What is the best course of action for a patient with multiple myeloma (MM) who is now experiencing diplopia (double vision)?

Urgent Neuroimaging and Ophthalmologic Evaluation Required

A multiple myeloma patient presenting with diplopia requires immediate neuroimaging (MRI of brain and orbits with contrast) to evaluate for extramedullary plasmacytoma causing mass effect, followed by urgent ophthalmologic consultation to assess for cranial nerve palsies, orbital involvement, or hyperviscosity retinopathy. 1, 2

Immediate Diagnostic Workup

Neuroimaging Priority

• Obtain MRI of brain and orbits with contrast emergently to evaluate for extramedullary plasmacytoma compressing cranial nerves (particularly CN III, IV, or VI) or causing orbital/sphenoid sinus involvement 1, 3
• CT scan may be needed if MRI is unavailable, though MRI provides superior soft tissue detail for evaluating plasmacytomas and nerve compression 1
• Sphenoid sinus involvement with optic nerve compression, though rare, can cause rapid visual deterioration and requires immediate identification 3

Ophthalmologic Assessment

• Complete ophthalmic examination with emphasis on sensorimotor evaluation including the three-step test to differentiate cranial nerve palsies from skew deviation 1
• Fundoscopic examination to evaluate for hyperviscosity retinopathy (dilated tortuous retinal veins, flame-shaped hemorrhages, cotton-wool spots) or papilledema 2
• Visual field testing to assess for compressive lesions 1
• Check for other ocular manifestations including proptosis, lid ecchymosis, or crystalline deposits 2

Laboratory Evaluation

• Serum protein electrophoresis with immunofixation and serum free light chains to assess disease activity 1, 4
• Complete blood count, serum calcium, creatinine, and viscosity measurement if hyperviscosity syndrome suspected 1, 2
• Beta-2 microglobulin and LDH for disease staging 4

Differential Diagnosis by Mechanism

Direct Infiltration/Mass Effect (Most Concerning)

• Extramedullary plasmacytoma causing cranial nerve compression (CN III, IV, or VI palsy) or orbital involvement 2, 3
• Sphenoid sinus plasmacytoma with optic nerve compression presents with rapid visual deterioration and requires urgent intervention 3
• Skull base involvement with direct nerve infiltration 2

Hyperviscosity Syndrome

• Occurs when serum viscosity increases due to high paraprotein levels, causing retinal vein engorgement and hemorrhages 2
• More common with IgM or IgA paraproteins 2
• Requires plasmapheresis if confirmed 2

Vasculopathic Cranial Nerve Palsy

• Sixth nerve palsy is most common vasculopathic cranial neuropathy, typically acute onset with horizontal diplopia worse at distance 1
• Associated with diabetes and hypertension risk factors 1
• Expected to resolve within 6 months if vasculopathic 1

Management Algorithm

If Extramedullary Plasmacytoma Confirmed

• Initiate high-dose dexamethasone-containing regimen immediately for urgent cytoreduction 1
• High-dose dexamethasone (40mg days 1-4,9-12,17-20) provides rapid tumor reduction when urgent intervention needed 1
• Localized radiotherapy to the plasmacytoma is highly effective for local control and symptom relief 3
• Consider triplet therapy with proteasome inhibitor (bortezomib) plus immunomodulatory agent (lenalidomide) plus dexamethasone for systemic disease control 1, 4
• Neurosurgical consultation if significant mass effect or spinal cord compression 1

If Hyperviscosity Syndrome Confirmed

• Urgent plasmapheresis to rapidly reduce paraprotein levels and improve blood flow 2
• Initiate systemic myeloma therapy concurrently to reduce paraprotein production 2
• Monitor visual symptoms closely as they should improve rapidly with viscosity reduction 2

If Vasculopathic Cranial Nerve Palsy

• Prism therapy may help manage diplopia during recovery period 1
• Optimize diabetes and hypertension control 1
• Monitor for recovery over 6 months; if no improvement by 6 months, approximately 40% have serious underlying pathology requiring further investigation 1

Critical Pitfalls to Avoid

• Do not delay neuroimaging assuming diplopia is simply a vasculopathic nerve palsy—extramedullary plasmacytomas can cause rapid, irreversible vision loss if not treated urgently 3
• Do not attribute diplopia to "myeloma in general" without identifying the specific mechanism, as treatment differs dramatically (radiation for plasmacytoma vs. plasmapheresis for hyperviscosity) 2, 3
• Do not miss spinal cord compression when evaluating for plasmacytomas—MRI should include spine if any back pain or neurologic symptoms present 1
• Do not forget that ophthalmic manifestations may be the first sign of disease progression or insufficient chemotherapy, requiring reassessment of systemic therapy 2

Treatment Setting and Monitoring

• Hospitalization is warranted for urgent evaluation and initiation of therapy given risk of permanent vision loss 1
• If extramedullary disease confirmed, this represents high-risk disease requiring aggressive systemic therapy 1
• Close ophthalmologic follow-up to monitor visual recovery after intervention 2, 3
• Repeat imaging after radiation/chemotherapy to assess response 3