Parkinson's Disease Center and Movement Disorders Clinic

Parkinson's Disease (PD)

Parkinson's disease is a common neurodegenerative disorder, affecting about 1 percent of the population over the age of 60 years. While the typical age at onset is in the sixth decade of life (average 55 years), about five percent of patients with PD have onset of their symptoms before age 40. Men are slightly more frequently affected than women.

Symptoms and Diagnosis

Asymmetric onset of tremor usually present when the affected body part such as the hand or foot are otherwise at rest is one of the most common presenting features. Besides tremor, the other "cardinal features" of PD include slowness of movement (bradykinesia), muscle stiffness (rigidity), and loss of balance (postural instability). Many patients, however, experience symptoms, such as shoulder pain and loss of sensation of smell, long before the onset of these motor features. Other typical symptoms of PD include loss of normal facial expression (hypomimia), drooling (sialorrhea), low volume slurred speech (dysarthria), difficulty swallowing (dysphagia), shuffling, and short steppage gait and inability to initiate gait or feeling as if the feet are glued to the floor (freezing). Other less specific, but often equally troublesome, symptoms, include fatigue, depression, loss of motivation, forgetfulness, and a variety of "autonomic" problems such as lightheadedness when standing (due to low blood pressure), urinary frequency and urgency, and constipation. Sleep disturbances may be present, and include excessive daytime sleepiness and vivid dreams associated to re-enactment of the dreams.

There is no blood or imaging test for PD, although some genetic forms of parkinsonism can be diagnosed by a DNA test. In most cases, however, the diagnosis is based on the clinical features and examination by an experienced clinician. A progressive disease, PD does not significantly alter life expectancy. Although, the symptoms can affect activities of daily living, interfere with work, and may adversely impact the quality of life, the prognosis varies markedly from one individual to another. The presence of tremor, rather than gait and balance problems, as the initial or dominant symptom suggests a favorable prognosis indicating a slowly progressive course. The postural instability and gait disorder type of PD has required higher doses of dopamine therapy. Younger onset of PD has been associated with more side effects of dopamine therapy, mainly abnormal movements called dyskinesias.

Causes

Although the cause of PD is still not completely understood, a remarkable progress has been made in our knowledge about the mechanisms of neuronal cell loss (neurodegeneration). The symptoms of PD start when there is about 60 percent loss of dopamine-producing neurons in the part of the midbrain called substantia nigra. There is growing body of evidence that these neurons die in part as a result of an abnormal accumulation and aggregation of cellular proteins which damage the neurons and impair their ability to produce dopamine. Dopamine is needed to act on other deep brain structures ("basal ganglia") to facilitate normal motor function. The current scientific evidence supports the notion that neurodegeneration associated with PD results from a complex interaction between genetic and environmental factors. Although only about 20 percent of patients have another family member with PD, genetic causes of PD are supported by the increasing number of mutated genes identified in PD patients with or without family history. The vast majority of patients with PD, however, have no identifiable gene mutation. Many epidemiological studies have suggested that certain environmental toxins, such as pesticides, may increase the risk of PD while others, such as smoking and caffeine, have been associated with lower risk of PD. No specific dietary, occupational or other environmental causative factors, however, can be identified as risk factors in most cases.

Treatments

The treatment of PD has improved dramatically since the introduction of anticholinergic drugs such as trihexyphenidyl (Artane) and amantadine (Symmetrel) in the 1950s. Levodopa was introduced in the 1960s and, when combined with carbidopa (levodopa-carbidopa or Sinemet), it has remained the most effective drug for the treatment of motor symptoms of PD. Because of concern about the possibility of loss of benefit (shortening of duration of response or "wearing-off effect") and development of abnormal involuntary movements ("dyskinesias") some clinicians have advocated delaying the onset of levodopa therapy until such time when the symptoms of PD begin to interfere with performance of activities of daily living or work. Therefore, in early stages of PD, before PD symptoms become troublesome, monoamine oxidase type B inhibitors (MAOB-I), such as selegiline (Eldepryl, Deprenyl), a sublingual preparation of selegiline (Zelapar), or rasagiline (Azilect), may be appropriate as these MAOB-I not only provide symptomatic relief in mild, early cases, but also delay the need for levodopa. When symptomatic therapy is needed dopamine agonists, such as pramipexole (Mirapex), ropinirole (Requip), and rotigotine (Neupro patch), are often prescribed as the initial dopaminergic therapy. However, when PD symptoms become troublesome various preparations of carbidopa/levodopa (Sinemet) are usually added. If patients experience wearing-off effect, which may occur after several years of levodopa therapy, then catechol-o-methyl transferase inhibitors (COMT-I), such as entacapone (Comtan), are added or the patients are switched to levodopa-carbidopa-entacapone combination (Stalevo). Apomorphine, which is also a dopamine agonist and is administered subcutaneously, may be used in selected patients with severe motor fluctuations. When the dosage is optimized most patients can tolerate these medications well, but some side effects may occur such as nausea, lightheadedness, drowsiness, hallucinations, dyskinesias, ankle swelling, and other adverse effects. If any of these, or other, adverse events occur, the patients should notify their physicians. Usually, appropriate adjustments can be made to improve the tolerability of anti-PD medications. For example, initiating the medication at the lowest possible dose and increasing it slowly or taking it with meals improves tolerability. Patients who experience motor fluctuations should generally avoid taking medications after protein meals as the amino acids would interfere with the absorption of levodopa in the small intestine. Also augmenting levodopa with additional carbidopa (Lodosyn) or adding anti-nausea medications, such as hydroxyzine (Vistaril), trimethobenzamide (Tigan), or domperidone (Motilium) usually prevents or alleviates levodopa-related nausea. Hallucinations and other psychiatric complications of levodopa can be managed effectively with the atypical neuroleptics, such as quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and clozapine (Clozaril). Drug-induced drowsiness can be effectively treated with modafinil (Provigil).

Neuroprotective Therapy

Despite intensive search for neuroprotective therapies, thus far no medication, vitamin or any nutritional supplement has been shown to protect the dopamine-producing neurons. Some drugs, such as the MAOB-I and dopamine agonists, however, have been found to delay the need for levodopa, although there is controversy whether they favorably modify the disease through any neuroprotective effect.

Surgery

Patients who continue to be troubled by their PD symptoms and experience levodopa-related motor complications, particularly fluctuations and dyskinesias, may be considered candidates for surgery. Deep brain stimulation (DBS) has replaced the older, ablative, procedures, such as thalamotomy and pallidotomy, as the surgical treatment of choice in patients whose symptoms cannot be adequately controlled despite optimal medical therapy. See Deep Brain Stimulation for additional information about the role of surgery in the treatment of PD.

Role of Physical Therapy and Exercise

Any discussion of management of PD would not be complete without emphasizing the importance of physical therapy and improved conditioning of patients with PD. Regular exercise program, combined with appropriate medical management, has been shown to delay the onset of physical disability associated with PD. Many studies have shown that exercise improves stamina and prevents fatigability, constipation, depression, sleep, osteoporosis, and memory loss. Several studies have also found that physical fitness or exercise. Are associated with brain gray matter volumes. Exercise also decreases the risk of stroke and heart attacks by reducing body weight, blood pressure, and risk of diabetes, and increasing the HDL ("good") cholesterol. For these and many other reasons ongoing vigorous exercise and physical fitness, which should include stretching, range of motion and conditioning exercises should be highly encouraged, particularly if there are no physical contraindications. Many patients wrongly assume that the "exercise" they get during their daily routines at work or at home, such as housecleaning, climbing stairs, and even mowing the lawn are sufficient forms of exercise. While these activities are encouraged, regular exercise program, tailored to the needs of the individual patient, is critical for continued well being. The exercises should be designed to improve strength (e.g. using free weights, weight machines, and elastic bands) and overall fitness (e.g. walking, swimming). Water aerobics and dancing have been found particularly effective and safe.

Incorporation of external sensory cues in the rehabilitation protocol has been shown to extend short-term benefits of physical therapy. For example, a visual cue provided by an inverted L-shaped cane, horizontal beam on a walker, or by rhythmical sound, such as listening to a marching music, can significantly help overcome gait freezing. Also, instructing the patient to take high steps or exaggerate their arm swing (e.g. simulating marching) may improve their gait and balance. Swimming or otherwise exercising in the water has the additional advantage in that there is very little stress on the joints and the resistance improves muscle strength. This low impact activity also increases endurance and balance. Some patients prefer stretching and muscle relaxing exercises such as Pilates, tai chi, and yoga and they are clearly useful additions but should not replace the various conditioning exercises. Recent animal research has provided strong evidence that exercise can increase brain levels of neurotrophic factors, increase resistance to brain insult or injury, and improve learning and mental as well as motor performance. Patients should always check with their physicians before launching into new exercise program. All precautions should be taken to prevent injuries.

Experimental Treatments

The Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine, is engaged in clinical trials testing cutting-edge, innovative therapies designed to improve symptoms of PD or to favorably modify its progression. Please, discuss your interest and willingness to participate in the therapeutic trials with one of our physicians or research coordinators. As new trials are being continuously approved, please consult ClinicalTrials.gov for the most up to date listing of available clinical trials for PD. Please use the following link which will automatically insert the "Parkinson's disease and Baylor" search terms for you.

Appendix

The Michael J. Fox Foundation for Parkinson's Research
Grand Central Station
P.O. Box 4777
New York, NY 10163-4777 
Toll free: (800) 708-7644

National Parkinson Foundation, Inc. 
200 SE 1st St., Suite 800
Miami, FL 33131
Toll-free: (800) 4PD-INFO (473-4636)
Fax: (305) 537-9901
Email: contact@parkinson.org

©2011 Joseph Jankovic, M.D.

Selected References

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