Parkinson’s Disease

1. Parkinson’s Disease Mariecken V. Fowler, M.D. Winchester Neurological Consultants Board Certified in : Neurology, Behavioral Neurology and Neuropsychiatry, and in Neuroimaging

2. What is Parkinson’s disease? • 1817: James Parkinson “An Essay on the Shaking Palsy” • Diagnosis requires 2 of 3: • Bradykinesia • Rigidity • Tremor (primarily at rest) • Onset insidious, unilateral  bilateral Parkinson’s disease (PD) is a chronic, progressive disease in which ordinary movement and other symptoms may worsen over time

3. Parkinson’s Disease Prevalence • Approximately 1 million people in the US have PD1 • More people have PD than have multiple sclerosis, muscular dystrophy, and Lou Gehrig’s disease combined1 • Average age of onset is around age 622 • Younger people can get PD (called young onset PD), but it is less common3 Statistics on Parkinson’s. Parkinson’s Disease Foundation. Available at www.pdf.org. Young onset diagnosis. Parkinson's Disease Foundation. Available at www.pdf.org. American Parkinson’s Disease Association. National Young Onset Center. Available at www.youngparkinsons.org.

4. Famous people with PD, past and present • Michael J. Fox • Janet Reno • Muhammad Ali • Sir Michael Redgrave • Pope John Paul II • Vincent Price • Deborah Kerr • Eugene McCarthy Wikipedia. List of Parkinson’s disease patients. Available at www.wikipedia.org.

5. Cause of PD still not known Experts believe PD is the result of interaction between genetic and environmental causes1,2 • PD is more common in some families than in others • Genes associated with PD have been found but are not thought to play a role in most cases • Exposure to certain pesticides may contribute to the development of PD Causes. Parkinson’s Disease Foundation. Available at www.pdf.org. Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.

6. Primary movement symptoms • 4 major movement (motor) symptoms1,2 • First 3 are most common in early PD and usually appear on one side of the body1,2 • Everyone experiences symptoms differently • Symptoms. Parkinson’s Disease Foundation. Available at www.pdf.org. • Jankovic J, In. Pahwa et al, eds. Handbook of Parkinson’s Disease. 3rd ed. NY, NY. Marcel Dekker, Inc.;2003.

7. Movement (motor) 1,2 Stooped posture Small handwriting Decreased arm swing Cramping Difficulty swallowing Changes in facial expression Shuffling Sexual dysfunction Nonmovement (nonmotor) 1,2 Depression, apathy, or anxiety Sleep problems Pain Slowed thinking Memory difficulty Constipation Urinary problems Fatigue Reduced sense of smell Loss of appetite Other symptoms • Symptoms. Parkinson’s Disease Foundation. Available at www.pdf.org. • Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

8. The pathology of PD • Neurons transmit messages to other neurons via chemical messengers, or neurotransmitters1,2 • One of the neurotransmitters that helps control movement is dopamine1,2 • In PD, neurons lose the ability to make and transmit dopamine1,2 • Loss of dopamine leads to difficulty controlling movement1,2 neuron dopamine What is Parkinson's disease (PD)? National Parkinson Foundation. Available at www.parkinson.org. What is Parkinson's disease? Parkinson's Disease Foundation. Available at www.pdf.org.

9. An evolving picture of PD PD begins in the mid-brain, in the substantia nigra substantia nigra Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

10. Pathology of PD • Neurodegenerative • ↓Dopamine-containing neurons in substantia nigra • Imbalance between dopaminergic outflow tracts in the basal ganglia causes the symptoms • Lewy bodies • Spherical hyalin masses • Present in most but not all forms of PD

11. An evolving picture of PD • A current hypothesis, called the Braak hypothesis, suggests PD begins long before movement symptoms appear1 • PD begins in the lower brainstem and progresses to other parts of the brain1 • Some nonmotor symptoms appear before diagnosis1 Adapted with permission from author (Braak H), taken from Braak H, Ghebremedhin E, Rub N, et al. Stages in the development of Parkinson’s disease–related pathology. Cell Tissue Res. 2004; 318:121-134. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

12. Putting PD treatment together

13. Your PD treatment team

14. Levodopa replaces dopamine COMT-inhibitors preserve levodopa MAO-B inhibitors preserve existing dopamine Dopamine agonists mimic dopamine How PD medications work Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006. Medications for motor symptoms of PD. National Parkinson Foundation. Available at www.parkinson.org.

15. Levodopa replaces dopamine Levodopa / Sinemet • Converts to dopamine once it enters the brain1 • Most effective drug to treat symptoms2 • However, new symptoms (called motor complications) emerge over time2 Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

16. “On” time • When levodopa is controlling PD symptoms • “Off” time • Return of PD symptoms before the next dose of levodopa Motor complications of levodopa • Motor fluctuations occur as levodopa loses its effectiveness • Dyskinesias: uncontrolled, jerky movements Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

17. Inhaled carbidopa/levodopa

18. Time- Release Levodopa-Carbidopa • Rytary- FDA approved in Jan 2015 • Time released levodopa-carbidopa • Holds medication in microspheres that break down at different rates • Advantages: Improved UPDRS scores, reduced off times. Mean off time reduction from 35% to 24% compared to Stalevo • Disadvantages: Increased number of pills per dosing, conversion to rytary slightly cumbersome

19. Levodopa-Carbidopa Intestinal Gel (Duopa) • Approved by FDA in Jan 2015 for treatment of motor fluctuations with advanced Parkinson’s • Medication in suspension and slowly infused through a tube into the jejunum • Advantages: Continuous therapy which reduces the pulsatile nature of oral levodopa • Disadvantages: expensive and high adverse event rates

20. Work to prevent the breakdown of levodopa so more dopamine will be available Always prescribed with levodopa COMT-inhibitors preserve levodopa COMT-inhibitors/ Comtan Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006.

21. Dopamine agonists mimic dopamine Dopamine agonists: Requip, Mirapex, Neupro patch • Mimic the activity of dopamine in the brain—act as the messenger1 • Can be used alone in early PD or with other drugs in later PD2 Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

22. Rotigotine Patch ( Neupro) • Transdermal delivery of Dopamine Agonist • Once daily treatment for PD and RLS • May be used in early or advanced disease • Reduces “off-time” • Patches available in 2,4,6,8 mg

23. Apomorphine SQ/ Pump (Apokyn) • Dopamine Agonist used for motor fluctuations and off time • Subcutaneous injection, available in pump but not FDA approved in US • Goal is to reduce amount of off time experienced by patients • Advantage: avoid ups and downs of levodopa • Disadvantage-difficult to use, multiple injections daily, can’t use if intolerant to DA • Apomorphine SL film was unable to get FDA approval

24. MAO-B inhibitors preserve existing dopamine MAO-B inhibitors: Azilect, selegiline • Work in the brain to prevent the breakdown of dopamine1 • One of these can be used alone in early disease and all can be used with other drugs in more advanced disease2 Waters CH. Diagnosis and Management of Parkinson’s Disease. 5th ed. West Islip, NY: Professional Communications Inc.; 2006. Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009;72(suppl 4):S1-S136.

25. Surgical options • Surgery is an option for patients : • Symptoms are no longer controlled with medications • Having side effects from medication • Quality of life is suffering • Have fluctuating symptoms throughout the day • Deep brain stimulation (DBS) uses an electrical implant to stimulate targeted areas of the brain and change nerve signals Surgical treatment options. National Parkinson Foundation. Available at www.parkinson.org.

26. Surgical options • Surgery may not be for you if: • Significant cognitive changes are present (dementia) • You have uncontrolled depression • You have atypical Parkinson’s • You never had a significant response to medications for Parkinson’s • Your Parkinson’s was caused by other medications (antinausea or psychiatric medications) Surgical treatment options. National Parkinson Foundation. Available at www.parkinson.org.

27. Surgical options- at WMC since 2012 • WMC offers new hope for • Parkinson’s disease patients • WINCHESTER, VA — Insertion • of electrodes and a stimulator • into a region of the brain and • in the upper chest, respectfully, • has proven to decrease symptoms • of Parkinson’s disease. • This surgical option for • Parkinson’s disease is now • offered at the Winchester Medical • Center. Key participants in neurosurgical first at Winchester Medical Center are L-R Mariecken Fowler, MD, neurologist Winchester Neurological Consultants, Dale Sines, first patient to undergo deep brain stimulation,and Lee Selznick, MD, neuronsurgeon Virginia Brain and Spine Center. Surgical treatment options. National Parkinson Foundation. Available at www.parkinson.org.

29. Exercise: an important part of therapy • Research shows regular exercise improves: • Tremor • Balance • Gait • Flexibility • Motor coordination Exercise. National Parkinson Foundation. Available at www.parkinson.org.

30. A balanced approach to exercise Exercise. National Parkinson Foundation. Available at www.parkinson.org.

32. Mind and body wellness Other nonmedical aspects of therapy: • Massage to relieve rigidity • Meditation to relieve anxiety • Tai chi to improve balance • Proper sleep for overall health • Hobbies, friends, and support groups for emotional well-being

33. Nutritional concerns in PD • Maintaining proper weight and calorie intake • Dealing with constipation • Supporting bone health • Managing protein and levodopa Holden K. Parkinson's disease: nutrition matters. National Parkinson Foundation. Available at www.parkinson.org.

34. PD resources • National Parkinson Foundation • www.parkinson.org • Parkinson’s Disease Foundation • www.pdf.org • American Parkinson’s Disease Association • www.apda.org • www.parkinsonshealth.com • www.winchesterneurological.com • Local Parkinson’s Support Group AZL101024304/101067

35. Questions? Dr. Mariecken Fowler Office phone: (540)667-1828