Neurosarcoidosis: Correlation of cerebrospinal fluid findings with diffuse leptomeningeal gadolinium enhancement on MRI and clinical disease activity

Abstract

Background

Cerebrospinal fluid (CSF) examination is considered important in the diagnosis of neurosarcoidosis, however, data on whether and how CSF parameters may be related to MRI findings and clinical disease activity of patients with neurosarcoidosis are scarce.

Objective

To correlate CSF findings in patients with neurosarcoidosis with MRI findings and clinical disease activity.

Material and methods

Results of 51 comprehensive CSF examinations of 25 patients with probable or definite neurosarcoidosis according to the Zajicek-criteria were analyzed retrospectively.

Results

Patients with diffuse leptomeningeal gadolinium enhancement on MRI had significantly higher cell counts (≥ 50 cells/μl in 80%), total protein (≥ 200 mg/dl in 80%), CSF/serum albumin quotients (Q_Alb, ≥ 30 in 80%), and lactate (≥ 30 mg/dl in 70%), but significantly lower glucose levels (≤ 40 mg/dl in 67%) than patients without leptomeningeal enhancement. Irrespective of MRI findings, activated lymphocytes and plasma cells were detected in the initial CSF examination in 60% and 47% of patients, and an intrathecal synthesis of IgG, IgA, and IgM in 22%, 29%, and 22%. Patients with clinically active disease had significantly higher CSF cell counts, total protein, Q_Alb, and lactate, but significantly lower glucose levels than patients with stable disease.

Conclusion

CSF abnormalities in neurosarcoidosis are most pronounced in patients with diffuse leptomeningeal enhancement on MRI. CSF analyses may thus aid in the distinction of different radiographic and pathologic manifestations of neurosarcoidosis. Furthermore, CSF examinations may allow monitoring disease activity in patients with neurosarcoidosis.

Introduction

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized histopathologically by non-caseating epithelioid granulomas, most often localized in the lung or draining mediastinal lymph nodes [1]. Manifestations of sarcoidosis within the nervous system occur in 5–15% of patients with systemic sarcoidosis, but post-mortem studies suggest an even higher incidence of clinically silent nervous system involvement [2], [3], [4]. Sarcoidosis can affect the brain, spinal cord, cranial nerves, and peripheral nerves [5]. Current diagnostic criteria for central nervous system (CNS) sarcoidosis (further referred to as neurosarcoidosis) were formulated by Zajicek and co-workers [1], [6]. Clinical as well as radiographic features of neurosarcoidosis are highly variable, with MRI findings ranging from multiple parenchymal white matter lesions without uptake of gadolinium to localized dural or diffuse leptomeningeal contrast enhancement [1].

Cerebrospinal fluid (CSF) examination is generally considered a key procedure in the diagnostic work-up of patients with presumed neurosarcoidosis [1], [4], [5]. Results of CSF examinations, in particular CSF cell counts and total protein levels, were previously reported in various series of patients with neurosarcoidosis (see Supplementary Data 1). Nevertheless, given the variable MRI appearance of neurosarcoidosis, it seems conceivable that CSF findings in patients with neurosarcoidosis may be related to different radiographic disease subtypes. CSF parameters may likewise correlate with disease activity, but both questions have hitherto not been investigated in depth. Furthermore, several potentially relevant CSF parameters, such as CSF lactate levels or intrathecal synthesis of immunoglobulin (Ig)A and IgM, were not studied in detail in patients with neurosarcoidosis so far.

Here, we comprehensively analyzed results of 51 CSF examinations of 25 patients with definite or probable neurosarcoidosis according to the Zajicek-criteria and correlated them with findings on cerebral MRI as well as with clinical disease activity, including CSF data from individual patients who underwent sequential CSF examinations during active and stable disease phases. We also reviewed the literature on CSF findings in sarcoidosis with neurological manifestations.