Parkinson s disease a world of promise
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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

Parkinson’s Disease: A World of Promise

Sarah Click

Dr. Julie Gurwell

Spring 2006


Background
Background

  • Movement disorder

  • Affects over 1 million people usually middle aged

  • 2nd most common ND disorder behind AD


Background cont d
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


Background cont d1

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


Drug therapy reminders
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


Surgeries
Surgeries

  • Three common

    • Thalamotomy

    • Pallidotomy

    • Deep brain stimulation


Thalamotomy and pallidotomy
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


DBS

  • The area targeted is the subthalamic nucleus (STN) or globus pallidus internus (GPi)

  • Procedure basically the same

  • Lesion not created

  • Electrode remains there


Why choose dbs
Why choose DBS?

  • Main goals

    • Increase motor functions

    • Increase ADL

    • Decrease need for levodopa


Stn dbs

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


Results of drapier et al
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


Stn dbs cont d

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


Krause et al results
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)


Krause et al results cont d
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


Adverse events in krause et al trial
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


Three other studies results
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)


Pyschosocial factors in dbs
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


Pyschosocial factors in dbs cont d
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%


Pyschosocial factors in dbs cont d1
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


Conclusion
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


Getting support
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


References
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.


References1
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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