In this article, the authors present the current understanding of the epidemiology, diagnostic findings, proposed pathogenesis, relevant genetics, and therapeutic options for neurosarcoidosis. Although corticosteroids are the most widely employed form of therapy, steroid-sparing immunosuppressive agents, such as methotrexate, azathioprine, cyclophosphamide, thalidomide, and more recently, tumor necrosis factor (TNF)-α inhibitor infliximab are showing promising results in treatment of this disease. The cytokine, TNF-α, is generated in granulomas, and reports and small case series have shown a treatment response with infliximab in refractory cases of neurosarcoidosis. However, lack of randomized, controlled studies demands careful clinical assessment prior to trial of such glucocorticoid-sparing immunosuppressive medications.
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• The etiology of neurosarcoidosis remains unclear.
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• Optic and facial nerve dysfunctions are common neurologic manifestations of neurosarcoidosis.
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• Definite diagnosis of neurosarcoidosis requires a positive central nervous system biopsy. There is no definitive noninvasive test for establishing a diagnosis of neurosarcoidosis. The CSF angiotensin-converting enzyme (ACE) level is not highly sensitive, and its level can be elevated in other conditions.
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• Selection of therapeutic agents ranging from corticosteroids to glucocorticoid-sparing immunosuppressants should be tailored to specific clinical needs.
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• Infliximab, a TNF-α inhibitor, has clinical benefit in refractory cases of neurosarcoidosis in small series and case reports.
Historical note and terminology
Sarcoidosis was initially described as a dermatologic disorder. Jonathan Hutchinson, an English physician, examined a patient with purplish, symmetric, nontender skin plaques in 1869 and concluded the condition was a manifestation of gout (42). The Norwegian dermatologist, Caesar Peter Moeller Boeck, proposed the term “sarkoid,” or sarcoma-like, after detailed histological studies (12). Recognition of the multisystem nature of the disease is generally credited to Jorgen Schaumann, a Swedish dermatologist who in 1936 described involvement of the liver, spleen, lungs, and bone (84). Involvement of the nervous system was reported perhaps most notably by Christian Frederick Heerfordt (38). This Danish ophthalmologist described 3 patients with parotid enlargement, uveitis, and facial nerve palsies in the setting of a febrile illness but attributed the condition to mumps. Interestingly, a retrospective diagnosis of sarcoidosis was given to Maximillien de Robespierre, who died in 1794 (Charlier and Froesch 2013). The diagnosis was based on an examination of his death mask and a historical account of persistent symptoms.