Hindsight Is 20/20

With relapsing symptoms and findings that are separate in distribution and time, two diagnoses become most likely, and both of these are most often diagnosed in young women. MS is common, and optic neuritis occurs in more than 50% of patients over the course of illness. Neuromyelitis optica spectrum disorder (NMOSD) is a rare condition that can exist in isolation or be associated with other autoimmune illnesses. While these entities are difficult to differentiate clinically, neuroimaging that demonstrates extensive intracerebral demyelinating lesions and cerebrospinal fluid with oligoclonal bands favor MS, whereas extensive, predominant spinal cord involvement is suggestive of NMOSD. Approximately 70% of NMO patients harbor an antibody directed against the aquaporin-4 channel, and these antibodies are not seen in patients with MS. A milder NMO-like disorder has also been associated with antimyelin oligodendrocyte antibodies (MOG).

Testing for antinuclear antibodies, anti–double-stranded DNA, anti-Ro (SSA), and anti-La (SSB) antibodies was negative. The level of C3 was 162 mg per deciliter (normal range 81-157) and C4 38 (normal range 13-39). T-spot testing for latent tuberculosis was negative.

There is no serological evidence of active systemic lupus erythematosus or Sjogren’s syndrome. The pretest probability of CNS tuberculosis was low in light of her presenting complaints, relatively protracted course, and overall clinical stability without antituberculous therapy. Tests for latent tuberculosis infection have significant limitations of both sensitivity and specificity for the diagnosis of active disease.

Optical coherence tomography showed optic disc edema in the left eye only. MRI of the head with contrast revealed abnormal signal intensity involving the posterior aspect of the pons, right middle cerebellar peduncle, anterior left temporal lobe, bilateral periventricular white matter, subcortical white matter of the frontal lobes bilaterally, and medulla with abnormal signal and enhancement of the left optic nerve (Figure, Panel A). MRI of the cervical and thoracic spine demonstrated multifocal demyelinating lesions at C3, C4, C7, T4, T5, T7, and T8 (Figure, Panel B). The lesions were not longitudinally extensive. There was no significant postcontrast enhancement to suggest active demyelination.

The cerebrospinal fluid analysis revealed glucose of 105 mg per deciliter and a total protein of 26.1 mg per deciliter. In the fourth tube, there were 20 red cells per cubic and four white cells with a differential of 62% neutrophils, 35% lymphocytes, and 3% monocytes. Epstein-Barr and herpes simplex virus DNA were negative. A Venereal Disease Research Laboratory test was negative. Multiple oligoclonal IgG bands were identified only in the cerebrospinal fluid. Aquaporin-4 IgG and MOG antibodies were negative.

In addition to the expected finding of enhancement of the optic nerve, MRI demonstrated numerous multifocal white matter lesions throughout the cerebrum, brainstem, and spinal cord. Many of the lesions were in “silent” areas, which is not directly attributable to specific symptoms, but several did correlate with the subtler deficits of weakness and dysmetria that were noted on examination. Although such lesions may be seen with a diverse group of systemic diseases including adrenal leukodystrophy, sarcoidosis, Behcet’s, cerebral lupus, and vasculitis, primary CNS inflammatory demyelinating diseases are much more likely. The extensive distribution of demyelination argues against NMOSD. The negative aquaporin-4 and MOG assays support this conclusion. Not all multifocal CNS demyelination is caused by MS and can be seen in posterior reversible encephalopathy syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, and adult polyglucosan body disease. Osmotic demyelination is increasingly being recognized as a process that can be more widespread rather than just being limited to the pons. Viral infections of the CNS such as the JC virus (PML) may also provoke multifocal demyelination. Acute disseminated encephalomyelitis is most often seen during childhood, usually after vaccination or after an infectious prodrome. The tempo of the progression of these other diseases tends to be much more rapid than this woman’s course, and often, the neurological deficits are more profound and debilitating. The clinical presentation of sensory-predominant myelopathy, followed by optic neuritis, absence of systemic inflammatory signs or laboratory markers, exclusion of other relevant diseases, multifocal white matter lesions on imaging, minimal pleocytosis, and presence of oligoclonal bands in cerebrospinal fluid, all point to a diagnosis of relapsing-remitting MS.

The patient was diagnosed with MS. She was admitted to the neurology service and treated with 1,000 mg IV methylprednisolone for 3 days with a prompt improvement in her vision. She was started on natalizumab without a relapse of symptoms over the past year.