Our data suggest that the measurement of RNU2-1f detected in CSF can be used as a diagnostic marker and also as a possible marker for treatment monitoring. These promising results need to be evaluated within a larger patient cohort.
Background
Brain tumor related epilepsy (BTRE) is a common complication of cerebral tumors and its incidence is highly dependent on the type of tumor, ranging from 10–15% in brain metastases to > 80% in low grade gliomas. Clinical management is challenging and has to take into account aspects beyond the treatment of non-tumoral epilepsy.
Main body
Increasing knowledge about the pathophysiology of BTRE, particularly on glutamatergic mechanisms of oncogenesis and epileptogenesis, might influence management of anti-tumor and BTRE treatment in the future. The first seizure implies the diagnosis of epilepsy in patients with brain tumors. Due to the lack of prospective randomized trials in BTRE, general recommendations for focal epilepsies currently apply concerning the initiation of antiseizure medication (ASM). Non-enzyme inducing ASM is preferable. Prospective trials are needed to evaluate, if AMPA inhibitors like perampanel possess anti-tumor effects. ASM withdrawal has to be weighed very carefully against the risk of seizure recurrence, but can be achievable in selected patients. Permission to drive is possible for some patients with BTRE under well-defined conditions, but requires thorough neurological, radiological, ophthalmological and neuropsychological examination.
Conclusion
An evolving knowledge on pathophysiology of BTRE might influence future therapy. Randomized trials on ASM in BTRE with reliable endpoints are needed. Management of withdrawal of ASMs and permission to drive demands thorough diagnostic as well as neurooncological and epileptological expertise.
Central nervous system lymphoma (CNSL) is diagnostically challenging. The identification of reliable and easy to measure biomarkers is desirable to facilitate diagnosis. Here, we evaluated the value of cerebrospinal fluid (CSF) osteopontin (OPN) as a diagnostic biomarker for CNSL. OPN concentrations in CSF from 37 patients with CNSL (29 with primary CNSL and 8 with secondary CNS involvement of systemic lymphoma) and 36 controls [6 patients with inflammatory CNS disease other than multiple sclerosis (MS), 8 with MS, 9 with glioblastoma (GBM) and 13 healthy controls] were determined using an enzyme-linked immunosorbent assay. Non-parametric tests and receiver operating characteristic (ROC) curves were performed for determination of diagnostic accuracy. Median CSF OPN level in all CNSL patients was 620 ng/mL and higher than in patients with inflammatory CNS disease (356 ng/mL); P < .05, MS (163 ng/mL); P < .01, GBM (41 ng/mL); P < .01, or healthy controls (319 ng/mL); P < .01. The area under the ROC curve was 0.865 [95 % confidence interval (CI) 0.745-0.985] for differentiating CNSL and patients with inflammatory CNS disease; 0.956 (95 % CI 0.898-1.000) for CNSL and MS patients; 0.988 (95 % CI 0.964-1.000) for CNSL and GBM patients, and 0.915 (95 % CI 0.834-0.996) for CNSL patients and healthy controls. In multivariate analysis, high CSF OPN level was associated with shorter progression-free (HR 1.61, 95 % CI 1.13-2.31; P = .009) and overall survival (HR 1.52, 95 % CI 1.04-2.21; P = .029). CSF OPN is a potential biomarker in CNSL.
Primary central nervous system lymphomas (PCNSLs) are mature B-cell lymphomas confined to the central nervous system (CNS). Blood-brain barrier (BBB) dysfunction drastically alters the cerebrospinal fluid (CSF) proteome in PCNSL patients. To reveal the interaction of PCNSL tumors with CNS structures and the vasculature, we conducted a whole-proteome analysis of CSF from PCNSL patients (n = 17 at initial diagnosis) and tumor-free controls (n = 10) using label-free quantitative mass spectrometry. We identified 601 proteins in the CSF proteome using a one-step approach without further prefractionation, and quantified 438 proteins in detail using the Hi-N method. An immunoassay revealed that 70% of the patients in our unselected PCNSL patient cohort had BBB dysfunction. Correlation analysis indicated that 127 (30%) of the quantified proteins were likely increased in PCSNL patients due to BBB dysfunction. After the exclusion of these proteins, 66 were found to differ in abundance (fold-change > 2.0, p < 0.05) between PCNSL and control CSF proteomes, and most of those were associated with the CNS. These data also provide the first evidence that proteomic changes in CSF from PCNSL patients are mainly associated with protein ectodomain shedding, and that shedding of human leukocyte antigen class 2 proteins is a mechanism of tumor-cell immune evasion.
Background
In patients with presumed primary CNS lymphoma (PCNSL) a systemic manifestation is found only in a small minority. Although bone marrow biopsy (BMB) is recommended for staging, its diagnostic value is unclear.
Methods
A retrospective analysis of 392 patients with presumed PCNSL from three university hospitals and 33 patients with secondary CNS lymphoma (SCNSL) and initial CNS involvement from a multicentre Germany-wide prospective registry was performed.
Results
A BMB was performed and documented in 320/392 patients with presumed PCNSL; 23 had pathologic results. One harboured the same lymphoma in the brain and bone marrow (BM), 22 showed findings in BM discordant to the histology of brain lymphoma; n=12 harboured a low grade lymphoma in the bone marrow, the other showed B-cell proliferation but no proof of lymphoma (n=5), monoclonal B-cells (n=3) or abnormalities not B-cell associated (n=2). In the group of SCNSL with initial CNS manifestation 32/33 patients underwent BMB; seven were documented with bone marrow involvement (BMI); one had concordant results in the brain and bone marrow with no other systemic manifestation. Six had additional systemic lymphoma manifestations apart from the brain and bone marrow.
Conclusions
In only two out of 352 (0.6%) patients with CNS lymphoma (320 presumed PCNSL and 32 SCNSL) BMB had an impact on diagnosis and treatment. While collected in a selected cohort these findings challenge the value of BMB as part of routine staging in presumed PCNSL.
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