Porth's Essentials of Pathophysiology, 4e

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Disorders of Neuromuscular Function

C h a p t e r 3 6

TABLE 36-1 Characteristics of Basal Ganglia–Associated Movement Disorders Movement Disorder Characteristics

Tremor

Involuntary, oscillating contractions of opposing muscle groups around a joint Usually fairly uniform in frequency and amplitude Can occur as resting tremors and postural tremors, which occur when the part is maintained in a stable position Slowness in initiating movement, and reduced range and force of the movement (bradykinesia) Irregular wriggling and writhing movements Accentuated by movement and by environmental stimulation; they often interfere with normal movement patterns May be grimacing movements of the face, raising the eyebrows, rolling of the eyes, and curling, protrusion, and withdrawal of the tongue In the limbs, the movements largely are distal; there may be piano playing–type movements with alternating extension and flexion of the fingers Continuous, wormlike, twisting and turning motions of the joints of a limb or the body Violent, sweeping, flinging motions, especially of the limbs on one side of the body (hemiballismus) Abnormal maintenance of a posture resulting from a twisting, turning movement of the limbs, neck, or trunk Often the result of simultaneous contraction of agonist and antagonist muscles Can result in grotesque and twisted postures Bizarre wriggling and writhing movements Frequently involve the face, mouth, jaw, and tongue, causing grimacing, pursing of the lips, or protrusion of the tongue Limbs affected less often Tardive dyskinesia is an untoward reaction that can develop with long-term use of some antipsychotic medications

Hypokinetic disorders

Chorea

Athetosis Ballismus Dystonia

Dyskinesias

Parkinson Disease Parkinson disease is a progressive degenerative disor- der of basal ganglia function that results in variable combinations of tremor, rigidity, and bradykinesia. 33,34 Parkinson disease is the second most common neuro- degenerative disease after Alzheimer disease. It usually begins after 50 years of age, with the prevalence increas- ing to 4% to 5% in those older than 85 years of age. 33 The clinical syndrome arising from the degenerative changes in basal ganglia function often is referred to as parkinsonism. Parkinson disease, the most common form of parkinsonism, is named after James Parkinson, a British physician who first described the disease in a paper he published in 1817 on the “shaking palsy.” 35 In Parkinson disease, also known as idiopathic parkinson- ism, dopamine depletion results from degeneration of the dopamine nigrostriatal system. Parkinsonism can also develop as a postencephalitic syndrome, as a side effect of therapy with antipsychotic drugs that block dopamine receptors, as a toxic reaction to a chemical agent, or as an outcome of severe carbon monoxide poisoning. 36 Drug- induced parkinsonism can follow the administration of antipsychotic drugs in high doses (e.g., phenothiazines, butyrophenones). These drugs block dopamine receptors and dopamine output by the cells of the substantia nigra. Symptoms of parkinsonism also may accompany con- ditions such as cerebral vascular disease, brain tumors, repeated head trauma, or degenerative neurologic dis- eases that structurally damage the nigrostriatal pathway. The primary brain abnormality found in persons with Parkinson disease is degeneration of the nigros- triatal pathway, with subsequent reduction in striatal

concentrations of dopamine. Other brain areas are affected to a lesser extent. 37,38 Although the cause of Parkinson disease is still unknown, it is widely believed that most cases are caused by an interaction of envi- ronmental and genetic factors. Over the past several decades, several pathologic processes (e.g., oxidative stress, apoptosis, and mitochondrial disorders) that might lead to degeneration have been identified. There is increasing evidence that the development of Parkinson disease may be related to oxidative metabo- lites and the inability of neurons to render these prod- ucts harmless. Of interest in terms of research was the development of Parkinson disease in several persons who had attempted to make a narcotic drug and instead synthesized a compound called MPTP (1-methyl- phenyl-2,3,6-tetrahydropyridine) . 37,38 This compound selectively destroys the dopaminergic neurons of the substantia nigra. This incident prompted investigations into the role of toxins that are produced by the body as a part of metabolic processes and those that enter the body from outside sources in the pathogenesis of Parkinson disease. One theory is that the auto-oxida- tion of catecholamines, such as dopamine, may injure neurons in the substantia nigra. MPTP is an inhibitor of the mitochondrial electron transport system that func- tions in the inactivation of these metabolites, suggesting that it may produce Parkinson disease in a manner simi- lar to that of the naturally occurring disease. The recent discovery of inherited forms of Parkinson disease suggests that genetic factors may also play a role in the pathogenesis of early-onset Parkinson dis- ease. 37–39 The first genetic mutation associated with