MR imaging profile and histopathological characteristics of tumour vasculature, cell density and proliferation rate define two distinct growth patterns of human brain metastases from lung cancer.

PURPOSE: Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis. METHODS: Preoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters. RESULTS: Applying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on their proliferative status: Ki67high BMs were larger (p = 0.02), showed less peritumoural oedema (p = 0.02) and showed a trend towards higher cell density (p = 0.05). Furthermore, Ki67high BMs were associated with higher DWI signals (p = 0.03) and reduced ADC values (p = 0.004). Vessel density was strongly reduced in Ki67high BM (p < 0.001). These features differentiated between lung cancer BM entities (p ≤ 0.03 for all features) with SCLCs representing predominantly the Ki67high group, while NSCLCs rather matching with Ki67low features. CONCLUSION: Interpretable and easy to obtain MRI features may not be sufficient to predict directly the primary tumour entity of BM but seem to have the potential to aid differentiating high- and low-proliferative BMs, such as SCLC and NSCLC.

SARS-CoV-2-related rapid reorganization of an epilepsy outpatient clinic from personal appointments to telemedicine services: A German single-center experience.

INTRODUCTION: When the SARS-CoV-2 pandemic reached Europe in 2020, a German governmental order forced clinics to immediately suspend elective care, causing a problem for patients with chronic illnesses such as epilepsy. Here, we report the experience of one clinic that converted its outpatient care from personal appointments to telemedicine services. METHODS: Documentations of telephone contacts and telemedicine consultations at the Epilepsy Center Frankfurt Rhine-Main were recorded in detail between March and May 2020 and analyzed for acceptance, feasibility, and satisfaction of the conversion from personal to telemedicine appointments from both patients' and medical professionals' perspectives. RESULTS: Telephone contacts for 272 patients (mean age: 38.7 years, range: 17-79 years, 55.5% female) were analyzed. Patient-rated medical needs were either very urgent (6.6%, n = 18), urgent (23.5%, n = 64), less urgent (29.8%, n = 81), or nonurgent (39.3%, n = 107). Outpatient service cancelations resulted in a lack of understanding (9.6%, n = 26) or anger and aggression (2.9%, n = 8) in a minority of patients, while 88.6% (n = 241) reacted with understanding, or relief (3.3%, n = 9). Telemedicine consultations rather than a postponed face-to-face visit were requested by 109 patients (40.1%), and these requests were significantly associated with subjective threat by SARS-CoV-2 (p = 0.004), urgent or very urgent medical needs (p = 0.004), and female gender (p = 0.024). Telemedicine satisfaction by patients and physicians was high. Overall, 9.2% (n = 10) of patients reported general supply problems due to SARS-CoV-2, and 28.4% (n = 31) reported epilepsy-specific problems, most frequently related to prescriptions, or supply problems for antiseizure drugs (ASDs; 22.9%, n = 25). CONCLUSION: Understanding and acceptance of elective ambulatory visit cancelations and the conversion to telemedicine consultations was high during the coronavirus disease 2019 (COVID-19) lockdown. Patients who engaged in telemedicine consultations were highly satisfied, supporting the feasibility and potential of telemedicine during the COVID-19 pandemic and beyond.

Long term seizure freedom on perampanel in highly drug-resistant epilepsy caused by bilateral periventricular nodular heterotopia: A case report.

•NMDA-receptor subunit expression of NR2A and NR2B is downregulated in heterotopias.•Glutamatergic transmission in the hyperexcitability of nodular heterotopias is implicated.•Mechanisms in PVNH to establish etiology specific therapies are still to be defined.

New MR perfusion features in primary central nervous system lymphomas: pattern and prognostic impact.

PURPOSE: Some MR perfusion features predict overall survival (OS) and progression-free survival (PFS) in glioblastomas. Prognostic value of MR perfusion in primary CNS lymphomas (PCNSL) remains unexplored being the aim of this investigation. METHODS: We retrospectively analyzed 3Tesla dynamic susceptibility contrast MR perfusion in 37 pre-surgical PCNSL for normalized regional cerebral blood volume rCBVmean and rCBVmax and for a PCNSL-typical shoulder-like increase of the time-signal intensity curve ("TSIC-shoulder"), indicating moderate vessel permeability. These MR perfusion features, tumor and edema size, number of lesions and patient characteristics were correlated with OS and PFS. RESULTS: Only patient's age was prognostic for OS (p = 0.0037) and PFS (p = 0.0088). 23 PCNSL had the TSIC-shoulder, a middle-sized diameter (39.5 ± 10.8 mm), volume (15.7 ± 11.3 ml), peritumoral edema (23 ± 8.7 mm) and moderately increased rCBVmean and rCBVmax (1.7 ± 0.5; 3.9 ± 1.2). Seven PCSNL with the TSIC-shoulder presented a sun-like pattern ("rCBV-sun") with a rim of marginally high rCBV. These unifocal PCNSL were larger (43 ± 11.2 mm; 25.62 ± 19.2 ml), with more peritumoral edema (32.8 ± 7.6 mm) and lower CBVmean (0.8 ± 0.3) and rCBVmax (2.2 ± 0.7), compared to the remaining six multifocal PCNSL without the TSIC-shoulder (26.3 ± 8.3 mm; 4.7 ± 4 ml; 16.3 ± 6.4 mm; 2.4 ± 1.6; 4.4 ± 2.3). CONCLUSIONS: Only patient age was predictive for OS and PFS of PCNSL; MR perfusion parameters and features were not. Most PCNSL revealed the TSIC-shoulder, moderate size, peritumoral edema and rCBV increase. However, larger, solitary PCNSL additionally had a rCBV-sun pattern and more edema, maybe due to a centrifugal vessel proliferation, whereas smaller, multifocal PCNSL contain apparently more concentrated and less permeable blood vessels represented by higher rCBV, no TSIC-shoulder and less edema.

Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases.

The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.