|Year : 2020 | Volume
| Issue : 3 | Page : 167-172
Does quality of sleep differ in familial and sporadic Parkinson’s disease?
Rohan R Mahale, Ravi Yadav, Pramod K Pal
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
|Date of Submission||13-Feb-2020|
|Date of Decision||12-Apr-2020|
|Date of Acceptance||25-Apr-2020|
|Date of Web Publication||07-Nov-2020|
Dr. Pramod K Pal
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru, Karnataka.
Source of Support: None, Conflict of Interest: None
Background: Sleep disturbances are commonly seen in Parkinson’s disease and are often under-recognized and under treated in clinical practice. Objectives: To determine the quality of sleep in patients with familial Parkinson’s disease (PD) and to note any difference from those with sporadic Parkinson’s disease. Methods: One hundred and fifty six patients with Parkinson’s disease (familial PD- 20, sporadic PD-136) were clinically examined and quality of sleep was determined using Pittsburgh sleep quality index (PSQI), Parkinson’s disease Sleep Scale (PDSS) and Epworth Sleep Scale (ESS). Other scales included Uniﬁed Parkinson’s Disease Rating Scale -part III (UPDRS-III), Hoehn & Yahr Stage, Mini Mental Status Examination, Hamilton anxiety rating scale and Hamilton depression rating scale. Results: Global PSQI score, percentage of patients with global PSQI score >5, total PDSS score, and percentages of patients with total PDSS scores < 82 was similar in both groups. The total ESS score was higher in sporadic PD as compared to familial PD (p=0.04) and the frequency of patients with total ESS score >10 was greater in sporadic PD (p=0.02). The frequency of insomnia, occurrence of nightmares, involuntary limb movements during sleep and sleep behaviour disrupting sleep continuity was similar in both groups. Conclusions: There was no difference in the sleep quality between familial PD and sporadic PD patients.
Keywords: Familial Parkinson’s disease, Parkinson’s disease, sleep, sporadic Parkinson’s disease
|How to cite this article:|
Mahale RR, Yadav R, Pal PK. Does quality of sleep differ in familial and sporadic Parkinson’s disease?. Ann Mov Disord 2020;3:167-72
|How to cite this URL:|
Mahale RR, Yadav R, Pal PK. Does quality of sleep differ in familial and sporadic Parkinson’s disease?. Ann Mov Disord [serial online] 2020 [cited 2021 May 7];3:167-72. Available from: https://www.aomd.in/text.asp?2020/3/3/167/300282
| Introduction|| |
Parkinson’s disease (PD) is characterized by the presence of resting tremor, bradykinesia, rigidity, and postural instability with asymmetric symptom onset. Apart from the aforementioned disabling motor symptoms, PD also has nonmotor symptoms such as anxiety, depression, autonomic dysfunction, psychosis (including hallucinations and delusions), sleep disorders (ranging from insomnia to parasomnias), and cognitive disturbances. The occurrence of sleep disorders is common in PD, accounting for two-third of patients having sleep disturbances throughout the disease course. They are not often recognized, and they do not receive treatment in clinical practice. Sleep disorders are due to neurochemical and neurodegenerative changes in central sleep regulatory centers such as the forebrain, thalamus, and midbrain dopamine neurons. Sleep disturbances may also be secondary to motor discomfort. Patients usually have difficulty in falling asleep, fragmented sleep by frequent and prolonged awakenings, early awakening, insufficient sleep during the night and excessive daytime sleepiness (EDS), snoring, nightmares, hallucinations, REM behavior disorder (RBD), and restless legs syndrome (RLS). These sleep disturbances have a negative impact on the quality of life in patients with PD. The initial description of genetic contribution to the risk of PD was by Gowers, and 15% of his patients had a family history of PD. There are conflicting reports on the quality of sleep and sleep disturbances in patients with familial PD as compared to sporadic PD. Few studies have found better quality of sleep with no or lower prevalence of sleep disturbances in patients with familial PD., Other studies have found higher incidence of sleep disturbances in patients with familial PD., This study was aimed at determining the quality of sleep in patients with familial PD and to note any difference from those with sporadic PD. The study was questionnaire based, and lack of polysomnographic confirmation was the key limitation of the study.
| Materials and Methods|| |
This was a prospective, cross-sectional, and hospital-based study. Patients presenting with features suggestive of Parkinsonism More Details (n = 156), who visited the neurology outpatient services, movement disorder clinic, and those admitted in neurology ward of the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India, were enrolled in the study. The enrolled patients satisfied the UK Parkinson Disease Society Brain Bank criteria for PD. The excluded patients were as per UK Parkinson Disease Society Brain Bank criteria. On the basis of the presence of family history, they were grouped into familial and sporadic PD. The study period was from October 2010 to December 2011, and the study was approved by the institutional ethics committee. All subjects gave written informed consent after full explanation and detail description of study method.
All patients were interviewed and examined with a documentation of demographic variables, disease profile (including age at onset of motor and nonmotor symptoms), and treatment profile. The staging of PD was done using modified Hoehn and Yahr staging (H&Y), and cognitive function was assessed using the Mini-Mental Status Examination (MMSE) scale., The total levodopa equivalent dose (TLED) was calculated in each patient.
Evaluation of sleep was carried out using the Parkinson’s Disease Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleep Scale (ESS).,, Assessment of anxiety and depression was done using Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D), respectively.,
The severity of motor symptoms of PD was assessed using Unified Parkinson Disease Rating Scale III (UPDRS III). The following subscores of UPDRS III were also calculated in all patients: (1) tremor score (UPDRS 20–21, maximum score 28), (2) rigidity score (UPDRS 22, maximum score 20), (3) bradykinesia score (UPDRS 23–26, 31, maximum score 36), (4) gait/postural stability score (UPDRS 27–30, maximum score 16), (5) bulbar abnormalities score (UPDRS 18–19, maximum score 08), (6) axial signs score (UPDRS 18–19, 22, 27–30, maximum score 42), and (7) limb signs score (UPDRS 20–26, maximum score 84).
The proportion of UPDRS III motor scores, accounted for by each subscore, was also calculated. For tremor score % of UPDRS III, the tremor score was divided by the total UPDRS III score. Similar derivations were made to assess the proportion accounted by rigidity, bradykinesia, gait/postural stability, and bulbar abnormalities. The tremor dominant subtype of PD was defined as patients with a ratio of tremor-to-bradykinesia score (bradykinesia, rigidity, and postural instability subscore from the UPDRS motor scale) of 0.5 or more, and the akinetic rigid subtype as patients with a ratio of <0.5. The criteria by Lazzarini et al., classifying patients of PD with positive family history into definite, probable, and possible familial PD, were used.
The data were entered into Microsoft Excel 2010 (Washington; USA) and analyzed using SPSS Statistical Software Package (release 22.0, SPSS Inc.; Chicago, Ill, USA). The qualitative data were analyzed using chi-square/Fischer’s exact test. The continuous variables were expressed as mean ± standard deviation, and categorical variables as frequency and percentage. The normality of the distribution was assessed by the skewness of the values. For the analysis of continuous variables, nonparametric test (Mann–Whitney test and Wilcoxon test) was used. A P value <0.05 was taken as statistically significant.
| Results|| |
The study included 156 patients with PD. Familial PD was diagnosed based on the presence of positive family history, all our patients with positive family history belonged to possible familial PD (n = 20; 12.8%). The remaining 136 patients did not have positive family history and were diagnosed as sporadic PD (87.2%). Autosomal-dominant inheritance was seen in six patients, autosomal-recessive inheritance in six patients, and eight patients’ inheritance was undetermined.
Demographic features and clinical characteristics
Patients with familial PD had significantly younger age at presentation and age at disease onset as compared to patients with sporadic PD. Young-onset PD (YOPD) (21–40 years) was significantly higher in familial PD group (60%). The duration of disease, duration of treatment, TLED, history of smoking, alcohol intake, side affected first with motor symptoms, site affected first, and type of PD were similar in both groups. The percentage of patients with falls and dyskinesias was similar in both groups [Table 1].
|Table 1: Clinical characteristics of familial and sporadic Parkinson’s disease patients|
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Motor scores and disease complications
There was no significant difference in mean UPDRS III motor score between the groups [Table 2]. The subscores of UPDRS III and subscores % (tremors, rigidity, bradykinesia, gait/postural stability, bulbar abnormalities, axial, limb signs, and axial:limb signs ratio) were similar in both groups. The mean MMSE score, patients with MMSE <24, mean H&Y staging scores, and patients with H&Y stage score ≥2 were similar in both groups. The mean HAM-A scores were similar in both the groups. However, the mean HAM-D scores were significantly higher in sporadic PD group (P = 0.05). The percentage of patients with moderate depression (HAM-D score, 18–24) was more in sporadic PD (P = 0.04).
|Table 2: Comparison of motor and non-motor scores between familial and sporadic PD|
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The comparison of sleep scales between the groups has been adjusted for baseline differences in age, duration of disease, dopaminergic medications, and so on [Table 3]. The mean hours of actual sleep per night were similar in both groups. There was no difference between the groups in the components score of PSQI. Global PSQI score, percentage of patients with global PSQI score >5, total PDSS score, and percentages of patients with total PDSS scores <82 were similar in both groups. The total ESS score was higher in sporadic PD as compared to that in familial PD (P = 0.04), and the frequency of patients with total ESS score >10 was greater in sporadic PD (P = 0.02). Sporadic PD had lower score for feeling refreshed in the morning (item 14) with no significant difference in the other items of PDSS. The frequency of insomnia, occurrence of nightmares, involuntary limb movements during sleep, and sleep behavior disrupting sleep continuity was similar in both groups. Patients with familial PD had similar sleep scale scores as that of sporadic PD with an exception of increased frequency of EDS and reduced refreshing sleep in patients with sporadic PD.
|Table 3: Comparison of sleep scales between familial and sporadic Parkinson’s disease|
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There was no significant difference in relation to medication dosage, duration of treatment, or frequency of patients receiving medications in both the groups [Table 4].
| Discussion|| |
Sleep disorders in PD are common. These include insomnia, EDS, and REM sleep behavior disorder (RBD). RBD, and possibly EDS, may precede the onset of motor parkinsonism in PD. The sleep disturbances in PD are multifactorial. The involvement of locus coeruleus, raphe nuclei, hypothalamic nuclei (paramammillary nuclei and posterior nucleus), amygdala and entorhinal cortex by alpha-synuclein pathology, mood disturbances such as anxiety and depression, motor disability due to parkinsonism such as nocturnal akinesia, effect of medications like dopaminergic agents, antidepressants., Identification of sleep disorders is of paramount importance as sleep disturbance has negative impact on the quality of life in patients with PD. Most of the studies on the sleep disturbance in PD have concentrated on the patients with sporadic PD. There are few studies on the sleep disturbances in familial PD, namely sleep quality assessment in a family of PARK6 mutations, video-polysomnographic assessment of sleep in LRRK2 (leucine-rich repeat kinase 2)-associated PD, RBD in parkinsonism with parkin mutations, and RBD, RLS, and hypersomnia in parkin mutation. We evaluated 156 patients to determine their sleep quality using well-validated sleep scales. The sleep quality was similar in both familial and sporadic PD in our study except for increased frequency of EDS in sporadic PD.
A study by Tuin et al., on sleep of a Spanish family of five siblings with PARK6, found good subjective and objective sleep quality in the five siblings with no occurrence of RLS or RBD in PARK6. A study by Kumru et al., on the occurrence of RBD in patients with parkin mutation, reported RBD in six patients based on the video-polysomnography. A study by Limousin et al., on 11 patients with PD with parkin mutation, showed that insomnia and RLS was common in patients with parkin mutation as compared to idiopathic PD. Approximately 9% of patients had definite RBD. A study by Vibha et al., on assessment of quality of sleep between familial and sporadic PD, showed that there was a lower prevalence of insomnia and RBD in familial PD. There was no difference in the occurrence of RLS and EDS between the groups. Video-polysomnography-based study by Ehrminger et al., on 10 patients with LRRK2-associated PD in comparison with four healthy LRRK2 mutation carriers, 20 patients with idiopathic PD, and 12 healthy controls, showed that sleep phenotype in LRRK2 mutations is similar to that of idiopathic PD, except for absent RBD in the presymptomatic and symptomatic stages of LRRK2 mutation–associated PD. Another video-polysomnography-based study by Pont-Sunyer et al., on 18 LRRK2-associated PD, 17 non-manifesting carriers of LRRK2 mutations, 14 non-manifesting noncarriers, and 19 unrelated idiopathic PD, showed that sleep-onset insomnia, sleep fragmentation, and early awakening were more common in LRRK2 mutation–associated PD as compared to idiopathic PD. EDS was similar, and RBD was less frequent and severe in LRRK2-associated PD in comparison with idiopathic PD.LRRK2 mutation is also a risk factor for sporadic PD.
To summarize the findings from the above studies, sleep quality was good in a family of PARK6; insomnia, RBD and RLS in patients with parkin mutation; occurrence of sleep-onset insomnia, sleep fragmentation, and early awakening with lesser frequency of RBD in presymptomatic and symptomatic stage of PD in patients with LRRK2 mutation–associated PD.
| Conclusion|| |
We found no difference in sleep quality between our patients with familial PD and sporadic PD. We have not analyzed the type of genetic mutation in patients with familial PD. The lack of video-polysomnography and the relatively small sample size of patients with familial PD in our study have been acknowledged. The future studies should aim at determining the sleep quality both subjectively and objectively with sufficient sample size in familial PD with different genetic mutations.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]