Pathophysiology of Primary and Secondary Movement Disorders

Abstract

Abstract Primary and secondary movement disorders can present different etiologies and physiopathology. However, the malfunctioning of the corticobasal ganglia loops is implicated in most movement disorders. Hypokinetic signs such as bradykinesia, rigidity, gait disturbance, micrographia, precision grip impairment, and speech problems are mostly explained by overactivation of the so-called direct pathway and hypofunctioning of the indirect pathway of the basal ganglia. Such a hypokinetic state is in many cases the result of degeneration of midbrain dopamine neurons (e.g., Parkinson’s disease) or the side effect of antipsychotic drugs. The low motivational state observed in many patients with depression can also be the result of reduced levels of dopamine in the mesolimbic pathway. On the other hand, many hyperkinetic movement disorders result from hyperactivation of the direct pathway and inhibition of the direct pathway. Overstimulation of dopamine receptors in the striatum and prefrontal cortex is the most common cause of hyperkinetic syndromes, such as the levodopa-induced dyskinesia of Parkinson’s disease, and akathisia of schizophrenia, and restless legs syndrome. In Huntington’s disease, chorea is caused mostly by the loss of indirect pathway neurons. Other movement disorders are caused by cerebellum and frontal cortex dysfunctions. This chapter aims to provide insights into the normal and pathologic basal ganglia activity and its implications for movement disorders.