Parkinson’s Disease
An 81-year-old man presents to his GP with his daughter. His daughter is concerned due to noticing involuntary, rhythmic movements in his hands for the past 6 months. The symptoms are worse at rest. He is now losing his ability to care for himself. Physical exam shows increased resistance to passive flexion and extension in the bilateral upper limbs. The GP also notices he is shuffling when being asked to move around. What is your likely diagnosis?
Parkinson's disease is a neurodegenerative condition caused by depletion of dopaminergic neurons, particularly in the basal ganglia. Understanding the basal ganglia is particularly important in this pathology. The basal ganglia is composed of an array of structures and has a major role in movement control and learned motor patterns. To produce coordinated movement, the motor cortex first communicates with the striatum (composed of the caudate nucleus and putamen). The striatum communicates with the globus pallidus interna and substantia nigra pars reticularis, which sends information to the thalamus, back to the cortex for motor function. However, there is an important interconnection through a structure called the substantia nigra pars compacta. Dopaminergic neurons are located here and degenerate in this pathology. This ultimately results in excessive inhibitory input to the thalamus, reducing the coordination and control of movement.
In the pre-clinical stage of Parkinson’s, symptoms include constipation, anosmia, and sleep disturbance. In the clinical stage, the clinical features of Parkinson’s are super easy to remember through this simple mnemonic. This is Parkinson’s TRAPS. This stands for tremor, rigidity, akinesia/bradykinesia, postural instability, and shuffling gait. Tremor is often described as a pill-rolling tremor, subsiding with voluntary movement. Rigidity refers to increased resistance to passive joint movement and is thus known as cogwheel rigidity. Akinesia or bradykinesia refers to slowed movement in combination with decreased amplitude and speed when moving.
Diagnosis of Parkinson’s is clinical, and additional tests such as imaging are not routinely required. However, the Levodopa challenge test involves determining if administering levodopa, a pharmacological agent relieving symptoms of this pathology, has a positive clinical effect. This brings us to treatment.
For patients under the age of 65, the following drugs are used:
Dopamine agonists (e.g., pramipexole) for decreased motor complications
MAO-B inhibitors (e.g., selegiline) that inhibit the MAO-B enzyme that metabolizes dopamine
COMT inhibitors (e.g., entacapone) that reduce levodopa catabolism
Monotherapy or in conjunction with levodopa (precursor amino acid metabolized to dopamine) plus carbidopa
If the patient is over 65 years of age, Levodopa plus carbidopa are usually considered. An important treatment option is deep brain stimulation. It is used for severe motor symptoms in patients who respond to levodopa but are not sufficiently controlled.