MKSAP Quiz: 1-year history of daily afternoon fatigue
A 51-year-old woman with a 5-year history of multiple sclerosis is evaluated for a 1-year history of daily afternoon fatigue that necessitates frequent naps and impairs her concentration at work. Following a physical exam and lab studies, what is the most appropriate management?
A 51-year-old woman is evaluated for a 1-year history of daily afternoon fatigue that necessitates frequent naps and impairs her concentration at the office, where she works as a lawyer. Lifestyle adjustments, such as improving sleep hygiene, getting regular exercise, yoga, and vitamin supplementation have not resolved this symptom. She has a 5-year history of multiple sclerosis. Medications are glatiramer acetate and a vitamin D supplement.
On physical examination, vital signs are normal. Depression screening is negative. The remainder of the physical examination is noncontributory.
Results of laboratory studies, including hemoglobin and serum thyroid-stimulating hormone levels, are unremarkable.
Which of the following is the most appropriate management?
A. Baclofen
B. Memantine
C. Modafinil
D. Substitution of an interferon beta for the glatiramer acetate
E. Tetrahydrocannabinol-cannabidiol combination
MKSAP Answer and Critique
The correct answer is C. Modafinil. This content is available to MKSAP 18 subscribers as Question 6 in the Neurology section. More information about MKSAP is available online.
This patient should receive modafinil. Chronic fatigue is a common symptom in multiple sclerosis (MS). The fatigue associated with MS can have various causes, such as depression, insomnia, or other comorbid conditions. However, patients with MS without these conditions also can experience significant fatigue, which is often described as a sensation of mental exhaustion, frequently occurring in the midafternoon. Lifestyle adjustments, such as improving sleep hygiene, getting regular exercise, and treating depression, can sometimes resolve this symptom. For those with refractory fatigue, stimulant medications can be used. The most common medications of this type used (off-label) in MS are modafinil, armodafinil, and amantadine. For fatigue that is refractory to these medications, amphetamine stimulants, such as methylphenidate, also can be considered.
Spasticity is a frequent consequence of damage to the corticospinal tract in MS. This symptom manifests clinically as increased muscle tone, painful muscle cramps, spasms, and contractures. Spasticity can be reduced by using muscle relaxants, such as baclofen, tizanidine, or cyclobenzaprine. Antispasticity drugs, such as baclofen, are not effective agents for the management of fatigue.
Memantine has been evaluated as a means of treating MS-related cognitive deficits but has proved ineffective for this purpose. There is no reported benefit for MS-related fatigue with memantine.
Substituting an interferon beta for the glatiramer acetate would not be an appropriate step. Her fatigue is not an adverse effect of glatiramer acetate (which might necessitate a therapeutic switch), but rather a treatable symptom of an MS relapse.
Cannabinoids, such as tetrahydrocannabinol-cannabidiol, have been tested in clinical trials for a number of MS-related symptoms but have not improved outcomes. Trials have included the treatment of disease progression, spasticity, pain, and muscle stiffness. There are no data on the effect of cannabinoids on fatigue.
Key Point
- Multiple sclerosis–related fatigue is most appropriately treated with a stimulant medication, such as modafinil.