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Pattern of Non Motor Symptoms in Parkinson’s Disease: A Prospective Observational Study From a Tertiary Care Centre, Bihar, India
Correspondence Address :
Abhay Ranjan,
Department of Neurology Bailey Road, Sheikhpura, Patna, Bihar, India.
E-mail: drabhayranjan97@gmail.com
Introduction: Non motor symptoms are highly prevalent in Parkinson’s Disease (PD) but are often overshadowed by the dominance of motor symptoms.
Aim: To assess non motor symptoms in patients with Parkinson’s disease.
Materials and Methods: In this prospective observational study, patients of PD fulfilling United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria were recruited, between August 2019 to July 2021, in the Neurology Department of Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. The pattern of Non Motor Symptoms (NMS) in PD was studied using detailed questionnaire and association of NMS with age, gender and modified Hoehn and Yahr stage were assessed. Chi-square test and Student's t-test was calculated where required.
Results: Total 102 patients were included, with male constituting 73.5% patients. The mean age was 60.14±13.55 years. Constipation (74, 72.55%) was the most common non motor symptom. Most of the patients belonged to mild stage (52.94%) followed by moderate (40.20%) and severe (6.86%) stages, according to modified Hoehn and Yahr classification. Rapid eye movement sleep behaviour disorder (n=15) and sexual dysfunction (n=28) were significantly more prevalent in male patients. Depression, REM sleep behaviour disorder, olfactory disturbance, visual disturbance, urinary urgency, sweating abnormality, constipation, vomiting and visual blurring were significantly common in patients with earlier disease stages while psychosis in patients with advanced stage.
Conclusion: This study showed the high prevalence of non motor symptoms in PD patient which is consistent with other studies, but there are differences in the frequency of individual symptoms which may relate to cultural and geographic differences.
Constipation, Depression, Modified Hoehn and Yahr staging, Sleep behaviour disorder, Urinary urgency
Parkinson’s Disease (PD) was first described by James Parkinson in 1817 as a disease ccharacterised by involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with propensity to bend the trunk forward, and to pass from a walking to a running pace, the senses and intellect being uninjured (1). Non Motor Symptoms (NMS) in PD constitute a major clinical challenge but are often overshadowed by the dominance of motor symptoms with the diagnostic criteria only based on motor features (2),(3).
Non motor symptoms may predate the diagnosis of PD and reported in around one-fifth of the patients at the time of diagnosis (4). There is marked variability in the frequency of non motor symptoms in the studies across the world with insomnia, urinary symptoms, memory impairment, constipation, fatigue and anxiety being the frequent NMS (5). Most of the literature on the non motor symptoms of PD is from the western countries with few studies from India, and a single study from Eastern India (6),(7),(8),(9),(10),(11),(12),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22),(23). This study is the comprehensive assessment of non motor symptoms of PD in a cohort of patients attending a tertiary care hospital of Bihar in Eastern India. A detailed study of non motor symptoms of PD would help to understand the burden of the illness and plan better care for such patients.
This prospective observational study was conducted in the Neurology Department at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India, between August 2019 to July 2021. The study was approved by the Institutional Ethics Committee (1115/IEC/IGIMS/2019). Informed written consent was taken from patients.
Inclusion and Exclusion criteria: All patients of Idiopathic PD fulfilling United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria were included in the study (24). Patients with history of recurrent strokes with step-wise progression of features, repeated head injury, definite encephalitis in the past, taking neuroleptic treatment at onset of symptoms, more than one affected relatives, exclusive unilateral features even after 3 years of onset, supranuclear gaze palsies, presence of cerebellar signs, early severe autonomic involvement, early severe dementia, presence of Babinski’s sign, presence of cerebral tumour or communicating hydrocephalus, negative response to large doses of levodopa were excluded from the study.
Data collection: Patients were evaluated and the following data were recorded
• Demographic data,
• Clinical manifestations
• Detailed clinical examination including various non motor and motor symptoms.
Modified Hoehn and Yahr staging
The questionnaire/scale used were Modified Hoehn and Yahr staging and detailed questionnaire on non motor symptoms (25). Modified Hoehn and Yahr stages were used to measure the severity of disease through stage 1 to 5. It was further classified into:
• Mild stage (1,1.5,2)
• Moderate stage (2.5,3)
• Severe stage (4,5)
The questionnaire for NMS were divided into subsets and used to assess whether or not NMS were present. Responses were marked in a yes or no answer.
Statistical Analysis
The study data were entered and results were calculated from Statistical Package for the Social Science (SPSS) software version 17.0. Mean, Standard deviation, Standard error of mean were calculated in this study. The categorical variables were compared using the Chi-square test (or Fisher exact test) and continuous variables were compared using the independent t-test. A p-value<0.05 has been considered significant.
Total 102 patients of PD were included in the study. The mean age of the patients were 60.14±13.55 years. Male to female ratio was 2.77:1. Most of the patients (58.82%) were above 60 years of age. Motor symptoms were present in all with bradykinesia (87.25%) being the most common. Majority of the patients were in Hoehn and Yahr stage 2 (30.39%) and least being in stage 5 (0.98%).
The most common non motor symptom was constipation (74, 72.55%) followed by anxiety (66, 64.71%) and depression (63, 61.76%). Rapid Eye Movement (REM) sleep behaviour disorder were present in 16 (15.69%) patients, cognitive impairment in 12 (11.76%) and olfactory disturbance in 24 (23.53%) patients.
Most of the patients (42.16%) had 1-5 non motor symptoms. Only five patients (4.9%) did not have any non motor symptoms. Mean number of non motor symptoms in males was 6.69±4.52 and in females was 5.70±4.14. There was an increase in the prevalence of non motor symptoms with increasing age. The number of non motor symptoms increased with severity of the disease, from mild to severe modified Hoehn and Yahr stage (5 vs 8.42).
Significant difference was observed between male and female patients among some non motor symptoms with Rapid eye movement sleep Behavior Disorder (RBD) (p-value=0.046) and sexual dysfunction (p-value= 0.001) were significantly more prevalent in male patients, while sweating abnormality in form of excessive sweating (p-value=0.021) were significantly more in female patients (Table/Fig 1). Significant difference was noted between modified Hoehn and Yahr stage of PD and few non motor symptoms i.e., depression (p-value= 0.028), REM sleep behaviour disorder (p-value= 0.033), olfactory disturbance (p-value= 0.002), visual disturbance (p-value= 0.000), urgency (p-value= 0.004), sweating abnormality (p-value= 0.030), constipation (p-value= 0.006), vomiting (p-value=0.045), psychosis (p-value= 0.001) and visual blurring (p-value= 0.015).
There was a significant difference while comparing some non motor symptoms within different age groups. Restless leg syndrome (n=3) was significantly more in age ≤40 years (p-value=0.015), while olfactory disturbance (n=19), sexual dysfunction (n=23), and constipation (n=50) were significantly more in age >60 years (p-value=0.038, 0.027, 0.009 respectively) (Table/Fig 2).
Non motor symptoms of PD has received relatively little attention, despite diverse presentation of these conditions and their impact on the quality of life. NMS is often not reported by patients himself thinking that it is not related to disease per se despite its high prevalence.
NMS were present in 95.09% of our patients similar to published studies showing prevalence of NMS ranging from more than two-third patients to involving all patients (6),(7),(8),(9),(10),(11),(12),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22),(23). The most common non motor symptom in this study was constipation, similar to studies by Mukhtar S et al., (11), Azmin NSS et al., (12) and Kumar S et al., (18). Constipation has been found to be the most common NMS in Asian studies which might be due to the dietary differences. Anxiety was the most prevalent NMS in study by de Souza A et al., (17) while it was second most common NMS in study by Mukhtar S et al., (11) and also in the present study.
The mean NMS value was lower compared to a previous multicenter study (6) and the study by Mukhtar S et al., (11). The mean presence of NMS progressively increased from mild to severe modified Hoehn and Yahr stages, similar to various published studies (13),(15),(17). The higher number of NMS is thought to be related to worsening of motor symptoms; however, it may vary and some symptoms can be seen in earlier stages or others in later stages. There was an increased prevalence of NMS with advancing age, similar to the study by de Souza A et al., (17). The increased prevalence of NMS in older patients could be due to physiological aging or comorbid conditions.
Depression, RBD, olfactory disturbance, visual disturbance, urinary urgency, sweating abnormality, constipation, vomiting, psychosis, and visual blurring significantly association with HY staging in our study. Kumar NSS et al., found that urinary disturbances, sexual problems, sleep related problems like difficulty to sleep, falls and double vision had significant statistical correlation with Hoehn and Yahr staging among the all NMS (18).
RBD and sexual dysfunction were found to be more prevalent in male patients while sweating abnormality were significantly more in female patients in our study. Mukhtar S et al., also found that sexual dysfunction was more prevalent in male patients as females are not comfortable discussing these issues (11). While, Martinez-Martin P et al., found that sweating disturbances were more prevalent in female population (26). RBD is found to be more prevalent in male patients in study by Zhou J et al., but a study by Haba-Rubio J et al., found no gender differences for RBD (27),(28). Restless Legs Syndrome (RLS) was more prevalent in age ≤40 years while olfactory disturbance, sexual dysfunction and constipation was significantly more prevalent in age >60 years. Similar to the present study, Breen KC et al., showed in their study that sexual dysfunction was more common in older PD patients whereas restless legs were common in young PD patients (29). Spica V et al., also found that olfactory disturbances and sexual dysfunction were significantly more prevalent in older PD patients while RLS were more prevalent in young patients (14).
All the previous studies from India show predominance of constipation, sleep disturbances, anxiety and urinary disturbances (15),(16),(17),(18),(19),(20),(21),(22),(23) (Table/Fig 3). There is variation in most common NMS and frequency of each NMS but pattern of NMS looks quite similar in all studies.
Limitations(s)
The study recruited a relatively small number of patients and was conducted at single centre, so there may be possibility of selection bias. The differentiation of NMS whether it is due to PD or the antiparkinsonism medication could not be done and also effect of co-morbid illnesses could not be estimated.
To conclude, non motor symptoms are highly prevalent in the present study and well recognition of these symptoms along with motor symptoms would help in diagnosis and management of PD patients. Though the prevalence of non motor symptoms in this study is similar and consistent with other studies, there are differences in the frequency of individual symptoms which may relate to cultural and geographic differences.
DOI: 10.7860/JCDR/2022/56861.16845
Date of Submission: Apr 04, 2022
Date of Peer Review: Jun 11, 2022
Date of Acceptance: Jun 28, 2022
Date of Publishing: Sep 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
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