|Year : 2019 | Volume
| Issue : 3 | Page : 102-108
Non-motor symptoms of Parkinson’s disease: its prevalence across various stages and its correlation with the severity of the disease and quality of life
Kranthi Pappala, Butchi Raju Garuda, Gopi Seepana, Sateesh Kumar Thalabaktula, Aruna Kumari Uppaturi
Department of Neurology, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India
|Date of Submission||22-Oct-2019|
|Date of Decision||29-Oct-2019|
|Date of Acceptance||05-Nov-2019|
|Date of Web Publication||04-Dec-2019|
Dr. Butchi Raju Garuda
Department of Neurology, 2nd Floor, Superspeciality Block, King George Hospital/Andhra Medical College, Maharanipeta, Visakhapatnam-530002, Andhra Pradesh.
Source of Support: None, Conflict of Interest: None
BACKGROUND: Non-motor symptoms (NMSs) were a real burden in Parkinson’s disease (PD) and contributed to severe disability, impaired quality of life (QoL), and shortened life expectancy. AIM: The aim of this study was to investigate the prevalence of NMSs in PD and their correlation of NMS with disease duration, severity, and Unified Parkinson's Disease Rating Scale (UPDRS) motor score and their impact on patient’s QoL. MATERIALS AND METHODS: This was a prospective cross-sectional study. Sixty-four patients who were diagnosed by United Kingdom Parkinson's Disease Brain Bank criteria were studied. Non-motor symptom scale (NMSS) analyzed NMS, and motor dysfunction was assessed by the UPDRS II and III during OFF condition and QoL by Parkinson’s Disease Questionnaire-39 (PDQ-39) questionnaire. RESULTS: The prevalence of NMS was 93.75% (n = 60). Most frequent NMS was difficulty in falling asleep (54.7%), urinary urgency (39%), and memory impairment (37.5%). Most disabling symptoms are difficulty in falling asleep (3.34 ± 4.1) and fatigue (2.48 ± 4.2). The total NMSS scores were correlated with Hoehn and Yahr stage, and Movement Disorder Society UPDRS and PDQ-39 scores, but not with duration of disease. Correlation between NMSS and PDQ-39 scores was stronger as compared to the relationship between UPDRS and PDQ-39 scores (r = 0.71 and 0.58, respectively, P = 0.00). CONCLUSION: This study showed the high prevalence of NMSs and value of NMS as predictors of QoL in patients with PD. Therefore, understanding the pathophysiology of these NMSs should be placed at the forefront to develop new therapeutic approaches by improving the QoL of patients with PD.
Keywords: Non-motor symptoms, non-motor symptom scale (NMSS), Parkinson’s disease, Parkinson′s Disease Questionnaire-39 score, Unified Parkinson′s Disease Rating Scale
|How to cite this article:|
Pappala K, Garuda BR, Seepana G, Thalabaktula SK, Uppaturi AK. Non-motor symptoms of Parkinson’s disease: its prevalence across various stages and its correlation with the severity of the disease and quality of life. Ann Mov Disord 2019;2:102-8
|How to cite this URL:|
Pappala K, Garuda BR, Seepana G, Thalabaktula SK, Uppaturi AK. Non-motor symptoms of Parkinson’s disease: its prevalence across various stages and its correlation with the severity of the disease and quality of life. Ann Mov Disord [serial online] 2019 [cited 2020 Jan 18];2:102-8. Available from: http://www.aomd.in/text.asp?2019/2/3/102/272290
| Introduction|| |
Parkinson’s disease (PD) was the second most common neurodegenerative disease of the Central Nervous System, affecting 1% of the population over 60 years old and about 4% in the older age population. Non-motor symptom (NMS) can present at any stage of PD, including the premotor phase. NMSs were a real burden in PD contributing to severe disability.,,
Despite the importance of NMS in PD, there are only a few studies from India, which studied the prevalence of NMS using a validated scale. We aimed to investigate the prevalence of NMS in PD and their correlation with disease duration, severity, and Unified Parkinson's Disease Rating Scale (UPDRS) motor score and their impact on patient’s quality of life (QoL).
| Materials and Methods|| |
We conducted a prospective cross-sectional, single-center, open-label study in 64 consecutive patients with PD who were diagnosed by United Kingdom Parkinson's Disease Brain Bank criteria attending Neurology Clinic of our tertiary care hospital from May 2017 to December 2018. The exclusion criteria of the study included Parkinson Plus Syndromes like, MSA, PSP, CBD, DLB, and other causes of secondary Parkinsonism More Details, including vascular parkinsonism, drugs, and toxins. Patients with diabetes mellitus (DM) were also excluded to prevent confounding with autonomic symptoms.
Informed written consent from patient or guardian was taken after explaining in their understandable language. Institutional ethics committee approval was received for the study. After taking subjects into the study, a detailed history was taken regarding symptoms, medication usage, associated premorbid conditions, especially DM, and a thorough clinical examination was conducted. For all patients, routine hematological investigations, such as hemogram, serum creatinine, random blood sugar, and HIV tests, were performed. The MRI brain scan was performed in all patients to rule out vascular parkinsonism and other conditions.
The same neurologist interviewed all the study subjects. The demographic data, the clinical manifestations, were noted. All patients were examined in the off state. The Hoehn and Yahr (H&Y) stage was used to measure disease severity, and Movement Disorder Society (MDS) UPDRS part II and III was used to measure motor score. The non-motor symptom scale (NMSS) was used to assess NMSs. QoL was evaluated by Parkinson’s Disease Questionnaire-39 (PDQ-39) questionnaire.
NMSS. It comprises 30 questions in nine domains. The NMSS not only assesses whether or not NMS were present but also it rates their frequency (range of 0–4) and severity (scale of 0–3). If the product of the frequency and severity was 1 or higher, then 1 point is assigned. The domains were the cardiovascular symptoms (two items), sleep/fatigue (four items), mood/cognition (six items), perceptual symptoms/hallucination (three items), attention/memory (three items), gastrointestinal symptoms (three items), urinary symptoms (three items), sexual functions (two items), and miscellaneous (four items).
PDQ-39 questionnaire. This questionnaire had 39 questions grouped into the following eight dimensions: mobility, activities of daily living, emotional wellbeing, stigma, social support, cognition, communication, and bodily discomfort. Each aspect had a scale from 0 to 100: 0––the best QoL and 100––the worst QoL. Following answering the questionnaire, a summary index for each dimension (subscales) was calculated using the following formula:
Then, the total score [PDQ-39 summary index (PDQ-39 SI)] was calculated by summation of the eight dimensions’ scores divided by 8.
Statistical analyses. All data were analyzed using Statistical Package for the Social Sciences software (version 23.0). Descriptive statistics were expressed as means and percentages. Correlation between NMS and H&Y stage, duration of disease, UPDRS motor score, and QoL were assessed using the Pearson’s correlation coefficient. A value of P < 0.05 was considered statistically significant.
| Results|| |
The clinical and demographic characteristics of patients with PD are shown in [Table 1].
Of 64 patients, 67.2% (n = 43) were male patients and 32.8% (n = 21) were female patients (M: F––2:1). The overall mean age of patients in our study was 56.1 ± 11.4 years. The median H&Y stage was 2.1 ± 0.8. The median duration of the disease was 36.79 ± 31.7 months. The median UPDRS score was 54.50 ± 27.57. The median PDQ-39 score was 158.3 ± 114. No significant difference was found in NMS mean score while comparing all the NMSs between male and female groups (P > 0.05).
NMS prevalence and correlations
Sixty patients (93.75%) had at least one NMS. In this study, most frequently affected domain was sleep (65%) followed by the urinary domain (61.6%), mood/cognition (50%), and attention/memory (40%). However, in this study, most severely affected domain with maximum mean NMSS scores was sleep (6.45 ± 9.18) followed by urinary domain (6.34 ± 9.38), mood/cognition (5.71 ± 9.58), and attention/memory (3.76 ± 7.39).
When 30 NMS in nine domains were analyzed as shown in [Figure 1], most frequent NMS was difficulty in falling asleep (54.7%), followed by urinary urgency (39%), memory impairment (37.5%), nocturia (35.9%), and fatigue (35.9%). Most severely affected NMSs were difficulty in falling asleep (3.34 ± 4.19), fatigue (2.48 ± 4.28), nocturia (2.42 ± 3.59), urinary urgency (2.26 ± 3.74), and pain (2.2 ± 4.4).
NMS total score was significantly correlated with H&Y stage, UPDRS motor score, and PDQ-39 scale but not with duration of the disease (P = 0.00, 0.00, 0.00, and 0.06, respectively) as shown in [Table 2].
Except for sexual domain, no other domain showed a significant correlation with duration of disease. Sleep, gastrointestinal (GIT), and urinary domains showed a significant positive correlation (P = 0.00, 0.004, and 0.05, respectively) with H&Y stage of the disease. Sleep, mood/cognition, GIT, urinary, and sexual domains showed a significant positive correlation ( P = 0.00, 0.04, 0.003, 0.03, and 0.003, respectively) with UPDRS score. All domains showed a significant positive correlation with the QoL.
There is a significant strong positive correlation between UPDRS motor score and PDQ-39 (P = 0.00). The correlation between NMSS score and PDQ-39 was stronger as compared to the relationship between UPDRS score and PDQ-39 rating (r = 0.71 and 0.58, respectively, P = 0.00), as shown in [Table 3].
|Table 3: Correlation of NMSS total score and MDS UPDRS score with PDQ-39 score|
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| Discussion|| |
There were only a few studies from India,,, reporting NMS in PD and to our knowledge; this is the only study from Andhra Pradesh. Prevalence of NMS and their correlation with duration, stage of the disease, and with UPDRS motor score and QoL were compared with other studies from India and other countries.
Mean age of our patients was 56.1 ± 11.4 years, with the majority being <50 years of age (34.4%) in this study. The lesser mean age of the patients compared to previous studies may be explained by the exclusion of older IPD patients with DM and HTN to avoid confounding with autonomic NMS.,, The preponderance of males is in keeping with the increased susceptibility of this gender to PD, as reported in various Indian studies,, and Morocco study.
Patients with PD for a longer duration were likely to be in a later H&Y stage (P = 0.04) and higher MDS UPDRS (part II and III) score, as discussed in this study (P = 0.01). These results are in good agreement with those given in the studies of Chandrasekaran et al., where patients with PD for a longer duration were found likely to be in a later H&Y stage (P < 0.001), and Kadastik-Eerme et al., where higher MDS UPDRS mean scores were seen in patients with a longer duration and advanced stages of the disease.
This study showed a high prevalence of NMS in patients with IPD (93.75%) and results are in line with previous studies by de Souza et al. (91.8%), Ravan et al. (100%), and Krishnan et al. (100%). Most frequently affected domain in this study is sleep (65%) followed by urinary domain (61.6%), mood/cognition (50%), and attention/memory (40%). Most severely affected domain with maximum mean NMSS scores in this study was sleep (6.45 ± 9.18) followed by the urinary domain (6.34 ± 9.38), mood/cognition (5.71 ± 9.58), and attention/memory (3.76 ± 7.39).
When 30 NMS in nine domains were analyzed, most frequent NMS was difficulty in falling asleep (54.7%) followed by urinary urgency (39%), memory impairment (37.5%), nocturia (35.9%), and fatigue (35.9%). Most severely affected NMSs were difficulty in falling asleep (3.34 ± 4.19), fatigue (2.48 ± 4.28), nocturia (2.42 ± 3.59), urinary urgency (2.26 ± 3.74), and pain (2.2 ± 4.4) in this study.
Sleep dysfunctions were prevalent in PD and represent an integral component of the disease, which may emerge over different phases of PD. It could be the result of the illness itself, secondary to other NMSs, or a side effect of drugs. It was affected 65% of patients with PD, and was most frequently and severely affected domain in this study. This was in line with previous studies by Krishnan et al. (89%) and Chaudhuri et al. The regulation of the normal sleep–wake cycle had been shown to involve the pedunculopontine nucleus (PPN) whose role is paramount. In PD, the PPN cholinergic neurons showed unique selective vulnerability.
Krishnan et al., a South Indian from Kerala, reported a higher frequency of NMS in all nine domains in patients with PD as compared with healthy controls. All patients had at least one NMS. The most frequently affected domains were sleep (89.7%), mood/cognition (88.5%), urinary (79.9%), and attention /memory (76.4%). These results were in line with those given in this study. Different domains were also frequently affected in Krishnan et al., which was least affected in this study (21.6%). Most severely affected domains are mood/ cognition (13.5 ± 13.8), and sleep (9.1 ± 7.8), urinary (7.0 ± 7.3), which were in line with this study.
Excessive daytime somnolence was less prevalent in this study (12.6%) as compared to that in Ravan et al.’s study (43%). No patient had reported restless leg syndrome in contrast to previous studies., Although REM Sleep Behavioral Disorder (RBD) symptom was not included in the NMSS, the symptoms related to RBD were asked in this study. None of the patients in this study had reported RBD symptoms. This was in contrast to Chandrasekaran et al.’s study, which reported RBD in 26% of patients and de Souza et al.’s study, which reported RBD in 36.6% of patients. Both the studies used different questionnaires for assessing the NMS.
Fatigue is also frequently reported and severely affected NMS (35.9%, mean 2.48 ± 4.2) in this study, and dizziness is the most common NMS of cardiovascular domain. Hallucinations are more common than delusions in the perceptual domain. Memory impairment is the most common inattention/memory domain. Increased urinary frequency followed by urgency and nocturia is involved in urinary domain.
Constipation is most commonly involved in GIT domain. The gastrointestinal domain is least affected in this study as compared to the previous studies.,,
No patient had reported double vision, swallowing difficulty, change in perception of smell, or taste, weight loss, excessive sweating in this study and different domains were less affected in this study which was in contrast to previous studies.,, This variation in some domains in the patients of this study may be due to underreporting of these symptoms.
The sexual domain was also less affected in this study (26.6%, mean: 2.1 ± 4.6) as compared to previous studies., This percentage may not represent the reality of sexual problems that the patients of this study face, and it is instead a cultural finding. Assessing these symptoms was the most difficult. Patients of this study tended to be reserved regarding their sexual life.
Regarding olfactory disorders, none of the patients in this study reported the olfactory dysfunction in contrast to previous studies., However, in more than 70% of cases, patients are unaware of their smell changes. Smell impairment is considered a marked warning of PD before motor symptoms, which is due to the early involvement of olfactory-related brain regions by alpha-synuclein according to Braak staging and has an excellent clinical predictive value for PD., Thus, there is a need for validated scale for assessing the olfaction other than NMSS.
The difference between the genders was not significant in this study, which was consistent with previous studies, and differed from Krishnan et al.’s study.
Almost all the previous studies indicated the predominance of symptoms in the sleep, mood, memory, and urinary domains,,,,,, as shown in [Table 4]. However, the studies do report minor differences in various domains as far as frequency is concerned. The cultural and social behavior, the sample size, and differences in sample characteristics, and questionnaires used for assessing NMS may also be responsible for this difference. Thus grossly, the pattern of NMS in Indian subjects seems to be similar to that of the PD population surveyed elsewhere.
NMS showed no correlation with the duration of disease except for sexual domain, which was more affected in patients with more than 5 years duration of illness. These results differ from previous studies., However, the results are somewhat closer to Krishnan et al.’s study, in which there was only a weak correlation with duration of symptoms was noted, and results are similar to Shalash et al.’s study.
In contrast, total NMSS score, as well as sleep, GIT, urinary domains, showed moderate correlations with severity of the disease. These results are in line with the previous studies., The stronger association of NMS burden with the severity of motor disability but not with duration of disease was compatible with Braak’s hypothesis that involvement of the autonomic nervous system and lower brain stem occurs prior to participation of the substantia nigra and spreads rostrally with more diffuse involvement of the cortex and brain stem as the disease advances.
Also, total NMSS score and sleep, mood/cognition, GIT, urinary, and sexual domains showed a significant moderate correlation with UPDRS. It indicates that sleep, mood/cognition, GIT, urinary, and sexual domains are more severely affected in patients with higher motor disability. The results of the previous studies,, were in line with this study.
Total NMSS score and all nine domains of NMSS showed a moderate-to-strong correlation with PDQ-39 scale. The results of this study were in line with previous studies,, indicating that the sleep domain has a strong correlation with QOL. In summary, the more severe the NMSs are, the more impaired QoL becomes in patients with PD.
In this study, a significant strong positive correlation was observed between UPDRS II and III, and PDQ-39 score. The correlation between NMSS and PDQ-39 scores was stronger as compared to the relationship between UPDRS and PDQ-39 scores (r = 0.71 and 0.58, respectively, P = 0.00). It indicates that the burden of NMS affects the QOL more than the motor symptoms, and NMS better reflects QOL. It was an essential finding in this study.
For many patients with PD, the hardest part of living with the disease is the detrimental effect that NMSs have on their QoL. This fact should encourage the physicians to give more importance to the NMS, diagnose them, and adequately treat them, given that they were more incriminated in the worsening of the QOL.
The novel aspect of this study was that it analyzes the data as a whole, using validated scales such as the NMSS specifically addressing NMSs and comparing the relative weights of NMSs and motor symptoms as assessed with the UPDRS III and IV and their effects on QOL as assessed with PDQ-39 questionnaire. To reduce inter-operator bias, a single interviewer in a face-to-face interview administered all questionnaires. This study also highlights the utility of the NMSS for the early identification, quantification, and management of NMSs in PD.
The drawback of the study was that some NMSs were prevalent in the elderly population without PD, and some were medication related. Therefore, a case-control study would elucidate whether the investigated NMSs are PD related. Other limitations were the relatively small sample size and the fact that the majority of enrolled patients came from a low socioeconomic class restricts the generalizability of our findings. Other limitations of this study were underreporting of sexual symptoms and restless leg syndrome and olfactory symptoms by the patients. Also NMSS, which was used in this study, does not include RBD symptom, although patients were asked regarding those symptoms.
In conclusion, this study demonstrated the high prevalence of NMSs in Indian patients with PD and the significant impact of NMSs on QoL. It is clear from the study that while treating a patient of PD, it must be born in mind that we should look beyond the motor disabilities. We should move toward a more holistic approach that considers the assessment of NMSs as well as motor symptoms. Treatment may include interventions independent of traditional, dopaminergic anti-Parkinson therapy. More studies are needed to understand the pathophysiology of NMSs to develop new and effective therapeutic approaches.
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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]