++
Movement disorders constitute a number of heterogeneous neurologic conditions with very different therapies. They include parkinsonism, Huntington disease, Wilson disease, and Gilles de la Tourette syndrome. Movement disorders, including athetosis, chorea, dyskinesia, dystonia, tics, and tremor, can be caused by a variety of general medical conditions, neurologic dysfunction, and drugs.
++
Parkinsonism (paralysis agitans) is a common movement disorder that involves dysfunction in the basal ganglia and associated brain structures. Signs include rigidity of skeletal muscles, akinesia (or bradykinesia), flat facies, and tremor at rest (mnemonic RAFT). In advanced parkinsonism, behavioral changes, delusions, and hallucinations may occur.
+++
1. Naturally occurring parkinsonism
++
The naturally occurring disease is of uncertain origin and occurs with increasing frequency during aging from the fifth or sixth decade of life onward. Mutations in the synuclein gene or the parkin gene are demonstrable in a significant fraction of patients. Incidence is decreased in individuals taking anti-inflammatory drugs chronically, but increased in farmers and those with lead or manganese exposure. Pathologic characteristics include a decrease in the levels of striatal dopamine and the degeneration of dopaminergic neurons in the nigrostriatal tract that normally inhibit the activity of striatal GABAergic neurons (Figure 28–1). Most of the postsynaptic dopamine receptors on GABAergic neurons are of the D2 subclass (negatively coupled to adenylyl cyclase) but D3 receptors may also play a role. The reduction of normal dopaminergic neurotransmission leads to excessive excitatory actions of cholinergic neurons on striatal GABAergic neurons; thus, dopamine and acetylcholine activities are out of balance in parkinsonism (Figure 28–1).
++++