Overview Snapshot A 63-year-old male is brought to the physician by his wife for the evaluation of a tremor. The tremor is worse at rest, and decreases in severity with purposeful movement. The patient reports to having difficulty with initiating voluntary movement, and his wife states that the patient’s movements have been slow. On exam, there is a “pill-rolling” resting tremor accentuated when the patient is asked to perform mental calculations. On gait testing, there was difficulty with initiating gait, as well as the patient taking short steps when walking forward. (Parkinson's disease) Introduction Main components caudate putamen globus pallidus subthalamic nucleus substantia nigra Function initiation of movement and gross movement control Direct pathway in relation to dopamine (DA) DA stimulates D1 receptors on the striatum leads to inhibition of the globus pallidus internus (GPi) thalamus becomes disinhibited sends excitatory input into the cortex Indirect pathway in relation to DA DA stimulates D2 receptors on the striatum prevents inhibitory input to the globus pallidus externus (GPe) allows GPe to inhibit the subthalamic nucleus (STN) prevents GPi from inhibiting the thalamus thalamus sends excitatory input into the cortex Role in disease parkinson's disease degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNc) decreased excitation of the direct pathway, and decreased inhibition of the indirect pathway net result: decreased movement due to decreased thalamic excitation hemiballismus lesion to the STN leads to contralateral spasmodic movement of the extremities huntington's disease striatal neuron degeneration impairs inhibition of GPe, allowing it to inhibit STN leads to hyperkinetic movement