PARKINSONISM

a neurologic disorder marked by a progressive loss of motor function resulting from the degeneration of neurons in the area of the brain that controls voluntary movement. Parkinsonism was first described in 1817 by the British physician James Parkinson in his Essay on the Shaking Palsy. Various types of the disorder are now recognized, but the disease described by Parkinson, called Parkinson's disease, primary parkinsonism, or paralysis agitans, is the most common form. It is also referred to as idiopathic parkinsonism because the cause of neurodegeneration in this form of the disorder is unknown. The average age of onset of Parkinson's disease is about 57. It often begins with a slight pill-rolling tremor of the hands and slowly progresses over 10 to 20 years, ending in paralysis, dementia, and death. In other types of parkinsonism, referred to as secondary parkinsonism, the causal agent of neuronal deterioration is known. Another type, called parkinson-plus disease, or multiple-system degenerations, includes diseases in which the main features of parkinsonism are accompanied by other symptoms. The four main signs of parkinsonism are tremor of resting muscles, particularly of the hands; muscular rigidity of the arms, legs, and neck; difficulty in initiating movement (bradykinesia); and loss of balance. A variety of other features may accompany these characteristics, including a lack or fixity of facial expression, difficulty in swallowing or speaking, stooped posture, a shuffling gait, depression, and dementia. Parkinsonism results from the deterioration of neurons in the region of the brain called the substantia nigra. These neurons normally produce the neurotransmitter dopamine, which sends signals to the basal ganglia, a mass of nerve fibres that helps to initiate and control patterns of movement. Dopamine functions in the brain as an inhibitor of nerve impulses and is involved in suppressing unintended movement. When the dopamine-producing (dopaminergic) neurons are damaged or destroyed, dopamine levels drop and the normal signaling system is disrupted. The features of parkinsonism do not appear until 60 to 80 percent of these neurons are destroyed. Although the cause of neuronal deterioration in primary parkinsonism is unknown, causal agents have been identified for some types of the disorder. A viral infection of the brain that caused a worldwide pandemic of the sleeping sickness encephalitis lethargica from 1918 to 1919 resulted in the subsequent development of postencephalitic parkinsonism in some survivors. (These patients were described by the British neurologist Oliver Sacks in his book Awakenings .) Some cases of parkinsonism have been attributed to sublethal poisoning with carbon monoxide, manganese, or cyanide. Pugilistic parkinsonism results from head trauma and has affected professional boxers such as Jack Dempsey and Muhammad Ali. Another type of parkinsonism appeared in persons using a contaminated form of heroin. The contaminant was a neurotoxin, called 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The ability of this substance to destroy neurons suggests that an environmental toxin similar to MPTP may be responsible for Parkinson's disease. The parkinsonism-dementia complex, which occurs among the Chamorro people of the Pacific Mariana Islands, is also thought to result from an unidentified environmental agent. In some individuals a genetic defect is thought to incur susceptibility to the disease. Both medical and surgical therapies are used to treat parkinsonism. The drug levodopa (L-dopa), a precursor of dopamine, is used in conjunction with the drug carbidopa to alleviate symptoms, although this treatment tends to become less effective over time. Other medications used are deprenyl, a type of drug that slows the breakdown of dopamine, and bromocriptine and pergolide, two drugs that mimic the effects of dopamine. Two relatively new surgical procedures used to treat parkinsonism are pallidotomy and fetal tissue transplantation. Pallidotomy involves the destruction of a part of the brain structure called the globus pallidus involved in motor control. Fetal tissue transplantation is an experimental technique using dopamine-producing tissue from fetuses aged 6 to 10 weeks that aims to replace the lost dopaminergic neurons of the patient.