Evaluating S100B as a serum biomarker for central neurosarcoidosis.

BACKGROUND: S100B is a calcium-binding protein found primarily in glial cells. In the setting of neuronal injury and disruption of the blood brain barrier, S100B can leak into the cerebrospinal fluid and systemic circulation. OBJECTIVES: To determine if serum S100B distinguishes patients with central neurosarcoidosis (NS) from patients with extra-neurologic sarcoidosis (ENS) and healthy controls, and if S100B levels correlate with MRI measures of disease burden. METHODS: Patients were enrolled from the Cleveland Clinic Sarcoidosis Center. Patients with traumatic brain injury, central nervous system (CNS) infections, CNS malignancy, neurodegenerative disorders, schizophrenia, bipolar disorder, or melanoma were excluded. S100B levels were compared between patients with NS, ENS, and healthy controls, and between NS patients with varying degrees of post-contrast enhancement on MRI. RESULTS: Median (interquartile range) S100B levels were 101 pg/mL (92, 136) for 11 NS patients, 89 pg/mL (73, 107) for 11 ENS patients, and 60 pg/mL (39, 74) for 26 healthy controls. There was a significant difference between NS and control groups (p = 0.01). The difference between NS and ENS groups did not rise to the level of statistical significance (p = 0.178). S100B levels were significantly different between NS patients with varying degrees of enhancement on MRI (p = 0.04). CONCLUSIONS: S100B deserves additional study as a biomarker for CNS injury in NS. It may be useful as a longitudinal measure of disease activity.

Endpoints for clinical trials of sarcoidosis.

Over the past few years an increasing number of prospective controlled sarcoidosis treatment trials have been completed. Unfortunately, these studies utilize different endpoints making comparisons between studies difficult. At the recent World Association of Sarcoidosis and other Granulomatous disease (WASOG) meeting, a session was dedicated to the evaluation of clinical endpoints for various disease manifestations. These included pulmonary, pulmonary hypertension, fatigue, cutaneous, and a classification of clinical disease phenotypes. Based on the available literature and our current understanding of the disease, recommendations for clinical evaluation were proposed for each disease category. For example, it was recommended that pulmonary studies should include changes in the forced vital capacity. Additionally, it was recommended that all trials should incorporate measurement of quality of life.

Metabolism-perfusion imaging to predict disease activity in cardiac sarcoidosis.

FDG-PET is a sensitive but not specific test for myocardial sarcoidosis and its ability to define prognosis remains unclear. Combination with perfusion scanning may improve accuracy by differentiating scar from inflammation. We conducted this retrospective chart review to ascertain the utility of a rubidium -FDG PET scan for assessment of disease activity in patients with cardiac sarcoidosis. The presence of any perfusion-metabolism mismatch or a mismatch of > 6% of the myocardium on the scan were compared with the clinical course. Among 18 subjects, mismatched segments were present in 11 scans, whereas 7 demonstrated mismatch > 6%. There was a suggestion of association between PET scan and active disease using the threshold of any mismatch (p=0.09), with sensitivity of 80% and specificity of 62.5%. The threshold of >6% mismatch improved the specificity to 100% with 70% sensitivity, and the association between PET findings and clinically active disease was highly significant (p=0.0002). Eight patients had follow-up Rb-FDG PET scans, all of which were concordant with the clinical course. The positive predictive value of Rb-FDG PET scan showing >6% mismatch for detecting clinically active cardiac sarcoidosis was 100%. However, the finding of any mismatch still portends a high chance of clinical activity. Further studies to define the utility of Rb-FDG PET scan for management of cardiac sarcoidosis are warranted.

Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis.

Leflunomide has been reported as an alternative therapy in sarcoidosis. However, the published data are limited. We performed a retrospective chart review of the tolerance and effects of leflunomide therapy in patients with sarcoidosis. 76 patients were included. The most common reasons for initiation were progression of disease or failure of other immunomodulator therapy. Side-effects attributable to leflunomide were noted in 34% of subjects, prompting discontinuation in 17%. The lungs were a target of therapy in 33 (44%) and extrapulmonary organs were a target in 45 (59%). The mean ± sd change in forced vital capacity in the 6 months prior to leflunomide was -0.1 ± 0.3 L, and it was +0.09 ± 0.3 L in the following 6 months (p=0.01). For extrapulmonary target organ response, 51% had a good response and 32% a partial response. The median corticosteroid dose at initiation was 10 mg (interquartile range 5-20) mg at baseline, and 0 (0-10) mg at the 6-month follow-up (p<0.001). Leflunomide is a viable alternative agent for pulmonary and extrapulmonary sarcoidosis. Leflunomide appears to facilitate reduction of steroid dose and can be considered as monotherapy or as add-on therapy in cases of progressive disease.

Detecting cardiac involvement in sarcoidosis: a call for prospective studies of newer imaging techniques.

Diagnosis of cardiac involvement in sarcoidosis is challenging and usually relies on a combination of clinical findings and imaging abnormalities. The case of a 53-yr-old female is described who presented with ventricular tachycardia and suspected angiosarcoma involving the right atrium and superior vena cava. A combination of magnetic resonance imaging and (18)F-2-fluoro-2-deoxyglucose-positron emission tomography were essential to the diagnosis of cardiac sarcoidosis. Reversibility of the disease was predicted more clearly by (18)F-2-fluoro-2-deoxyglucose-positron emission tomography than by magnetic resonance imaging, and clinical activity was predicted by persistent hypermetabolism on serial (18)F-2-fluoro-2-deoxyglucose-positron emission tomography.

Photosynthesis and photorespiration in algae.

The CO(2) exchange of several species of fresh water and marine algae was measured in the laboratory to determine whether photorespiration occurs in these organisms. The algae were positioned as thin layers on filter paper and the CO(2) exchange determined in an open gas exchange system. In either 21 or 1% O(2) there was little difference between (14)CO(2) and (12)CO(2) uptake. Apparent photosynthesis was the same in 2, 21, or 50% O(2). The compensation points of all algae were less than 10 mul 1(-1). CO(2) or (14)CO(2) evolution into CO(2)-free air in the light was always less than the corresponding evolution in darkness. These observations are inconsistent with the proposal that photorespiration exists in these algae.