Neurosarcoidosis: diagnosis, therapy and biomarkers

Abstract

Sarcoidosis is a multi-organ immune-mediated disease, which manifests as neurosarcoidosis (NS) in approximately 10% of all affected patients. The diagnosis of NS requires a high degree of suspicion as well as histological confirmation. Neurological symptoms in patients with systemic sarcoidosis should not be assumed to be due to NS unless proven true. The etiopathogenesis of NS is not yet fully elucidated and a reliable biomarker assessing disease progression is missing. As a probable result, there is no definitive cure for NS. The goals of available treatments include: halting inflammation, prevention of disease worsening and restoring neurological functions whenever possible. With immunosuppression, clinical remission of NS occurs in the majority of patients. However, in some others, the disease may still progress, as no permanent cure is yet available.

Keywords:

• biomarkers cerebrospinal fluid
• granuloma
• leptomeningeal enhancement
• magnetic resonance imaging
• monocolonal antibodies
• myelitis
• neuropathy
• neurosarcoidosis

Acknowledgements

We thank A Vortmeyer (Yale University, Department of Neuropathology) for providing pathology slides and photographs shown in Figure 1. We thank S Pawate (University of Vanderbilt, Department of Neurology) for permitting use of the data from the Vanderbilt patient cohort reported in Figure 2.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Neurosarcoidosis (NS) was first reported in 1904. Ever since, diagnosing and managing NS has remained challenging and histology is still required for confirmation.

• The diagnosis of NS requires a high degree of suspicion. Neurological symptoms in patients with systemic sarcoidosis should not be assumed to be due to NS unless reasonably proven to be so by excluding infection and malignancy.

• Cerebrospinal fluid analysis may show a non-specific pattern of CNS inflammation.

• Spinal cord and brain intra- and extra-axial imaging findings are highly heterogeneous and non-specific of NS. A combination of intra- and extra-axial findings elevates the suspicion of NS.

• There are no randomized clinical trials that have investigated the effect of different medications in NS, and treatment is based upon observations made in case series studies.

• With immunosuppression, clinical disease remission occurs in up to 79% of the patients.

• Patients failing prednisone have the option to switch or add non-steroidal immunosuppressive medications, the use of which, however, does not guarantee a favorable clinical outcome.

• Infliximab, an anti-TNF-α chimeric monoclonal antibody, appears highly promising for the treatment of NS; but the high frequency of relapses following its discontinuation mandates close follow-up of patients once infliximab is stopped.

• Research is needed to identify surrogate biomarkers of disease to confirm a diagnosis (instead of biopsy) and to follow disease progression over time before clinical deterioration becomes apparent.

• Research is needed to identify long-term medications with a safe side effect profile that one can use to prevent disease exacerbation in NS patients.

Notes