A Rare Case of Steroid-Resistant Neurosarcoidosis of the Cavernous Sinus With Optic Neuropathy: A Case Report

Abstract

Sarcoidosis is an inflammatory disease that presents with nervous system involvement in 5-10% of cases, commonly known as neurosarcoidosis.¹ While there are no randomized controlled trials for the treatment of neurosarcoidosis, expert opinion supports initial treatment with corticosteroids and the use of steroid-sparing or anti-TNF agents in refractory or severe cases. We report a case of a 48-year-old African American male with a past medical history of biopsy-proven hepatic and renal sarcoidosis and progressive headache, dizziness, and blurry vision for 5 months, presenting with an acute exacerbation of right-sided vision loss over one day. MRI of the brain revealed a dural-based mass extending into the right cavernous sinus and compressing the right optic nerve. Given the pathological confirmation of systemic granulomatous disease consistent with sarcoidosis, clinical manifestations, bilateral hilar and mediastinal lymphadenopathy, MRI findings typical of central nervous system inflammation, and exclusion of other possible etiologies, the patient was diagnosed with probable neurosarcoidosis. Corticosteroids initially resolved his symptoms; however, he suffered an acute relapse. Combination therapy with corticosteroids plus mycophenolate mofetil (MMF) led to the eventual resolution of his symptoms. Only 8 cases of neurosarcoidosis involving the cavernous sinus have been reported. Our patient represents the only reported case of probable neurosarcoidosis of the cavernous sinus with optic neuropathy successfully treated with corticosteroid plus MMF combination therapy. We highlight the need to consider early, aggressive treatment in cases of neurosarcoidosis with optic neuropathy and to develop criteria to guide treatment strategy based on neurolocalization and the degree of neurological disability.

Introduction

Sarcoidosis is an inflammatory disease that presents with nervous system involvement in 5-10% of cases, commonly known as neurosarcoidosis.¹ While there are no randomized controlled trials for the treatment of neurosarcoidosis, retrospective studies support initial treatment with corticosteroids. The addition of steroid-sparing or anti-TNF agents is important in treating refractory or severe cases of neurosarcoidosis. We present a rare case of steroid-resistant neurosarcoidosis of the cavernous sinus with optic neuropathy.

Case Description

A 48-year-old African American male with a past medical history of biopsy-proven hepatic and renal sarcoidosis and progressive headache, dizziness, and blurry vision for 5 months presented with an acute exacerbation of right-sided vision loss over one day. Liver and kidney biopsies from prior records confirmed the presence of non-caseating granulomas. The patient also had a family history of sarcoidosis in his mother. Neurological exam revealed deficits in the right visual field and skew deviation in the right eye. MRI of the brain with and without contrast demonstrated dural thickening and enhancement extending into the right cavernous sinus and right greater sphenoid wing, with mass effect compressing the right optic nerve (Figure 1A). Workup included a CT of the chest, which demonstrated enlarged bilateral hilar and mediastinal lymph nodes. Laboratory tests for thyroid function, erythrocyte sedimentation rate, and C-reactive protein were normal. Serum antinuclear antibodies, p-ANCA/MPO, c-ANCA/PR3, HIV 1/2 antibody, IgG4 antibodies, anti-smooth muscle antibodies, LKM antibodies, QuantiFERON-TB Gold assay, Syphilis enzyme immunoassay, and Hepatitis panel were negative. Serum ACE and lysozyme were elevated at 97 μL (ref. 8-53 μL) and 13.4 μg/mL (ref. 5-11 μg/mL), respectively. The patient was diagnosed with probable neurosarcoidosis and started on 1 g IV methylprednisolone for 3 days. Corticosteroid treatment led to a complete resolution of his symptoms, and the patient was discharged on a prednisone taper over 6 weeks.

Figure 1.

Dural and cavernous sinus involvement of 48-year-old patient with neurosarcoidosis. A, Coronal (left) and axial (right) contrast-enhanced T1 MRI of the brain showing dural enhancement and cavernous sinus infiltration. B, Coronal (left) and axial (right) contrast-enhanced T1 MRI of the brain showing increase in the size of the dural-based mass with additional involvement of right inferior rectus and oblique muscles.

Two months later, the patient presented with an acute relapse of symptoms, with superimposed right lateral gaze palsy, ptosis of the right eyelid, and an enlarged right pupil. MRI of the brain revealed an increase in the size of the dural-based mass, with additional enhancement involving the right inferior rectus and right inferior oblique muscles (Figure 1B). The patient was again treated with 1 g IV methylprednisolone for 4 days, which significantly improved his ocular symptoms. He was discharged on a prolonged prednisone taper to prevent future recurrences, starting at 120 mg and tapering 10 mg every 2 weeks. Concurrently, the patient was started on Mycophenolate Mofetil (MMF) 500 mg BID. MMF was selected over methotrexate to avoid further liver toxicity, given the presence of biopsy-proven hepatic sarcoidosis. At discharge, his symptoms remained stable, and his vision returned to baseline.

One month later, the patient had another acute relapse despite compliance with prednisone 90 mg daily and MMF 500 mg BID. His dose of prednisone was then up-titrated to 120 mg daily. On this new treatment regimen, the patient’s headache and visual deficits resolved in 1 week. His prednisone was subsequently decreased to 100 mg with instructions to follow up in 1 month for rheumatologic consultation and consideration for initiation of infliximab to minimize long-term steroid toxicity.

Discussion

In accordance with the Neurosarcoidosis Consortium Consensus Group, the patient meets the diagnostic criteria of probable neurosarcoidosis given pathological confirmation of systemic granulomatous disease consistent with sarcoidosis, clinical manifestations, bilateral hilar and mediastinal lymphadenopathy, MRI findings typical of central nervous system inflammation, and exclusion of other likely etiologies. Biopsy of the dural-based mass to meet the diagnostic criteria of definite neurosarcoidosis was considered but deferred due to the risk of permanent neurological deficits induced by the procedure.²

In our workup, other pathologies that commonly cause granuloma formation and cavernous sinus lesions were considered, including systemic and CNS infections (e.g., neurosyphilis, tuberculosis, etc.), neoplastic processes (e.g., systemic lymphoma, CNS tumors, etc), and other neuro-inflammatory and autoimmune disorders (e.g., granulomatosis with polyangiitis, IgG4-related hypertrophic pachymeningitis, etc.). The subacute onset of symptoms, negative autoimmune and preliminary infectious workup, lack of classic B-symptoms including fever, unexplained weight loss, or night sweats, and eventual resolution of symptoms with corticosteroid and MMF combination therapy suggest that these alternative etiologies are much less likely.

Although CSF studies aid in ruling out infectious and neoplastic processes, the findings lack specificity for neurosarcoidosis. The patient’s probable neurosarcoidosis and family history of sarcoidosis, in conjunction with his initial rapid improvement with corticosteroids and eventual resolution of symptoms with adjunct MMF therapy, led to the decision to defer a lumbar puncture (LP). If improvement was not sustained clinically or on repeat imaging, an LP would be reconsidered to assess for alternative etiologies.

Our patient represents the only reported case of probable neurosarcoidosis of the cavernous sinus with optic neuropathy successfully treated with corticosteroid plus MMF combination therapy. Steroid monotherapy was unsuccessful in our patient, and this treatment-resistance is hypothesized to be due to a mechanism of exaggerated TNF-α release by alveolar macrophages.³ To our knowledge, only 8 other cases of neurosarcoidosis involving the cavernous sinus have been reported. In 7 of these cases, corticosteroid monotherapy alone was shown to be effective in the resolution of symptoms.^4-8 In one of these patients, early combination therapy with corticosteroid plus methotrexate therapy was used as first-line treatment and led to rapid improvement within a few days and near-complete clinical resolution of symptoms at 3 months.⁹

Given the lack of clinical trial data, the treatment of neurosarcoidosis is largely based on observations from case series and case reports. Expert opinion and small retrospective studies support early, aggressive treatment for severe cases of neurosarcoidosis, as relapses are frequent.¹ This case presentation supports the need to develop criteria for classifying patients with neurosarcoidosis into mild, moderate, and severe cases to guide treatment decisions. These criteria may be based on neurolocalization and the degree of neurological disability, with the notable exception of isolated facial nerve paralysis, which can most often be treated with only a few weeks of prednisone monotherapy and rarely recurs.¹ Given its potentially devastating neurological consequences, we would classify optic neuropathy as a severe case of neurosarcoidosis, similar to cases of spinal cord disease. In severe cases of neurosarcoidosis, steroids and steroid-sparing agents in addition to anti-TNF agents, especially infliximab, are initiated earlier on in the course of treatment.¹ Presumably, our patient’s optic neuropathy would have resolved sooner with earlier initiation of corticosteroid and MMF combination therapy and/or infliximab. To prevent permanent visual loss and other neurologic sequelae, early, aggressive initiation of treatment should be considered in neurosarcoidosis with optic neuropathy.