Very-Late-Onset Neuromyelitis Optica Spectrum Disorder Presenting as Isolated Optic Neuritis in an 85-Year-Old Woman: A Diagnostic and Management Challenge

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder of the central nervous system (CNS), classically presenting with optic neuritis, longitudinally extensive transverse myelitis, or both. Optic neuritis in NMOSD is typically severe, often bilateral and rapidly progressive, with a high risk of recurrence and permanent visual loss. Serum aquaporin-4 immunoglobulin G (AQP4-IgG) autoantibodies represent the most specific diagnostic biomarker, reflecting pathogenic astrocyte targeting and inflammatory injury, although their absence does not exclude the diagnosis of NMOSD.1 Although NMOSD typically presents in young adults and occasionally in children, late-onset NMOSD, defined as onset after age 50, is increasingly recognized.2 The rarity of NMOSD onset beyond age 80 complicates diagnosis and treatment, with paraneoplastic NMOSD tending to present at an older age. We report a rare case of NMOSD in an 85-year-old woman who presented with unilateral optic neuritis as the initial manifestation and exceptionally elevated AQP4-IgG titers, despite advanced age and presumed immunosenescence. To our knowledge, this is the oldest reported case of NMOSD initially presenting with isolated optic neuritis. An 85-year-old Caucasian Hispanic woman presented with a 2-day history of painless, sudden-onset vision loss in the right eye, described as a “dark curtain” obscuring the lower visual field. She had no significant medical conditions, reported no systemic symptoms, and was taking low-dose aspirin, multivitamins, and Ginkgo biloba. Best-corrected visual acuity was counting fingers in the right eye and 20/20 in the left eye with a right afferent pupillary defect. Intraocular pressures were 16 mm Hg and 17 mm Hg, respectively. The slit-lamp examination was unremarkable. The visual field of the right eye demonstrated inferior and temporal defects (Fig. 1). The fundus examination was unremarkable (see Supplemental Digital Content, Supplemental File, https://links.lww.com/WNO/A968). Optical coherence tomography analysis, including retinal nerve fiber layer (RNFL) and ganglion cell layer + inner plexiform layer (GCL + IPL) thicknesses, was normal. Brain and orbital MRI with contrast demonstrated enhancement of the intraorbital, intracanalicular, and intracranial portions of the right optic nerve (Fig. 2), with no other CNS lesions except for an incidental 2-cm cribriform plate meningioma. Erythrocyte sedimentation rate was 57 mm/hour, C-reactive protein level was <0.1 mg/dL, and serum AQP4-IgG and other autoimmune and infectious serologic tests were sent.FIG. 1.: Automated 30-2 visual fields at presentation demonstrating temporal and inferior visual field loss in the right eye.FIG. 2.: Postcontrast T1 MRI with fat suppression at presentation showing enhancement of the right optic nerve (white arrows).The patient was treated with intravenous (IV) methylprednisolone 1,000 mg daily for 3 days, followed by oral prednisone 40 mg daily (1 mg/kg/day) for 2 days. Serum AQP4-IgG testing returned strongly positive at 706 U/mL (normal 0–3 U/mL), confirming a diagnosis of NMOSD. Other autoimmune and infectious serologies, including myelin oligodendrocyte glycoprotein, antinuclear antibody, and antineurtrophil cytoplasmic antibody, were normal. The visual field of the right eye worsened, and IV corticosteroid was resumed immediately for a total of 13 days, followed by prednisone 50 mg daily. Cervical and thoracic spine MRI with contrast showed no transverse myelitis. Satralizumab was initiated, and prednisone was tapered off slowly. At 3 months after onset, vision improved to 20/60 in the right eye with improved visual field with a central scotoma, GCL + IPL thinning, and temporal RNFL loss (see Supplemental Digital Content, Supplemental File, https://links.lww.com/WNO/A968). The patient has no history of cancer and declined oncologic imaging. At month 8, the patient was evaluated at the emergency room and diagnosed with deep vein thrombosis. Cellulitis, a known adverse event to satralizumab, was subsequently ruled out. No neurologic or systemic symptoms have developed. Although NMOSD has been reported in patients in their 90s, those cases presented with longitudinally extensive transverse myelitis rather than isolated optic neuritis.3,4 To our knowledge, this 85-year-old patient represents the oldest reported case of NMOSD initially presenting with isolated optic neuritis. Serologic testing for AQP4-IgG was essential in confirming the diagnosis. Despite presumed immunosenescence, the patient had a strikingly elevated antibody titer of 706 U/mL, well above the high-titer threshold of 100 U/mL by enzyme-linked immunosorbent assay, suggesting a robust autoimmune response. This raises concerns regarding immune activation in the elderly and whether strong antigenic stimuli, such as tumor-associated proteins, may override age-related immune decline. Paraneoplastic NMOSD is rare, and AQP4-IgG positivity has been associated with malignancies, commonly lung, breast, and ovarian carcinomas. In rare instances, tumors have been shown to express AQP4 or mimic antigens, triggering NMOSD via immune cross-reactivity.5 However, the patient's favorable response to steroids and satralizumab, without tumor-directed therapy, makes a paraneoplastic etiology less likely. The patient has no history of cancer and declined a cancer work-up, and at month 8 remained without neurologic or systemic symptoms. Regardless, paraneoplastic etiology remains a consideration with continued follow-up. Clinical trials of U.S. Food and Drug Administration (FDA)-approved NMOSD therapies, eculizumab, ravulizumab, inebilizumab, and satralizumab have largely underrepresented patients aged 65 and older, resulting in limited safety and efficacy data for this population, as reflected in their FDA labels. Our patient responded well to satralizumab, an interleukin-6 receptor–targeting monoclonal antibody. Five months into treatment, she presented to the emergency room with deep vein thrombosis (DVT). Cellulitis was ruled out, and although DVT has been reported in patients receiving satralizumab, the relatively late onset in this case makes a causal relationship uncertain. The possibility of an alternative etiology, including malignancy-associated thrombosis (Trousseau sign), cannot be excluded. This highlights the need for careful monitoring and individualized risk assessment in elderly patients with NMOSD receiving immunotherapy. This case underscores that NMOSD may present as isolated optic neuritis, even in very elderly patients. Despite presumed age-related immunosenescence, robust autoimmune responses may still occur, reinforcing the diagnostic importance of serum AQP4-IgG testing regardless of age. Although an elevated antibody titer at advanced age raises suspicion for paraneoplastic NMOSD, a positive response to immunotherapy may lessen but not exclude this concern. Clinicians should remain alert to possible underlying malignancy. Given the limited safety and efficacy data for FDA-approved NMOSD therapies in older adults, careful monitoring is essential. STATEMENT OF AUTHORSHIP Conception and design: S. Kang, B. L. Lam, P. E. Ravenna, D. G. Teijelo; Acquisition of data: B. L. Lam, S. Kang, P. E. Ravenna, D. G. Teijelo; Analysis and interpretation of data: B. L. Lam, S. Kang, P. E. Ravenna, D. G. Teijelo. Drafting the manuscript: S. Kang; Revising the manuscript for intellectual content: B. L. Lam, S. Kang, P. E. Ravenna, D. G. Teijelo. Final approval of the completed manuscript: B. L. Lam.