Hypokinetic movement disorders: Clinical practice

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Hypokinetic movement disorders: Clinical practice

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 An 82-year-old man comes to the office because of generalized fatigue for 2 years. He states that over the last year he has also had some difficulty walking and using his hands. He finds that his hands now shake, especially when he is watching television. Examination shows a thin appearing man with reduced facial expressions. He has a broad-based, hesitant gait, and a tremor of the left hand. Which of the following provides the best explanation for the cause of this patient's movement symptoms?    

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Content Reviewers:

Rishi Desai, MD, MPH

The cerebrum, cerebellum, and basal ganglia all help coordinate movements, so movement disorders can be traced back to these structures.

Broadly - there are hypokinetic disorders which cause slowness of movement, and hyperkinetic disorders, which cause excessive involuntary movement. We’ll be talking about the hypokinetic disorders.

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.

These “parkinson-plus” syndromes include Lewy body dementia, multiple system atrophy, and progressive supranuclear palsy.

Parkinsonism can also be caused by medications, including antipsychotics like haloperidol and anti-emetics like metoclopramide.

The four cardinal symptoms of parkinsonism can be remembered with the mnemonic “TRAP”.

“T” for tremor, which is classically described as a resting, pill-rolling tremor, because it looks like someone is rolling a pill between their thumb and index finger.

“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.

Cogwheel and lead-pipe rigidities are distinct from clasp-knife rigidity that results from upper motor neuron lesions.

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.

“P” stands for postural instability, which causes a stooped posture, problems with balance, and an increased frequency of falls.

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.

Now, within the basal ganglia there’s a balance between dopamine, which promotes movement, and acetylcholine, which inhibits movement.

In Parkinson’s disease, the loss of dopaminergic neurons, results in less movement, as well as difficulties in speech and swallowing.

In fact, a common complication in Parkinson’s disease is aspiration pneumonia.

Parkinson’s disease also causes cognitive symptoms, like dementia in the later stages of the disease, affective symptoms, like depression, sleep disturbances, and a loss of the ability to smell.

Interestingly, seborrheic dermatitis, an oily skin rash that appears on the scalp, face, chest and axilla has also been associated with Parkinson’s disease.

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.

Treatment of Parkinson’s disease is mainly aimed at relieving symptoms, either by increasing dopamine’s effect or by decreasing acetylcholine’s effect.

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.

At the same time, combining levodopa with carbidopa alleviates some of levodopa’s peripheral side effects, such as nausea, hypertension, and cardiac arrhythmias. Two birds, one carbidopa.

There are also dopamine agonists, which include the ergot-alkaloids bromocriptine, cabergoline and pergolide, and the non-ergot medications pramipexole and ropinirole.

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.

Other medications aim to decrease acetylcholine’s effect by blocking the acetylcholine receptor at the basal ganglia, and these include benztropine and trihexyphenidyl.

Finally there’s amantadine, which has a mechanism of action in Parkinson’s disease that’s still being worked out.

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.

In response, individuals often need an increase in the frequency of levodopa/carbidopa, and if that doesn’t work, then a COMT or MAO-B inhibitor can be added.