AssessmentsHypokinetic movement disorders: Clinical practice
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 75-year-old man comes to the clinic with his son because of symptoms of psychosis noticed by his son. He states that his father has been experiencing auditory hallucinations and delusions secondary to dementia associated with his Parkinson disease. He has been on multiple medications to help with dementia and psychosis but his symptoms have worsened. Which one of the following agents would be the best choice to treat his psychosis and dementia in this situation?
Content Reviewers:Rishi Desai, MD, MPH
Alright, when it comes to hypokinetic disorders, the term “parkinsonism” refers to several conditions including Parkinson’s disease itself, and other syndromes called “parkinson-plus” syndromes, which cause parkinsonism plus other clinical features.
The four cardinal symptoms of parkinsonism can be remembered with the mnemonic “TRAP”.
“R” stands for rigidity, which is often described as a cogwheel-like rigidity. This means that when attempting to passively move a limb, there are a series of stops or stalls, kind of like a cog on a wheel. There’s also lead-pipe rigidity, which is when a limb is rigid throughout the entire passive movement, kind of like trying to move a lead-pipe.
In clasp-knife rigidity, the limb is initially rigid like a lead-pipe, but then it gives away, kind of like opening a clasp-knife.
“A” stands for akinesia, which is the absence of movement, and is a severe form of the more common finding of bradykinesia, which is slowness of movement. This can manifest as a narrow-based shuffling gait or a decreased facial expression, almost to the point where the individual’s face looks like they’re wearing a mask.
Usually, these symptoms are asymmetric, with the exception of medication-induced parkinsonism, which usually causes symmetric symptoms.
Now, Parkinson’s disease is a slowly progressive genetic disorder that primarily affects individuals over 50 years old.
The disease results from accumulation of the protein alpha-synuclein within neurons of the substantia nigra, which normally secrete dopamine. These intracellular inclusion bodies are called Lewy bodies.
The diagnosis of Parkinson’s disease requires the presence of bradykinesia in addition to another one of the “TRAP” symptoms, and ruling out other potential causes.
Two groups of medications help increase dopamine’s effect. The first group are medications that directly stimulate the dopamine receptor, like levodopa, which is a precursor molecule that’s converted to dopamine by a decarboxylase enzyme.
Now, levodopa is given orally and when it’s absorbed, it’s converted to dopamine by a decarboxylase enzyme. This conversion can happen peripherally in the systemic circulation, or centrally in the central nervous system.
But because our goal is to get most of the levodopa to the central nervous system, we combine it with carbidopa, a peripheral decarboxylase inhibitor. This decreases the peripheral conversion of levodopa to dopamine, and increases the central conversion of levodopa to dopamine.
The second group are medications that indirectly increase endogenous dopamine levels by preventing its degradation by certain enzymes. These include the monoamine-oxidase B, or MAO-B inhibitors like selegiline, or catechol-o-methyltransferase or COMT-inhibitors like tolcapone and entacapone.
Now, levodopa/carbidopa is the best treatment available for Parkinson’s disease, and is particularly effective at controlling motor symptoms like bradykinesia. However, its effectiveness can “wear off” after a number of years, and individuals can develop motor fluctuations where the symptoms begin to reappear.