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Prevalence and profile of Restless Legs Syndrome in Parkinson's disease and other neurodegenerative disorders: A case-control study

Authors:
  • NIMHANS &Parkinson & Aging Research Foundation, Bangalore, INDIA

Abstract and Figures

Background: Restless Legs Syndrome (RLS) is associated with impaired central dopaminergic neurotransmission. Though a link between RLS and parkinsonism has been proposed, the prevalence of RLS in parkinsonian disorders is poorly documented. Objective: To determine the prevalence of RLS in patients with Parkinson's Disease (PD), Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB). Methods: We evaluated 187 consecutive patients with parkinsonian disorders (PD = 134, PSP = 27, MSA = 21, DLB = 5) and 172 healthy controls. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria and the severity of RLS was assessed in patients with definite RLS. Quality of sleep was evaluated with established scales. Results: The prevalence of RLS was higher in patients compared to controls (9.6% vs. 2.9%; p = 0.009) and was highest in PD (11.9%). RLS was present in only one patient each with MSA and PSP and none with DLB. The mean IRLSSG severity score of patients was 16.2 ± 6.5. The global Pittsburgh Sleep Quality Index score and Epworth Sleepiness Scale score were significantly higher in patients compared to controls (p < 0.001). PD patients with RLS had lower Parkinson's Disease Sleep Scale (PDSS) score compared to patients without RLS (p = 0.023). There was no significant difference in gender, age, duration and severity of PD between the two groups. Conclusions: Our study found a higher prevalence of RLS in PD compared to healthy controls or other parkinsonian disorders. Apart from PDSS score, there was no significant difference in the clinical characteristics of PD patients with and without RLS.
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Prevalence and prole of Restless Legs Syndrome in Parkinsons
disease and other neurodegenerative disorders: A case-control study
[Universally Available]
Ketaki Bhalsing, K. Suresh, Uday B. Muthane, Pramod Kr. Pal
*
Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, Karnataka, India
article info
Article history:
Received 30 August 2012
Received in revised form
8 December 2012
Accepted 31 December 2012
Keywords:
Parkinsons Disease
Restless Legs Syndrome
Progressive Supranuclear Palsy
Multiple System Atrophy
Dementia with Lewy Bodies
Sleep disorder
abstract
Background: Restless Legs Syndrome (RLS) is associated with impaired central dopaminergic neuro-
transmission. Though a link between RLS and parkinsonism has been proposed, the prevalence of RLS in
parkinsonian disorders is poorly documented.
Objective: To determine the prevalence of RLS in patients with Parkinsons Disease (PD), Progressive
Supranuclear Palsy (PSP), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB).
Methods: We evaluated 187 consecutive patients with parkinsonian disorders (PD ¼134, PSP ¼27,
MSA ¼21, DLB ¼5) and 172 healthy controls. RLS was diagnosed using the International RLS Study Group
(IRLSSG) criteria and the severity of RLS was assessed in patients with denite RLS. Quality of sleep was
evaluated with established scales.
Results: The prevalence of RLS was higher in patients compared to controls (9.6% vs. 2.9%; p¼0.009) and
was highest in PD (11.9%). RLS was present in only one patient each with MSA and PSP and none with
DLB. The mean IRLSSG severity score of patients was 16.2 6.5. The global Pittsburgh Sleep Quality Index
score and Epworth Sleepiness Scale score were signicantly higher in patients compared to controls
(p<0.001). PD patients with RLS had lower Parkinsons Disease Sleep Scale (PDSS) score compared to
patients without RLS (p¼0.023). There was no signicant difference in gender, age, duration and
severity of PD between the two groups.
Conclusions: Our study found a higher prevalence of RLS in PD compared to healthy controls or other
parkinsonian disorders. Apart from PDSS score, there was no signicant difference in the clinical char-
acteristics of PD patients with and without RLS.
Ó2013 Elsevier Ltd. All rights reserved.
1. Introduction
Restless Legs Syndrome (RLS) is primarily a sensory condition
characterised by an abnormal urge to move the limbs that occurs
during rest and improves with voluntary movement of the affected
limb [1]. The prevalence of RLS varies from 0.1% to 15% among
different ethnic populations [2,3]. The disorder can occur as a pri-
mary disorder, most likely caused by a genetic predisposition, or
secondary to other medical conditions, including iron deciency
anaemia, end-stage renal disease, neuropathy, pregnancy, rheu-
matoid arthritis and diabetes mellitus.
The aetiology of RLS is still poorly understood, but one important
clue to its aetiology may be its benecial response with dop-
aminergic treatment [4]. The ability of dopaminergic antagonists to
aggravate RLS and evidence of central dopaminergic hypo function
on various neuroimaging studies [5] further supports the
Editors comment: Given how common restless legs syndrome is, and its link with dopaminergic dysfunction, it is perhaps surprising that
the association between PD and RLS is in fact quite poorly documented. The study by Bhalsing and colleagues conrms that RLS has
a higher prevalence in PD than in controls. Interestingly, this study, and others, has failed to show a connection between PD stage and
severity of RLS. Furthermore, the authors found that, as occurs with RLS in patients without PD, patients with RLS and PD have indicators
of excessive daytime sleepiness. Of the non-motor symptoms of PD, RLS is eminently treatable, and it is important to routinely enquire as
to its presence.
Jonathan Carr, Associate Editor, Head Division of Neurology, Tygerberg Hospital & University of Stellenbosch, Tygerberg 7505, South Africa
*Corresponding author. Tel.: þ91 80 26995147; fax: þ91 80 26562829.
E-mail address: pal.pramod@rediffmail.com (P.Kr. Pal).
Contents lists available at SciVerse ScienceDirect
Parkinsonism and Related Disorders
journal homepage: www.elsevier.com/locate/parkreldis
1353-8020/$ esee front matter Ó2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.parkreldis.2012.12.005
Parkinsonism and Related Disorders 19 (2013) 426e430
involvement of the dopaminergic system in RLS. Hence, a link be-
tween RLS and neurodegenerative disorders (with dopaminergic cell
loss) has beenproposed. From this point of view, several studies have
examined the possible etiological association between RLS and
Parkinsons disease (PD). These studies have showed prevalence of
RLS in PD ranging from 0.5% to 19.5% [6,7]. However there are only
few studies which have evaluated the prevalence of RLS in atypical
parkinsonian disorders.
In this study, we prospectively studied prevalence of RLS and its
inuence on sleep in patients with PD, Progressive Supranuclear
Palsy (PSP), Multiple System Atrophy (MSA) and Dementia with
Lewy Bodies (DLB).
2. Subjects and methods
Consecutive patients with a diagnosis of PD and other parkinsonian disorders eMSA,
PSP or DLB, who fullled the inclusion criteria (see below), were recruited from the
outpatient clinic of Department of Neurology, National Institute of Mental Health and
Neurosciences (NIMHANS), India.
The diagnosis of various neurodegenerative disorders was made based on
standard clinical criteria i.e. United Kingdom Parkinsons Disease Society Brain Bank
criteria for PD [8], National Institute of Neurological Disorders and Stroke and the
Society for PSP (NINDS-PSP) clinical criteria for PSP [9], diagnostic criteria by Gilman
for MSA [10], revised criteria by Mc Keith for DLB [11].
A total of 187patients were recruited between June 2007 and January 2009. One
hundred seventy two age and gender matched healthy individuals, including care-
givers of other patients and hospital employees were recruited as controls. Mini-
mental status Examination (MMSE) was done in all subjects. Subjects with MMSE
score of 25 or less, family history of neurodegenerative disorders or history of
exposure to any neuroleptic drugs were excluded. The study was approved by the
Institutions Ethics Committee and all subjects consented to participate in this study.
2.1. Assessment of subjects
(a) For RLS:
i. Diagnosis: A positive diagnosis of RLS was made (in both patients and
controls) only when they had symptoms in agreement with all four
statements listed in the International Restless Legs SyndromeStudy Group
(IRLSSG) criteria [12].
ii. Severity: The severity of RLS in patients was measured with the IRLSSG
rating scale [13].
(b) Sleep scales:
All subjects underwent assessment of sleep by Pittsburgh sleep quality in-
dex (PSQI) [14] questionnaire and of excessive daytime sleepiness by
Epworth sleepiness scale (ESS) [15]. In addition, PD patients underwent
further evaluation of sleep by the revised Parkinsons Disease Sleep Scale
(PDSS) [16].
(c) Assessment of stage and severity of PD:
All PD patients underwent Hoehn and Yahr (H&Y) [17] staging and rating by
the Unied Parkinsons Disease Rating Scale (UPDRS) [18]. The assessments
were performed at the time of recruitment irrespective of time of intake of
dopaminergic drugs.
2.2. Statistical analysis
Statistical analysis was performed by using SPSS 15.0 software. Data was pre-
sented as mean SD in case of continuous measurements and as number (%) in case
of categorical measurements. Differences between groups were analysed with
Analysis of variance (ANOVA) test in case of continuous variables and by Chi-square/
Fisher Exact test in case of categorical variable. A pvalue <0.05 was considered
signicant.
3. Results
A totalof 187patients and 172 controls were recruited.Distribution
of patients was as follows: PD ¼134; PSP ¼27; MSA ¼21 (MSA-
Cerebellar type ¼10; MSA-Parkinsonian type ¼6; MSA-Mixed
type ¼5); DLB ¼5. Themean age of the patients was56.7 13.2 yea rs.
3.1. Prevalence of RLS
The prevalence of RLS was signicantly higher in patients than
in the controls (9.6% vs. 2.9%; p¼0.009). Among the patients, the
highest prevalence was in PD patients (16 out of 134 patients;
11.9%). Only one patient each of MSA and PSP had RLS and none in
the DLB group had RLS (Fig. 1).
3.2. Severity of RLS
The mean IRLSSG severity score of patients was 16.2 6.5. Four
PD patients had mild RLS (score: 1e10); 10 had moderate RLS
(score: 11e20) and 2 had severe RLS (score 21e30). The IRLSSG
severity score was 13 in the PSP patient and 26 in the MSA patient.
No patient had very severe RLS (score: 31e40).
3.3. Quality of sleep
In general, patients showed higher PSQI and ESS scores than
controls (p<0.001) (Table 1). These scores were higher in atypical
parkinsonian disorders than in PD patients (Table 2) though the
difference did not reach statistical signicance. In PD, the mean
global PSQI 6.9 2.5 and the mean total ESS score was 6.3 3.0
respectively, whereas PSP patient with RLS had PSQI and ESS score
of 11 and 7 and MSA patient with RLS had score of 9 and 8
respectively. Table 2 shows individual scores of PSQI and ESS in
patients with PD, PSP, MSA and DLB.
The comparison of patients and controls is summarised in
Table 1.
4. RLS in PD
RLS was present in 16 (11.9%) of 134 PD patients. The age at onset
of RLS was 55.9 11 years and duration of RLS was 1.6 0.9 years.
Fig. 1. Prevalence of Restless Legs Syndrome (RLS) among parkinsonian disorders. PD
eParkinsons Disease, PSP eProgressive Supranuclear Palsy, MSA eMultiple System
Atrophy, DLB eDementia with Lewy Bodies.
Table 1
Comparison between patients and controls.
Parameters Patients
(n¼187)
Controls
(n¼172)
pvalue
Age (years) 56.7 13.2 55 13.8 NS
Men:women 1.9:1 2.1:1 NS
Subjects with RLS (%) 18 (9.6%) 5 (2.9%) 0.009
Mean age at onset of RLS (years) 57.3 11.1 58 4.7 NS
Global PSQI score 6.4 3.7 3.5 2.3 <0.001
ESS score 6.1 3.9 4.4 2.6 <0.001
ESS eEpworth Sleepiness Scale, NS eNot Signicant, PSQI ePittsburgh Sleep
Quality Index, RLS eRestless Legs Syndrome.
K. Bhalsing et al. / Parkinsonism and Related Disorders 19 (2013) 426e430 427
None of the patients with RLS had a family history of RLS. All pa-
tients, except one, reported that the RLS symptoms appeared after
the onset of PD, and the mean period between the onset of PD and
RLS was 1.5 1.0 years.
4.1. Anatomical distribution of RLS
All patients reported symmetrical appearance of RLS symp-
toms, without any correlation between the predominantly
affected side of RLS and that of PD. All but one patient reported
that RLS symptoms were clearly restricted only to the lower
limbs. One patient reported arm restlessness in addition to leg
restlessness.
A comparison of clinical features between PD patients with and
without RLS is shown in Table 3. The levodopa equivalent daily dose
(LEDD) was comparable between the two groups and there was no
signicant difference in any of the clinical parameters, including
the H&Y stage, UPDRS total, motor and the subscores of tremor,
rigidity or bradykinesia. Among the sleep scores, though the PSQI
and ESS were comparable, the PDSS score was lower in RLS patients
(111.7 15.3) compared to those without RLS (122.1 17.2), the
difference being statistically signicant (p¼0.023).
4.2. Severity of RLS and PD
Statistically signicant correlation was not observed between
severity of RLS and age at onset of PD (p¼0.76), duration of disease
(p¼0.63), UPDRS (p¼0.84), H & Y stage (p¼0.14), PSQI (p¼0.38),
ESS (p¼0.42) and PDSS (p¼0.17) scores.
5. Discussion
This is the rst large study on the prevalence of RLS in parkin-
sonian disorders. We found a higher prevalence of RLS in the pa-
tients than in the controls (9.6% vs. 2.9%; p¼0.009). The prevalence
of RLS in our patients is lower than in the Caucasian population
[2,19]. This nding could be due to ethnic differences in the pop-
ulations studied, as studies have shown that RLS was less frequent
in a Southeast Asian population with prevalence of 0.6e2% com-
pared to 6e20% in Caucasian population [3,20].
Among the patients, the highest prevalence was in PD. RLS was
present in only one patient each of MSA and PSP, but none in those
with DLB. RLS has not been commonly reported in atypical par-
kinsonian disorders. A study by Gama et al. [21] found that RLS was
less frequent in MSA than in PSP and PD. Among the 14 patients
with PSP studied, RLS was found in 58% in contrast to 3.7% among
the 27 PSP patients reported here. In 16 PD patients studied by
Gama et al. 50% had RLS in contrast to our observation of 11.9% in
134 PD patients. Although the reasons for this difference in prev-
alence of RLS is not clear, possible explanations include: (a) younger
age of patients in our cohort, as RLS prevalence increases with age
[22], (b) neurodegeneration progresses along with disease duration
and our patients had disease of a lesser duration (mean disease
duration: PD ¼4.6 3.4 years, PSP ¼2.7 1.6 years) compared to
patients studied by Gama et al. (mean disease duration of
PD ¼63.7 years, and of PSP ¼5.7 2.3 years), (c) there may be
cultural and ethnic differences.
5.1. Quality of sleep
In our study patients showed higher PSQI and ESS scores than
controls (p<0.001). PSQI and ESS scores were higher in atypical
parkinsonian disorders than PD, despite having lower prevalence of
RLS. The nding is similar to that of Ghorayeb et al. [23] suggesting,
causes other than RLS (RBD, stridor, sleep-disordered breathing
etc.) responsible for poor sleep quality in these patients. A study by
Gama et al. reported a higher risk of sleep apnea than RLS in pa-
tients with MSA [21].
5.2. RLS in PD
Among PD patients, 11.9% experienced RLS compared to 2.9% in
the control group, a nding which probably supports an etiological
link between RLS and PD, and is comparable to previous studies
[24,25]. Dysfunction of dopaminergic diencephalo-spinal pathway
(A11) in the hypothalamus is proposed to play an important role in
the pathophysiology of RLS [26]. It is possible that in PD, during the
course of the disease, these neurons degenerate, along with
nigrostriatal neurons, leading to the development of RLS and thus
a higher prevalence rate [27].
PD patients with RLS scored lower on PDSS compared to pa-
tients without RLS (p¼0.023), suggesting higher severity of sleep
disturbances in PD patients with RLS. The nding is similar to the
study by Nomura et al. [7]. The difference in the score was observed
mainly in questions related with limb restlessness, numbness or
tingling and painful muscle cramps.
The prevalence of RLS is known to be more among women [22].
Hormonal factors and iron deciency may predispose women to
RLS. Our results did not reveal gender based difference between the
two groups of PD. However, there are conicting reports on the
inuence of gender on RLS in PD patients. Findings by Krishnan
et al. [24] and Nomura et al. [7] are similar to our study whereas
study by Loo and Tan [28] had demonstrated higher prevalence of
RLS in women PD patients.
Table 2
Comparison patients with PD and atypical parkinsonian disorders.
PD
(n¼134)
PSP
(n¼27)
MSA
(n¼21)
DLBD
(n¼5)
Age (years) 55 14.3 62.7 8.3 57.7 8.5 67.2 10.1
Men:women 2.2:1 2:1 1.3:1 2:3
Age at onset (years) 50.5 14.5 60 8.6 54 8.3 65.2 9.9
Duration (years) 4.6 3.4 2.7 1.6 2.7 1.7 2 1
PSQI score 5.8 3.5 7.2 3.1 8.1 4.7 9.4 3.5
ESS score 5.5 3.9 7.3 3.6 8.1 3.5 6.8 4.5
ESS eEpworth Sleepiness Scale, PSQI ePittsburgh Sleep Quality Index.
Table 3
Clinical features of PD patients with and without RLS.
Parameters With RLS
(n¼16)
Without RLS
(n¼118)
Men:women 2.2:1 2.2:1
Age (Years) 55.9 11 54.9 14.7
Age at onset of PD (years) 52.6 11.8 50.2 14.8
Duration of PD (Years) 3.4 2.5 4.8 3.5
Young onset PD (<40 years) 6.3% 18.6%
UPDRS eTotal score 45.4 27.9 43.8 23
UPDRS eMotor score 31.9 18.6 31.4 16.2
UPDRS eTremor subscore 10 2.6 9 2.9
UPDRS eRigidity subscore 8 4.6 7 4.2
UPDRS eBradykinesia subscore 9 2.8 9 2.4
LEDD (mg) 585.02 175.9 608.34 222.3
H & Y stage 2.6 0.7 2.2 0.6
PSQI score 6.9 2.5 5.7 3.6
ESS score 6.3 3 5.4 4
PDSS score* 111.7 15.3 122.1 17.2
*p¼0.023.
ESS eEpworth Sleepiness Scale, H & Y eHoehn and Yahr, PD eParkinsonsDisease,
LEDD elevodopa equivalent daily dose, PDSS eParkinsons Disease Sleep Scale,
PSQI ePittsburgh Sleep Quality Index, UPDRS eUnied Parkinsons Disease Rating
Scale.
K. Bhalsing et al. / Parkinsonism and Related Disorders 19 (2013) 426e430428
The prevalence of RLS has been reported to increase with age
[22]. However an association between RLS and age in PD patients is
inconsistent. Results of our study are in agreement with the study
by Ondo et al. [25] who observed that there was no difference in the
age of PD patients with and without RLS. In contrast to the above
observations, Krishnan et al. [24] found that PD patients with RLS
were older and Nomura et al. [7] reported that PD patients with RLS
were younger.
In idiopathic RLS, a family history, with an autosomal dominant
mode of inheritance may be present in more than half of the cases
[29]. In the present study as well as the study by Krishnan et al. [24],
none of the patients had a family history of RLS, whereas Nomura
et al. [7] found a positive family history of RLS in only 2 such pa-
tients. These ndings suggest a lack of genetic basis in case of RLS in
PD.
The relation between the duration of PD and onset of RLS
symptoms has been evaluated. In many studies including the pre-
sent one, duration of PD did not differ signicantly in patients with
and without RLS [7,24,28], whereas Peralta et al. [30] found earlier
onset of PD in patients with RLS.
All patients, except one, reported onset of RLS after the onset of
motor symptoms of PD, supporting the hypothesis that PD may be
one of the risk factors for RLS. Arm restlessness has been reported
in 22e50% of patients with idiopathic RLS [29], although we found
this distribution in a single patient only and Krishnan et al. [24]
found none.
In idiopathic RLS, though most cases have bilateral symptoms,
a signicant proportion of patients (41.7%) report either right or left
lateralisation [29]. In patients with PD and RLS, Krishnan et al.
observed that while most had bilateral symptoms, majority of them
(70%) were able to lateralise to a side, mostly to the right. Similarly,
Nomura et al. observed that 35% of their PD patients with RLS were
able to lateralise RLS symptoms. But in both these studies, laterality
did not correlate with the side of onset of motor symptoms of PD. In
our study, while all patients with PD with RLS had bilateral
symptoms, lateralisation of severity of RLS was not observed
though the motor symptoms of PD were asymmetric. A lack of
correlation between the side of motor symptom of PD and RLS and
the absence of arm restlessness suggest degeneration in other
dopaminergic pathways than the nigrostriatal in the pathogenesis
of RLS in idiopathic PD [26].
We did not observe any signicant difference in the severity
and/or stage of PD between patients with and without RLS. This
nding is in accordance with previous studies [24,28]. However,
since the assessment was performed regardless of the time of
intake of dopaminergic drugs, these observations should be inter-
preted with caution.
In general RLS was of moderate severity and no one was on
treatment for RLS at the time of interview, which supports the
report by Nomura et al. [7] that RLS in PD is often mild. However, at
the time of investigation, all patients were on dopaminergic drugs,
which are well known to suppress RLS. This bias should be taken
into consideration when analysing the severity of RLS in PD
patients.
5.3. Limitations
Even though care was taken to exclude other conditions that
mimic RLS, the overlap of symptoms of RLS with sensorimotor
manifestations of PD could not be ruled out. A detailed neurological
examination was done in all subjects, but conditions such as iron
deciency anaemia, peripheral neuropathy were not excluded. Our
study was a questionnaire based study which may suffer from recall
bias. At the same time such studies make it possible to screen
abroader and more representative sample of patients.
In conclusion, our study found a higher prevalence of RLS in PD
compared to healthy controls and the other parkinsonian disorders
eMSA and PSP. There were no clinical characteristics which dif-
ferentiated PD patients with and without RLS, except for greater
abnormalities of sleep on PDSS scale in patients with RLS. Further
studies on larger cohorts of patients with parkinsonism and RLS are
required to validate our ndings.
Financial Disclosure
None of the authors have any nancial disclosure to make.
Source of funding
Nil.
Conict of Interest
None of the authors have any conict of interest.
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K. Bhalsing et al. / Parkinsonism and Related Disorders 19 (2013) 426e430430
... In the general population, RLS commonly leads to sleep disturbances and may have a negative impact on quality of life, though it represents an underdiagnosed syndrome [19]. In PwPD, RLS has been reported to impair sleep parameters and quality of sleep [20,21]. Previous studies have also demonstrated an association between RLS and anxiety and depression [22,23]. ...
... For each question, possible answers ranged from 4 (very severe) to 0 (none). The total IRLS score was used for establishing the severity of RLS: very severe (>31), severe (21)(22)(23)(24)(25)(26)(27)(28)(29)(30), moderate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), and mild (0-10) [26]. Sleep characteristics were assessed with several validated scales. ...
... On the contrary, Krishan et al. [47] reported more RLS symptoms in older patients, while Nomura et al. [48] identified RLS in younger people. Previous studies have not found significant differences in the severity of PD assessed by H&Y stages between patients with and without the diagnosis of RLS [20,46,47], but this aspect is under controversy as well. Swensson et al. observed a higher frequency of RLS symptoms in stages 1 and 2 H&Y compared with stages 3 and 4, but patients with advanced PD (H&Y 5) were not included in the study [39]. ...
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Background: Restless legs syndrome (RLS) might worsen sleep quality and quality of life in people with Parkinson's disease (PwPD). Objective: The main aim of the present study is to explore the associations between RLS and sleep, quality of life and other non-motor symptoms (NMS) in a sample of PwPD. Methods: We compared the clinical features of 131 PwPD with and without RLS, in a cross-sectional study. We used several validated scales for assessment: the International Restless Legs Syndrome Study Group rating scale (IRLS), Parkinson's Disease Sleep Scale version 2 (PDSS-2), Parkinson's Disease Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQ) and International Parkinson and Movement Disorder Society Non-Motor Rating Scale (MDS-NMS). Results: Thirty-five patients (26.71%) out of the total PwPD met the RLS diagnostic criteria, without significant differences between male (57.14%) and female (42.87%) (p = 0.431). Higher total scores of PDSS-2 were recorded among PwPD + RLS (p < 0.001), suggesting worse sleep quality. Significant correlations were observed between the diagnosis of RLS and some types of pain (especially nocturnal pain), physical fatigue and probable sleep-disordered breathing, according to the MDS-NMSS assessment. Conclusions: RLS has a high frequency in PwPD and it requires proper management, considering its consequences on sleep and quality of life.
... This suggests that males and females with PD share similar predisposition to RLS and OSA. However, some studies have reported notable differences in RLS among their cohorts (22,23), indicating potential sex differences dependent on additional factors such as environmental exposures. ...
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Parkinson’s disease (PD) is a neurodegenerative disorder affecting 10 million people worldwide. PD results in both motor and non-motor symptom manifestations. Notably, sleep disorders are one of the most common non-motor symptoms of PD and exhibit sex differences in frequency and severity. Although studies have identified variations in sleep disorder manifestation and genetic variants between male and female PD patients, few have examined the connection between PD sleep disorders and genetic risk factors with consideration of biological sex. To address the hypothesis that sex-specific sleep dysfunction in PD patients is associated with genetic risk variants, this study compares sleep symptom frequency and PD-associated genetic variants between males and females. The findings of this study reveal that the differential prevalence of a leucine-rich repeat kinase 2 (LRRK2) mutation (G2019S) between male and female PD patients may underlie sex differences in PD sleep disorders, including rapid eye movement (REM) behavior disorder (RBD) and insomnia. This suggests the potential of sex-specific genetic treatments in effectively managing the sleep symptoms of PD patients.
... Deterioration of night sleep quality was reported to be associated with RBD [78] and RLS [79]. However, some studies demonstrated no difference in subjective sleepiness between PD patients with or without RBD and RLS [80]. Moreover, the deterioration of night sleep quality can be produced by anxiety and depression, and cognitive dysfunction in PD patients [63]. ...
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Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting 1% of the population above sixty years. It is caused by an interaction between genetic and environmental risk factors. Loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) is pathologically characterizing the disease and responsible for the cardinal motor symptoms, most notably, bradykinesia, rest tremors, rigidity, and loss of postural reflexes. Non-motor signs such as olfactory deficits, cognitive impairment, sleep behavior disorders, and gastrointestinal disturbances are reflecting disturbances in the non-dopaminergic system. They precede dopaminergic neuronal degenerations by 5–10 years and are considered the main contributors to patients’ disability, particularly after the successful implementation of levodopa (L-dopa) treatment of motor symptoms. The present general review aimed to briefly update non-motor signs and their underlying pathophysiology in PD.
... In India, it is estimated that there are currently around 4 million people living with dementia, and this number is expected to increase to around 7.7 million by 2030 (Chowdhary et al., 2021;Parle et al., 2005;Verma & Asopa, 2018). The prevalence of dementia in South Asia was 1.9% in 2005, and in 2020 it was 3.6 million and expected to rise by7.5 million by 2040 (Bhalsing et al., 2013;Ru et al., 2021;Salahuddin et al., 2020). Dementia has a varied incidence rate in India, ranging from 2 per 1000 to 35 per 1000 people, according to epidemiological studies (de Villiers, 1983;Lakshman et al., 2016;Taquet et al., 2022). ...
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Dementia is a rapidly growing concern in India, with a projected increase in the number of affected individuals in the coming years. People over the age of 60 are expected to account for 19.1% of the overall population by 2050. This population ageing is likely to be accompanied by a significant increase in the prevalence of dementia. A number of prospective longitudinal investigations on the aetiology of dementia have been conducted in North America and Europe; however, the conclusions of this research cannot be simply applied to the Indian population. In terms of socioeconomic, cultural, linguistic, geographical, lifestyle-related, and genetic aspects, India's population is extraordinarily varied. This review provides an in-depth look at the current situation of dementia in India, including its prevalence, risk factors, available treatments, and the impact it has on individuals, families, and society as a whole. Despite the increasing number of people living with dementia in India, the country still lacks adequate resources and awareness about the condition. This highlights the need for a comprehensive national strategy for the prevention, treatment, and care of people with dementia in India. With a growing aging population, addressing the issue of dementia in India is of utmost importance to ensure that affected individuals receive the care and support they need to live dignified and fulfilling life.
... Leg restlessness is a frequent symptom in PD and the epidemiological link between PD, leg restlessness and RLS is complex, as the prevalence of RLS in PD shows diverging results ranging from 0 to 50% (13), with prospective studies identifying a more trustable prevalence of 10-20% (14). Such variability is mainly caused by the heterogeneity of methods used for RLS screening: from having the symptom of "irresistible desire to move the legs, particularly at night" used in the former data on prevalence (15), to the use of the IRLSSG diagnostic criteria (which have undergone two revisions since their first publication in 1995) in the latter (16). ...
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Background Non-motor manifestations are the main features of Parkinson's disease (PD). These have been associated with vitamin D abnormalities, but the role of parathormone (PTH) is still obscure. Among the non-motor symptoms of PD, the pathogenesis of restless leg syndrome (RLS) is still debated, but it has been associated with the vitamin D/PTH axis in other disease models. Our study deepens the association between vitamin D and PTH with the prevalence of non-motor symptoms of PD and explores such a relationship in patients reporting leg restlessness. Methods Fifty patients with PD were extensively investigated with motor and non-motor scales. Data on serum levels of vitamin D, PTH, and related metabolites were obtained, and patients were stratified as having vitamin D deficiency or hyperparathyroidism according to standardized criteria. Results Overall, 80% of patients with PD exhibited low vitamin D levels, and hyperparathyroidism was diagnosed in 45%. The analysis of the non-motor symptoms profile using the non-motor symptom questionnaire (NMSQ) revealed 36% of leg restlessness, a main feature of RLS. This was significantly associated with worse motor symptoms, quality of sleep, and quality of life. Moreover, it was associated with hyperparathyroidism (OR: 3.48) and with PTH levels, independent of vitamin D, calcium/phosphate levels, and motor status. Conclusion Our results suggest a significant association between the vitamin D/PTH axis and leg restlessness in PD. PTH has a putative role in nociceptive modulation, and previous evidence on hyperparathyroidism has suggested a possible interrelation with RLS. Further investigations are necessary to add PTH to the non-dopaminergic non-motor landscape of PD.
... In the context of PD, RLS is more frequently observed with a prevalence of 14% [57]. RLS is rarely reported in patients with multiple system atroph (MSA), progressive supranuclear palsy and HD [58][59][60]. The relatively high prevalence of RLS in PD may be attributed to the common dysfunction of the dopaminergic system as some researchers proposed [61]. ...
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Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine. In this review, we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies, focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration. These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.
... This proves that basal ganglia are not only involved in the somatomotor loop but also in the occulomotor loop of frontal sub cortical circuit. 15 Increased speech impairment, restless leg syndrome (RLS), 16 impulse control disorders, 17 both obstructive and restrictive patterns of respiratory n -Control = 30; Intervention = 30 dysfunction were very common in PD. 18 Decreased response of heart rate and blood pressure to autonomic stimulation revealed the presence of cardiac autonomic dysfunction in PD patients. 19 It was reported that the combined effect of reduction in muscle strength, decreased proprioception, visual sense, and narrow base of support leads to the imbalance in PD. 20 Ayurvedic treatment like cleansing or eliminating therapy (panchakarma) followed by mixture of cow's milk, Mucunapruriens, Hyoscyamusreticulatus seeds, Withaniasomnifera, and Sidacordifolia roots were useful to improve the activities of daily living in PD patients. ...
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Background: The existing treatments for PD were associated with side effects and does not offer complete cure. Hence there is a need of alternative therapy which can prevent or delay the onset of PD with less or no side effects. Aim and objective: The overall objective of the present study was to assess the effectiveness of electrical vestibular nerve stimulation in the management of Parkinson’s disease. Materials and methods: 60 cases with PD, including both males and females, were recruited in the study by convenient sampling after obtaining written and informed consent. They were randomly grouped with 30 participants in each group. Control group received sham stimulation and the intervention group received electrical vestibular nerve stimulation for 12 weeks. After recording the baseline biochemical parameters, post intervention assessment was performed after 6 weeks and 12 weeks of intervention and compared. Results: Demographic variables were not statistically significant among the control and intervention groups. There was a significant increase in the dopamine and GABA levels followed by the intervention. Conclusion: The present study results support the positive impact of non-invasive electrical vestibular nerve stimulation in modulating neurotransmitters in patients with Parkinson’s disease. A further detailed translational study is required in this area with a larger sample size to generalize the results.
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Non-motor symptoms frequently develop throughout the disease course of Parkinson’s disease (PD), and pose affected individuals at risk of complications, more rapid disease progression and poorer quality of life. Addressing such symptom burden, the 2023 revised “Parkinson’s disease” guideline of the German Society of Neurology aimed at providing evidence-based recommendations for managing PD non-motor symptoms, including autonomic failure, pain and sleep disturbances. Key PICO (Patient, Intervention, Comparison, Outcome) questions were formulated by the steering committee and refined by the assigned authors. Recommendations were drafted based on relevant studies, systematic reviews, meta-analyses and high-quality guidelines identified by the literature search. They were subsequently reviewed, revised, and voted by the Guideline Group in online consensus conferences. Consensus was achieved in case of > 75% agreement among the group members. The consensus was considered strong, if agreement was > 95%. The guideline entails: (i) 10 PICOs and 23 recommendations on the diagnosis and treatment of urogenital, cardiovascular and gastrointestinal autonomic failure; (ii) four PICOs and four recommendations on the possible types of pain in PD individuals, their diagnosis and treatment; (iii) 11 PICOs and 11 recommendations on the screening, diagnosis and treatment of sleep disturbances and excessive daytime sleepiness in PD individuals, as well as on their prognostic implications. Thirty-one out of 38 recommendations achieved a strong consensus. The current German PD guideline provides a practice-oriented and etiology-driven stepwise approach to the diagnosis and treatment of autonomic failure, pain and sleep disturbances in PD individuals.
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Background: Parkinson's disease is one of the major causes of disability in the field of neurology and also the disease is chronic progressive. This disease is caused by the lack of dopamine levels in the body, especially the brain. Parkinson's disease affects a small part of the midbrain called susbstantia nigra. Parkinson's disease usually begins between the ages of 50 and 65, affecting about 1% of the entire population. Total cases of deaths from Parkinson's disease in Indonesia are ranked 12th in the world or 5th in Asia, with a prevalence of 1100 deaths in 2002.Aim: This research aimed to know the prevalence of sleep disorders in patients with Parkinson Disease in Neurology Poly of RSUD Wangaya Denpasar.Method: This research was a descriptive observational study with a cross-sectional approach. The subjects was 61 patients diagnosed with Parkinson Disease and did the treatment in Neurology Poly of RSUD Wangaya Denpasar from January 1, 2017, until December 31, 2017. This research is using primary data from the interview.Results and Conclusion: Patients suffered Parkinson’s disease was 45.9% in 61 - 70 age group; 60.7% men; educational background of subjects was 62.3% senior high school; 36.1% private employee; 85.2% subjects had sleep disorders; 54.1% subjects had insomnia; ; 72.1% subjects didn’t have RLS; 82% subjects didn’t have EDS; 91.8% subjects didn’t have Nocturia. Latar Belakang: Penyakit Parkinson adalah salah satu penyebab utama disabilitas di bidang neurologi dan juga penyakit ini bersifat kronik progresif. Penyakit ini disebabkan oleh kurangnya kadar dopamine dalam tubuh khususnya otak. Penyakit Parkinson memengaruhi bagian kecil dari otak tengah yang bernama susbstantia nigra. Penyakit Parkinson biasanya dimulai antara usia 50 dan 65, menyerang sekitar 1 % dari seluruh populasi. Total kasus kematian akibat penyakit Parkinson di Indonesia menempati peringkat ke-12 di dunia atau peringkat ke-5 di Asia, dengan prevalensi mencapai 1100 kematian pada tahun 2002.Tujuan: Penelitian ini bertujuan mengetahui prevalensi munculnya gangguan tidur pada penderita Parkinson di Poli Saraf Rumah Sakit Umum Daerah Wangaya Denpasar tahun 2017.Metode: Penelitian ini merupakan penelitian deskriptif observasional dengan rancangan penelitian cross sectional. Subjek penelitian adalah 61 pasien yang terdiagnosis menderita Parkinson dan melakukan pengobatan di Poli Saraf RSUD Wangaya Denpasar pada rentang waktu 1 Januari 2017 s.d. 31 Desember 2017. Data penelitian adalah data primer yang diperoleh dari wawancara.Hasil dan Kesimpulan: Pasien Parkinson terbanyak yaitu 45,9% berusia 61-70 tahun; 60,7% berjenis kelamin laki-laki; 62,3% memiliki tingkat pendidikan SMA; 36,1% pegawai swasta; 85,2% mengalami gangguan tidur; 54,1% mengalami insomnia; 72,1% tidak mengalami RLS; 82% tidak mengalami EDS; 91,8% tidak mengalami nokturia.
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The Movement Disorder Society Task Force for Rating Scales for Parkinson's Disease prepared a critique of the Unified Parkinson's Disease Rating Scale (UPDRS). Strengths of the UPDRS include its wide utilization, its application across the clinical spectrum of PD, its nearly comprehensive coverage of motor symptoms, and its clinimetric properties, including reliability and validity. Weaknesses include several ambiguities in the written text, inadequate instructions for raters, some metric flaws, and the absence of screening questions on several important non-motor aspects of PD. The Task Force recommends that the MDS sponsor the development of a new version of the UPDRS and encourage efforts to establish its clinimetric properties, especially addressing the need to define a Minimal Clinically Relevant Difference and a Minimal Clinically Relevant Incremental Difference, as well as testing its correlation with the current UPDRS. If developed, the new scale should be culturally unbiased and be tested in different racial, gender, and age-groups. Future goals should include the definition of UPDRS scores with confidence intervals that correlate with clinically pertinent designations, "minimal," "mild," "moderate," and "severe" PD. Whereas the presence of non-motor components of PD can be identified with screening questions, a new version of the UPDRS should include an official appendix that includes other, more detailed, and optionally used scales to determine severity of these impairments.
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Background: There is a need for an easily administered instrument which can be applied to all patients with restless legs syndrome (RLS) to measure disease severity for clinical assessment, research, or therapeutic trials. The pathophysiology of RLS is not clear and no objective measure so far devised can apply to all patients or accurately reflect severity. Moreover, RLS is primarily a subjective disorder. Therefore, a subjective scale is at present the optimal instrument to meet this need. Methods: Twenty centers from six countries participated in an initial reliability and validation study of a rating scale for the severity of RLS designed by the International RLS study group (IRLSSG). A ten-question scale was developed on the basis of repeated expert evaluation of potential items. This scale, the IRLSSG rating scale (IRLS), was administered to 196 RLS patients, most on some medication, and 209 control subjects. Results: The IRLS was found to have high levels of internal consistency, inter-examiner reliability, test-retest reliability over a 2-4 week period, and convergent validity. It also demonstrated criterion validity when tested against the current criterion of a clinical global impression and readily discriminated patient from control groups. The scale was dominated by a single severity factor that explained at least 59% of the pooled item variance. Conclusions: This scale meets performance criteria for a brief, patient completed instrument that can be used to assess RLS severity for purposes of clinical assessment, research, or therapeutic trials. It supports a finding that RLS is a relatively uniform disorder in which the severity of the basic symptoms is strongly related to their impact on the patient's life. In future studies, the IRLS should be tested against objective measures of RLS severity and its sensitivity should be studied as RLS severity is systematically manipulated by therapeutic interventions.
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Background: Restless legs syndrome is a common yet frequently undiagnosed sensorimotor disorder. In 1995, the International Restless Legs Syndrome Study Group developed standardized criteria for the diagnosis of restless legs syndrome. Since that time, additional scientific scrutiny and clinical experience have led to a better understanding of the condition. Modification of the criteria is now necessary to better reflect that increased body of knowledge, as well as to clarify slight confusion with the wording of the original criteria.Setting: The restless legs syndrome diagnostic criteria and epidemiology workshop at the National Institutes of Health.Participants: Members of the International Restless Legs Syndrome Study Group and authorities on epidemiology and the design of questionnaires and scales.Objective: To modify the current criteria for the diagnosis of restless legs syndrome, to develop new criteria for the diagnosis of restless legs syndrome in the cognitively impaired elderly and in children, to create standardized criteria for the identification of augmentation, and to establish consistent questions for use in epidemiology studies.Results: The essential diagnostic criteria for restless legs syndrome were developed and approved by workshop participants and the executive committee of the International Restless Legs Syndrome Study Group. Criteria were also developed and approved for the additional aforementioned groups.
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The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2–4). Although a “modified HY scale” that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should “rate what you see” and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained. © 2004 Movement Disorder Society
Article
The co-morbidity between Parkinson's disease (PD) and restless legs syndrome (RLS) is currently controversial, mainly because in most of the studies so far conducted, the patients were already on therapy with dopamine(DA)ergic drugs. This study has been carried out to assess the prevalence of RLS in de novo PD patients previously unexposed to DAergic drugs. One hundred nine cognitively unimpaired outpatients with PD (70M/39F), mean age 66.89 years±9.37 SD were included in the study. The mean duration of PD was 15.81 months±11.24 SD, and the median Hoehn and Yahr (H&Y) stage was 2 (range 1.5-3). All patients underwent interview to assess the occurrence of overall life-time and current "primary" form of RLS according to the criteria of the International RLS Study Group (IRLSSG). One hundred sixteen age and sex matched subjects (74M/42F, mean age 66.52.years±8.65 SD) free from a history of neurological diseases, were taken as controls and likewise interviewed. "Secondary" forms of RLS in both patients and controls were subsequently excluded. No significant difference was found (chi-square test) in the frequency of overall life-time and of current "primary" RLS between PD patients and controls (6 out of 109 versus 5 out of 116 and 3 out of 109 versus 3 out of 116, respectively). This survey does not support the concept of a co-morbid association between the two conditions and confirm indirectly the findings of previous studies reporting the onset of RLS after diagnosis of PD has been made in the great majority of patients and so likely on ongoing DAergic treatment. Therefore, we speculate that RLS occurring in these patients could be related to DAergic therapy for PD.
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We report the results of a consensus conference on the diagnosis of multiple system atrophy. We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible multiple system atrophy requires one criterion plus two features from separate domains. The diagnosis of probable multiple system atrophy requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite multiple system atrophy requires pathological confirmation.