When Granulomas Meet Aquaporin-4: Diagnostic and Therapeutic Challenges in Necrotizing Neurosarcoidosis
Sulafa Saffarini1, Ayush Gupta2, Lakshman Arcot Jayagopal3, Rana Zabad2
1Neurology, University of Nebraska Medical Center, 2University of Nebraska Medical Center, 3Nebraska Medical Center
Objective:
To report a case of probable neurosarcoidosis with atypical necrotizing granulomatous inflammation and coexisting aquaporin-4 antibody positivity. 
Background:
Necrotizing sarcoid granulomatosis of the CNS is rare, and coexistence with anti-aquaporin-4 antibodies is exceedingly uncommon. Research focuses on each disorder separately, and no clear management guidelines exist, creating a practice gap in diagnosis and treatment.
Design/Methods:

We describe a 60-year-old African American female who initially presented with progressive numbness, tingling, and pain in the feet, evolving into bilateral leg weakness, right foot drop, gait instability, and recurrent falls. Examination revealed bilateral optic disc pallor and saccadic intrusions, right-predominant leg weakness, generalized hyperreflexia, bilateral positive Hoffman signs, wide-based gait, and impaired coordination. Brain MRI showed multiple punctate enhancing foci in the posterior fossa. Spine MRI revealed multifocal leptomeningeal enhancement throughout the cervical, thoracic, and lumbar regions, while whole-body PET demonstrated tracer uptake in the spinal canal and pelvic and inguinal lymph nodes. CSF analysis revealed lymphocytic pleocytosis (95 WBC/µL, 88% lymphocytes), hypoglycorrhachia (20 mg/dL; normal 40-70), elevated protein (197 mg/dL; normal 15-45), markedly increased IgG synthesis rate (232 mg/day; normal 0-8), elevated IgG index (1.49; normal 0.3-0.7), and 11 CSF-restricted oligoclonal bands; infectious and autoimmune panels were negative. Inguinal lymph node biopsy demonstrated focally caseating granulomatous inflammation concerning for atypical necrotizing sarcoid granulomatosis, probable neurosarcoidosis. Unexpectedly, serum aquaporin-4 IgG antibody was strongly positive at 1:1280 via cell-based assay. The patient received high-dose corticosteroids with partial improvement, and recurrent deficits prompted initiation of Rituximab therapy, resulting in clinical benefit.

Results:
NA
Conclusions:
The presence of anti-aquaporin-4 antibodies may indicate autoimmunity in CNS sarcoidosis, though coexistence is exceedingly rare. Recognizing this overlap is critical, as it impacts diagnosis and treatment in complex neuroinflammatory disorders. Rituximab is a plausible therapeutic option due to its off-label use and reported benefit in targeting both NMOSD and refractory sarcoidosis.
Generative AI Usage
Yes, used generative AI in the drafting or editing in this abstract.

Tool, version, and prompt(s) used, as well as area of the abstract affected
The authors used ChatGPT (OpenAI, GPT-5.3) for language editing and clarity of the abstract text. AI assistance was limited to grammar and wording improvements and did not contribute to data generation, analysis, or interpretation.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.