Is India ready for Continuous Subcutaneous Apomorphine Infusion for Parkinson’s Disease 

Is India ready for Continuous Subcutaneous Apomorphine Infusion for Parkinson’s Disease 

HS Deva Kumar1,  Neeharika Sriram2, Srinivas Raju2, Anil Ramakrishna2, Prashanth LK1,2

1Center for Parkinson’s Disease and Movement Disorders, and 2Department of Neurology, Manipal Hospital, Miller’s Road, Bengaluru, India

Background:  Continuous Subcutaneous Apomorphine Infusion (CSAI) remains crucial in the management of moderately advanced Parkinson’s Disease (PD).

Objective: Audit of CSAI in Indian subjects.

Methodology: Clinical audit of case records of PD subjects with motor fluctuations who were initiated on CSAI pumps (Rusan Pharmaceuticals / Ever Pharma)

Results: Twenty three PD subjects (M:F- 11:12) who were on CSAI therapy were audited. The mean age was 61 ± 9 years (range : 45-78 years) and the mean duration of symptoms was  8.5 ± 5 years (range :1 – 22).  The indications were motor fluctuations / disabling dyskinesia (n=20) and suboptimal benefits with Deep Brain stimulation (DBS, n=3).  4/23 discontinued CSAI within one month due to autonomic dysfunction  (n=1, had pre-existing symptoms), lack of social support (n=1), suboptimal benefit (n=1) and discomfort of carrying pump (n=1).  Patients who were on CSAI for at least 1 month and above (n=19), the mean apomorphine infusion was 47±16  mg /day (28-54 mg/day).  The mean flow rate was 3.6±1.6 mg/hr.  The duration of apomorphine infusion varied from 12 to 16 hours. There was considerable improvement in the ON periods with reduction in motor fluctuations.  The subjective improvement on visual analog scale of 0 (No benefit) to 10 (Best benefit), the average score was 6.7 (range : 4-10).  The common adverse effects noted included skin nodules(n=9), drowsiness(n=3), weight loss(n=2), and variable dyskinesias(n=7).  Five patients are on CSAI for more than a year (12 months, 20 months, 35 months (n=2), and 40 months). 7/19 patients discontinued CSAI at various intervals (3 at 6 months, 1 at 9 months, 2 at 1 year, and 1 at 2 years) for varied reasons (weight loss -1, suboptimal benefits -3, financial constraints -1, personal choice -1, underwent DBS-1).Conclusion:  CSAI in India is currently an established treatment options with predictable effects over long durations. Most of the adverse effects are mild and manageable.  Patient education, support systems and better technologies would make CSAI a regular treatment option for PD in India.  

Are patients with Parkinson’s disease in India exercising enough?

Objective: To study the effect of exercise on parkinsonism symptoms, level of motivation inpatients with PD

Background: Regular exercise improves bradykinesia, gait and balance in Parkinson’s disease (PD)

Methodology: We conducted a questionnaire regarding exercise habits in 307 patients with PD

Results: In this study, we enrolled 307 patients with PD with mean age of 62±7.7 years(age range42-78 years)and male: female ratio 5:1. Presenting symptoms include rigidity (40%), tremors (29%), bradykinesia (24%) and balance issues (8%) and dyskinesias and falls (1% each). Patients reported subjective improvement in rigidity (21%), tremors (15%), gait (8%) and bradykinesia (2%) with regular exercise. Doctors advised exercise in 78% of patients at every visit, occasionally in 20% patients. Among PD patients, only 6% exercise regularly, 10% at times and 83% do not exercise at all[figure1]. There was no correlation between education level and exercise. Patients with early PD < 3 years duration exercised more than those with advanced disease. Out of the exercising patients, 54% started exercising after developing PD. Types of physical activity include walking (25%), brisk walking (2%), running/jogging (2%), yoga (4%), tennis (2%), strengthening exercises (2%) and stretching (8%) and 55% of patients practice multiple types of exercises together [figure 3]. Patients described improvement in general health, PD symptoms, someone regularly pushing to exercise, support groups as their motivational factors. Most patients (98%) couldn’t exercise due to their PD symptoms. There was no correlation between education level and exercise. Patients with early PD< 3 years duration exercised more than those with advanced disease [figure 2]. Most patients exercised for 31-60 min/day (50%). Overall,62% of patients felt that their PD symptoms improved with exercise, 31% didn’t notice any improvement and 8% were not sure of any improvement.

Conclusions: Exercise improved symptoms of PD in 62% patients with predominant improvement in rigidity in 40% cases. Only 16% of PD patients exercise indicating the need to increase emphasis and awareness about exercise.

Are Indians Geared Up  for the Healthcare expenses of Ageing Disorders?

Objective : To assess the knowledge of ageing related disorders and financial preparedness.

Background : India is at the brink of ageing related disorders and health care is a private affair.  

Methodology : An structured interview (Q1-30) to assess the knowledge of ageing disorders and health care preparedness was conducted.

Results : Responses of 214 (M:F=141:73) people with mean age of  65+/-12 yrs (Range: 18-91years) were analyzed.   The education background varied in the cohort (No-schooling – 3.3%, to Masters degree – 15.9%).  The cohort represented various geographical distribution (Villages – 9.8%, Towns – 5.1%, Districts – 15.4%, Metropolitan – 66.8% and Abroad – 2.3%) and Socio-economic backgrounds (Annual cumulative incomes – <1lakh – 14%, 1-10 Lakh – 40%, 41-50 lakhs – 35%, 51-100lakhs – 14%, >100lakhs – 4.2%).  More than 50% of ageing related disorders were not commonly recognized. Arthritis (86%) and Malignancy (4.2%) were the most and least acknowledged ageing disorders respectively. Monthly medication costs (76%) and spiritual health expenses (15.4%) were the most and least recognized healthcare expenses categories.  Only 4/10 ageing related health care expenses were recognized by >50% of respondents.  39% never specifically planned for ageing related health care.  The most common assumption for average cumulative savings required was 5-10 lakh INR (19%).  About 31%, didn’t have any idea of what should be a decent cumulative saving for health expenses.  The savings were either in the form of liquid cash (10%), Health insurance (21%),  or a mix (29%).  About 22% of respondents were clearly dependent on children for their health expenses.  Among the people who had insurances, only 21%, had their insurances specifically covered for chronic health expenses for out patient consults/therapies/daily medications.  In the subgroup of patients who were 50 years and over (83%), 67% of respondents were dissatisfied with their post retirement health care savings, and 33% claimed that their health care expenses broke into other savings.   Sub group analysis showed differences in knowledge and attitudes based on geographic and socio-economic status. 

Conclusion : There is paucity of gauge of ageing related disorders and categories where health care expenses occur in chronic conditions.  Albeit a general trend of preparation is present, but there are differences based upon geographical location and socioeconomic status. 

Pan India Registry for Progressive Supranuclear Palsy (PAIR-PSP)

Prashanth LK, Ravi Gupta, Soaham Desai, Sahil Mehta, Deepika Joshi, Niraj Kumar, Rukmini Mridula, Lulup Kumar Sahoo, Adreesh Mukherjee, Vijayshankar P, Sakthivel Murugan, Divya KP, Susinder Sundaram, Roopa Rajan, Ramesh Menon, Kuldeep Shetty, Praveena L. Samson, Syam Krishnan, Manjari Deshmukh, Pettarusp M Wadia, Charugulla Sandeep, Pankaj Aggarwal, Suvorit, Hrishikesh Kumar, Atanu Biswas, Vinay Goyal, Somashekar Seshagiri, Rupam Borgohain, Ramprasad VL. – Parkinson Research Alliance of India (PRAI)

Presented as abstract at the International Parkinsons and Movement Disorders Society Conference held in September 2022 at Madrid, Spain.


Progressive Supranuclear palsy (PSP) is a neurodegenerative disorder. Insights into its pathophysiology and newer clinical  phenotypes are  increasingly being recognized. There is a lack of data on the clinical phenotypes and genetics of PSP in India.


PAIR-PSP is a prospective multicenter registry, initiated across India, to provide an insight into novel clinical and genetic aspects of PSP. Currently fifteen clinical centers under Parkinson Research Alliance of India (PRAI) and Medgenome Labs are participants  of this consortium, with a target to recruit 1000 PSP subjects. 


Clinical Phenotype: 

Currently 142 PSP subjects (M:F-53:89) have been enrolled, (mean age, 65±8 years) from across India.  The diagnostic certainty varied on MDS-PSP criteria with 75% having met Probable PSP, 19% with Possible PSP, and 5% were suggestive of PSP.  The mean age at onset of symptoms was 62 years with mean duration of 40 months.  Consanguineous parentage was noted in 7% , and family history of similar symptoms in 3%.  Clinical presentation patterns varied – motor presentations (91%), behavioral (7%) and cognitive features (2%).  Among the initial presenting symptoms the most common were: Falls (23%), slowness in ADL (19%), Tremors (14%), Poor balance (11%), change in gait (10%). The clinical phenotypes include PSP-RS (29%), PSP with predominant CBS (21%), PSP with predominant parkinsonism (18%), PSP with frontal presentation (11%), PSP with predominant postural instability (12%), PSP with progressive gait freezing (7%),PSP with predominant ocular motor dysfunction, and PSP with predominant speech/language disorder (1%). The mean total MDS-NMS score was 59.6 and total PSP-RS was 41.1±17.2 (Range:8-89).  The PSP-CDS score was 10.7±4.1 (Range 2-21).

Genetic Works : Genotyping has been done using Illumina Global Screening Array version 3. The GWAS analysis was done using PLINK 1.9. The GWAS analysis revealed 62 markers passing a genome-wise threshold of 1e-08. Further we performed the GWAS results annotation using the FUMA tool. The MAGMA module for gene enrichment results identified genes known in several functional pathways and are expressed in the brain (SYNGR4, TTL11 etc). Further analysis and interpretations are in progress. 


This large ongoing clinical registry of PSP  gives valuable  insights into the clinical phenotypes, socio-demographic variations and genetic aspects of the disease in the Indian subcontinent.  

Genetics Of Parkinson’s in India – Young Onset Parkinson’s Disease (GOPI-YOPD) : Genetics of Juvenile, Young, and Early Onset Parkinson’s Disease

Prashanth LK, Vinay Goyal, Thenral S Geetha, Ramesh Menon, Rukmini Mridula Kandadai, Hrishikesh Kumar, Rupam Borgohain, Adreesh Mukherjee, Pettarusp M Wadia, Ravi Yadav, Soaham Desai, Niraj Kumar, Ravi Gupta, Sakthivel Murugan, Atanu Biswas, Pramod K Pal, Merina Oliver, Susinder Sundaram, Manjari Deshmukh, Akshi Bassi, Charugulla Sandeep, Nitin Mandloi, Uday Muthane,  Shymal K Das, Somasekar Seshagiri, Vedam L Ramprasad, – Parkinson Research Alliance of India (PRAI)

Presented as abstract at the International Parkinsons and Movement Disorders Society Conference held in September 2022 at Madrid, Spain.

Genetics of Parkinson’s in India – Young Onset Parkinson’s Disease – Poster presented at IPMDS, Madrid, Spain, September 2022.


To determine the genetic and demographic patterns of juvenile-onset (JOPD, <20 years), young-onset (YOPD, 20-40 years), and early onset (EOPD, 40-50 years) Parkinson’s disease (PD) in India.


GOPI-YOPD is a prospective multicenter, collaborative study to analyze clinical and genetic patterns of JOPD, YOPD, and EOPD1.  Genetic data of 662 samples ( Whole Genome Genotyping = 572, Whole Exome Sequencing =572; Whole Genome Sequencing=90) were analyzed. Rare and known pathogenic and risk SNVs/InDels and CNVs in primary PD genes (11), risk PD genes (12), and additional PD genes (40) were analyzed.


Clinical cohort: A total of 668 subjects (M:F 455:213) were recruited with a mean age at onset of 38.7 ± 8.1 years. The mean duration of symptoms at the time of study was 8 ± 6 years. Fifteen percent had a family history of PD and 13% had consanguinity. JOPD had the highest consanguinity rate (53%). YOPD and JOPD cases had a higher prevalence of consanguinity, dystonia, and gait and balance issues compared to those with EOPD. In relation to nonmotor symptoms, panic attacks and depression were more common in YOPD and sleep-related issues more common in EOPD subjects. Overall, dyskinesias were documented in 32.8%. YOPD subjects had a higher frequency of dyskinesia than EOPD subjects (39.9% vs. 25.5%), but they were first noted later in the disease course (5.7 vs. 4.4 years).

Genetic findings:  Among PD cases we prioritized 617 variants in 402 samples. Pathogenic and likely pathogenic variants were identified in 5.1% and 4.7% PD cases respectively. In a large number of PD cases (51%) variants of uncertain significance (VUS) were identified. Risk variants were identified in another 5.9% of the PD cases. The most frequent genes with pathogenic variants included PRKN (n=36, 5.4%), PLA2G6 (n=12, 1.8%), PINK1(n=8, 1.2%), CHCHD2 (n=4, 0.6%),VPS13C(n=4), PANK2 (n=3), SPG11 (n=3), SYNJ1 (n=3), ATP13A2 (n=2), FBX07 (n=1), MAPT (n=1), PRRT2 (n=1), WDR45 (n=1), GCH1 (n=1).  Many risk variants/VUS were identified in GBA (n= 59 / 8.9%) and LRRK2 (n=27 /4.1%). In several PD cases we found homozygous deletion in the PRKN gene (n=20 / 3%). Overall, the diagnostic yield is found to be high in JOPD (43.7%), followed by YOPD (10.9%) and EOPD (4%). We also generated PD polygenic risk scores (PRS) using SARGAM genotyping array data. PRS revealed that the PD cases with no prioritized pathogenic/likely pathogenic variants have significantly (p-value < 0.001) higher PD PRS as compared to control population and PD with prioritized pathogenic/likely pathogenic variants. 


This large cohort shows differing genetic patterns in JOPD, YOPD, and EOPD cases. PRKN gene is the commonest pathogenetic variant and has large pathogenetic deletions. In addition to pathogenic mutations, a high percentage of VUS indicates untapped genetic understanding. The PRS carries diagnostic utility for possible regular use. 


  1. Kukkle PL, Goyal V, Geetha TS, Mridula KR, Kumar H, Borgohain R, Mukherjee A, Wadia PM, Yadav R, Desai S, Kumar N, Gupta R, Biswas A, Pal PK, Muthane U, Das SK, Quinn N, Ramprasad VL; Parkinson Research Alliance of India (PRAI). Clinical Study of 668 Indian Subjects with Juvenile, Young, and Early Onset Parkinson’s Disease. Can J Neurol Sci. 2022 Jan;49(1):93-101. doi: 10.1017/cjn.2021.40.