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Background: The incidence of lymphomatous involvement of the central nervous system (CNS) has been increasing in recent years. However, the rarity of the disease has resulted in a scarcity of available data regarding its clinical presentation, natural history, and prognosis. We aimed to investigate the neurological characteristics of uncommon lymphomatous involvements confined to the CNS and to identify key variables that could serve as predictive biomarkers for treatment outcomes. Methods: We identified patients presenting with neurological symptoms and diagnosed with CNS-restricted lymphomatous involvement between 2005 and 2023. Results: We identified 44 cases, 93% of which were diagnosed with primary central nervous system lymphoma (PCNSL) and 7% with intravascular lymphoma. The median time from symptom onset to diagnosis was 47 days (range: 6–573 days), with no statistically significant difference between patients older and younger than 60 years (p = 0.22). The median follow-up time was 1144 days (range: 27–3501 days). Cognitive deterioration was the most common presenting symptom, occurring in 19 out of 44 patients (43%). Brain MRI revealed that lobar lesions were the most frequent location of lesions, found in 24 out of 44 patients (55%). By the end of the study period, 30 patients (68%) had died, with a median survival of 666 days (range: 17–3291 days). Death was significantly more common in patients who experienced relapses (p = 0.04; 95% CI: 0.99–0.03), with these patients having a four times higher chance of death (HR = 4.1; 95% CI: 1.01–16.09). The time to diagnosis significantly correlated with survival (p = 0.02; 95% CI: 0.005–0.54), as did the Eastern Cooperative Oncology Group (ECOG) performance status at the last follow-up (p = 0.006; 95% CI: 0.0012–0.62). Patients aged over 60 years did not exhibit a higher likelihood of death (p = 0.19; HR = 2.3; 95% CI: 0.63–8.61); however, the threshold age at diagnosis for the maximally predicted mortality was 64 years (ROC = 0.73; p = 0.03). Conclusions: Patients had significant delays in diagnosis, affecting patient outcomes. Cognitive deterioration and lobar lesions were prominent clinical and radiological features. Mortality was notably higher in patients with relapses and those who had a longer time to diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Examining the safety of theBNT162b2 mRNA vaccine in multiple sclerosis (MS) patients remains inconclusive, particularly regarding the potential for disease exacerbations. This study aims to assess the effects of BNT162b2 COVID‐19 vaccination on disease activity in MS patients through sequential MRI imaging. Methods: A retrospective study of 84 MS patients from five Israeli hospitals was conducted. MS lesion load was determined from three brain MRI scans, one postvaccination and two prevaccination scans. A post hoc analysis compared subgroups featuring vaccinated and unvaccinated patients respectively, with early onset MS. Results: The cohort included 70 women with early onset (mean age 16.4 ± 0.8 years) and adult onset (mean age 34.9 ± 1.1 years) MS. Among the early onset group, vaccinated patients showed an increased risk of new lesions (p =.00026), while there was no increased risk among adult‐onset patients. Additionally, a comparison between early onset vaccinated and nonvaccinated groups revealed a higher risk of increased lesions in the vaccinated group (p =.024). Discussion: Overall, the study suggests that the BNT162b2 vaccine is generally safe in MS patients, with no association found between vaccination and new lesions in most patients. However, close MRI follow‐up is recommended for early‐onset MS cases to monitor lesion development. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a rare disease with an incidence of 0.4/per 100,000 person‐years. As there is a limited number of prospective randomized trials in PCNSL, large retrospective studies on this rare disease may yield information that might prove useful for the future design of randomized clinical trials. We retrospectively analyzed the data of 222 newly diagnosed PCNSL patients treated in five referral centers in Israel between 2001 and 2020. During this period, combination therapy became the treatment of choice, rituximab has been added to the induction therapy, and consolidation with irradiation was largely laid off and was mostly replaced by high‐dose chemotherapy with or without autologous stem cell transplantation (HDC‐ASCT). Patients older than 60 comprised 67.5% of the study population. First‐line treatment included high‐dose methotrexate (HD‐MTX) in 94% of patients with a median MTX dose of 3.5 g/m2 (range 1.14–6 g/m2) and a median cycle number of 5 (range 1–16). Rituximab was given to 136 patients (61%) and consolidation treatment to 124 patients (58%). Patients treated after 2012 received significantly more treatment with HD‐MTX and rituximab, more consolidation treatments, and autologous stem cell transplantation. The overall response rate was 85% and the complete response (CR)/unconfirmed CR rate was 62.1%. After a median follow‐up of 24 months, the median progression‐free survival (PFS) and overall survival (OS) were 21.9 and 43.5 months respectively with a significant improvement since 2012 (PFS: 12.5 vs. 34.2 p = 0.006 and OS: 19.9 vs. 77.3 p = 0.0003). A multivariate analysis found that the most important factors related to OS were obtaining a CR followed by rituximab treatment and Eastern Cooperative Oncology Group performance status. The observed improvement in outcomes may be due to multiple components such as an intention to treat all patients regardless of age with HD‐MTX‐based combination chemotherapy, treatment in dedicated centers, and more aggressive consolidation with the introduction of HDC‐ASCT. [ABSTRACT FROM AUTHOR]

Background and purpose: Advanced analysis of electroencephalography (EEG) data has become an essential tool in brain research. Based solely on resting state EEG signals, a data‐driven, predictive and explanatory approach is presented to discriminate painful from non‐painful diabetic polyneuropathy (DPN) patients. Methods: Three minutes long, 64 electrode resting‐state recordings were obtained from 180 DPN patients. The analysis consisted of a mixture of traditional, explanatory and machine learning analyses. First, the 10 functional bivariate connections best differentiating between painful and non‐painful patients in each EEG band were identified and the relevant receiver operating characteristic was calculated. Later, those connections were correlated with selected clinical parameters. Results: Predictive analysis indicated that theta and beta bands contain most of the information required for discrimination between painful and non‐painful polyneuropathy patients, with area under the receiver operating characteristic curve values of 0.93 for theta and 0.89 for beta bands. Assessing statistical differences between the average magnitude of functional connectivity values and clinical pain parameters revealed that painful DPN patients had significantly higher cortical functional connectivity than non‐painful ones (p = 0.008 for theta and p = 0.001 for alpha bands). Moreover, intra‐band analysis of individual significant functional connections revealed a positive correlation with average reported pain in the previous 3 months in all frequency bands. Conclusions: Resting state EEG functional connectivity can serve as a highly accurate biomarker for the presence or absence of pain in DPN patients. This highlights the importance of the brain, in addition to the peripheral lesions, in generating the clinical pain picture. This tool can probably be extended to other pain syndromes. [ABSTRACT FROM AUTHOR]

Alemtuzumab (ALM) effectively prevents relapses of multiple sclerosis (MS). It causes lymphocyte depletion with subsequent enhancement of the T‐regulatory cell population. Direct administration of ALM to T cells causes cytolysis. However, the T cells may be indirectly affected by monocyte‐derived cells, which are resistant to ALM cytotoxicity. We aimed to examine whether ALM modulates monocytes and whether the crosstalk between monocytes and lymphocytes previously exposed to ALM would result in anti‐inflammatory effects. The CD14+ monocytes of 10 healthy controls and 10 MS (treatment naive) patients were isolated from peripheral blood mononuclear cells (PBMCs), exposed to ALM and reintroduced to PBMCs depleted of CD14+ cells. The macrophage profile was assessed and T‐cell markers were measured. ALM promoted M2 anti‐inflammatory phenotype as noted by an increased percentage in the populations of CD23+, CD83+ and CD163+ cells. The CD23+ cells were the most upregulated (7‐fold, P = 0.0002), and the observed effect was higher in patients with MS than in healthy subjects. ALM‐exposed macrophages increased the proportion of T‐regulatory cells, without affecting the proportion of T‐effector cells. Neutralizing the CD23+ monocytes with antibodies reversed the effect specifically on the CD4+CD39+ T‐regulatory cell subpopulation but not on the CD4+CD25hiCD127loFOXP3+ subpopulation. ALM induces the conversion of monocytes into anti‐inflammatory macrophages, which in turn promotes T‐regulatory cell enhancement, in a CD23‐dependent manner. These findings suggest that the mechanism of action of ALM is relevant to aspects of MS pathogenesis. [ABSTRACT FROM AUTHOR]