Muscle Diseases - Parkinson's disease

Parkinson's disease is a potentially devastating neurological disease that results in a progressive loss of muscle control. Patients with parkinsonism are easily recognized because of the characteristic symptoms of gradually worsening tremors, rigidity, decreased ability to make voluntary movements and, in many cases, loss of cognitive functions. Scientifically described nearly a century and a half ago, the disease is associated with the death, or degeneration, of the brain cells that supply dopamine, a chemical that transmits signals between nerve cells. Such degeneration is normal in the human brain, but in patients suffering from Parkinson's disease the loss of dopamine-producing neurons occurs at an accelerated rate. The onset of parkinsonism may follow encephalitis, a brain injury, or exposure to toxic substances, but the symptoms usually occur in patients who are middle-aged or older and, in these instances, there is no known cause for the degeneration of the nerve cells.

Symptoms

The tremors or shaking usually involve the fingers and the wrist, but sometimes the arms, legs, or head are involved to the extent that the entire body shakes. Characteristically, the tremors occur when the patient is at rest. The tremors stop or are much less marked during a voluntary muscle movement. Tremors do not occur when the patient is asleep.

Early in the disease, the patient notices what appear to be the normal signs of aging—a little shakiness, stiffness, jerky motions, and difficulty with movements such as rising out of a low, deep chair. Very gradually the signs increase. The shaking begins to interfere with daily activities and other signs develop, including what most patients with parkinsonism perceive as the most distressing symptom, bradykinesia , the gradual loss of spontaneous movement. In advanced stages of the disease, such bradykinesia results in periods when the patient's body is completely unable to move itself. These “frozen” periods are known as akinesia . And, while the emotional balance of the parkinsonian patient is generally unaffected by the disease, he may lose the ability to control the facial and vocal muscles which allow him to convey a range of different emotions. Although the patient may continue to have natural emotional responses, he cannot indicate them in the normal manner, by smiling or frowning or by raising or lowering his voice. Instead, his face appears expressionless, his voice flat. The patient frequently experiences periods of depression and tremendous frustration.

While most patients with Parkinson's disease continue to retain their cognitive abilities, in severe or advanced cases, the patient may suffer some degree of mental deterioration or dementia.

Treatment

Once it was determined nerve pathways in the brains of patients with parkinsonism were depleted of dopamine, modern treatment of the disease began to focus on providing the remaining healthy nerve cells with the means to make it. First introduced in the 1960s, levodopa, a natural brain chemical also used by the nerve cells to make dopamine, is the traditional treatment for sufferers of Parkinson's disease. Levodopa (or L-dopa), and levodopa-containing compounds, force the dying nerve cells in the brain to produce more dopamine. L-dopa also reduces all of the main symptoms of the disease. However, because the dopamine-producing cells continue to die, levodopa is usually rendered useless within ten years. For this reason, physicians sometimes delay treatment until a patient shows more severe symptoms. The drug, selegiline, also known as deprenyl, works to increase and extend the effects of Levodopa.

Side effects associated with L-dopa include nausea, involuntary movements, some mental changes, cardiac irregularities, and urinary retention. The undesirable side effects of nausea and confusion have been somewhat countered by the use of drugs like carbidopa, an extracerebral decarboxylase inhibitor , that prevent the levadopa from changing into dopamine before it enters the brain. “End-of-dose” akinesia, the return of symptoms a few hours after taking medication, can be relieved in some cases by taking the patient off drug treatments entirely for several days. Patients are usually hospitalized during this “drug holiday” and some take part in speech and physical therapy programs.

Other drugs include those in the anticholinergic and dopamine agonist categories. Anticholinergic drugs are used to treat the early stages of the disease and include: trihexyphenidyl hydrochloride, benztropine mesylate, diphenhydramine hydrochloride, biperiden, and procyclidine hydrochloride. All of these drugs reduce tremors and rigidity to a modest degree, but none affects bradykinesia. Patients using the drugs may experience such side effects as gingivitis or inflammation of the gums, constipation, mild dizziness, nausea, nervousness, and slightly blurred vision. More serious side effects could include urinary retention, confusion, and psychosis. The two drugs in the dopamine agonist category, bromocriptine and pergolide, stimulate the brain's dopamine receptors, “convincing” the receptors they are dopamine. Bromocriptine and pergolide are used alone and in conjunction with levodopa.

While drug therapy remains the primary course of treatment, research has made advances in other areas, such as studies of possible environmental causes and factors and experimental surgeries involving the transplant of adrenal glands from the parkinsonian patient and the implantation of fetal tissue.