Can you determine the most likely diagnosis for a 41-year-old woman who visits her outpatient provider to evaluate muscle pain and tightness that’s more prominent in the lower extremities and worsen with movement? Let’s learn more about the case!
A 41-year-old woman presents to her outpatient provider to evaluate muscle pain and tightness. These symptoms are most prominent in the lower extremities and worsen with movement. She currently has difficulty ambulating and requires assistance with a walker. Past medical history is notable for hypertension, hyperlipidemia, and poorly-controlled multiple sclerosis. She experiences multiple acute exacerbations of multiple sclerosis each year and currently takes glatiramer acetate. Temperature is 37.3°C (99.1°F), blood pressure is 148/93 mmHg, and pulse is 67/min. Increased muscle tone is present in the bilateral lower extremities on physical examination. There is resistance to active and passive range of motion in the foot and ankle joints, which is more prominent with rapid movements. The patient is started on a new medication to treat muscle spasticity. This medication’s side effects include hyporeflexia, sedation, and tolerance with prolonged use.
Which of the following best describes this medication’s mechanism of action?
A. Activation of GABA receptors within the spinal cord
B. Inhibition of ryanodine receptors in muscle cells
C. Induction of B-cell and T-cell apoptosis
D. Inhibition of cyclooxygenase enzymes
E. Antagonization of 5-HT2 receptors within the spinal cord
Scroll down for the correct answer!
The correct answer to today’s USMLE® Step 1 Question is…
A. Activation of GABA receptors within the spinal cord
See Main Explanation.
Incorrect Answer Explanations
B. Inhibition of ryanodine receptors in muscle cells
Incorrect: Dantrolene inhibits ryanodine receptors, thereby reducing calcium release from the sarcoplasmic reticulum of muscle cells. Dantrolene can be used to treat neuroleptic malignant syndrome and malignant hyperthermia. However, this medication is not used to treat muscle spasticity that develops as a complication of multiple sclerosis.
C. Induction of B-cell and T-cell apoptosis
Incorrect: Glucocorticoids are a class of immunosuppressants that work via several mechanisms, one of which is induction of immune cell apoptosis. Intravenous glucocorticoids are effective for treating acute flares of multiple sclerosis. However, the medication would not be effective in treating muscle spasticity as a complication of poorly-controlled multiple sclerosis.
D. Inhibition of cyclooxygenase enzymes
Incorrect: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase enzymes, thereby reducing prostaglandin synthesis. NSAIDs effectively treat musculoskeletal pain but are not typically used to treat muscle spasticity.
E. Antagonization of 5-HT2 receptors within the spinal cord
Incorrect: Cyclobenzaprine is a centrally-acting muscle relaxant. Its exact mechanism of action is unclear, but the medication is thought to antagonize 5-HT2 receptors within the spinal cord. Cyclobenzaprine is more commonly used to treat musculoskeletal pain (e.g. low back pain) and fibromyalgia, but not muscle spasticity that arises from multiple sclerosis.
Main Explanation
This patient with multiple sclerosis presents with muscle spasticity, defined as a velocity-dependent increase. Baclofen therapy can be used for symptomatic management.
Baclofen is a muscle relaxant that activates presynaptic and postsynaptic γ-aminobutyric acid b (GABA b) receptors within the spinal cord. In the presynaptic membrane, baclofen increases potassium efflux and reduces calcium influx, leading to decreased excitatory neurotransmitter glutamic acid release. In the postsynaptic membrane, baclofen reinforces the action of the inhibitory neurotransmitter GABA. As a result, baclofen causes muscle relaxation both presynaptically and postsynaptically.
Baclofen is indicated for managing muscle spasticity caused by chronic neurological disorders, such as multiple sclerosis or cerebral palsy. In addition, baclofen can treat dystonia, which is characterized by involuntary muscle contractions that result in abnormal movements or postures.
Side effects include hyporeflexia, muscle weakness, hypothermia, drowsiness, and hypotension. In rare cases, baclofen can also lead to coma. Chronic baclofen use can lead to tolerance, which means that patients develop progressively reduced responses to the medication and, therefore, an increased dose to achieve the initial response.
Major Takeaway
Baclofen is a muscle relaxant that activates GABA b receptors within the spinal cord. The condition can be used to treat muscle spasticity as well as dystonia. Side effects include muscle weakness, drowsiness, and tolerance to prolonged use.
References
- Ghanavatian, S., Derian, A. (2020) “Baclofen”. StatPearls [Internet]. Web Address: https://www.ncbi.nlm.nih.gov/books/NBK526037/.
- Patejdl, R., Zettl, U.K. (2017) Spasticity in multiple sclerosis: Contribution of inflammation, autoimmune mediated neuronal damage and therapeutic interventions. Autoimmunity Reviews. 16(9), 925-936. Doi: 0.1016/j.autrev.2017.07.004.
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