Deciphering the surgical treatment gap for drug-resistant epilepsy (DRE): A literature review

Patients with drug-resistant epilepsy (DRE) rarely achieve seizure freedom with medical therapy alone. Despite being safe and effective for select patients with DRE, epilepsy surgery remains heavily underutilized. Multiple studies have indicated that the overall rates of surgery in patients with DRE have stagnated in recent years and may be decreasing, even when hospitalizations for epilepsy-related problems are on the rise. Ultimately, many patients with DRE who might otherwise benefit from surgery continue to have intractable seizures, lacking access to the full spectrum of available treatment options. In this article, we review the various factors accounting for the persistent underutilization of epilepsy surgery and uncover several key themes, including the persistent knowledge gap among physicians in identifying potential surgical candidates, lack of coordinated patient care, patient misconceptions of surgery, and socioeconomic disparities impeding access to care. Moreover, factors such as the cost and complexity of the preoperative evaluation, a lack of federal resource allocation for the research of surgical therapies for epilepsy, and difficulties recruiting patients to clinical trials all contribute to this multifaceted dilemma.     

Prevalence and risk factors of silent brain infarcts in patients with AF detected by 3T-MRI

Journal of Neurology - Silent brain infarcts (SBI), a finding on neuroimaging, are associated with higher risk of future stroke. Atrial Fibrillation (AF) has been previously identified as a cause...     

Partial‐volume modeling reveals reduced gray matter in specific thalamic nuclei early in the time course of psychosis and chronic schizophrenia

The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial‐volume‐based over probabilistic‐based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex‐matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel‐wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub‐region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect.     

Epilepsia partialis continua revealing idelalisib-associated PML-IRIS: clinical and pathological features

Journal of NeuroVirology - Idelalisib, a selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, is a newly approved second-line drug for patients with chronic lymphocytic leukemia....     

uPAR Controls Vasculogenic Mimicry Ability Expressed by Drug-Resistant Melanoma Cells

Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of melanoma rapidly develop resistance to the BRAFV600E inhibitor vemurafenib, with fast tumor dissemination, a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenibresistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid progression and dissemination of the disease.