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New Perspectives in Parkinson's Disease

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7. Annual Discussion of Rehab Options

This includes physical therapy: gait training, strengthening, balance, LSVT-BIG, exercise, exercise bicycle, aerobic exercise, Tai Chi; occupational therapy – home safety evaluation; speech therapy – swallow study, Lee Silverman voice training (LSVT).

 

8. Annual Discussion of Safety Issues

This includes balance and falls- avoidance of ladders, safety with ADLs, orthostatic hypotension, daytime sleepiness. Driving safety can become an issue for many reasons, both physical and cognitive. Visuospatial difficulties can be problematic when a PD patient misjudges his landing on attempting to sit in a chair. This can be catastrophic when it involves the momentum of a several ton vehicle. “The responsibility for determination of driving competence in early to mid duration patients with PD is the responsibility of patients, family and physicians. Driving should be discussed and referral to a driver RHB specialist considered if necessary.”23

 

9. Discussion of Motor Complications at All Visits

This has been the classic focus of attention in therapeutic intervention.  As alluded to above, following the administration of L –Dopa the majority of PD patients develop over several years a pharmacodynamic change in their response to the drug. Continued loss of DA cells and alterations in downstream processing of striatal signal in the globus pallidus result in diminished duration of action of L-dopa and the re-emergence of PD symptoms prior to the next scheduled dose (wearing off) as well as the appearance of dyskinesias.24 Early morning painful foot dystonias may signal the first evidence of wearing off. Protein ingestion with meals may compete with L-dopa for transport across the jejunal mucosa and blood brain barrier causing loss of dose efficacy. The pattern of the PD patient’s response to medication throughout the course of the day (and night) is assessed. Based upon this information the practitioner applies the appropriate knowledge of pharmacology and pharmacokinetics to attempt to achieve as smooth a response to medication as possible with maximal on time, minimal off time and minimal side effects. The therapeutic armamentarium includes immediate release and sustained release L-dopa, DA agonists (oral, injectable, transcutaneous), L-dopa catabolic enzyme inhibitors (COMT and MAOB), amantadine and anticholinergics.

 

10. Annual Discussion of Medical and Surgical Treatment Options

When optimal control of motor symptoms can no longer be obtained by use of oral medications other options can be considered. This is usually in the setting of a patient with motor fluctuations whose off periods can only be controlled at the expense of intolerable dyskinesias. Continuous enteral L-dopa infusion has been found to ameliorate motor fluctuations. L-dopa gel (DUODOPA) for jejunal infusion is currently available in Europe and Canada( not currently available in US). Deep Brain Stimulation has proven a valuable therapeutic option for patients with uncontrollable motor fluctuations25.DBS is also of benefit for patients with PD in whom severe tremor is a predominant symptom not adequately responsive to medications. Both the Subthalamic nucleus(STN) as well as the Globus Pallidus interna (GPi) have been successfully targeted in PD. Careful patient selection is critical.

 

Quality of Life in PD and Conclusion

     Thus, of the 10 quality measures discussed, five of the ten address non-motor symptoms and seven of the ten address quality of life issues. In a recent multicenter study26 to assess the impact of non-motor symptoms on quality of life it was found that the most prevalent symptoms of which patients complained were nocturia (68%), fatigue (66%) and sialorrhea (57%). Non-motor symptom scales showed higher correlation with diminished perception of health related quality of life (HRQoL) than did motor scales. The authors questioned why it might be so that non-motor symptoms were better predictors of HRQol than motor symptoms and proposed three possible explanations.

1) We do a better job at treating DA symptoms than non DA symptoms.

2) Patients are unaware of nonDA symptoms as related to their disease and don’t tell us about them. They consequently go unattended.

3) Physicians are unaware of non-motor symptoms as related to PD or don’t have time to deal with them.

Hopefully this article will help to increase physician awareness of the many difficulties faced by the patient with PD that go beyond the traditional tremor, bradykinesia, and rigidity. Awareness of these many non-motor aspects of the disease will enable us to significantly improve the quality of life of PD patients. The management of PD will now require two more advances – the development of drugs that will halt or definitively slow disease progression and a socioeconomic environment which can make feasible our paying adequate attention to the many problems faced by our patients with this most fascinating and debilitating disorder.

 

References

1. Parkinson's, J an Essay on the Shaking Palsy, London: Sherwood, Neely and Jones, 1817

2. Carlsson, a Half-Century of Neurotransmitter Research: Impact on Neurology and Psychiatry,

Nobel Lecture, Dec 8, 2000

3. Cotzias GC, Papavasiliou PS,  Gellene R, Modification of Parkinsonism-chronic treatment with l-dopa.

NEJM.1969; 280:337-345

(4)Rascol O, Lozano A, Stern M, Powew W, Milestones in Parkinson's disease therapeutics. Mov Disord 2011;26(6):1072-1082

5. Hely MA, Morris JG, Reid WG, Trafficante R, Sydney Multicenter Study of Parkinson's disease: non-L-dopa responsive problems dominate at 15 years. Mov Disord 2005 Feb; 20(2): 190-9

6. Braak H, et al, Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003; 24: 197-211

7. Stern MB, Siderowf A, . Parkinson's at risk syndrome: can Parkinson's disease be predicted? Mov Disord. 2010;25(Suppl 1): S89-S93

8.Braune S. The role of cardiac metaiodobenzylguanidine uptake in the differential diagnosis of Parkinsonian syndromes. Clin Auton Res. 2001; 11: 351-355

9. Derkinderen P, Rouaud T, Lebouvier T, et al, Parkinson's disease: The enteric nervous system spills its guts. Neurology 2011; 77(19):1761-1767

10. Abbott RD, Ross GW, Petrovitich H et al, Bowel movement frequency in late life and incidental Lewy bodies. Mov Disord. 2007; 22:1581-1586

11 Stacy M, Hauser R, Oertel W et al, End-of-dose wearing off in Parkinson's disease: a 9-question survey assessment. Clin Neuropharmacol. 2006 Nov-Dec;29(6):312-321

12. Weintraub D, Koester J, Polenza MN, Impulse control disorders in Parkinson's disease: a cross-sectional study of 3090 patients. Arch Neurol. 2010 May; 67(5): 589-595

13. Ungerstedt U, Stereotactic mapping of the monoamine pathways in the rat brain. Acta Phys Scand 1971; Suppl 367:1-48

14. Cheng EM, Tonn S, Swain-Eng R, Factor S, Weiner WJ, Bever Jr CT, Quality improvement in neurology: AAN Parkinson's disease quality measure. Neurology 2010; 75: 2021-2027

15. Hughes AJ, Daniel SE, Ben-Schlomo Y, Daniel SE, Lees AJ. What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. Neurology 1992; 42:1142-1146

16. Weintraub D, Burn DJ, Parkinson's disease: the quintessential neuropsychiatric disorder. Mov Disord 2011; May26 (6):1022-1031

17. Friedman JH, Parkinson's disease psychosis 2010: a review article. Parkinsonism Relat Disord 2101 Nov; 16(9):553-556

18. Emre M, Treatment of dementia in Parkinson's disease. Parkinsonism Relat Disord 2007; 13 Suppl 3: S457-456

19. Mostile G, Jankovic J, Treatment of dysautonomia associated with Parkinson's disease. Parkinsonism Relat Disord 2009 Dec; 15 Suppl 3: S 224-232

20.Haq IZ, Naidu Y, Reddy P, Chaudhuri KR, Narcolepsy in Parkinson's disease. Expert Rev Neurother 2010 Jun; 10(6):879-884

21. Schenk CH, Boeve BF, The strong presence of REM sleep behavior disorder in PD: clinical and research implications. Neurology 2011 Sep 13;77(11):1030-1032

22. Michalowska M, Fiszer U, Krygowska-Wajs A, Owczarek K, Falls in Parkinson's disease. Causes and impact on patients’ quality of life. Funct Neurol 2005:20(4):163-168

23. Factor SA, Weiner WJ, Driving. In: Parkinson's Disease; Diagnosis and Clinical Management, Second Edition. Demos Publishing. New York,NY 2008. Pp: 779-790

24. Olanow CW, Stern MB, Sethi K, The scientific and clinical basis for the treatment of Parkinson's disease(2009).Neurology 2009;72(21) Suppl.4:S22-27

25. Weaver FM, Follett KA, Stern M, et al, Bilateral deep brain stimulation vs. best medical therapy for patients with advanced Parkinson's disease: a randomized controlled trial. JAMA 2009; 301(1): 63-73

26. Martinez-Martin P, Rodriguez-Blazquez C, Kurtis M, et al, The impact of non-motor symptoms on health related quality of life of patients with Parkinson's disease. Mov. Disord. 2011; 26:399-405

 

Disclosure

Speaker’s bureau for TEVA.


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