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Treating Parkinson's Disease

Ahmed S. Ali, M.D., and John E. Morley, M.D.

Dr. Ali is a visiting scientist in the Division of Geriatric Medicine at Saint Louis University Health Sciences Center.

Parkinson's Disease (PD), of unknown cause, is the most common type (approximately 80%) of Parkinsonism, a condition characterized by changes in the brain's motor control areas (basal ganglia).1 First described by James Parkinson in 1817, it is the name given to a whole group of conditions in which disruptions of motor and nerve function occur.2 PD usually occurs between the ages of 40 and 70 years, with peak age of onset in the sixth decade, and it is rare before the age of 30. The symptom first noticed by a patient is a tremor at rest, often in the hand, which appears early in the disease and may remain throughout. Other secondary factors can cause the remaining 20% of Parkinsonism:

Toxins
  • Methanol (rubbing alcohol)
  • Carbon monoxide intoxication
  • Cyanide
  • Carbon disulfide intoxication
  • Manganese intoxication
Infections
  • Creutzfeldt-Jakob disease
  • AIDS
  • Fungal infections
Vascular Problems
  • Multi-strokes
Metabolic Disorders
  • Chronic hepatocerebral (liver-brain) degeneration
  • Hypocalcemia
Drug-induced
  • Lithium
  • Dopamine receptor blockers (neuroleptics)
  • Dopamine depleters (tetrabenazine, reserpine)
Parkinson's Disease is progressive, the symptoms worsening over the years. The main symptoms can be remembered with mnemonic PART:
Postural reflex impairment (stooped posture)
Akinesia/Bradykinesia (loss of voluntary movement)
Rigidity (cogwheel) (stiff movements)
Tremor (resting)

When to Start Treatment
Initiation of treatment (especially drug therapy) is a very important decision in the management of PD and is highly individualized.3 If the symptoms of disease do not affect the patient's life, treatment is usually not helpful. It is recommended that the disease be left untreated until it limits motor functions.

Treatment
When treatment becomes necessary, physical therapy, with emphasis on posture and gait, should be the first component. Visualization techniques to improve gait can be particularly useful. Next, drugs and surgical techniques will need to be considered.

Drugs for PD
Many drugs are available. They are divided into four major categories:

Levodopa Direct Dopamine Agonists Catechol-O-methyltransferase (COMT) Inhibitors Anticholinergics
  • Procyclidine (Kemadrin®)
  • Trihexyphenidyl (Artane®)
  • Benztropine (Cogentin®)
Other drugs include: Future drugs
  • Ethyl Ester of levodopa5
  • Remacemide
  • Immunophilins18,19
Which Drug Should You Use?
Because many of these drugs act on the brain, your doctor will very carefully need to decide which drug to use, balancing a drug's benefits against its side effects. Levodopa remains the gold standard against which all the other drugs will be measured but almost all patients who take levodopa on a long-term basis develop complications. Nevertheless, it is appropriate to start with levodopa if symptoms interfere with activities.

Drug Side Effects
The most frequent side effects include:

Levodopa (Dose-Related)
  • Early morning inability to move
  • Fidgetiness or restlessness
  • Loss of refreshing effect of sleep
Orthostatic Hypotension
Low blood pressure upon sitting up or standing (orthostatic hypotension) may be caused by the disease itself or may be a side effect of the anti-parkinsonian medications5 (most likely direct dopaminergic agonist). If minimal, no treatment is necessary. Otherwise the following may help:
  1. Elevate head of bed
  2. Drink a large glass of water in morning
  3. Adequate salt intake
  4. Do not limit late evening fluid intake
  5. Compression stockings (need to be put on while in bed)
  6. Bedside urinal and walker
  7. Florinef®
  8. Midodrine® (new alpha 1-adrenoreceptor agonist)
Gastrointestinal Side Effects
Nausea
  • Most commonly due to all dopaminergic drugs; taking medication with food is helpful.
  • Carbidopa can be used as supplement.
Constipation
Treat with
  1. High fiber diet
  2. Increase fluid intake
  3. Bran, psyllium, and docusates
  4. Cisapride (propulsid)
  5. Anticholinergic and narcotic containing drugs should be avoided.
Psychiatric and Behavioral Disorders

Psychiatric/Behavioral Disorder Treatment
Psychosis and hallucinations Reduce dosage of levodopa
Stop or reduce:
  • Dopamine agonist
  • Adjunctive medications
      (e.g., anticholinergics
      amantadine)
      Olanzapine
      Clozapine
Depression Antidepressant
If apathy is major feature, use stimulating antidepressant.
If sleep disturbance is major feature, use sedating antidepressant.
Sleep Disorders Caffeine
Increase activity
Sleep fragmentation Sedating antidepressant
Benzodiazepine (short-acting)
Controlled-release carbidopa/levodopa
Vivid dreams/nocturnal vocalizations Decrease dopaminergic medication near bedtime


Non-drug Management of PD
From the onset of symptoms and throughout the course of PD, psychological support will be needed.16 A team approach, involving the family (primary care) physician, neurologist, family members and physical, occupational and speech therapists, works best.4

Patient Education
Patients and family members should be provided with the latest and most reliable information about the course and the prognosis of the disease, which is often helpful in relieving the fear and anxiety associated with the disease.

Environmental Modifications
These include an elevated bed to allow the patient to rise easily, a chair with armrests and a firm seat, a urinal or commode near the bed, raised toilet seat and a grab bar. Utensils with large handles, easy hold cups and nonskid plates. Specific spoons to control tremor are available.

Driving
This is a very important aspect of the PD patient's life, so they need careful consideration in assessing their driving capability, e.g., mental status, judgment and reaction speed.

Psychotherapy
Especially when depression occurs, psychological counseling may be useful and antidepressants helpful.

Occupational Therapy
To help the patient manage the activities of daily living.

Speech Therapy
Breathing control exercises; patients practice augmentation of voice loudness and variation in pitch. Loud reading and singing. Swallowing difficulties may need assessment and dietary modifications.

Physical Therapy
Simple exercises, such as swimming, walking and bicycling, should be encouraged. As the disease advances, prescribed exercises likely to improve postural instability, stooped posture and shuffling gait should be instituted. Strength training needs to be continued throughout life. Visualization techniques to teach the patient to step over objects may improve gait.

A recent report suggests that a special exercise program can improve mobility in patients with early and mid-stage PD.17

Dental Care
Daily flossing and tooth brushing with fluoride or tartar-control toothpaste are recommended.

Family Counseling
All available information should be provided to the family members and caregivers so they understand the PD and its complications. Caregiver support groups can be helpful.

Nutritional Disturbances
Diet should be well balanced and dietary consultation is often helpful.

When Drug Therapy Isn't Enough
Different surgical techniques have been tried to relieve PD symptoms, especially the motor disturbances. Tiny areas of the brain are either removed or frozen, or their connections to other parts of the brain severed.

A newer procedure, deep-brain stimulation (DBS), is an alternative to surgery that may reduce postural rigidity and some of the pain associated with PD. A stimulatory device, much like a cardiac pacemaker, is implanted in the upper torso and wires are threaded to the brain's motor areas. Though it provides functional improvement, the disadvantages of DBS are that the stimulatory device may need replacement because of fracture or infection and the battery will need to be replaced after several years.

Another new approach, primarily for advanced PD patients, involves transplantation of adrenal gland cells or fetal nerve cells.6 At present, there is little human data supporting this approach.

Future techniques include electromagnetic brain stimulation which has, in some individuals, produced dramatic improvement and the direct delivery into the brain of genes or cells engineered in the laboratory to reverse some of the cellular damage that occurs as part of Parkinson's.

October 1999 Email this article to a friend

References
1. Jankovic J. The extrapyramidal disorders. In: Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: WB Saunders Co; 1996;2040-2046. return

2. Adams RD, Victor M, Ropper AH. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill; 1997:1067-1078. return

3. Calne DB. Initiating treatment for idiopathic Parkinsonism. Neurology. 1994;44(7):S19-S22. return

4. Goetz CG, Jankovic J. Koller WC, Lieberman A, Taylor RB, Waters CH. Nonpharmacological approaches to the management of Parkinson's disease. Continum. 1995;1(4):114-129. return

5. Waters CH. Management of patients with complicated Parkinson's disease. Syllabus, Course 127. American Academy of Neurology Annual Meeting, Seattle, WA 1995:33-42. return

6. Kordower JH, Goetz CG, Freeman TB, Olanow CW. Dopaminergic transplants in patients with Parkinson's disease: neuroanatomical correlates of clinical recovery. Exp Neurol. 1997;144:41-46. return

7. Ahlskog JE. Treatment options for mild and moderate Parkinson's disease. Syllabus, Course 236. American Academy of Neurology 48th Annual Meeting: San Francisco, Calif: 1996;25-42. return

8. Mizuno Y, Kondo T, Narabayashi H. Pergolide in the treatment of Parkinson's disease. Neurology 1995;45(3, suppl 3):S13-S21. return

9. Tulloch IF. Pharmacologic profile of ropinirole: a nonergoline dopamine agonist. Neurology, 1997 (suppl 1):S58-S62. return

10. Standaert DG, Young AB. Treatment of central nervous system degenerative disorders: Parkinson's disease. In: Hardman JG, Limbird LE, Molinoff N , Ruddon RW, Gilmon AG, ed. Goodman and Gilman's The Pharmacologica Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1996:506-513. return

11. Koller WC. Treatment of Parkinson's disease: Mild and moderate treatment options. Syllabus. Course 127. American Academy of Neurology Annual Meeting; 1995; Seattle, Wash. return

12. Stern MB. Contemporary approaches to the pharmacotherapeutic management of Parkinson's disease overview. Neurology, 1997;;40 (1 suppl 1):S2-S9. return

13. Koller WC. Neuroprotective therapy for Parkinson's. return

14. Lees AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined selegiline in patients with early, mild Parkinson's disease. Parkinson's Disease Research Group of the United Kingdom. BMJ. 1995;311:1602-1607. return

15. Blanpied TA, Boeckman FA, Aizenman E, Johnson JW. Trapping channel block of NMDA-activated responses by amantadine and memantine. J Neurophysiol 1997;77:309-323. return

16. Golbe LI, Sage JI. Medical treatment of Parkinson's disease. In: Kurlan R, ed. Treatment of Movement Disorders. Philadelphia, PA: JB Lippincott Co; 1995:1-56. return

17. Schenkman M, Toni M., et al. Exercise to improve spinal flexibility and function for people with Parkinson's Disease: A randomized, controlled trial. J Am Geriat Soc 46:1207-1216, 1998. return

18. Snyder SH, Sabatini DM, Lai MM, Steiner JP, Hamilton GS, Suzdak PD: Neural actions of immunophilin ligands. Trends in Pharmacol Sci 19(1):21-26, 1998. return

19. Pratt WB. The hsp90-based chaperone system: involvement in signal transduction from a variety of hormone and growth factor receptors. Proc Soc Exp Bio & Med 217(4):420-434, 1998. return




  

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