Summary

Several aspects of movement control by neuronal pathways in the basal ganglia are summarized. Evidence from neurochemical analyses in various neurodegenerative disorders is presented to demonstrate that a severe loss of dopamine in the putamen does not of itself represent a necessary condition for the appearance of extrapyramidal symptoms, and that the appearance of extrapyramidal symptoms or sensitivity to antipsychotics eliciting extrapyramidal symptoms is not solely dependent on a lack of striatal dopamine. The strategies of reduction of cholinergic activity and of reduction of the firing rate of the serotonergic neurons are alternatives to the traditional dopamine replacement therapy in the management of extrapyramidal symptoms. Inhibition of dopaminergic activity by dopamine D2 receptor blockers, as a means of controlling psychotic symptoms is considered inappropriate in disorders such as Lewy body dementia with a potential for increased sensitivity to such medication.

Introduction

The major extrapyramidal features of resting tremor, cogwheel rigidity, akinesia and disturbance of posture are most commonly regarded as clinical symptoms of Parkinson's disease (PD), and neurochemically are associated with lesions of the dopaminergic projections to the corpus striatum from the zona compacta of the substantia nigra. However, these abnormal motor movements also occur in Lewy body dementia (LBD) and in other categories of patients, examples of which are listed in Table 34.1.

In considering these disorders, the questions under discussion are whether extrapyramidal features are always a result of loss of dopaminergic neurotransmission and, if not, what neurochemical environment is responsible for the absence or presence of parkinsonian symptoms in patients with variable losses of nigrostriatal dopaminergic function.