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Parkinson’s Disease: A World of Promise

Parkinson’s Disease: A World of Promise. Sarah Click Dr. Julie Gurwell Spring 2006. Background . Movement disorder Affects over 1 million people usually middle aged 2 nd most common ND disorder behind AD. Background cont’d. Progression due to loss of DA neurons in the brain

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Parkinson’s Disease: A World of Promise

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  1. Parkinson’s Disease: A World of Promise Sarah Click Dr. Julie Gurwell Spring 2006

  2. Background • Movement disorder • Affects over 1 million people usually middle aged • 2nd most common ND disorder behind AD

  3. Background cont’d • Progression due to loss of DA neurons in the brain • These neurons normally project into the striatum and eventually cause inhibition of the STN • Without them, there is hyperactivity of this portion of the brain that controls motor fxn

  4. Cardinal symptoms Bradykinesia Resting tremor Stiffness Postural instability Standard criteria to diagnose is 2 of these Other symptoms Dyskinesias Depression Sleep disturbances Psychotic symptoms Decrease in balance performance and gait Hoarseness Hypophonia (motor) Background cont’d

  5. Drug Therapy– reminders • Overall goal is to increase DA • Dopamine agonists • Inhibit breakdown • Anticholinergics • Limited long-term efficacy of drug treatment • Undesirable side effects • Dyskinesias

  6. Surgeries • Three common • Thalamotomy • Pallidotomy • Deep brain stimulation

  7. Thalamotomy and Pallidotomy • Local anesthesia • CT, MRI, or ventriculography • Location is determined by stimulation with an electrode • Looking for the greatest effect on symptoms with the least amount of side effects. • Once target is identified, a lesion is made • This is permanent • Several lesions are normally made in different parts to maximize effects

  8. DBS • The area targeted is the subthalamic nucleus (STN) or globus pallidus internus (GPi) • Procedure basically the same • Lesion not created • Electrode remains there

  9. Why choose DBS? • Main goals • Increase motor functions • Increase ADL • Decrease need for levodopa

  10. Drapier et al. studied 27 patients that underwent bilateral STN DBS between 1999 and 2002 19 men and 8 women took part in the study Goal was to determine quality of life before and after surgery Inclusion Criteria Age ≤ 75 Severe PD Drug induced dyskinesias Exclusion Criteria Cognitive impairment Marked cerebral atrophy on MRI Major depression before surgery STN DBS

  11. Results of Drapier et al. • Significant difference in the motor functions between pre-op off-med and post-op off-med/on-stimulation conditions with p<0.001 • L-dopa dosage decreased an average of 29% • Quality of life increased by 21.1% at follow-up

  12. Krause et al studied 27 patients that underwent bilateral STN DBS in 1997 Age range from 44-72 Symptom duration 7-25 yrs Mean follow-up time ~29.8 months (range 23-55) Goal similar to previous study Inclusion criteria Patients with advanced PD Severe pharmacological side effects Exclusion criteria None listed STN DBS cont’d

  13. Krause et al. Results • 3 patients lost to follow up due to • Intraventricular hemorrhage • Corrected by a temporary external ventriculostomy in which the lead was not replaced • Dysphagia and death • Patient had dysphagia before the surgery, stimulation made it worse, so it was turned off • Patient died of suffocation unrelated to surgery 1 ½ yrs later • No comment on last patient (not by me, by the researchers)

  14. Krause et al. Results cont’d • Significant improvement in ADL, dyskinesias, and fluctuations post-surgery • Sig. imp. in freezing after 1 yr, stable for 30 months • Off-medication motor score significantly improved by 40-44% & stable • Motor score sig. imp. On-med/on-stim (p<0.04). • Tremor suppression much better with stimulation than with medication (p<0.05) • Stimulation improved rigidity and bradykinesia more than the medication alone could do in this trial, results stable • SIGNIFICANT DECREASE IN LEVODOPA-EQUIVALENT DOSE BY 39% AT 1 YR FOLLOW-UP AND 30% AT 3 YR FOLLOW-UP (P<0.05) • This caused a decrease in fluctuations and dyskinesias

  15. Adverse events in Krause et al. trial • Intraventricular hemorrhage (n=1) • Dysphagias (n=3) • Pneumonia (n=1) • Transient hyperhidrosis (n=6) • Moderate dysarthria (n=3) • Lasting hyperkinesias (n=2) • Increased falling (n=4) • Increased libido (n=1) • Maybe an alternative to Viagra? Note: most adverse events were related to amplitude and could be fixed if the IPG was turned down

  16. Three Other studies’ results • Sig. imp. in off-med scores by 39% • 42% reduction in dyskinesias • Reduction in L-dopa Equiv. dose by 24% (p<0.017) • Adverse Events: • Intracranial hemorrage (n=1) • Did not have to discontinue this study once resolved • Dyskinesias (n=1) • Paresthesias (n=1) • Apraxia of lid opening (n=1) • Mood change with apathy (n=1)

  17. Pyschosocial factors in DBS • One study showed a suicide rate of 4.3% • Patients observed had PD, ET, primary and secondary dystonias, or MS-associated tremor • All but 1 were young men with a chronic neurological cond’n • Most had episodes of severe depression before or during the course of the disease prior to DBS, but only 2 had frank suicidal ideations or suicide attempts • Each of these patients showed significant improvement in their motor function following DBS surgery • No sig. changes in medications or other attributing factors to the lifestyle of the patients before each of the suicides • Need more extensive inclusion criteria

  18. Pyschosocial factors in DBS cont’d • Another study shows cognitive decline in patients post-op • Increased risk for cognitive impairment, without any early signs of dementia, in the elderly • Suggested there might not be enough neurologic reserve for the DBS to work in patients past a certain point • Also observed mental slowness • Medications were reduced in this study by 46% in the older patients and 47% in the younger, although they cited studies that showed medication reductions of up to 100%

  19. Pyschosocial factors in DBS cont’d • Cognitive improvement observed in another study • No signs of suicide ideation (0/76 or 0% of patients for all you math majors!) • Psychomotor speed and working memory was sig. imp. with stim-on • No cognitive decrease at 1 year post-op in attention, construction, initiation, conceptualization, or memory scores

  20. Conclusion • DBS is a great alternative to high L-dopa dosages • There are some side effects that should be considered before deciding to have the surgery • More emphasis should be placed on psychological function before approving the surgery

  21. Getting Support • American Parkinson Disease Association • 888-400-2732 • www.apdaparkinson.org • National Parkinson Foundation • 800-327-4545 • www.parkinson.org • Parkinson’s Disease Foundation • 800-457-6676 • www.pdf.org

  22. References 1. Burch D, Sheerin F. Parkinson's disease. Lancet 2005;365:622-7. 2. Thiruchelvam MJ, Powers JM, Cory-Slechta DA, Richfield EK. Risk factors for dopaminergic neuron loss in human alpha-synuclein transgenic mice. Eur J Neurosci 2004;19:845-54. 3. Dewey RB, Jr. Management of motor complications in Parkinson's disease. Neurology 2004;62:S3-7. 4. Filali M, Hutchison WD, Palter VN, Lozano AM, Dostrovsky JO. Stimulation-induced inhibition of neuronal firing in human subthalamic nucleus. Exp Brain Res 2004;156:274-81. 5. Ferreira JJ, Rascol O. Drug-related sleep disturbances and Parkinson's disease: effects of dopaminergic antiparkinsonian drugs on sleep and wakefulness. European J Neurol 2000;7(Suppl. 4):26-35. 6. Nilsson MH, Tornqvist AL, Rehncrona S. Deep-brain stimulation in the subthalamic nuclei improves balance performance in patients with Parkinson's disease, when tested without anti-parkinsonian medication. Acta Neurol Scand 2005;111:301-8. 7. Hindmarch, I. Possible causes of daytime sleepiness with particular regard to patients with Parkinson's disease. European J Neurol 2000; 7(Supp. 4):9-14. 8. Deleu D, Hanssens Y, Northway MG. Subcutaneous apomorphine : an evidence-based review of its use in Parkinson's disease. Drugs Aging 2004;21:687-709. 9. Straits-Troster K, Fields JA, Wilkinson SB, et al. Health-related quality of life in Parkinson's disease after pallidotomy and deep brain stimulation. Brain Cogn 2000;42:399-416. 10. Yoshor D, Hamilton WJ, Ondo W, Jankovic J, Grossman RG. Comparison of thalamotomy and pallidotomy for the treatment of dystonia. Neurosurgery 2001;48:818-24; discussion 824-6. 11. Breit S, Schulz JB, Benabid AL. Deep brain stimulation. Cell Tissue Res 2004;318:275-88.

  23. References 12. Esselink RA, de Bie RM, de Haan RJ, et al. Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD: a randomized trial. Neurology 2004;62:201-7. 13. Krause M, Fogel W, Mayer P, Kloss M, Tronnier V. Chronic inhibition of the subthalamic nucleus in Parkinson's disease. J Neurol Sci 2004;219:119-24. 14. Berney A, Vingerhoets F, Perrin A, et al. Effect on mood of subthalamic DBS for Parkinson's disease: a consecutive series of 24 patients. Neurology 2002;59:1427-9. 15. Drapier S, Raoul S, Drapier D, et al. Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson's disease. J Neurol 2005;252:583-8. 16. Kulisevsky J, Berthier ML, Gironell A, Pascual-Sedano B, Molet J, Pares P. Mania following deep brain stimulation for Parkinson's disease. Neurology 2002;59:1421-4. 17. Minguez-Castellanos A, Escamilla-Sevilla F, Katati MJ, et al. Different patterns of medication change after subthalamic or pallidal stimulation for Parkinson's disease: target related effect or selection bias? J Neurol Neurosurg Psychiatry 2005;76:34-9. 18. Burkhard PR, Vingerhoets FJ, Berney A, Bogousslavsky J, Villemure JG, Ghika J. Suicide after successful deep brain stimulation for movement disorders. Neurology 2004;63:2170-2. 19. Saint-Cyr JA, Trepanier LL, Kumar R, Lozano AM, Lang AE. Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. Brain 2000;123 ( Pt 10):2091-108. 20. Alegret M, Junque C, Valldeoriola F, et al. Effects of bilateral subthalamic stimulation on cognitive function in Parkinson disease. Arch Neurol 2001;58:1223-7. 21. Pillon B, Ardouin C, Damier P, et al. Neuropsychological changes between "off" and "on" STN or GPi stimulation in Parkinson's disease. Neurology 2000;55:411-8.

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