Cavernous Sinus Involvement in Multiple Myeloma

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doi:10.62055/47099956Qn

INTRODUCTION

Welcome to the “Neuro Nuggets” column within the Journal of Medical Optometry (JoMO)!  This column aims to make neuro-ophthalmic disease more approachable by blending real-world clinical cases with evidence-based medicine.  The patient in this edition’s column features a combination of neuro-ophthalmic findings that help to clinically localize the etiologic lesion.  Enjoy!

CASE PRESENTATION

A 74-year-old male presented to the optometry clinic for a problem-focused evaluation. The patient was followed regularly for pigmentary glaucoma, which was stable and managed on topical latanoprostene and timolol in each eye. The patient’s past medical history was notable for mitral valve regurgitation, atrial fibrillation, obstructive sleep apnea, hypertension, and hyperlipidemia. He was previously diagnosed with monoclonal gammopathy of undetermined significance (MGUS) with subsequent progression to IgG kappa multiple myeloma nine years prior to presentation. His prior treatment for multiple myeloma included ixazomib, stem cell transplant, venetoclax bcl2-i, chimeric antigen receptor (CAR) T-cell therapy with idecabtagene vicleucel (Abecma), and elotuzamab/revlimid. At the time of presentation to the eye clinic, the patient was managed with ontalquetamab-tgvs (Talvey) and was clinically stable.  He had previously had myelomatous lesions throughout the body including the left humerus, right femur, ribs, and skull base.

The patient presented with new-onset right upper eyelid ptosis which started five days prior to presentation. He reported mixed horizontal and oblique binocular diplopia, worst in right gaze while viewing distant targets. The patient also noted a mild “ache” around the right eye.

On examination, the patient’s best-corrected visual acuity was 20/20 in each eye.  Pupils were isocoric in bright and dim illumination. Ocular motility evaluation revealed notable supraduction and adduction deficits in the right eye and a mild abduction deficit in the right eye; ductions in the left eye were normal. There was also reduced levator function in the right eye. The remainder of the cranial nerve exam was normal. Visual field testing was normal in all quadrants for each eye.  The anterior segment evaluation was normal and age-appropriate in each eye.  Intraocular pressure was at goal and normotensive in each eye. No new optic disc abnormalities or retinal findings were present on posterior segment evaluation. The clinical presentation was worrying for a partial right cranial nerve (CN) 3 palsy and mild right CN 6 palsy, raising concern for a possible cavernous sinus lesion.

Emergent brain magnetic resonance imaging (MRI) with and without gadolinium contrast was obtained. Magnetic resonance angiography (MRA) was recommended but not obtained. At the patient’s request, the initial brain MRI was obtained at an outside facility and interpreted as normal. Acetylcholine receptor antibody (ACHR), muscle-specific tyrosine kinase (MuSK), and low‐density lipoprotein receptor-related protein 4 (LRP4) labs were obtained to evaluate for myasthenia gravis. The myasthenia labs were all negative or within normal limits.

Two weeks later, the patient demonstrated worsening right upper eyelid ptosis and worsening supraduction deficit of the right eye, now with a 30 prism-diopter right hypotropia in upgaze. The pain around and behind the right eye was still present.  Pupillary reaction to light was more sluggish in the right eye, and horizontal saccadic eye movements had also worsened. Repeat brain MRI and MRA with and without gadolinium contrast at our facility revealed a 1.3 x 2.2 cm homogenously enhancing lesion in the right cavernous sinus with mild extension towards the sella turcica (Figure 1). No intracranial aneurysm was identified on neuroimaging. The lesion was initially suspected to represent a meningioma, but after further discussion it was believed to be sequelae of the patient’s multiple myeloma. Due to its location, the lesion was deemed to be surgically inoperable by neurosurgery.

Figure 1. Magnetic resonance imaging (MRI) of the brain. A= axial T1 FLAIR, B = axial T1 FLAIR with gadolinium contrast, C = axial T2. Note the homogenously enhancing lesion at the right cavernous sinus. FLAIR = Fluid attenuated inversion recovery

The patient was admitted to his cancer treatment facility where he underwent five cycles of focal radiation to the right cavernous sinus lesion for a total treatment dose of 20 gray. His systemic treatment was also changed to carfilzomib, dexamethasone, and cyclophosphamide. Five weeks after initial presentation, the patient’s abduction was markedly worse with minimal abduction ability in the right eye; the right upper eyelid ptosis, supraduction, and adduction deficits remained similar to prior (Figure 2).

Figure 2. Ocular motility five weeks after initial presentation. Note significant limitations in abduction, adduction, and supraduction of the right eye. Also note right upper eyelid ptosis.

Unfortunately, the patient’s overall health declined shortly after the onset of his neuro-ophthalmic findings, and he died three months after symptom onset.

DISCUSSION

The cavernous sinus is part of the brain’s dural venous sinus anatomy and contains several important neuroanatomical structures relevant to eye care providers. Situated bilaterally to the sella turcica, the cavernous sinus contains venous blood flow that drains from multiple vascular branches, including the superior ophthalmic vein. The internal carotid and its sympathetic plexus, oculomotor nerve (CN 3), trochlear nerve (CN 4), abducens nerve (CN 6), and the first two divisions of the trigeminal nerve (V1, V2) all travel through the cavernous sinus and are susceptible to injury in cases of pathology at this level of the brain.

The onset of new neuro-ophthalmic signs and symptoms should prompt clinicians to thoroughly search for an underlying etiology, particularly in patients with cancer. In our case, the combination of CN 3 and CN 6 palsies was helpful in localizing pathology to the level of the cavernous sinus. A high level of clinical suspicion allowed identification of the cavernous sinus lesion which accounted for the patient’s neuro-ophthalmic presentation. Myasthenia gravis was also considered as a possibility but unlikely given the negative serologies, presence of periocular pain, and the cavernous sinus lesion identified on neuroimaging.

Multiple myeloma is a hematologic malignancy in which monoclonal plasma cells accumulate in the bone marrow, increasing levels of monoclonal immunoglobulins and often resulting in organ dysfunction.¹ Immunoglobulins contain a heavy chain (IgA, IgD, IgE, IgG, or IgM) and two light chains (kappa or lambda).² The diagnosis of multiple myeloma can be made on the basis of blood work, clinical manifestations, and, in some cases, bone marrow biopsy.² Systemic sequelae from multiple myeloma may include renal dysfunction, hypercalcemia, anemia, and osteolytic bone lesions.¹ Though uncommon, virtually any part of the eye can be impacted by multiple myeloma.² Many eye care providers are aware of the possibility of retinopathy stemming from multiple myeloma, but other vascular structures (such as the cavernous sinus) may also be impacted.

Central nervous system (CNS) involvement in multiple myeloma is rare and reported to occur in as few as 1% of cases.^3,4 CNS lesions stemming from multiple myeloma often portend a poor prognosis with most patients surviving only a few months after diagnosis.^3,4 Additionally, multiple myeloma may impact the CNS even in patients thought to have complete systemic remission.^3,5  Cavernous sinus involvement in multiple myeloma is even less common with sparse case reports reported in the literature.^2,6-14 This case serves as a sobering reminder that eye care providers may be the first clinicians to uncover neuro-ophthalmic sequelae of cancer.

CLINICAL PEARLS

• Clinical localization of neuro-ophthalmic signs can be of significant value in anatomically identifying the likely site of the lesion and directing neuroimaging accordingly
• Though rare, multiple myeloma can potentially invade the cavernous sinus and result in cranial nerve dysfunction
• CNS involvement in multiple myeloma is associated with poor overall survival outcomes

REFERENCES

1. van de Donk NWCJ, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021 Jan 30;397(10272):410-427. doi: 10.1016/S0140-6736(21)00135-5.
2. Silverman RF, Hanson L, Salahi N,Li Z, Boruk M and Hodgson NM (2022) Case Report: Cavernous Sinus Syndrome as the Initial Presentation of Multiple Myeloma. Front. Ophthalmol. 2:849343. doi: 10.3389/fopht.2022.849343
3. Nieuwenhuizen L, Biesma DH. Central nervous system myelomatosis: review of the literature. Eur J Haematol. 2008 Jan;80(1):1-9. doi: 10.1111/j.1600-0609.2007.00956.x.
4. Fassas AB, Muwalla F, Berryman T, Benramdane R, Joseph L, Anaissie E, Sethi R, Desikan R, Siegel D, Badros A, Toor A, Zangari M, Morris C, Angtuaco E, Mathew S, Wilson C, Hough A, Harik S, Barlogie B, Tricot G. Myeloma of the central nervous system: association with high-risk chromosomal abnormalities, plasmablastic morphology and extramedullary manifestations. Br J Haematol. 2002 Apr;117(1):103-8. doi: 10.1046/j.1365-2141.2002.03401.x.
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6. Çelik A, Özdoğan S. Evaluation of diplopia as a vital and remarkable ocular finding among cancer patients. Ir J Med Sci. 2023 Aug;192(4):1621-1627. doi: 10.1007/s11845-022-03177-6.
7. Galea M, Mcmillan N, Weir C. Diplopia and Variable Ptosis as the Sole Initial Findings in a Case of Orbital Plasmacytoma and Multiple Myeloma. Semin Ophthalmol (2015) 30(3):235–7. doi: 10.3109/13506129.2013.839807
8. Gozzetti et al, Multiple Myeloma Involving the Cavernous Sinus: A Report of 3 Cases and Response to Bortezomib, Clinical Lymphoma and Myeloma, 2007, 376-378, doi:10.3816/CLM.2007.n.017.
9. Ko S, Huang SY, Liu CY. Extramedullary Plasmacytoma Masquerading as Tolosa-Hunt Syndrome: A Case Report. BMJ Case Rep (2009) 2009: bcr08.2008.0804. doi: 10.1136/BCR.08.2008.0804
10. Lam S, Margo CE, Beck R, Pusateri TJ, Pascucci S. Cavernous Sinus Syndrome as the Initial Manifestation of Multiple Myeloma. J Clin Neuroophthalmol (1987) 7(3):135–8
11. Movsas TZ, Balcer LJ, Eggenberger ER, Hess JL, Galetta SL. Sixth nerve palsy as a presenting sign of intracranial plasmacytoma and multiple myeloma. J Neuroophthalmol. 2000 Dec;20(4):242-5.
12. Na JH, Park SH, Shin SY. Multiple myeloma manifesting as a fluctuating sixth nerve palsy. Korean J Ophthalmol. 2009 Sep;23(3):232-3. doi: 10.3341/kjo.2009.23.3.232.
13. Sundaresan N, Noronha A, Hirschauer J, Siqueira EB. Oculomotor palsy as initial manifestation of myeloma. JAMA. 1977 Nov 7;238(19):2052-3.
14. Thalambedu N, Damalcheruvu P, Ogunsesan Y, et al. (June 26, 2023) Sixth Nerve Palsy From Multiple Myeloma in Central Nervous System: Case Series and Review of Current Literature. Cureus 15(6): e40998. DOI 10.7759/cureus.40998

The author has no financial disclosures, and no sponsorship or funding was involved in this work.

Joseph Kane OD, FAAO

Boston VA Healthcare System | Boston, MA

Dr. Kane graduated from New England College of Optometry in 2015 and went on to complete an ocular disease/primary care residency at VA Boston Jamaica Plain from 2015-2016. He is currently an attending optometrist at VA Boston. His interests include clinical teaching, neuro-ophthalmic disease, retinal vascular disease, glaucoma, and ocular manifestations of systemic disease.