Journal of Neuro-Ophthalmology:
Shimada, Yoshiaki MD; Shibuya, Masayuki MD; Ohki, Ryutaro MD; Yoneya, Shin MD; Nakamura, Yuichi MD
Departments of Ophthalmology (YS, MS, RO, SY) and Hematology (YN), Saitama Medical School, Saitama, Japan.
Address correspondence to Yoshiaki Shimada, MD, Department of Ophthalmology, Saitama Medical School, 38 Morohongo, Moroyama, Iruma, Saitama 350-0495, Japan; E-mail: email@example.com
A 51-year-old man had reduced vision and bilateral optic disc swelling as the initial clinical manifestation of multiple myeloma. Brain imaging failed to disclose any abnormalities. Before any therapy was begun, visual function began to improve substantially. Three months after chemotherapy was started, visual function and optic disc appearance returned to near normal. There were no features to suggest polyneuropathy-organomegaly-endocrinopathy-M protein-skin changes (POEMS) syndrome. Visual loss in myeloma is usually caused by compression or infiltration of the optic nerves by tumor. The mechanism of the optic neuropathy in this case remains unknown.
Multiple myeloma can be associated with optic neuropathy, which may be the first sign of the disease (1-3). Compression of the optic nerve by a myeloma tumor (1,2) or infiltration by myeloma cells (3) usually causes the optic neuropathy (4).
We present a case of multiple myeloma that presented with bilateral optic neuropathy in which no compression or imaging abnormalities of the optic nerves could be demonstrated and in which swollen optic discs and visual function partially resolved spontaneously.
A 51-year-old man first noted a bilateral decrease in vision one month before he noted swelling of his abdomen and edema of his lower extremities. He was examined two months later and immediately hospitalized for severe hydroperitoneum. Laboratory tests showed a low hemoglobin level (62 g/l) and elevated total serum protein (134 g/l) and creatinine (2.39 mg/dl) levels. Serum and urine values revealed an IgG-kappa monoclonal component and Bence-Jones protein. Bone marrow analysis showed a 21.5% infiltration of atypical, partly binucleated plasma cells.
A skeletal survey was normal, and serum calcium levels were within normal limits. Additional neurologic and cutaneous signs were not present, and endocrinopathy and hepatosplenomegaly were not detected. A diagnosis of multiple myeloma was made, and he was referred for chemotherapy.
At the initial neuro-ophthalmologic examination, best-corrected visual acuity was 20/400 in the right eye and 20/200 in the left eye, with a relative afferent pupillary defect in the right eye. Both optic discs were swollen, and the adjoining retinas were edematous with radial hemorrhages (Fig. 1A). Goldmann perimetry showed a superior altitudinal depression bilaterally (Fig. 1B). Brain and orbital MRI were normal (Fig. 2).
Without receiving any medications, he reported improvement in vision over the next days. Four days after the initial neuro-ophthalmologic examination, visual acuity had improved to 20/60 in the right eye and 20/100 in the left eye. The next day, the patient was begun on three cycles of vincristine 1.6 mg/m2 and doxorubicin 36 mg/m2 continuous intravenous injection on days 1 through 4 and dexamethasone 40 mg orally on days 1-4, 9-12, and 17-20 of each cycle.
Three months after chemotherapy had begun, best-corrected visual acuity was 20/25 in the right eye and 20/20 in the left eye (Fig. 3). The optic discs appeared nearly normal (Fig. 4A), and the visual field defect in both eyes had essentially recovered (Fig. 4B). In the subsequent ten months, no significant changes were observed, and visual acuity was 20/20 in both eyes.
Our case is unusual in that optic neuropathy was the presenting sign of multiple myeloma, and substantial recovery of vision occurred spontaneously. It resembles the case of Cox et al (4) of a 64-year-old man whose initial clinical manifestation of multiple myeloma was also an optic neuropathy. Initial visual acuity was counting fingers in the right eye and 20/100 in the left eye. He was diagnosed with multiple myeloma after the detection of IgA-lambda M-protein by laboratory tests. Their case differs from ours in that visual recovery began only after initiation of chemotherapy with prednisolone and melphalan. Visual acuity improved to 20/30 in both eyes over the next two weeks and stabilized at 20/20 in both eyes for more than three years. Fundi remained normal at all times.
In contrast to the patient of Cox et al (4), our patient had swollen optic discs at the initial visit, which is more typical of the polyneuropathy-organomegaly-endocrinopathy-M protein-skin changes (POEMS) syndrome (5), an unusual form of myeloma. In POEMS syndrome, there is a markedly increased vascular endothelial growth factor, which has been suggested to be a causative factor and may give rise to vasogenic edema within the optic nerve head (6,7). Although optic disc swelling is common in the POEMS syndrome (5,8), a reduction of vision is rare (8,9). Bolling and Brazis (8) reported eight patients with POEMS and optic disc edema in whom visual reduction was found in only one patient-a constriction of the visual fields and enlargement of the blind spots. Two patients had slightly reduced visual acuities, but these deficits were not attributed to optic neuropathy. In our case, POEMS was excluded by the absence of polyneuropathy, organomegaly, endocrinopathy, and skin changes.
The normal imaging and pretreatment partial recovery of vision in our case argue against myelomatous infiltration of the optic nerve as the cause of visual loss (1).
A possible mechanism for the optic neuropathy in our case and other cases of optic neuropathy in multiple myeloma is an effect of high immunoglobulin levels on neural conduction. High levels of immunoglobulin are documented to cause peripheral neuropathy through a humoral mechanism (4). Extravasated IgG was shown in rats to stimulate infiltration of neutrophils, which disappeared quickly without killing nerve cells (10). Neural conduction in the optic nerve may be compromised by excessive IgG. To account for the spontaneous improvement of vision in our patient, we speculate that correction of fluid and electrolyte imbalance before anti-myeloma therapy may have reduced the serum monoclonal IgG concentration and improved nerve conduction.
1. Knapp AJ, Gartner S, Henkind P. Multiple myeloma and its ocular manifestations. Surv Ophthalmol
2. Fung S, Selva D, Leibovitch I, et al. Ophthalmic manifestations of multiple myeloma. Ophthalmologica
3. Gudas PP Jr. Optic nerve myeloma. Am J Ophthalmol
4. Cox JG, Steiger MJ, Pearce JM. Optic neuropathy and multiple myeloma. Br J Hosp Med
5. Bardwick PA, Zvaifler NJ, Gill GN, et al. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes: the POEMS syndrome: report on two cases and a review of the literature. Medicine (Baltimore)
6. Watanabe O, Arimura K, Kitajima I, et al. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet
7. Soubrier M, Dubost JJ, Serre AF, et al. Growth factors in POEMS syndrome: evidence for a marked increase in circulating vascular endothelial growth factor. Arthritis Rheum
8. Bolling JP, Brazis PW. Optic disk swelling with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS syndrome). Am J Ophthalmol
9. Witoonpanich R, Phankhian S, Jootar S, et al. POEMS syndrome with venous sinus thrombosis and visual failure: a case report. J Med Assoc Thai
10. Kadota E, Muramatsu Y, Nonaka K, et al. Biological functions of extravasated serum IgG in rat brain. Acta Neurochir Suppl
© 2006 Lippincott Williams & Wilkins, Inc.