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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.



A. Pathophysiology

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).


Schematic representation of the sequence of neurons involved in parkinsonism and Huntington chorea. Top: Neurons in the normal brain. Middle: Neurons in parkinsonism. The dopaminergic neuron is lost. Bottom: Neurons in Huntington disease. The GABAergic neuron is lost. (Reproduced with permission from Katzung BG: Basic & Clinical Pharmacology, 10th ed. New York, NY: McGraw Hill; 2007.)

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High-Yield Terms to Learn
Athetosis Involuntary slow writhing movements, especially severe in the hands; “mobile spasm”
Chorea Irregular, unpredictable, involuntary muscle jerks that impair voluntary activity
Dystonia Prolonged muscle contractions with twisting and repetitive movements or abnormal posture; may occur in the form of rhythmic jerks
Huntington disease An inherited adult-onset neurologic disease characterized by dementia and bizarre involuntary movements
Parkinsonism A progressive neurologic disease characterized by shuffling gait, stooped posture, resting tremor, speech impediments, movement difficulties, and an eventual slowing of mental processes and dementia
Tics Sudden coordinated abnormal movements, usually repetitive, especially about the face and head
Tourette syndrome A neurologic disease of unknown cause that presents with multiple tics associated with snorting, sniffing, and involuntary vocalizations (often obscene)
Wilson disease An inherited (autosomal ...

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