Primary Central Nervous System Lymphoma (PCNSL) is a rare neoplasm that can involve brain, eye, leptomeninges, and rarely spinal cord. PCNSL lesions most typically enhance homogeneously on T1-weighted magnetic resonance imaging (MRI) and appear T2-hypointense, but high variability in MRI features is commonly encountered. Neurological symptoms and MRI findings may mimic high grade gliomas (HGGs), tumefactive demyelinating lesions (TDLs), or infectious and granulomatous diseases. Advanced MRI techniques (MR diffusion, spectroscopy, and perfusion) and metabolic imaging, such as Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) or amino acid PET (usually employing methionine), may be useful in distinguishing these different entities and monitoring the disease course. Moreover, emerging data suggest a role for cerebrospinal fluid (CSF) markers in predicting prognosis and response to treatments. In this review, we will address the challenges in PCNSL diagnosis, assessment of response to treatments, and evaluation of potential neurotoxicity related to chemotherapy and radiotherapy.

PGRN is strongly expressed in MS brains, by macrophages/microglia in active lesions, and by activated microglia in the NAWM; PGRN CSF concentrations in MS are correspondingly increased in conditions of enhanced macrophage/microglia activation, such as during relapses and in progressive MS.

Our findings suggest that pregnancy after MS onset is associated with a slower long-term disability progression. Whether this represents a biological/immunological effect, or reflects a higher propensity toward childbearing in women with milder disease, it remains uncertain deserving further investigations.

GRN genetic polymorphisms likely influence disease course and relapse recovery in MS.

When designing a clinical trial on brain metastases the choice of end points is critical. The Response Assessment in Neuro-Oncology (RANO) International Group has recently critically reviewed the different end points used in the clinical trials on brain metastases [1,2].Some factors heavily influence the choice of end points. First, patients with solid tumors may differ in prognosis and competing risk of extracranial progression. Second, the trial setting (Phase II vs Phase III trials) and type of intervention (CNS-directed vs systemic therapies) also require different end points.The knowledge of prognostic factors, in other words, of those factors influencing the outcome regardless of treatments, is critical in order to identify subgroups of patients with different outcomes (e.g., Recursive Partitioning Analysis [RPA] and Graded Prognostic Assessment [GPA] classes) [3][4][5]. In clinical trials, these subgroups are essential either as a stratification factor or inclusion criteria or even for post hoc analyses.There are key issues in imaging brain metastases in clinical trials: modalities and frequency of assessment, type and magnitude of change used to define response or progression of disease, and incorporation of steroid use and neurological symptoms/signs with current imaging definitions of response and progression. Last but not least, the ability to differentiate tumor-related and treatment-related changes is another critical point.The objective response is used to screen the activity of novel compounds and represents a primary end point in Phase II trials. It may be a surrogate for other markers of clinical benefit, such as neurological symptoms, neurocognitive function or survival. The interlesional variability of response to treatment can render problematic the evaluation of response in multiple metastases. A methodological open issue is whether it is preferable a randomized Phase II trial or a single arm Phase II trial with historical control in large datasets (e.g., Radiaition Therapy Oncology Group [RTOG] datasets) when larger Phase III trials are not feasible.The criteria of response used in brain metastasis trials in the past were quite heterogeneous. The use of MRI for response assessment was not always a standard procedure. There were major areas of difference across trials on brain metastases regarding the evaluation of response to treatment: definition of a target lesion (not defined, ≥1 cm); number of lesions (variable); type of measurement (unidimensional, bidimensional, volumetric); degree of tumor shrinkage required for response (≥30%, ≥50%); requirement for confirmatory scans (more commonly not required); inclusion of steroids and neurological symptoms (more commonly not done); evaluation of extracranial disease (more commonly not included). Overall, none of the Standard Response Criteria (Response Evaluation Criteria In Solid Tumors [RECIST], WHO, MacDonald and RANO for high-grade gliomas) were designed specifically to evaluate brain metastases, thus investigators have not consistently ch...