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INTRODUCTION

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Movement disorders constitute a number of heterogeneous neurologic conditions with very different therapies. They include parkinsonism, Huntington’s disease, Wilson’s disease, and Gilles de la Tourette’s 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.

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PARKINSONISM

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A. Pathophysiology
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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).

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1. Naturally occurring parkinsonism
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The naturally occurring disease is of uncertain origin and occurs with increasing frequency during aging from the fifth or sixth decade of life onward. 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). 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).

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FIGURE 28–1

Schematic representation of the sequence of neurons involved in parkinsonism and Huntington’s chorea. Top: Neurons in the normal brain. Middle: Neurons in parkinsonism. The dopaminergic neuron is lost. Bottom: Neurons in Huntington’s disease. The GABAergic neuron is lost. (Reproduced, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology, 9th ed. McGraw-Hill, 2004: Fig. 28–1).

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2. Drug-induced parkinsonism
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Many drugs can cause parkinsonian symptoms; these effects are usually reversible. The most important drugs are the butyrophenone and phenothiazine antipsychotic drugs, which block brain dopamine receptors. At high doses, reserpine causes similar symptoms, presumably by depleting brain dopamine. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a by-product of the attempted synthesis of an illicit meperidine analog, causes irreversible parkinsonism through destruction of dopaminergic neurons in the nigrostriatal tract. Treatment with type B monoamine oxidase inhibitors (MAOIs) protects against MPTP neurotoxicity in animals.

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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 shufflinq 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, ...

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