This patient's serum 25-hydroxyvitamin D level should be measured. He most likely has experienced a breakthrough relapse of multiple sclerosis (MS), which should be treated with intravenous methylprednisolone. Given his 2 years without relapses, the MS is relatively well-controlled. However, his care is not fully optimized because he rarely takes the vitamin D supplement. Accumulating evidence suggests that disease activity in MS is highly linked with serum vitamin D levels, with less frequent relapses and fewer new MRI lesions in patients with higher levels. This patient's serum 25-hydroxyvitamin D level should thus be measured to determine if he is vitamin D deficient. Vitamin D supplementation as an adjunctive treatment in MS has been shown to be superior to disease-modifying therapy alone and has become a standard of care for MS patients, especially those who are vitamin D deficient, although the ideal dosing regimen and serum 25-hydroxyvitamin D level are still unknown. Pharmacodynamic studies are under way that may help inform dosing regimens. Vitamin D supplementation also protects against osteoporosis, for which patients with MS are at higher risk.

This patient has no clear indications supporting discontinuation of natalizumab at this time. Natalizumab is the most highly effective drug for MS currently available, which is borne out by his relapse-free status for 2 years and stable brain MRI results. Although this drug is sometimes associated with progressive multifocal leukoencephalopathy (PML), his recent negative result on JC virus antibody testing place him at a very low risk for development of PML, and the spinal cord localization of this current relapse also argues against PML, which does not affect the spinal cord.

The bilateral leg weakness and sensory level around the umbilicus (T10) are consistent with localization to the thoracic spinal cord. Therefore, an MRI of the lumbar spine would not be appropriate.

This patient has no indication for antibiotic therapy, which makes a 5-day course of trimethoprim-sulfamethoxazole inappropriate.