Parkinson’s disease (PD) is a neurodegenerative disorder caused by the death of dopamine-generating cells in the substantia nigra, leading to neurologic symptoms including tremor, rigidity, slowness of movement and difficulty with walking.
Early PD, showing L>R rest tremor, awkward movement of the L hand, rest tremor walking, and increased tone in the L arm:
More advanced PD, showing stooped posture, rest tremor, slow hesitant gait and difficulty turning, and poor postural reflexes (risk of falls).
Modern treatments are effective at managing the early motor symptoms of the disease, by:
1. Taking extra dopamine, in the form of the precursor drug L-Dopa,
2. Taking MAO-B or COMT inhibitors, which inhibit the breakdown of dopamine, or
3. Taking synthetic dopamine agonist drugs, which bypass dopamine, and bind directly to the dopamine receptors.
Patient with moderately severe PD, fist untreated (left panel), then after taking L-Dopa medication (right panel).
Unfortunately, as the disease progresses, patients develop motor complications characterized by involuntary movements called dyskinesias and fluctuations in the response to medication. As this occurs, PD patients a can change from phases with good respon trophic nerve growth factose to medication and few symptoms (“on” state, center panel in video below), to phases with no response to medication and significant motor symptoms (“off” state, left panel in video below), then to dyskinesias (right panel in video below). It becomes harder and harder to keep the patient “on” (middle panel) with medical treatment.
Another solution is continuous enteral medication delivery.