A 37-year-old man reported a 5-day history of progressive bilateral vision loss and pain with eye movement. There was no neurological or ocular medical history. Ophthalmologic evaluation revealed visual acuities of count fingers at 2 feet in the right eye and count fingers at 6 feet in the left eye with bilateral optic disc edema. MRI revealed 2 subcortical circumscribed lesions in the frontal lobes (Fig. 1A). No vasogenic edema, mass effect, or other white-matter plaques were noted. On lumbar puncture, the opening pressure was normal as were the glucose and protein levels. The cerebropinal fluid contained 10 white blood cells/mm3. The patient was treated with intravenous methylprednisolone 250 mg 4 times daily ×5 days and discharged with a prednisone taper.
Two weeks later, he was evaluated in the emergency department with worsening of vision to light perception in both eyes. In addition to bilateral optic disc edema, there was retinal venous sheathing in the inferotemporal arcade of the right eye (Fig. 1B). Repeat brain MRI revealed lesion expansion to 4.1 × 2.7 cm in left frontal lobe and 4.6 × 3.8 cm in right frontal lobe. MRI also showed bilateral optic nerve enhancement and an enhancing lesion in the thoracic spinal cord. Testing for neuromyelitis optica antibodies was negative, and he was diagnosed with tumefactive multiple sclerosis (TMS). Five cycles of plasma exchange were initiated, which improved his vision to count fingers in the right eye and hand motions in the left eye. The patient was discharged after a 16-day hospitalization with a prednisone taper.
At 1-year follow-up, visual acuities were 20/400 in both eyes, and optical coherence tomography revealed retinal nerve fiber layer thinning (56.7 µm, right eye; 57.0 µm, left eye). Venous sheathing in the inferotemporal arcade of the right eye remained stable.
A 40-year-old woman presented to the emergency department with a 5-day history of progressive vision loss in her left eye. Ophthalmologic examination revealed visual acuities of 20/40 in the right eye and count fingers in the left eye, with a relative afferent pupillary defect in the left eye. The right fundus appeared normal while there was left optic disc edema. Ophthalmoscopy of the left eye revealed mild optic disc edema and pallor with perivascular bone spicule pigmentation along the inferonasal arcade (Fig. 1C).
Brain MRI demonstrated a circumscribed lesion in the left frontal lobe (Fig. 1D). Multiple T2 hyperintense lesions were located periventricularly and along cervical and upper thoracic spinal cord. CSF testing revealed a single oligoclonal band on isoelectric focusing. The patient was diagnosed with TMS and underwent 5 cycles of plasma exchange and was discharged from the hospital on rituximab.
Five months after initial presentation, visual acuity had improved to 20/30 in the left eye. The patient continues to experience symptoms of MS including motor dysfunction, scanning speech, and incontinence.
TMS is a variant of MS characterized by lesions >2 cm in diameter with mass effect, edema, and/or ring enhancement on MRI (1). The diagnosis is often one of exclusion due to the indistinguishable appearance on MRI of tumefactive demyelination from neoplasms and other lesions of the central nervous system (2).
Retinal vascular sheathing has been well described in patients with MS. The perivascular lymphocytic infiltration and accompanying edema, which characterizes demyelinating lesions of MS, is likely the mechanism responsible for retinal periphlebitis and sheathing of retinal vessels (3). A similar etiology also has been proposed for the occurrence of uveitis and pars planitis in MS (4). In a large case series, Green et al (5) reported that the inflammatory cellular infiltrates in the retinal veins of patients with primary, secondary, relapsing–remitting, and chronic MS were lymphocytes and phagocytes.
Retinal bone spicule pigmentation occurring in a patient with tumefactive MS is unusual. In a mouse model, Jaissle et al (6) postulated that pathological contact between retinal vessels and the retinal pigment epithelium (RPE) stimulates RPE cells to migrate and surround nascent aberrant vessels to re-establish the blood–retina barrier. In our patient, the autoimmune periphlebitis, or ischemia secondary to venous sheathing, could have stimulated the RPE cells with subsequent development of bone spicule pigmentation.
STATEMENT OF AUTHORSHIP
Category 1: a. conception and design: J. Chacko; b. acquisition of data: R. Sanders and J. R. Burks; c. analysis and interpretation of data: A. Neuhouser, R. Sanders, and J. R. Burks. Category 2: a. drafting the manuscript: A. Neuhouser; b. revising it for intellectual content: R. Sanders and J. Chacko. Category 3: a. final approval of the completed manuscript: A. Neuhouser, R. Sanders, J. R. Burks, and J. Chacko.
1. Ashrafi MR, Tavasoli AR, Alizadeh H, Zare Noghabi J, Parvaneh N. Tumefactive multiple sclerosis variants: report of two cases of schilder and balo diseases. Iran J Child Neurol. 2017;11:69–77.
2. Kaeser MA, Scali F, Lanzisera FP, Bub GA, Kettner NW. Tumefactive multiple sclerosis: an uncommon diagnostic challenge. J Chiropr Med. 2011;10:29–35.
3. Lightman S, McDonald WI, Bird AC, Francis DA, Hoskins A, Batchelor JR, Halliday AM. Retinal venous sheathing in optic neuritis: its significance for the pathogenesis of multiple sclerosis. Brain. 1987;110:405–414.
4. Forooghian F. Uveitis and the diagnosis of multiple sclerosis. Can J Neurol Sci. 2017;44:334–335.
5. Green AJ, McQuaid S, Hauser SL, Allen IV, Lyness R. Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain. 2010;133:1591–1601.
6. Jaissle GB, May CA, van de Pavert SA, Wenzel A, Claes-May E, Giessl A, Szurman P, Wolfrum U, Wijnholds J, Fischer MD, Humphries P, Seeliger MW. Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model. Graefes Arch Clin Exp Ophthalmol. 2010;248:1063–1070.