Evolving Approaches in Neurosarcoidosis: Analyzing Immunosuppressive Strategies

Neurologists face a daunting challenge in treating neurosarcoidosis due to its rarity and the unpredictable response to immunosuppressive therapies, underscoring the urgent need for robust management strategies to improve patient outcomes. Recent consensus recommendations emphasize that initial treatment should be tailored to the patient's specific phenotype and symptom severity, with glucocorticosteroids as the cornerstone of therapy.

As a granulomatous disease of the central nervous system, neurosarcoidosis is underrecognized in neurology despite its potential to cause cranial neuropathies, myelopathies and cognitive deficits. Clinicians often deploy immunosuppressants such as cyclophosphamide, infliximab and methotrexate, but selecting the optimal regimen is hampered by limited head-to-head data. Cyclophosphamide, infliximab and methotrexate have distinct safety profiles which influence treatment decisions.

New data from a multicenter retrospective study provide observational comparisons of these therapies, offering clinicians much-needed evidence on treatment efficacy, safety, and corticosteroid-sparing potential.

Among the agents evaluated, infliximab demonstrated notable efficacy in reducing corticosteroid dependency in neurosarcoidosis. Patients receiving infliximab were able to taper corticosteroids more rapidly and maintain neurological stability compared with other regimens. Specifically, a multi-institutional study reported a favorable clinical response in 77% of patients and MRI improvements in 82% of those treated with infliximab.

Radiographic improvements were also more pronounced with infliximab, reinforcing its clinical advantage in patients with persistent central nervous system lesions. This aligns with data from the earlier report, where infliximab-treated individuals showed greater lesion resolution on MRI over follow-up. In the same study, near-complete resolution of MRI contrast enhancement was observed in all patients over a median span of 5.7 months.

Balancing these benefits are safety considerations: cyclophosphamide carries risks of cytopenias and hemorrhagic cystitis, infliximab poses infection and infusion-reaction risks, and methotrexate requires monitoring for hepatotoxicity and pulmonary complications. As previously noted, these nuances inform personalized treatment plans based on patient comorbidities and tolerance.

Infliximab emerges as a strong candidate for reducing corticosteroid exposure and enhancing radiographic remission in neurosarcoidosis. However, it is essential to acknowledge the limitations of retrospective data, the potential for selection bias, and the lack of randomized controlled trials. Additionally, considerations such as treatment costs, accessibility, and the availability of alternative therapies like methotrexate or mycophenolate mofetil should be factored into clinical decision-making. As therapies evolve, integrating emerging data into multidisciplinary discussions will refine long-term management strategies.

Key Takeaways:

• Infliximab significantly reduces corticosteroid dependency in neurosarcoidosis treatment.
• The distinct safety profiles of cyclophosphamide, infliximab, and methotrexate influence clinical decisions.
• Infliximab shows superior radiographic improvement in certain cases of neurosarcoidosis.
• Continued research is necessary to refine long-term treatment strategies and patient management.