Non-Motor symptoms burden in early stages of parkinson's disease
Zomer Sardar1, Sumayyah Liaquat2, Qudsum Yousaf3, Safia Bano4, Ahsan Numan4
1 Department of Neurology, District Hospital Nankana Sahib, Lahore, Pakistan
2 Department of Neurology, Hussain Lakhani Hospital, Karachi, Pakistan
3 Department of Neurology, Central Park Teaching Hospital, Lahore, Pakistan
4 Department of Neurology, King Edward Medical University, Lahore, Pakistan
Correspondence Address:
Zomer Sardar
District Hospital Nankana Sahib Lahore
Pakistan
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/aian.aian_483_22
Background: Non-motor symptoms (NMSs) in Parkinson's disease (PD) are often overlooked and thus can impede clinical management and significantly reduce the patient's quality of life. Aims: The study aimed to determine the burden of NMS in the early stages of PD. Material and Methods: A 1-year observational cross-sectional study was conducted at Mayo Hospital, Lahore, in 2019. The MDS-PD criteria were used to diagnose PD patients. The study included patients with Hoehn and Yahr (HY) stages 1–3. The frequency of NMSs was assessed using a non-motor symptom questionnaire (NMSQ), and the non-motor symptom scale (NMSS) score was derived using the NMSS. Results: A total of 100 PD patients were enrolled in the study. Sixty-three (63%) were males and 37 (37%) were females. Their age ranged between 45 and 75 years with a mean ± SD of 57.46 ± 8.46. At least one NMS was reported by 84% of patients, with neuropsychiatric symptoms (68%) preponderant, followed by a change in taste and smell (64%). The mean NMSS score is 46.22 ± 22.098 (median 44) with a range from 0 to 88, with the trend being increasing score with the advancing stage. Conclusion: The use of the NMSQ and NMSS tools should be standard in clinical practice to identify the severity of the disease and commence appropriate care.
Keywords: Hoehn and Yahr stage, non-motor symptoms, non-motor symptom questionnaire, non-motor symptom scale, Parkinson's disease
Non-motor symptoms (NMSs) in Parkinson's disease (PD) include neuropsychiatric disturbances and cardiovascular, urinary, and gastrointestinal symptoms among others.[1] The majority of PD patients experience gastrointestinal dysfunction (60–80%), followed by neuropsychiatric disturbances (84%), and sleep disorders in varying percentages (38–98%).[2] NMS can be assessed by a non-motor symptom questionnaire (NMSQ), and the frequency and severity of NMSs are determined by a non-motor symptom scale (NMSS) score.[3] Both are validated tools for the assessment of the NMS in PD.[3] The unified PD rating scale (UPDRS) is a tool that not only assesses non-motor and motor symptoms but also evaluates complications with therapy and the disease's impact on the activities of daily life. However, the UPDRS is a lengthy tool and usually is used by a neurologist.
We aim to appraise the NMS burden in Hoehn and Yahr (HY) stages 1–3 of PD. Our secondary objective is to raise awareness among neurologists about the impact of NMSs on management.
Materials and MethodsAn observational cross-sectional study was conducted in the Department of Neurology, Mayo Hospital Lahore, Pakistan. The duration of this study was of 1 year, spanning from January 2019 to December 2019. A total of 100 patients who fulfilled the inclusion criteria were recruited after approval from the chairman of the Department of Neurology, Mayo Hospital, Lahore. Approval from the Ethics committee is obtained. Reference number 812/RC/KEMU.
Newly and previously diagnosed PD patients (treatment naïve or under treatment) between HY stages of 1–3 were included in the study. Patients were diagnosed with idiopathic PD using Movement Disorder Society – Parkinson's Disease criteria 2015 (MDS-PD) by a neurologist.[4] Patients were further classified in stages by modified HY scale criteria.[5] Informed consent was obtained from all patients. Patients with Parkinson's plus (cortico-basilar degeneration, progressive supranuclear palsy, and multisystem atrophy) and who had cognitive impairment on mini-mental state examination (score <24), and those with HY stage >3 were excluded from the study.[6]
Demographic data (age and gender) of patients were recorded on pre-designed proforma. All patients were screened for NMS with a self-reported NMSQ (assisted by a resident, if necessary).[3] If any symptom was present, it was marked “yes” and marked “no” if the symptom was not experienced. Symptoms displayed on the NMSQ, their frequency, and severity were further evaluated by NMSS and the total NMSS score was noted. The NMSS score was obtained by interview. The score of each item in nine domains is determined by multiples of frequency (1–4) and severity (0–3).[7]
Data were analyzed using IBM SPSS version 22. The qualitative variables like gender, PD stage, and NMS were presented in frequency and percentages. The mean and standard deviation were calculated for quantitative variables like age and NMSS score. Post-stratification of data was carried out using Chi-square tests according to the NMSS score with age groups and gender. A P value ≤0.05 was taken as significant.
ResultsThe total number of patients enrolled was 100. Their age ranged between 45 to 75 years with a mean ± SD of 57.46 ± 8.46. Fifty patients (50%) were in the age group of 50 to 65 years, whereas 21 (21%) were aged more than 65 years, and 29 (29%) were younger than 50 years. A preponderance of males was observed in our study. There were 63 (63%) males, and only 37 (37%) were females [Table 1].
PD severity as evaluated by the modified HY scale, showing most of the patients in stage 2 and stage 2.5 (27% each), followed by stage 1, stage 1.5, and stage 3 with 19 (19%), 18 (18%), and 9 (9%) patients, respectively [Figure 1].
Although the type of NMSs experienced by our sample was quite variable, 84% (n = 84) of patients, out of 100 PD patients screened, were reported to have at least one of the 23 symptoms.
Neuropsychiatric symptoms (mood/cognition domain) were preponderant in our study with 68% (n = 68) of patients reporting feeling worried for no apparent reason (anxiety). Depressive symptoms were present in 60 (60%), whereas 52 (52%) patients complained of flat mood without normal highs and lows (apathy).
The second most frequent symptom experienced was a change in taste/smell (64%) followed by lightheadedness or fainting on standing from sitting or lying position in 63 (63%) patients. In the sleep/fatigue domain, fatigue or lack of energy (not slowness) was present in 59 (59%) patients, followed by insomnia, excessive daytime sleepiness, and restless leg syndrome in 50%, 49%, and 48%, respectively.
Problems with memory and sustaining concentration were described by 42% and 46% of patients respectively. Sixty-one percent of patients suffered from constipation. Urinary symptoms were reported by 63% of patients. The frequency of NMSs according to NMSQ is listed in [Table 2].
The mean NMSS score is 46.22 ± 22.098 (median 44) with a range from 0 to 88 [Figure 2].
The mean NMSS scores were 29.79 ± 16.69 in stage 1, 43.06 ± 23.52 in stage 1.5, 48.26 ± 15.54 in stage 2, 44.89 ± 18.09 in stage 2.5, and 85.11 ± 2.47 in stage 3 [Table 3]. Stratified analysis of the NMSS score with gender (P: 0.53) and age groups (P: 0.97) demonstrated no significant association.
DiscussionNMSs are frequent in early PD and reflect multisystem involvement and heterogeneity of the disease.[8] It is increasingly recognized that a NMS is as debilitating as motor symptoms and is frequently under-appreciated in clinical practice.[9] Missed or delayed diagnosis of NMS in the early stages of PD may have implications on patient care and management and has been shown to negatively impact the quality of life.[9],[10],[11],[12]
The NMSQ is a self-reported screening questionnaire to flag patients in busy clinics.[4] The NMSS was developed and validated in 2007 to simply and comprehensively assess the frequency and severity to determine the burden of the NMS.[5] NMSS is translated into many languages, but its translation to Urdu does not exist yet.
The observed prevalence of NMS in our study was slightly higher in males than females with a mean age and standard deviation of 57.6 + 8.45 years. The mean age of the patients in other studies is reported to be higher than what we observed in our study. A cross-sectional study by Ojo OO et al. evaluated the NMS burden in PD in a Nigerian population. In their study, the mean age in a population of 825 was 63.7 ± 10.1 years.[6] Another study by Gökçal E et al.[7] also had a mean age of 65.22 ± 10.7 (range: 34–85) with male predominance.
Neuropsychiatric symptoms were dominating our study. Anxiety and depression were reported in 68% and 60% of patients, respectively. A change in taste/smell was the second most common symptom experienced by 64% of subjects. Lightheadedness/fainting and constipation were experienced by 64% and 61% of subjects in the NMSQ, respectively. Lightheadedness was observed in 69% in a study by Karri et al.[13] We observed that 84% of our patients reported at least one NMS in the screening questionnaire, which is consistent with a study carried out in Russia. They also concluded that more than 80% of subjects experienced at least one NMS. In the above study, sleep disturbances followed by psychiatric complaints predominated in HY stages 1–2. Psychiatric symptoms were experienced by a majority in stages 3–5.[12] Similarly, in the PRIAMO study, cognitive and psychiatric symptoms predominated in HY stages 1.5–3.[14] Our study showed the same trend of frequent neuropsychiatric disturbances in the early stages of the disease.[12],[14]
The mounting evidence on NMSs suggests that the NMS burden increases with the advancement of the disease.[15],[16] The majority of our cases were in HY stages 2 and 2.5, and NMS predominated in HY stages 2.5 and 3. Our results also demonstrated that the NMSS rose 4–5 times with the progression of the disease stage (the NMSS in stage 1 was 29.79 ± 16.69, and in stage 3, it was 85.11 ± 2.47), similar to the study by Chaudhuri K et al.[15]
In earlier studies, the burden of NMSS was graded into levels: 0 (none, score 0), 1 (mild, score 1–20), 2 (moderate, score 21–40), 3 (severe, score 41–70), and 4 (very severe, score ≥71).[17] According to this grading system of NMSS burden, our subjects with HY stage 1 disease fall into level 2 (moderate burden) and patients with stage 3 into level 4 (very severe). The burden of NMS in our population in the early stages of the disease is conspicuously shown to be high, which is somewhat similar to previous studies.[15],[17] A validation study, the Italian version of NMSS, 2017, by Cova et al.,[18] reported that the median of the HY stage was 2 and the mean NMSS score was 39.8 (0-154). In contrast, the overall mean NMSS score in our sample was slightly higher than what was observed in the Italian study (46.22 ± 22.09). The NMSS score in the Taiwanese population is rather contrasting. The mean NMS severity score (NMSSI) in one Taiwanese study was 39.1 ± 34.9 in males and 32.8 ± 33.9 in females.[19] Another study by Martinez-Martin et al.[20] reported a NMSSI of 47.6 ± 40.1 in males and 55.1 ± 43.4 in female cases.
According to Picillo M et al., male patients experienced more severe NMSs in contrast to females.[21] Chen et al.[16] also observed sex differences in some of the domains of NMSS (attention/memory, urinary, and miscellaneous domains). In contrast, no sex differences in NMSS were observed in a Chinese study.[22] Males exhibited a higher number of NMSs compared to females in our study. The determination of sex differences in the NMSS score in our population was not determined as this was not the scope of this study. However, further study can be carried out to elucidate the gender differences among our population.
Furthermore, NMS has also demonstrated an association with motor fluctuations/complications in studies. Chaudhuri K et al.[15] group observed a positive association between NMS burden, stages of the disease, and the quality of life. According to Santos-García et al.,[23] the NMS score was found to be higher in patients who presented with motor fluctuations.
To the best of our knowledge, this is the first study in Pakistan in which NMSS burden has been determined in our populace of PD patients in HY stages 1–3. From this study, we report two important findings: first, NMS burden is not uncommon in the early stages of the disease, and second, the NMSS score increases with the advancement of the disease.
ConclusionNMS detection and management can help patients and their caregivers feel better, and it can also contribute to a reduction in institutional load. Screening for NMSs should thus be emphasized in clinical practice. We also propose that Urdu translation of NMSS by experts according to international standards should be carried out to accurately and effectively estimate the burden of NMSS scores in our population.
Limitations
This study has several limitations. Firstly, the UPDRS score was not included in the study. Secondly, other tools for the validation of NMSs were not used. Furthermore, the NMSS burden was not determined in treated and treatment naïve patients separately.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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