Parkinson’s Disease :: Patients face tough treatment ‘Balancing Act’

Last week, in one of TV ad Actor Michael J. Fox appeared with his disturbingly uncontrolled movements. And, his opponents in the stem-cell debate accused him of either acting or purposefully not taking his medications, in an effort to gain sympathy, quoted by news agencies worldwide. Nothing could be further from the truth, according to Parkinson’s experts. In fact, Fox’s disordered movement — a condition called dyskinesia — was mainly due to his taking medication to help control his Parkinson’s, they said.

Parkinson’s disease (PD) is a degenerative disorder of the central nervous system. It was first described in 1817 by James Parkinson, a British physician who published a paper on what he called “the shaking palsy.” In this paper, he set forth the major symptoms of the disease that would later bear his name.

Researchers believe that at least 500,000 people in the United States currently have PD, although some estimates are much higher. Society pays an enormous price for PD. The total cost to the nation is estimated to exceed $6 billion annually. The risk of PD increases with age, so analysts expect the financial and public health impact of this disease to increase as the population gets older.

Parkinson’s disease belongs to a group of conditions called movement disorders. The four main symptoms are tremor, or trembling in hands, arms, legs, jaw, or head; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance. These symptoms usually begin gradually and worsen with time. As they become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. Not everyone with one or more of these symptoms has PD, as the symptoms sometimes appear in other diseases as well.

PD is both chronic, meaning it persists over a long period of time, and progressive, meaning its symptoms grow worse over time. It is not contagious. Although some PD cases appear to be hereditary, and a few can be traced to specific genetic mutations, most cases are sporadic ? that is, the disease does not seem to run in families. Many researchers now believe that PD results from a combination of genetic susceptibility and exposure to one or more environmental factors that trigger the disease.

PD is the most common form of parkinsonism, the name for a group of disorders with similar features and symptoms. PD is also called primary parkinsonism or idiopathic PD. The term idiopathic means a disorder for which no cause has yet been found. While most forms of parkinsonism are idiopathic, there are some cases where the cause is known or suspected or where the symptoms result from another disorder. For example, parkinsonism may result from changes in the brain’s blood vessels.

Several genes have now been definitively linked to PD. The first to be identified was alpha-synuclein. In the 1990s, researchers at NIH and other institutions studied the genetic profiles of a large Italian family and three Greek families with familial PD and found that their disease was related to a mutation in this gene. They found a second alpha-synuclein mutation in a German family with PD. These findings prompted studies of the role of alpha-synuclein in PD, which led to the discovery that Lewy bodies from people with the sporadic form of PD contained clumps of alpha-synuclein protein. This discovery revealed a potential link between hereditary and sporadic forms of the disease.

At present, there is no cure for PD. But medications or surgery can sometimes provide dramatic relief from the symptoms.

Medications for PD fall into three categories. The first category includes drugs that work directly or indirectly to increase the level of dopamine in the brain. The most common drugs for PD are dopamine precursors ? substances such as levodopa that cross the blood-brain barrier and are then changed into dopamine. Other drugs mimic dopamine or prevent or slow its breakdown.

The second category of PD drugs affects other neurotransmitters in the body in order to ease some of the symptoms of the disease. For example, anticholinergic drugs interfere with production or uptake of the neurotransmitter acetylcholine. These drugs help to reduce tremors and muscle stiffness, which can result from having more acetylcholine than dopamine.

The third category of drugs prescribed for PD includes medications that help control the non-motor symptoms of the disease, that is, the symptoms that don’t affect movement. For example, people with PD-related depression may be prescribed antidepressants.

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