Association of Prognostic Factors and Immunosuppressive Treatment With Long-term Outcomes in Neurosarcoidosis

Abstract

IMPORTANCE Prognostic factors are lacking in neurosarcoidosis (NS), and the association of immunosuppressive treatments with outcomes are unclear.OBJECTIVES To identify prognostic factors of and analyze the association of immunosuppressive treatment with relapse of NS. DESIGN, SETTING, AND PARTICIPANTSIn this retrospective study, a cohort of 234 patients fulfilled the diagnostic criteria for NS in a tertiary referral center in Paris, France, from January 1, 1990, through December 31, 2015. The median follow-up was 8 years (range, 2 months to 23 years). MAIN OUTCOMES AND MEASURESAll neurologic and extraneurologic data and treatments were analyzed. Functional outcomes measured by the absolute value and the variation from baseline of the Expanded Disability Status Scale (EDSS) score at 60 months after the diagnosis, overall survival, and relapse-free survival (RFS) were assessed. Analyses were stratified by the period of NS diagnosis (1990-1999 vs 2000-2015). RESULTSThe 234 patients undergoing assessment included 117 women (50.0%) and 117 men (50.0%); median age was 42 years (interquartile range, 32-53 years). The probable 10-year survival rate was 89% (95% CI, 84%-94%). Older age (hazard ratio [HR] per 10 years, 1.64; 95% CI, 1.19-2.27; P = .003), peripheral nervous system involvement (HR, 6.75; 95% CI, 2.31-19.7; P < .001), and higher baseline EDSS score (HR per point, 1.21; 95% CI, 1.06-1.39; P = .005) were associated with mortality. The estimated 10-year RFS rate was 14% (95% CI, 9%-22%) for all relapses and 28% (95% CI, 20%-38%) for neurologic relapses. Encephalic involvement was associated with shorter neurologic RFS (HR, 2.35; 95% CI, 1.44-3.83; P < .001). A lower risk for relapse was associated with cyclophosphamide (HR, 0.26; 95% CI, 0.11-0.59; P = .001), methotrexate sodium (HR, 0.47; 95% CI, 0.25-0.87; P = .02), and infliximab (HR, 0.16; 95% CI, 0.02-1.24; P = .08) treatments. Follow-up was greater than 60 months in 160 patients (68.4%). An elevated baseline EDSS score (odds ratio [OR] per point, 1.92; 95% CI, 1.55-2.37; P < .001), tobacco use (OR, 3.64; 95% CI, 1.36-9.73; P = .01), encephalic symptoms (OR, 3.04; 95% CI,; P = .03), and less than 4 extraneurologic sarcoidosis localizations (OR, 3.06; 95% CI, 1.04-8.98; P = .04) were associated with an EDSS value of at least 2.5 at 60 months. Encephalic involvement (16 of 17 patients [94.1%]; P = .008) and peripheral nervous system involvement (5 of 17 patients [29.4%]; P = .03) were associated with worsening of the EDSS score at 60 months.CONCLUSIONS AND RELEVANCE This study identifies putative factors affecting morbidity and mortality in patients with NS. Immunosuppressive therapies (ie, intravenous cyclophosphamide, methotrexate, and infliximab) in these patients may be associated with lower relapse rates.

Clinical Manifestations of Neurosarcoidosis in the Netherlands

“…It is highly likely that these differences can be explained by the small sample sizes and mainly retrospective design of these previous studies [9], and by the tertiary setting of our neurosarcoidosis population. A comparison between our results and those reported from other referral centres showed that results were similar [16,24,33].…”

“…Neurosarcoidosis can involve any part of the nervous system, causing a variety of neurological symptoms. A meta-analysis showed that the most common manifestations of neurosarcoidosis were cranial nerve dysfunctions and myelopathy [16,17]. Since neurologic involvement is the first presenting symptom in 50-70% of the neurosarcoidosis patients, and 52% of the patients have isolated neurosarcoidosis without systemic involvement [18][19][20][21][22], it can be difficult to diagnose.…”

Clinical and MRI phenotypes of sarcoidosis-associated myelopathy

“…23 Moreover, compared with many pathologies affecting the spinal cord, neurosarcoidosis is a treatable condition-often responding well to steroids, immunosuppressive therapies, or certain monoclonal antibodies. 24,25 Of interest, although disability status of SAM in a subset of patients in our cohort showed improvement in 52% after 1-year follow-up, almost 26% had worsening disability, a finding that may reflect the refractory and aggressive neuroinflammatory process in SAM in some patients or the delay in diagnosis and treatment that may also affect the overall outcome. Thus, it is essential for clinicians to recognize the clinical characteristics, CSF, and imaging findings associated with this disorder.…”

Engorgement of Deep Medullary Veins in Neurosarcoidosis: A Common-Yet-Underrecognized Cerebrovascular Finding on SWI

“…1 Neurologic manifestations occur in 5% of patients, and mortality can be as high as 11% in the 10 years after initial diagnosis. 2,3 Neurosarcoidosis has a predilection for perivascular dissemination but can also lead to parenchymal, leptomeningeal, or pachymeningeal disease and may result in a granulomatous angiitis. 4,5 CNS complications can be diverse and are a function of the nature and extent of tissues involved.…”