Comprehensive Care Centre for Movement disorders (CCCMD)

INTRODUCTION

“Movement Disorders” are a group of neurological ailments manifesting either as “paucity” of movements (slowness of movements, often associated with stiffness of muscles and loss of balance – also called “Parkinsonism”) or unwanted excess of movements without the individual’s control (Involuntary movements). Movement disorders are not uncommon; “Parkinson’s disease” is one of the most widely known diseases which cause a movement disorder. Movement disorders generally result from abnormal functioning of “basal ganglia” - which are structures located deep within the brain. Stroke or other neurological diseases which cause weakness of muscles or ‘paralysis’, are not classified as ‘movement disorders’ though they also impair movements.

The Movement Disorders Section of the Neurology Department of SCTIMST started its functioning in July 1996. The Comprehensive Care Centre for Movement Disorders (CCCMD) at SCTIMST was established in 1998 in collaboration with the Department of Neurosurgery and is one of the first of its kind in India. The aim of the Centre is to provide the most advanced forms of medical and surgical treatment and ancillary services to patients afflicted with various movement disorders. The centre also trains post-graduate students in Neurology in the diagnosis and treatment of movement disorders, offers post-doctoral fellowship courses and PhD programs (Please click here for more information on PDF course in Movement Disorders and PhD Programs) and conducts research aimed at improved diagnosis and treatment of movement disorders. CCCMD is also actively involved in the dissemination of scientific knowledge.

Inauguration of the Comprehensive Care Centre for Movement Disorders, by Sri EK Nayanar, Chief Minister of Kerala.

Sri Arif Mohammad Khan, Hon’ble Governor of Kerala, inaugurated “MDSICON 2020”, an international conference of Movement Disorder specialists organised by the CCCMD of SCTIMST in 2020. The conference was attended by nine international faculty from the USA, Canada, UK, France and Australia; around 80 national faculty and more than 550 delegates from all over India and nearby SAARC countries.

CLINICAL SERVICES

MOVEMENT DISORDERS CLINIC

The Comprehensive Care Centre for Movement Disorders (CCCMD) conducts a weekly movement disorder clinic every Monday, dedicated to the follow-up treatment of all cases of Movement Disorders referred to this centre. Kindly note that the Movement Disorders Clinic does not register new cases directly and is dedicated to review / follow-up patients. Fresh patients referred for evaluation and treatment of movement disorders and coming to SCTIMST for the first time are registered as new cases in the general neurology outpatient clinic conducted by the faculty of CCCMD on Wednesdays and Thursdays and will subsequently be transferred to Movement Disorder clinic for follow-up. For first-time consultations for patients with Movement Disorders, kindly contact the Hospital Information Centre (0471-2524621) or CCCMD directly (0471-2524262) and fix up an appointment to register and consult in Neurology OP on Wednesdays or Thursdays). [Please click here for information on how to take appointment for consultation]

The common movement disorders referred to this clinic include Parkinson’s disease (PD) (Please click here to know more about Parkinson’s disease) other Parkinsonian disorders (“Atypical” Parkinsonism, Vascular Parkinsonism etc), which mimic Parkinson’s disease, other diseases causing tremor, various forms of Dystonia (click here to know more about dystonia ), Tics, Chorea, Myoclonus etc. Patients with movement disorders who are not controlled with optimal medical therapy are selected for surgical treatment from the movement disorders clinic. (Please click here to know more about surgical treatment of Movement Disorders) The clinic also provides counselling, education and neuropsychological and psychiatric evaluation and support. Physiotherapists attached to the clinic provide guidance on exercise regimens, avoidance of falls, improvement of mobility, walking aids etc. The clinic has 2000 to 2400 annual patient visits. Awareness programs are organized periodically for the patients and care givers to know more about their disease and the treatment options.

CCCMD regularly conducts awareness programs for patients with Parkinson’s disease, their care givers, and the general public, in connection with the World Parkinson day (April 11) every year

BOTULINUM TOXIN CLINIC

Botulinum Toxin Injections are used for the treatment of a wide variety of movement disorders. The program offers freehand and EMG-guided Botulinum toxin for all Movement Disorder indications, through the clinic. The centre has vast experience in Botulinum Toxin therapy and round 300-400 treatment sessions are conducted annually. (Please click here to know more about Botulinum Toxin Treatment) Botulinum toxin treatment is offered to patients with diseases like hemifacial spasm, blepharospasm, various forms of dystonia like neck dystonia, jaw dystonia and Writer’s cramp, and conditions causing “spasticity” including cerebral palsy and spasticity occurring after stroke.

Electromyogram is used to target the muscles correctly for Botulinum Toxin injections, in complex dystonic conditions.

MOVEMENT DISORDER SURGICAL PROGRAM

The CCCMD is one among the pioneers of Deep Brain Stimulation (DBS) surgery for Parkinson’s disease in India, with the first procedure of Globus Pallidus deep brain stimulation performed in 1999. It is currently one of the leading centres in this field in the country in the Government sector. Deep Brain Stimulation surgery is done under image- and micro-electrode recording (MER) guidance (Surgical Planning and Neuro-navigation systems). DBS treatment is also offered to patients with intractable Tremor and Dystonia. (Click here to know more about DBS) Those who are interested may also go through the information brochures in English and Regional Languages, available in the drop-down menu on the taskbar above under “Information for patients”.

Deep Brain Stimulation is an advanced stereotactic Neurosurgical procedure done for Parkinson’s disease and other selected movement disorders

The centre also undertakes MR-guided radiofrequency lesioning surgeries for Movement disorders. In these surgeries (e.g., Thalamotomy, Pallidotomy), a carefully planned “lesion” is made in certain crucial areas of the brain, so as to relieve the symptoms of movement disorders. These are generally considered when the patients cannot afford DBS, or there are some contra-indications for DBS surgery. A multidisciplinary dedicated team is involved in the systematic workup to assess suitability for DBS surgery, surgical planning, post-operative care and long-term management of patients who undergo DBS. Until 2023, the centre has performed over 500 surgeries for medically refractory Movement Disorders, including more than 300 DBS surgeries. The faculty have presented the results at several international meetings and published their experience in reputed international journals (Please see below, under “Selected Publications”).

PERMANENT FACULTY AND STAFF

Movement Disorder Specialists

• Dr. Syam K.
  Professor
  
• Dr. Divya K. P.
  Additional Professor
  
• Dr. Asish Vijayaraghavan
  Assistant Professor
  

Stereotactic and Functional Neurosurgeons

• Dr. Krishna Kumar K.
  Professor
  

Psychologist / Public Relations Officer

Sri. S. Gangadhara Sarma. MA, PGDip
            Phone: +91-471-2524262(office), +91-9387774689 (Mobile Phone)
            E-mail: mov@sctimst.ac.in

APPOINTMENT FOR CONSULTATIONS - FOR PATIENTS

New patients with Movement Disorders who wish to consult the Comprehensive Care Centre for Movement Disorders, have to be registered in the Neurology OP clinic on Wednesdays or Thursdays. Such new patients (patients who plan to consult Parkinson's and Movement Disorders services of SCTIMST, for the first time) can take appointment for the same in the following ways

1. By calling the information desk of the Neurology Registration Counter. Kindly ask for appointment on Thursdays (to consult Dr Syam K) or Wednesdays (to consult Dr Divya KP). The Neurology Registration Counter can be called directly (Phone Number 0471-2524621) or through the Hospital’s main telephone line (0471-2443152 – you will be attended by the reception staff, who will forward the call to the Neurology Registration Counter [Extension 4621], at request). Kindly call on working days, during working hours.
2. By contacting the PRO (Mr Gangadhara Sarma) of CCCMD directly. Kindly call 0471-2524262, on working days, between 9 AM and 4 PM. You can also contact through email (mov@sctimst.ac.in) or on Cell Phone (9387774689; kindly call only during working hours)
3. Through the Medical Records Department (mrd@sctimst.ac.in)

The Movement Disorders Clinic on Mondays is solely dedicated for further follow-up of patients who have been registered and evaluated at least once on Wednesday or Thursday OPD. Appointment for follow up in Movement Disorders Clinic will be given after the initial registration and assessment in the Neurology OP clinic on Wednesdays and Thursdays.

ACADEMIC AND RESEARCH ACTIVITIES

The CCCMD has been involved in several research projects addressing the biological mechanisms underlying Parkinson’s disease and other movement disorders, clinical aspects and treatment. The centre has also participated in several international clinical trials testing new drugs for Parkinson’s disease and dystonia. In addition, CCCMD is also involved in biomedical technology and medical device development, collaborating with the Biomedical Technology Wing of the institute and other national research centres. CCCMD has won research grants from international and national funding agencies like the Dystonia Medical Research Foundation, the Michael J Fox Foundation (USA), the Indian Council of Medical Research (ICMR), the Department of Biotechnology (DBT), Government of India and the Department of Science and Technology (DST), Government of India.

The following is a list of some of the recent research projects undertaken by CCCMD

1. Long-term follow-up of cognitive functions in patients with Parkinson’s disease (Funded by the ICMR)
2. Alterations in the intestinal bacterial flora of patients with Parkinson’s disease, and their relationship with metabolomic profile (Collaboration with Cochin University of Science and Technology; funded by ICMR)
3. Genome-wide Association study to map the Genetic architecture of Indian patients with Parkinson’s disease (International Multi-centre Collaborative Project, funded by Michael J Fox Foundation, USA; CCCMD of SCTIMST has been one among the nodal centres)
4. Diagnosis and quantification of tremor subtypes in various tremor disorders, using artificial intelligence (Collaboration with AIIMS New Delhi and NIMHANS, Bangalore; funded by the Department of Biotechnology, Government of India)
5. Clinical registry of movement disorders (Funded by the Movement Disorders Society of India)
6. Quantitative Susceptibility Mapping (an advanced MRI technique) in the diagnosis of atypical Parkinsonian disorders (Funded by the Department of Biotechnology, Govt. of India)
7. LRRK2 gene variants in Indian patients with Parkinson’s disease (Funded by the Michael J Fox Foundation, USA)
8. Encoding of interhemispheric interactions in mirror dystonia: a window to the physiology of dystonia (Funded by the Dystonia Medical Research Foundation).
9. Effect of Yoga on motor cortex plasticity, motor learning and motor deficits of Parkinson’s disease (Funded by the Department of Science and Technology, Government of India)
10. Cerebellar control of synaptic depotentiation at the primary motor cortex and implications for levodopa induced dyskinesias.
11. Resting state connectivity between the basal ganglia and cerebellum in health and Parkinson’s disease: a combined functional magnetic resonance and diffusion tensor imaging study.
12. Study of factors that promote aggregation of alpha synuclein and their influence on the clearance mechanisms: relevance to sporadic Parkinson's disease.
13. Effect of Subthalamic Nucleus-Deep Brain Stimulation surgery on impulsivity in Parkinson’s Disease.
14. Contribution of DRD3 genetic polymorphisms to impulsivity in Parkinson’s disease patients.
15. Non-motor symptoms and non-motor fluctuations in Parkinson’s disease- prevalence and effects of Deep Brain Stimulation

POST DOCTORAL FELLOWSHIP AND PHD PROGRAMS

Post-Doctoral Fellowship

Comprehensive Care Centre for Movement Disorders, Sree Chitra Tirunal Institute for medical Sciences and Technology, Kerala, currently offers 1-year Post-Doctoral Fellowship Program in Movement Disorders. The programs begin on the 1^st of January every year. Applications for the January admission are invited by the Institute in September / October (The aspirants are advised to visit the Institute website during this period for information) of the previous year and notified through national dailies and the institute’s website.

Prerequisite for applicants: Postdoctoral fellowship positions are open to candidates who are interested in movement disorders and have 1) a doctoral degree of DM (Neurology) or its equivalent (like DNB Neurology) and 2) registration with the central/ state medical council.

Training includes:

1. Participation in the Movement Disorders Clinic catering to patients with the full range of movement disorders
2. Training in the diagnosis and protocol-based treatment of various movement disorders
3. Video sessions of unusual and interesting disorders and their diagnosis and management.
4. Active participation in the botulinum toxin clinic with opportunity for hands-on experience in a wide variety of conditions including hemifacial spasm, all dystonic conditions (Cervical dystonia, oro-mandibular and other types of cranial dystonia, Writer’s cramp and other types of limb dystonia etc.), cerebral palsy and spasticity resulting from other causes.
5. Exposure to the pre-operative assessment, intra-operative monitoring, post-operative care and follow-up of patients undergoing surgical procedures like Deep Brain Stimulation, stereotactic thalamotomy and pallidotomy. Training in Deep Brain Stimulation programming.
6. Opportunity to participate in clinical research and publish research papers.

For more details on PDF program, please contact:
E-mail: drsyam@sctimst.ac.in
Tel: 0471-2524268

PhD Programs

Faculty of CCCMD are approved PhD guides and guide PhD students in Movement Disorders-related basic science and clinical topics. Kindly contact the Academic Division of the Institute for more information on eligibility and admission to PhD program.

SELECTED PUBLICATIONS

1. Krishnan S, George SS, Radhakrishnan V, Raghavan S, Thomas B, Thulaseedharan JV, Puthenveedu DK. Quantitative susceptibility mapping from basal ganglia and related structures: correlation with disease severity in progressive supranuclear palsy. Acta Neurol Belg. 2023 Aug 14. doi: 10.1007/s13760-023-02352-5. Online ahead of print. PMID: 37580639
2. Vijayaraghavan A, Urulangodi M, Ajit Valaparambil K, Sundaram S, Krishnan S Movement Disorders in GRIA2-Related Disorder – Expanding the Genetic Spectrum of Developmental Dyskinetic Encephalopathy. Mov Disord Clin Pract 2023 Jun 12;10(8):1222-1224. doi: 10.1002/mdc3.13797. eCollection 2023 Aug.
3. Radhakrishnan V, Gallea C, Valabregue R, Krishnan S, Kesavadas C, Thomas B, James P, Menon R, Kishore A. Cerebellar and basal ganglia structural connections in humans: Effect of aging and relation with memory and learning. Front Aging Neurosci. 2023 Jan 26;15:1019239. doi: 10.3389/fnagi.2023.1019239. eCollection 2023.PMID: 36776439
4. Patel Khushboo Subhas, Vijayaraghavan Asish, Krishnan Syam, Puthenveedu Divya Kalikavil. Huffing and puffing sign in functional axial jerks with secondary gait impairment. Annals of Movement Disorders. 6(1):30-32, Jan-Apr 2023.
5. Cherian A, Vijayaraghavan A, K.P. Divya, Krishnan S. Botulinum neurotoxin for the treatment of movement disorders: Practical considerations. Annals of Movement Disorders. 5(1):38-48, Jan-Apr 2022.
6. Patel K, Vijayaraghavan A, Krishnan S, Puthenveedu DK, Cherian A. Hemifacial spasm resulting from vertebrobasilar dolichoectasia in three siblings: A case report. Annals of Movement Disorders. 5(3):202-204, Sep-Dec 2022.
7. Kishore A, James P, Rajeswari P, Sarma G, Krishnan S, Meunier S, Popa T. Depotentiation of associative plasticity is intact in Parkinson's disease with mild dyskinesia. Parkinsonism Relat Disord. 2022 May 1;99:16-22. doi: 10.1016/j.parkreldis.2022.04.019.
8. Saraf U, Chandarana M, Divya KP, Krishnan S (Corresponding author). Oromandibular dystonia – a systematic review. Ann Indian Acad Neurol. 2022 Jan-Feb;25(1):26-34. doi: 10.4103/aian.aian_242_21. PMID: 35342238
9. Kesavapisharady K, Krishnan S. Role of lesioning procedures in the Deep Brain Stimulation era. In: Paniker D et al. (Editors). Progress in Clinical Neurosciences Volume, First Edition. Thieme Medical and Scientific Publishers, Mumbai, 2022. Page 135-138. ISBN 978-93-90553-94-5.
10. Jain K, Ramesh R, Krishnan S (Corresponding author), Kesavapisharady K, Divya KP, Sarma SP, Kishore A. Cognitive outcome following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease-a comparative observational study in Indian patients. Acta Neurol Belg. 2022 Apr;122(2):447-456. doi: 10.1007/s13760-021-01778-z. PMID: 34448152
11. Raina A, Rajan R, Sarma G, Krishnan S, Kesavapisharady K, Kishore A. Learning from negative consequences is impaired by STN-DBS and levodopa in Parkinson’s disease. Ann Mov Disord 2021;4:66-72.
12. Krishnan S. Autoimmune Movement Disorders. In: Ranganathan L N, Krishnan M, Iyer RS (Editors). Monograph Immune Mediated Neurological Disorders, 1st Edition, Jaypee Brothers Publishers, New Delhi, 2022. Page 67-75. ISBN: 9789352704514.
13. Asish Vijayaraghavan, Patel Khushboo Subhash, Divya KP, Syam Krishnan. Tremor disorders In: Ranganathan L N (Editor). Reviews in Neurology 2020. Movement Disorders: Indian Perspective (Published in 2021), Wolters Kluwer (India) Pvt. Ltd., New Delhi, 2021. Page 94-105. ISBN: 978-93- 90612-88-8. ISSN: 0971-5924.
14. Vijayaraghavan A, Cherian A, Kalikavil Puthenveedu D, Krishnan S, Pavuluri H. Anti Zic4 Paraneoplastic Neurological Syndrome Presenting as Oscillopsia. Mov Disord Clin Pract. 2021 Sep 6;8(7):1134-1136. doi: 10.1002/mdc3.13331.
15. Saraf UU, Jose J, Krishnan S, Sreedharan SE. Mucopolysacharidosis Type I Presenting as Bipolar Affective Disorder: A Case Report. Neurol India 2021;69:1753-5.
16. Kishore A, James P, Popa T, Thejaus A, Rajeswari P, Sarma G, Krishnan S, Meunier S. Plastic responsiveness of motor cortex to paired associative stimulation depends on cerebellar input. Clin Neurophysiol. 2021 Aug 5;132(10):2493-2502. doi: 10.1016/j.clinph.2021.06.029. PMID: 34454278.
17. Chandarana MV, Cherian A, K P D, Krishnan S, Glenda M, Saraf U. Writer's cramp presentation of Woodhouse-Sakati Syndrome- "out of the woods" Can J Neurol Sci. 2021 Aug 24:1-9. doi: 10.1017/cjn.2021.201. PMID: 34425922.
18. Chandarana M, Saraf U, Divya KP, Krishnan S (Corresponding author). Huntington’s disease presenting as adult-onset Tourettism: a case report. Ann Mov Disord 2021;4:153-6.
19. Krishnan S (Corresponding author), Shetty K, Puthanveedu DK, Kesavapisharady K, Thulaseedharan JV, Sarma G, Kishore A. Apraxia of Lid Opening in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease-Frequency, Risk Factors and Response to Treatment. Mov Disord Clin Pract. 2021 Apr 12;8(4):587-593. doi: 10.1002/mdc3.13206. PMID: 33981792.
20. Cherian A, Chandarana M, Susvirkar AA, Divya KP, Saraf UU, Krishnan S. Abnormal Saccades Differentiate Adolescent Onset Variant Ataxia Telangiectasia from Other Myoclonus Dystonia. Ann Indian Acad Neurol. 2021 Jul- Aug;24(4):630-632.
21. Saraf U, Chandarana M, Puthenveedu DK, Kesavapisharady K, Krishnan S (Corresponding author), Kishore A. Childhood-Onset Dystonia Attributed to Aicardi-Goutières Syndrome and Responsive to Deep Brain Stimulation. Mov Disord Clin Pract. 2021 Apr 19;8(4):613-615. doi: 10.1002/mdc3.13205. PMID: 33981798.
22. Mitesh Chandarana, Udit Saraf, Divya K.P., Krishnan S (Corresponding Author), Asha Kishore. Myoclonus – a review. Ann Indian Acad Neurol. 2021 May-Jun;24(3):327-338. doi: 10.4103/aian.AIAN_1180_20. PMID: 34446993.
23. Saraf U, Chandarana M, Divya KP, Krishnan S (Corresponding author). ADCY5-related dyskinesia with myoclonus-dystonia syndrome: Clues to diagnosis. Ann Mov Disord 2021;4:86-8.
24. Cherian A, KP Divya, Paramasivan NK, Krishnan S. Pearls and Oysters: Levodopa Responsive Adult NCL (Type B Kufs Disease) Due to CLN6 Mutation. Neurology. 2021 Apr 19:10.1212/WNL.0000000000011997. doi: 10.1212/WNL.0000000000011997. Online ahead of print.
25. Mahale RR, Krishnan S, Divya KP, Jisha VT, Kishore A. Gender differences in progressive supranuclear palsy. Acta Neurol Belg. 2021 Feb 17. doi: 10.1007/s13760-021-01599-0. PMID: 33595832.
26. Mahale RR, Krishnan S, Divya KP, Jisha VT, Kishore A. Subtypes of PSP and prognosis: A retrospective analysis. Ann Ind Acad Neurol 2021. DOI: 10.4103/aian.AIAN_611_20.
27. Zafar SM, Rajan R, Krishnan S, Kesavapisharady K, Kishore A. Interleaved Stimulation for Freezing of Gait in Advanced Parkinson's Disease. Neurol India. 2021 Mar-Apr;69(2):457-460. doi: 10.4103/0028-3886.314570. PMID: 33904475.
28. Cherian A, Paramasivan NK, Puthanveedu DK, Krishnan S, Nair AR. Generalized Chorea Due to Secondary Polycythemia Responding to Phlebotomy. J Mov Disord. 2021 Jan;14(1):89-91. doi: 10.14802/jmd.20081. PMID: 33121224.
29. Cherian A, Divya KP. Genetics of Parkinson’s disease. Acta Neurol Belg. 2020 Dec;120(6):1297-1305. doi: 10.1007/s13760-020-01473-5
30. Krishnan S, Kishore A. Parkinson’s disease. In: Shirly G, S K Kunnath, Anne Varghese, Vinitha Mary George (Editors) Disability: An Overview, In the Context of the Rights of Persons with Disabilities (RPwD) Act, 2016. 1st Edition, Published by NISH (National Institute of Speech and Hearing), Thiruvananthapuram, 2019. Page 241-260. ISBN: 9788193985007
31. Krishnan S, Pisharady KK, Rajan R, Sarma SG, Sarma PS, Kishore A. Predictors of dementia-free survival after bilateral subthalamic deep brain stimulation for Parkinson's disease. Neurol India. 2019 Mar-Apr;67(2):459-466. doi: 10.4103/0028-3886.258056.
32. Shetty K, Krishnan S (Corresponding author), Thulaseedharan JV, Mohan M, Kishore A. Asymptomatic Hearing Impairment Frequently Occurs in Early-Onset Parkinson's Disease. J Mov Disord. 2019 May;12(2):84-90. doi: 10.14802/jmd.18048.
33. Kishore A, Ashok Kumar Sreelatha A, Sturm M, von-Zweydorf F et al Understanding the role of genetic variability in LRRK2 in Indian population. Mov Disord. 2018 Nov 28. doi: 10.1002/mds.27558. [Epub ahead of print]. PMID: 30485545
34. Rajan R, Krishnan S, Sarma G, Sarma SP, Kishore A. Dopamine Receptor D3 rs6280 is Associated with Aberrant Decision-Making in Parkinson's Disease. Mov Disord Clin Pract. 2018 Jul 19;5(4):413-416. doi: 10.1002/mdc3.12631. eCollection 2018 Jul-Aug. PMID: 30363458
35. Krishnan S, Pisharady KK, Divya KP, Shetty K, Kishore A. Deep brain stimulation for movement disorders. Neurol India. 2018 Mar-Apr;66(Supplement):S90-S101. doi: 10.4103/0028-3886.226438. PMID: 29503331
36. Popa T, Hubsch C, James P, Richard A, Russo M, Pradeep S, Krishan S, Roze E, Meunier S, Kishore A. Abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions in cervical dystonia. Sci Rep. 2018 Feb 2;8(1):2263. doi: 10.1038/s41598-018-20510-1.
37. Caligiore D, Pezzulo G, Baldassarre G, Bostan AC, Strick PL, Doya K, Helmich RC, Dirkx M, Houk J, Jörntell H, Lago-Rodriguez A, Galea JM, Miall RC, Popa T, Kishore A, Verschure PF, Zucca R, Herreros I. Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex. Cerebellum. 2017 Feb;16(1):203-229. doi: 10.1007/s12311-016-0763-3.
38. Krishnan S, Pisharady KK. Surgical treatment of levodopa-induced dyskinesia in Parkinson’s disease. Ann Indian Acad Neurol 2017;20:199-206.
39. Nandakumar S, Vijayan B, Kishore A, Thekkuveettil A. Autophagy enhancement is rendered ineffective in presence of α-synuclein in melanoma cells. J Cell Commun Signal. 2017 Jul 26. doi: 10.1007/s12079-017-0402-x. [Epub ahead of print]
40. Rajan R, Popa T, Quartarone A, Ghilardi MF, Kishore A. Cortical plasticity and levodopa-induced dyskinesias in Parkinson's disease: Connecting the dots in a multicomponent network. Clin Neurophysiol. 2017 Jun;128(6):992-999.
41. Kishore A, James P, Krishnan S, Yahia-Cherif L, Meunier S, Popa T. Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease. Parkinsonism Relat Disord. 2017 Feb;35:55-62.
42. Mandali A, Chakravarthy VS, Rajan R, Sarma S, Kishore A. Electrode position and current amplitude modulate impulsivity after subthalamic stimulation in Parkinson’s disease - A computational study. Front Physiol. 2016 Nov 29;7:585. e-Collection 2016.
43. Krishnamoorthy S, Rajan R, Banerjee M, Kumar H, Sarma G, Krishnan S, Sarma S, Kishore A. Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients. Parkinsonism Relat Disord. 2016 Jun 15. pii: S1353-8020(16)30217-6. doi: 10.1016/j.parkreldis.2016.06.005
44. Rajan R, Krishnan S, Kesavapisharady K, Kishore A. Malignant subthalamic nucleus deep brain stimulation withdrawal syndrome in Parkinson’s disease. Movement Disorders Clinical Practice 2016. Published online in Wiley InterScience (www.interscience.wiley.com). DOI:10.1002/mdc3.12271
45. Krishnan S, Prasad S, Pisharady KK, Sarma G, Sarma SP, Kishore A, The decade after subthalamic stimulation in advanced Parkinson's disease: A balancing act., Neurol India. , 2016, 64(1):81-9, http://www.ncbi.nlm.nih.gov/pubmed/26754997
46. Krishnan S, Justus S, Meluveettil R, Menon RN, Sarma SP, Kishore A., Validity of Montreal Cognitive Assessment in Non-English speaking patients with Parkinson's disease., Neurol India. , 2015, 63(1):63-7., http://www.ncbi.nlm.nih.gov/pubmed/25751471
47. Kishore A, Popa T. Cerebellum in levodopa-induced dyskinesias: the unusual suspect in the motor network. Front Neurol. 2014 ; 18;5:157
48. Kishore A, Popa T, James P, Yahia-Cherif L, Backer F, Varughese Chacko L, Govind P, Pradeep S, Meunier S. Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation. Neurobiol Aging. 2014;35:2541-51.
49. Kishore A, Meunier S, Popa T. Cerebellar influence on motor cortex plasticity: behavioral implications for Parkinson's disease. Front Neurol. 2014; 6;5:68.
50. Syambabu Chandran, Syam Krishnan, Gangadhara Sarma S, Sankara Sarma P, Asha Kishore., Gender influence on selection and outcome of deep brain stimulation for Parkinson's disease., Ann Indian Acad Neurol, 2014, 17:66-70., http://www.ncbi.nlm.nih.gov/pubmed/24753663
51. Kishore A, Popa T, Balachandran A, Chandran S, Pradeep S, Backer F, Krishnan S, Meunier S, Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson's disease: clues from dyskinetic patients., Cereb Cortex., 2014, 24(8):2055-67, http://www.ncbi.nlm.nih.gov/pubmed/23535177
52. Hubsch C, Roze E, Popa T, Russo M, Balachandran A, Pradeep S, Mueller F, Brochard V, Quartarone A, Degos B, Vidailhet M, Kishore A, Meunier S. Defective cerebellar control of cortical plasticity in writer's cramp. Brain. 2013 Jul;136(Pt 7):2050-62. doi: 10.1093/brain/awt147
53. Sarathchandran S, Soman S, Sarma SG, Krishnan S, Kishore A., Impulse control disorders in Indian patients with Parkinson?s disease., Mov Disord, 2013, 28: 1901-1902., http://www.ncbi.nlm.nih.gov/pubmed/23801595
54. Kishore, Asha; Popa, Traian; Velayudhan, Balu; Joseph, Thomas; Balachandran, Ammu; Meunier, Sabine, Acute dopamine boost has a negative effect on plasticity of the primary motor cortex in advanced Parkinson's disease., Brain, 2012, http://www.ncbi.nlm.nih.gov/pubmed/22609619
55. Popa, T; Velayudhan, B; Hubsch, C; Pradeep, S; Roze, E; Vidailhet, M; Meunier, S; Kishore, A, Cerebellar Processing of Sensory Inputs Primes Motor Cortex Plasticity., Cereb Cortex, 2012, , http://www.ncbi.nlm.nih.gov/pubmed/22351647
56. Krishnan, Syam; Sarma, Gangadhara; Sarma, Sankara; Kishore, Asha, Do nonmotor symptoms in Parkinson's disease differ from normal aging?, Mov Disord, 2011, 26; 2110-3, http://www.ncbi.nlm.nih.gov/pubmed/21661056
57. Kishore, Asha; Joseph, Thomas; Velayudhan, Balu; Popa, Traian; Meunier, Sabine, Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson's disease., Clin Neurophysiol, 2011, , http://www.ncbi.nlm.nih.gov/pubmed/21945457
58. Kishore A, Rao R, Krishnan S et al., Long term stability of effects of subthalamic stimulation in Parkinson?s disease: Indian experience., Mov Disord. , 2010, 25:2438-44., http://www.ncbi.nlm.nih.gov/pubmed/20976738
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INFORMATION FOR PATIENTS AND PUBLIC

PARKINSON'S DISEASE

What is Parkinson’s disease (PD)?

Brain is an organ subserving a wide variety of functions like perception of sensations, initiation, control and co-ordination of movements of the body, maintenance of consciousness, intellectual functions etc.

Parkinson’s disease is a “degenerative disease” affecting the brain. As you may be aware, brain is made up of billions of very tiny nerve cells, or “neurons”. “Degenerative disease” (Also called “neuro-degenerative disease”) is the name given by scientists to a group of brain diseases which result from progressive and premature death of nerve cells of the brain. “Alzheimer ’s disease” which causes progressive memory and cognitive (intellectual) decline in the elderly, is the commonest and the most popularly known degenerative disease. PD is yet another degenerative disease and is next only to Alzheimer’s disease in commonness. In PD, the nerve cells predominantly affected are those concerned with posture of the body and movement; patients with PD, therefore, have predominantly movement related symptoms (tremor, slowness of activities, stiffness of limbs, loss of balance and difficulty to walk etc.). However, the disease process in PD is not solely confined to the areas of brain controlling movement. Other areas like those concerned with sleep, mood, autonomic functions (like control of blood pressure, bowel movements and urinary bladder functions), behaviour and intellect could also get affected to a variable degree. Abnormal functioning of these areas of the brain can result in ‘non-motor’ manifestations like a variety of sleep disturbances, depression, anxiety, psychiatric symptoms (like “hallucinations” in which the patients report seeing or hearing things and voices, which are actually not present, delusions, irritability, behavioral disturbances etc.) constipation, incontinence of urine and memory dysfunction, in addition to the well-known movement-related (motor) symptoms in PD.

What causes PD?

What causes PD is not fully clear to scientists even now. It could be due to defects in certain genes (which mean macro-molecules inside cells which control the properties and functions of the cell and also play an important role in heredity). Genetic problems directly causing PD are rare (1-2% of cases only). Genetic factors may only predispose the individual to PD, rather than causing PD directly. Certain factors in the environment are also thought to contribute to PD. For example, exposure to insecticides and drinking well water, have been found to have a role in the genesis of PD in some patients. Most of the times, environmental and genetic factors interact and result in PD. It is often very difficult to point out the factor which has caused the disease in individual patients.

What are the clinical features of PD?

Patients with PD usually have tremor of limbs, stiffness of limbs (rigidity), slowness of activities (bradykinesia) and stooped posture with a tendency to loose balance. All of them need not be present in all patients. For example, some patients have tremor as their predominant symptom, while others may have no tremor at all. The symptoms usually begin on one side and gradually spread to the other side. Some patients can have a phenomenon called freezing of gait, in which the patient feels that his feet are glued to the ground, on trying to walk. Freezing can significantly interfere with mobility. Patients with later stages of the disease can have difficulty in speaking, swallowing food etc. Other symptoms, unrelated to movement can occur, even in early stages (“non-motor symptoms”). They include reduced sleep, depression of mood, anxiety, urinary bladder dysfunction leading to involuntarily passing urine, sexual dysfunction etc. Non-motor symptoms which occur in some patients in late stages include memory and intellectual problems, psychosis (Symptoms of psychosis include the patient seeing animals, objects or persons who are not actually present. This phenomenon is called ‘hallucination’) repeated falls etc.

How is PD diagnosed? What are the other diseases which mimic PD?

The diagnosis of PD is largely clinical, and is arrived at by a careful analysis of the patient’s history, clinical examination, and the response to treatment. As of now, there is no laboratory investigation or imaging study (like CT, MRI or other types of brain scans) which confirms the diagnosis of PD with 100% accuracy, excluding all other conditions. Certain other rarer degenerative disorders (eg: Progressive Supranuclear palsy (PSP), Multiple System Atrophy (MSA) etc- together lumped as “Atypical Parkinsonisms” or “Parkinson Plus” syndromes) have symptoms very similar to Parkinson’s disease initially. In some cases, a careful observation of the patient, and his / her response to treatment over a period of time (sometimes a few years) may be necessary to reach a conclusion regarding whether it is PD or “Atypical Parkinsonism”. However, as there is no specific curative or “progression-preventing” treatment available to any of these degenerative diseases, the initial, inevitable delay in making a confidant diagnosis does not do any harm to the patient. The symptomatic treatment is similar for Parkinson’s disease and the other, “atypical” Parkinsonisms. The atypical Parkinsonisms as a whole respond poorly to medical treatment and do not improve with Deep Brain Stimulation surgery.

How is PD treated?

In PD most of the movement related symptoms and some of the other ‘non motor symptoms’ result from deficiency of a chemical called ‘Dopamine’ in the brain. Dopamine is produced by some nerve cells located in a region called ‘substantia nigra’ in the ‘mid-brain’. These nerve cells are the ones undergoing premature death in patients with PD. The mainstay of treatment of PD is replacement of dopamine in the brain. This is achieved by administrating a drug called Levodopa which, on reaching the brain, is converted to dopamine. There are some medications called Dopamine agonists (like Pramipexole, Ropinirole etc) which mimic the action of dopamine in the brain. They are also useful in the treatment of PD. Some other medications (Entacapone, Rasagiline) act by interfering with the function of the enzymes (enzymes are very large molecules controlling the biochemical reactions leading to productions of chemicals inside the brain and their destruction) causing destruction of dopamine. These drugs help dopamine to be present in the brain for longer period and act longer.

As we saw earlier PD is associated with other non-motor symptoms also. These often need to be treated with medications for depression & anxiety, medications for good sleep, medications to control behaviour etc.

Currently there is no treatment available to restore the cells which have died off or to prevent further damage to the brain by arresting further nerve cell death. All the currently available treatment modalities aim at correcting the chemical deficiencies in the brain resulting from death of cells. Thus, the currently available treatment modalities only relive the patient’s symptoms and improve the quality of life. None of them can prevent the disease from worsening over the course of time.

What are the limitations of medical treatment of PD?

As pointed out earlier, the neuro-degenerative processes (progressive death of nerve cells) happening inside the brain will go on, in spite of all the currently available treatments. Thus, the disease is likely to become more severe in due course of time, even though treated early and optimally. As the disease progresses, the patient will require more and more medications to control the symptoms. A condition called ‘motor fluctuation’ develops - three or four doses of medications fail to give relief to symptoms through-out the day. Each dose of Levodopa will result in a period of “On” characterized by relief of symptoms. This is followed by an “Off” period where all the symptoms recur. The patient will have to take the next dose to turn “On” again. The duration of improvement with each dose of medication gradually comes down and the patient will require a greater number of doses to remain active throughout the day Another problem faced with in late stages is ‘drug induced dyskinesia’. This is characterized by abnormal, excessive ‘dancing’ movements of the body during the period when the patient is experiencing the beneficial effect of the drug. At this stage, the treating doctors are put into a dilemma in which a reduction in dose leads to worsening of symptoms of PD and any increase in dose to relive these results in abnormal excessive movements.

DEEP BRAIN STIMULATION

What is Deep brain stimulation (DBS)?

Deep brain stimulation is a surgical procedure done in “intermediate” stages of PD when medical therapy alone fails to control the patient’s symptoms adequately. It is done in patients with “motor fluctuations” with or without “dyskinesias” (please see above) who require frequent doses of medications to control their symptoms (each dose gives benefit for only a short time). In most of the patients who come for DBS, the medication doses also result in abnormal excessive movements (dyskinesias). DBS is done typically in patients in whom there is good improvement (which may or may not be accompanied by dyskinesias) of symptoms with medications, but the improvement lasts only for a limited period with each dose. In very advanced stages of PD, the patients start experiencing symptoms which improve only poorly (eg: imbalance and falls, “freezing” of gait, disturbances of speech) or not at all (eg: memory and intellectual decline) with levodopa and other medications. Such patients are unlikely to have any useful overall improvement of their status with DBS and hence surgery is not advisable in them. DBS is offered to patients with many other movement disorders also, for controlling symptoms.

What are the beneficial effects of doing DBS?

DBS can relieve the motor (movement- related) symptoms of the disease- like stiffness of limbs, tremor and slowness- to a significant degree. Research done all over the world including our centre indicate that the overall improvement in these symptoms vary from 50-60% approximately. DBS provides a stable baseline control of symptoms (Which is around 50 % or so of the symptom control obtained in the best “on” period with oral medications. However, unlike the symptom control provided by medications, which fluctuates related to the administration of each dose, the benefits provided by DBS tend to remain stable throughout the day). This allows reduction in the dose of medicines considerably in most cases, thus reducing the ‘drug induced dyskinesia’ (abnormal “dance-like” movements occurring during the beneficial period (“ON”) of medicines). Thus, DBS, along with the modified dose of medications, provides a more predictable and sustained relief of symptoms than that provided by medical treatment alone before surgery, by reducing the ‘fluctuations’ or ups and downs of medical treatment. Even though reduction in the dose of medications is possible in the majority, only a small percentage of patients can be totally free of medications after surgery. The aim of DBS is not to withdraw medications completely, but to improve the quality of life by reducing the “motor fluctuations” (reducing the ‘off’ time parkinsonian symptoms and duration of “off” time) and ‘on’ time dyskinesias. In a well-chosen case with properly supervised concurrent medical therapy, most patients do well and are able to carry out most of their daily activities independently. It may be possible for some patients to return to work.

Will all movement related problems improve with DBS?

The symptoms like stiffness of limbs, tremor and slowness of activities are likely to have a very good response to DBS. Certain disturbances in walking (like imbalance/ falls/ “Freezing of gait” etc) may not have a similar excellent response. The reason is that these sorts of problems could also occur due to neuro-degeneration (nerve cell death) happening in areas in the “brain-stem” outside those targeted by DBS, in Parkinson’s disease. Freezing of gait and other walking disturbances, which responds initially to DBS, may re-appear later because of the gradual progression of Parkinson’s disease and involvement of these areas in the brainstem crucial to walking function. Generally, patients with Parkinson’s disease in whom the Freezing improves in “on” period with drugs, are likely to have improvement of Freezing with DBS also, at least temporarily. Disturbances of speech and swallowing function will not improve with DBS.

What is the effect of DBS on the non motor symptoms of PD?

Deep Brain Stimulation may give partial improvement to some of the non motor symptoms of PD, like sleep dysfunction and urinary bladder problems. However, DBS doesn’t give relief to most of the other non-motor problems, like memory and intellectual dysfunction, depression, anxiety, hallucination, psychosis etc. Some of the intellectual functions like word output and fluency of speech could worsen slightly after DBS. Apart from this, DBS has not been found to have any functionally significant deleterious consequences on memory or intellectual functions. Many patients may perceive some loss of clarity of speech, after DBS, though this rarely results in any limitation in their ability to communicate verbally. Patients with depression, anxiety, hallucinations, psychosis etc need correction of these problems before undergoing surgery; otherwise there could be a worsening in the post-operative period sometimes resulting in serious medical /social consequences. Impulse control disorders (This denotes patient’s inability to control the urge to do certain pleasurable activities. The examples include gambling behaviour, hypersexuality, excessive craving for certain food items and eating too much, spending too much on shopping indiscriminately etc) could improve, remain stable or could worsen in some patients after DBS. Careful screening for intellectual, psychiatric and other ‘non-motor’ problems (many of which may not be evident on a routine office consultation) by specialized ‘neuro-psychological’ tests are required as part of the selection process of patients for DBS. Patients with such problems before surgery will need close psychiatry follow up after surgery.

What is the effect of DBS on progression of PD?

DBS is NOT a cure for PD or a remedy to arrest the progression of the disease or to maintain the same state. It is only a symptom-control measure to relieve the “movement-related” symptoms of Parkinson’s disease. As discussed in detail earlier, PD is a progressive neurodegenerative disease and there is no established therapy to arrest the progressive death of nerve cells happening in PD. This applies to DBS also- in spite of doing DBS, the disease continues to progress naturally. As a result, patients with DBS can later develop significant disability due to emergence / worsening of symptoms not amenable to DBS (like memory and intellectual dysfunction, bladder dysfunction, behavioural problems, freezing of gait, imbalance, speech and swallowing disturbances etc). Medical scientists all over the world are actively engaged in research to find out a remedy for the progressive nerve cell death in Parkinson’s disease. Let us be optimistic that such a remedy will be available in near future, and that will be the answer to this problem.

Can all patients with advanced PD undergo DBS?

Not all patients with Parkinson’s disease are good candidates for DBS surgery. The interested readers may refer to the DBS Information Brochure available in the drop-down menu under “Information for patients” in the Menu Bar at the top of this page, for further details on patient selection for DBS. Patients with PD who have a significant degree of nonmotor problems (like memory and intellectual dysfunction, psychosis, depression) will not generally be selected for DBS, as these are not amenable to DBS. Very advanced stage patients (those who have severe walking disturbances/ balance problems/ falls/ freezing of gait, and disabled because of Parkinsonism even in drug “on” state) may not benefit from DBS. Those with advanced age and poor general health because of co-existence of other illnesses (eg: long history of diabetes/ high blood pressure; heart diseases; chronic lung diseases etc) may not be selected for DBS because their surgical risks and risks of an unsatisfactory outcome may outweigh expected benefits. There is a rigorous selection process whereby patients are put through a series of clinical evaluation tests before being identified as candidates for surgery.

How is the Deep Brain Stimulator system implanted?

The system is implanted by the Stereotactic Neurosurgeon with clinical and electrophysiological guidance by the Movement disorder specialist trained in the procedure. The neurosurgeon uses a ‘stereotactic head frame’ and imaging (MRI/ CT scan) to map the brain and locate the target within the brain. The scan is done after fixing the metallic frame on the head. Subsequently, the patient is shifted to the operating room.

Fixing a stereotactic frame on the patient’s head, is an important step in DBS surgery

The first stage is implantation of the DBS electrodes inside the brain. The target selected for implantation is an area in the brain called subthalamic nucleus, whose cells function abnormally in PD, resulting in the motor symptoms of the disease. In some patients, other targets like the “Globus Pallidus” are selected. The patient remains awake and alert during this stage, so that the neurosurgeon and a movement disorder specialist can test the stimulation to maximize benefits and minimize side effects. The patient’s scalp is anesthetized to minimize discomfort, a small hole (called Burr Hole) is put in the skull and wires are passed through it into the brain. The brain itself has no nerves to sense pain or discomfort; hence electrodes can be passed through the brain of the awake patient without any discomfort. The first set of wires passed are called ‘micro-electrodes’. These wires are passed to record the electrical activity from the target. The target (“Subthalamic Nucleus”, in the case of Parkinson’s disease) has a peculiar pattern of electrical activity, and recording it correctly ensures that the electrodes are placed at the correct position, mapped by the Neurosurgeon from the scans. This is very important as DBS system implantation is a ‘closed’ neurosurgical procedure (means that the surgery is not done by opening the skull and exposing the brain; instead, it is done through a small hole) and the surgeon is not directly seeing the target while operating. To double-check and ensure that the positioning of the electrode is correct, test current is given, and the patient is tested for improvement of Parkinsonian symptoms and signs and also for any unexpected side effects. During the testing, patients are asked to speak, to move their limbs and hands and to perform simple tasks while test stimulation is done. Patients are also asked about any side effects (like ‘double vision’, tingling sensation of one side of the body, difficulty to speak out) they might occur during test stimulation. All these require the patient to remain very alert and co-operative during the procedure. Improvement of Parkinsonian symptoms and signs without any adverse effects, on giving the test current confirms correct placement of electrodes. After achieving this, the ‘micro-electrodes’ are removed and the DBS electrode is placed at the same site. The whole procedure is repeated for the other side of the brain. The next stage is implantation of the Implantable Pulse Generator (Neurostimulator / “Battery”) under the skin over the chest wall. As this does not require the co-operation of the patient and is painful if done without good anaesthesia, this part of the surgery is done under general anaesthesia.

"Micro-electrode recording" (recording of electrical activity from nerve cells deep inside the brain) helps to confirm the accuracy of targeting, in DBS surgery.

Deep Brain Stimulation leads ("electrodes") implanted in the brain, seen in MRI scan

How does DBS work?

A device called the Neurostimulator which is similar to a cardiac pacemaker is implanted over the chest wall, under the skin. It is a device containing a battery and microelectronic circuitry. It generates electrical signals that are delivered to the brain via a thin wire with electrodes attached at the tip. The electrodes are implanted in the brain on both sides and the cables that connect it to the neurostimulator are tunneled under the scalp and the skin of the neck. Deep Brain Stimulation works by high frequency electrical stimulation of the target areas (the Subthalamic Nuclei) deep within the brain that control movements. These areas function abnormally in PD, resulting in the disabling “motor symptoms” (tremor/ slowness of activities/ stiffness of limbs etc) of the disease. High frequency electrical stimulation of these areas alters the function more towards normalcy and relieves the motor symptoms. As the non-motor symptoms of PD are generated by dysfunction of other areas of the brain, they may not be relieved by DBS of the subthalamic nucleus. Similarly, if the Neurostimulator is switched off for a few hours, the Subthalamic Nucleus goes back to the original abnormal state and all the symptoms will recur. Thus, DBS is not a permanent cure for PD.

What is meant by programming?

The frequency, intensity etc of the stimulation, and the “point” on the tip of the electrode through which the electrical pulses are delivered can be changed in a number of ways to give maximum benefit to the patient. This is called programming and is done by the movement disorder specialist, using a special device. Programming is much like tuning a radio - the stimulation parameters are adjusted until the optimal effect is obtained. Stimulation with higher intensities of current / stimulation of certain areas in the subthalamic nucleus can sometimes result in adverse effects like difficulty to speak out, and minor behavioral problems. The advantage of DBS over the other ‘lesioning’ surgeries mentioned below is that the adverse effects, if they occur, can be abolished / minimized by altering the stimulation parameters. Programming is done to ensure that the patient gets maximum control of the symptoms of PD at the cost of no or minimum adverse effects. The initial programming done (usually a few days after surgery) may not give the best results, as surgery related factors (for example, swelling of the brain areas concerned, resulting from the trauma of the surgery) may interfere with it. The patient often requires re-programming a few weeks later. Minor adjustments can be done by the patient, using the therapy controller unit provided.

What are the complications of DBS surgery?

The surgical procedure is associated with complications like bleeding inside the brain and infection of the implants, in a small minority of cases. Bleeding serious enough to cause paralysis and other neurologic problems are rare and occur in only around 1.5% of patients undergoing surgery. Infections in the implants (which may necessitate explantation and discarding of the DBS system) have been reported to occur in around 2-3% of the patients undergoing DBS all over the world. Problems with the DBS hardware (the equipment and the wires), like errors in positioning, fracture of the electrodes etc could also occur in a similar minority. The second part (implantation of the stimulator) of the surgery is done under general anesthesia and carries all the risks of anaesthesia as in any other surgery. Minor complications like epileptic fits during/ immediately after the procedure, transient mental changes like confused behaviour, urinary incontinence etc are more common in the post-operative period and can be managed fairly easily. Minor behavioral and cognitive problems (like reduced fluency of speech, reduced initiative to do activities, changes in mood etc) can occur in some patients as a result of stimulation and can be corrected / minimized by programming, as discussed above. Some patients show a tendency for increased appetite, resulting in weight gain. Overweight can result in worsening mobility and should be controlled with appropriate dietary adjustments / exercises.

The risk of surgical complications could vary from patient to patient depending on factors like age, presence of other illnesses (eg: high blood pressure increases the risk of bleeding during surgery; cardiac problems may predispose to complications during anaesthesia; diabetes may increase the risk of infections) etc

What is the approximate length of hospital stay?

The length of hospitalization varies. Normally it takes around 14 days. Four to five days of hospital stay is required prior to surgery for various pre-operative assessments. One more week is needed after surgery for wound healing and suture removal. During the week after surgery, preliminary programming is also done.

Ideally, when should a patient with Parkinson's disease undergo DBS?

There is no simple, one-word answer to this question. As discussed above, deep brain stimulation surgery is a symptom-relieving measure offered to patients with PD. DBS has not so far been shown to have any ability to retard the progression of Parkinson’s disease or to prevent or delay the problems of very advanced stage Parkinson’s disease, like memory and intellectual dysfunction, psychiatric problems etc. Some of the symptoms of PD show very good improvement with DBS (eg: tremor/ stiffness of limbs); certain others may not improve that much (eg: freezing while walking; other sorts of disturbances in walking) ; a third group of symptoms may even worsen slightly following DBS (eg Clarity of speech, fluency). The profile and severity of the symptoms and the rate at which the disabilities progress in Parkinson’s disease vary widely from person to person. For example, some patients are severely disabled by tremor in spite of relatively preserved walking capabilities while some others never experience any tremors; slowness and walking difficulties predominate in them. Some patients have severe symptoms interfering with daily activities 6 or 7 years into the illness, while certain others remain active and independent with medications alone even after living for 12 -15 years with PD. The degree of handicap caused by the symptoms also depends on one’s professional and social status. For example, the implications of the disease in a manual labourer who is the sole bread-winner of a family, and another, who is leading a retired life will be totally different, even if the severity of the symptoms is identical – the former would desire for a better control of symptoms even at the risks of a major surgery while the latter may not accept this risk. The decision regarding when to go for Deep Brain Stimulation surgery has to be individualized, taking into consideration various factors like the nature of symptoms and severity, expected improvement (which vary depending on the profile of symptoms in individual patient), expectations of the patient and family, employment status, surgical risks, family / social support (as the patient needs to be under the regular follow-up of the specialized team for life-long, after undergoing DBS) etc.

The average duration of Parkinson’s disease, for a patient undergoing DBS surgery had been typically 11-13 years till mid 2010s; however, there has been recent studies which showed that doing DBS earlier (before the disabilities become sufficient enough to warrant DBS as per conventional guidelines) in carefully selected patients may improve the overall quality of life of the patients. The expected benefits of DBS (improvement of symptoms, improved ability to perform daily activities, likelihood of resuming employment, better quality of life) in the individual patient has to be weighed against the potential risks and disadvantages (the small, but definite surgical risks elaborated above, need for a subsequent life-long specialized care, cost etc).

The simplest answer to the question is that “DBS should be considered when the needs and expected benefits in the individual patient outweigh the estimated risks and disadvantages of the surgery in him/her”. For example, a patient with no illnesses other than Parkinson’s disease (thus, the risks of surgery are relatively low) and in need of continuing employment (being the sole breadwinner of the family) may choose to do DBS ‘relatively early’, even when the disability resulting from PD is only moderate. On the contrary, the wise decision in another patient retired from employment and also having other illnesses like high blood pressure or heart disease (implying a higher surgical risk), will be to wait till the disability becomes sufficient enough to justify taking the higher risks of surgery.

Summarizing, patient with Parkinson’s disease can be considered for DBS, if the following general guidelines are met: (1) The duration of disease is sufficiently long enough – minimum of 4 years is generally recommended- so that the doctors have had a sufficiently long period of observation and follow-up to make a confident diagnosis of PD (2) The patient has an excellent (even though persisting only for a brief “on” period) response to medications like Levodopa (3) The “motor fluctuations” and “dyskinesias” are judged by the patient to be disturbing and needing better control than what is possible with optimum drugs (4) There are no major memory or other intellectual dysfunction, or depression or other psychiatric disturbances resulting from PD (5) There are no other major illnesses increasing the risks of surgery / other illnesses present are well controlled and taking the increased surgical risk due to them is justified by the severity of the motor fluctuations and dyskinesias in the judgment of the patient, family members and the team of doctors. (6) The patient and family have understood well the pros and cons of DBS and the expectations are realistic (7) The patient has adequate social support to maintain a constant access to the specialized care which he / she will require throughout the rest of his / her life.

The team of doctors will assess the patient and explain in detail the expected risks and benefits in the individual patient; the final decision should come from the patient and family.

Is there any need to replace the Neurostimulator?

There are different types of neurostimulators available, including rechargeable ones. The service life will vary from 4-15 years depending on the type. When the neurostimulator reaches the end of its service life, it needs to be replaced. Replacing the neurostimulator is a minor surgical procedure and does not involve any brain surgery.

What are the other movement disorders in which DBS is used as treatment?

DBS is used for the treatment of other conditions like dystonia and various tremor disorders, including Essential Tremor. In these conditions, the brain target used is different from the one used in PD (subthalamic nucleus/ Globus Pallidus).

What are the other surgical procedures used to treat PD and other movement disorders?

The other surgical procedures include stereotactic thalamotomy and pallidotomy. In these procedures, a small surgical “lesion” is produced in the brain target, to alter its function and relieve the symptoms. The patient is selected for these lesioning surgeries, when symptoms cannot be controlled by medical management alone and DBS is not possible due to technical or other (eg: financial) reasons. These procedures are much less expensive than DBS; however the results are also inferior to those of DBS. Generally, these lesioning surgeries can be done only on one side, as doing the surgery on both sides of the brain can have complications like significant degree of speech disturbance.

What all precautions should be taken by somebody with an implanted DBS system?

Regular follow-up is needed after surgery, to detect promptly and correct if possible those symptoms which are not amenable to DBS. These include depression, urinary bladder disturbances, behavioural problems, cognitive dysfunction etc. The patient also may require programming or adjustment of medications for movement-related symptoms worsening over time.

Patients with DBS system implanted should consult the movement disorder specialist before going for any other major investigation or treatment, particularly radiological investigations and surgical treatments. This is because some of the equipment used for certain scans, tests and surgical procedures can interfere with the DBS system. Kindly refer to the DBS Information Brochure for details or consult your doctor.

How much experience does SCTIMST have in functional surgeries for movement disorders?

SCTIMST is one among the pioneers of Deep Brain Stimulation (DBS) surgery for Parkinson’s disease in India, with the first procedure of Globus Pallidus deep brain stimulation performed in 1999. CCCMD of SCTIMST has performed more than 500 functional neurosurgical procedures, including more than 300 DBS for advanced PD and other Movement Disorders till 2023. Our surgical results, indicating sustained benefit of stimulation on the cardinal signs of the disease and quality of life of the patients followed-up regularly for up to 10 years, have been published in international journals.

DYSTONIA

What is meant by dystonia?

Dystonia is a movement disorder characterized by involuntary muscle contractions, which force certain parts of the body into abnormal, sometimes painful, twisted postures, occasionally accompanied by jerky movements. Dystonia can affect any part of the body including the arms and legs, trunk, neck, eyelids, face, or vocal cords. There are different names given to describe various forms of dystonia, usually based on the affected body part (eg: blepharospasm, oromandibular dystonia), whether dystonia is present alone or along with other neurological abnormalities (Eg: isolated dystonia, combined dystonia) or number of areas involved (eg: focal dystonia, segmental dystonia and generalized dystonia)

What causes dystonia?

The mechanisms underlying dystonia are not fully known. Dystonia could occur due to abnormal functioning of the basal ganglia, (which are structures located deep in the brain and involved in the control of movement), cortex of the brain, or both. Abnormalities in the interaction between basal ganglia structures and cortex also may play a role

Is dystonia a genetic disorder?

Some forms of dystonia are due to genetic causes. Some patients with dystonia due to genetic causes are said to have ‘primary dystonia’; in such patients, dystonia will generally be the only manifestation of Nervous system dysfunction. The patient’s intellect and other aspects of nervous system function will usually be normal. Primary dystonia staring in childhood or early adult hood tends to spread to multiple parts of the body or even the whole body with passage of time while those starting during mid or late adult hood tend to remain confined to one or a few of the body parts. “Secondary dystonia” result from specific causes like exposure to certain medications and toxins, traumatic injury to brain, certain hereditary and “degenerative” conditions affecting the brain, infections or stroke. Sometimes dystonia can occur due to degenerative diseases causing widespread nervous system dysfunction; in such cases, manifestations other than dystonia (like intellectual dysfunction, imbalance, epileptic fits etc) also occur very often.

Focal Dystonia is one which affects only one part of the body. The common forms include: Blepharospasm: Affects the muscles of the eyelids, forcing them to close. The spasm may become sufficiently severe to render the patient unable to see, although the eyes and vision are normal. Cervical dystonia: Affects muscles in the neck and shoulders. The muscle spasms can be painful and cause the neck to twist to one side (Torticollis), forward (antecollis), or backward (retrocollis). Oromandibular dystonia: The muscles of the lower face undergo spasm. The jaw muscles that pull the mouth open or close may be involved. Writer’s Cramp: This is a ‘task-specific’ dystonia in which the hand and forearm muscles contract during the act of writing. The patient usually has no symptoms while doing other activities (like buttoning his shirt or eating) with the affected hand. Similar ‘task-specific’ dystonia may arise in musicians when a violin is played or certain fingers are moved while playing a flute or other musical instrument.

Hemifacial Spasm: This is very similar to dystonia and is treated similarly with botulinum toxin injections. However, in hemifacial spasm the signals for the abnormal movements are generated not inside the brain, but more peripherally, in the nerve supplying the muscles of face (Facial Nerve). As a result of this, the muscles on one side of the face contract irregularly. Rarely, this is secondary to inflammation or irritation of the facial nerve.

Diagnosis of Dystonia:

The diagnosis of dystonia is clinical, and a Neurologist trained in movement disorders can make it by carefully observing the abnormal movements which the patient is having. Certain electrophysiological tests can assist the diagnosis in difficult cases by demonstrating simultaneous activity in various muscle groups, during the movements. Other investigations like MRI scan, blood tests and genetic studies may be required to find out the underlying cause and to differentiate between primary and secondary dystonia.

Treatment of Dystonia: The treatment can be with oral medications, botulinum toxin injection and functional neurosurgery. The aim of treatment is to relieve the muscle spasm and abnormal movements and postures so that the patient can function normally.

Botulinum Toxin:

Botulinum Toxin Injections are used for the treatment of a wide variety of indications in movement disorders. The common conditions for which botulinum toxin is used include various types of focal and segmental dystonia including torticollis, writer’s cramp, blepharospasm, oromandibular dystonia etc as well as other conditions like hemi-facial spasm and post-stroke spasticity (stiffness of muscles occurring in a limb, paralysed by stroke). Free hand injections are used for some conditions like blepharospasm and hemifacial spasm, while others like writer’s cramp and cervical dystonia may require EMG (electromyogram) guidance. The involved muscles are identified and injected using special equipment including EMG. A single session gives relief of symptoms (generally varying from 50% to 80% generally, depending on the condition and the muscles involved) for around 3-4 months, on an average. Subsequently, the symptoms gradually recur and the patient may require re-injection. Botulinum toxin acts by blocking the abnormal signals from nerves, from reaching the muscles injected. Botulinum toxin injections are generally safe. The most common side effect (apart from the pain resulting from injection) is a transient weakness of the muscle injected; the weakness will completely disappear spontaneously over a few days to weeks.

Surgical treatment of Dystonia is done for patients with refractory and troublesome segmental / generalized dystonia who are significantly disabled in spite of optimal medical therapy. The surgical treatment is usually offered for patients with primary dystonia only. The preferred surgical treatment is Deep Brain Stimulation (DBS), discussed in detail under the heading ‘Parkinson’s disease (PD)’. The target in the brain selected for DBS in patients with dystonia is different from the target selected in PD. Other treatment options include ablative surgeries (a small ‘lesion’ is produced in a strategic location of the target) like pallidotomy.

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