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed. CONCLUSION: Our study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms.

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

Although nocturnal hypokinesia represents one of the most common nocturnal disabilities in Parkinson disease (PD), it is often a neglected problem in daily clinical practice. We have developed a portable ambulatory motion recorder (the NIGHT-Recorder), which consists of 16-bit triaxial integrated microelectromechanical system inertial sensors that are specifically designed to measure movements, register the position of the body with respect to gravity, and provide information on rotations on the longitudinal axis while lying in bed. The signal processing uses the forward derivative method to identify rolling over and getting out of bed as primary indicators. The prototype was tested on six PD pairs to measure their movements for one night. Using predetermined definitions, 134 movements were captured consisting of rolling over 115 times and getting out of bed 19 times. Patients with PD rolled over significantly fewer times than their spouses (p = 0.03), and the position change was significantly smaller in patients with PD (p = 0.03). Patients with PD rolled over at a significantly slower speed (p = 0.03) and acceleration (p = 0.03) than their spouses. In contrast, patients with PD got out of bed significantly more often than their spouses (p = 0.02). It is technically feasible to develop an easy-to-use, portable, and accurate device that can assist physicians in the assessment of nocturnal movements of patients with PD.