Relapsing White Matter Disease and Subclinical Optic Neuropathy: From the National Multiple Sclerosis Society Case Conference Proceedings

Abstract

A 16-year-old adolescent boy presented with recurrent episodes of weakness and numbness. Brain MRI demonstrated subcortical, juxtacortical, and periventricular white matter T2 hyperintensities with gadolinium enhancement. CSF was positive for oligoclonal bands that were not present in serum. Despite treatment with steroids, IV immunoglobulins, plasmapheresis, and rituximab, he continued to have episodes of weakness and numbness and new areas of T2 hyperintensity on imaging. Neuro-ophthalmologic examination revealed a subclinical optic neuropathy with predominant involvement of the papillomacular bundle. Genetic evaluation and brain biopsy led to an unexpected diagnosis.

Figure 1. Timeline of the Patient's History

COVID-19 = coronavirus disease 2019; IVIG = IV immunoglobulin; OCB = oligoclonal band; PLEX = plasmapheresis; URI = upper respiratory infection.

Figure 2. Initial MRI

(A) T2 FLAIR imaging revealing hyperintensities within the white matter of the left frontoparietal lobe (3.2 cm), left parietal lobe (3.6 cm), and right periatrial region (4.1 cm). (B) Post-contrast imaging revealing partial enhancement of all lesions. (C) MR spectroscopy revealed lactate doublets and a decreased NAA:Cr ratio in the area of hyperintensity.

Figure 3. Repeat MRI and Biopsy Results

(A) T2 FLAIR imaging revealed new and enlarging lesions, some with enhancement (not shown), involving the bilateral frontal, parietal, occipital lobes, pons, and middle cerebellar peduncle. (B) Post-biopsy site (yellow circle) in the area of hyperintense lesion as seen on MRI. (C–J) Biopsy results. (C and D) Hypercellular white matter with perivascular and parenchymal histiocytic inflammation (H&E stains). (E) A Luxol H&E stain demonstrates intact myelination of the white matter. (F) Neurofilament IHC highlights several axonal swellings, consistent with axonal injury (arrowheads). (G) CD163 IHC highlights histiocytes in a perivascular and parenchymal distribution. (H) CD3 IHC reveals few scattered T cells in a predominantly perivascular distribution. (I) GFAP IHC highlights diffuse gliosis and the cell bodies of reactive astrocytes (arrows). Scale bar = 100 μm (C–I). (J) Myxovirus protein A (MXA) expression is highlighted in the endothelium of microvessels (IHC; 1,000×).