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Introduction During surgery for lesions in eloquent areas the goal is to achieve the widest resection possible, without loss of neurological function. Intraoperative seizures may lead to abandonment of the procedure or damages to the patient. Awareness regarding the predictors of IOS would help the surgeon. The aim of this retrospective study was to identify the factors associated with the occurrence of IOS in patients who underwent awake surgery for removal of gliomas in eloquent areas. Methods This was a retrospective analysis of prospectively collected data of 109 patients who underwent awake craniotomy between January 2010 and December 2017 for removal of gliomas. IOS were defined as tonic–clonic seizures or loss of consciousness resulting in communication difficulties with the patient occurring during cortical and subcortical mapping. Results A total of 109 patients were included in this study and IOS occurred in 9 (8.2%) patients. Demographic and clinical factors were comparable between patients with and without IOS. In the IOS group, 7 (77.8%) patients had seizures preoperatively and 4 (57.1%) were on more than one perioperative antiepileptic drugs (AED). Conclusions The current series add some hints to the poorly studied IOS risk during awake surgery. The risk of IOS appears to be relatively higher in patients with anteriorly located tumors and in patients operated without intraoperative brain activity monitoring and different patterns of stimulation for language and sensory-motor mapping. Further studies are needed to clarify the role of intraoperative techniques.

The COVIVAX study assessed the association between COVID-19 vaccination and the risk of common neurological disorders in a multicenter case-control design. Vaccination exposure was compared between individuals with a first diagnosis of a neurological disorder (cases) and age- and sex-matched controls. A total of 624 participants were enrolled, and after random 1:1 matching 265 cases and 265 matched controls (total 530 participants) were included in the analyses. The most frequent neurological diagnosis in cases were stroke (60.4%), multiple sclerosis (11.3%) and seizures (6.4%). The proportion of vaccinated participants was 72.1% among cases and 79.6% among controls. A protective role of vaccination on the risk of developing a new neurological disorder was detected in the unadjusted analysis (OR 0.50; 95% CI 0.29–0.86; p  = 0.0114). After adjustment for confounders, the number of vaccination doses received was associated with a reduced risk of developing new neurological disorders for participants aged over 60 years ( p  = 0.0472; OR 0.14, 95% CI 0.03–0.68), with pre-existing comorbidities ( p  = 0.0122; OR 0.04, 95% CI 0.01–0.99) and for stroke ( p  = 0.0232; OR 0.04, 95% CI 0.02–0.97). The COVIVAX study provided no warning sign regarding an increase in the risk of developing new neurological disorders following COVID-19 vaccination of any type or doses. A potentially protective effect of multiple doses of COVID-19 vaccines against the risk of stroke in people aged over 60 needs to be confirmed by further studies.

Background Epilepsy is a frequent symptom in patients with glioma. Although treatment with antiepileptic drugs is generally effective in controlling seizures, drug-resistant patients are not uncommon. Multidrug resistance proteins (MRPs) and P-gp are over-represented in brain tissue of patients with drug-resistant epilepsy, suggesting their involvement in the clearance of antiepileptic medications. In addition to their anticonvulsant action, some drugs have been documented for cytotoxic effects. Aim of this study was to evaluate possible in vitro cytotoxic effects of two new-generation antiepileptic drugs on a human glioma cell line U87MG. Methods Cytotoxicity of brivaracetam and lacosamide was tested on U87MG, SW1783 and T98G by MTS assay. Expression of chemoresistance molecules was evaluated using flow cytometry in U87MG and human umbilical vein endothelial cells (HUVECs). To investigate the putative anti-proliferative effect, apoptosis assay, microRNA expression profile and study of cell cycle were performed. Results Brivaracetam and lacosamide showed a dose-dependent cytotoxic and anti-migratory effects. Cytotoxicity was not related to apoptosis. The exposure of glioma cells to brivaracetam and lacosamide resulted in the modulation of several microRNAs; particularly, the effect of miR-195-5p modulation seemed to affect cell cycle, while miR-107 seemed to be implicated in the inhibition of cells migration. Moreover, brivaracetam and lacosamide treatment did not modulate the expression of chemoresistance-related molecules MRPs1-3-5, GSTπ, P-gp on U87MG and HUVECs. Conclusion Based on antineoplastic effect of brivaracetam and lacosamide on glioma cells, we assume that patients with glioma could benefit by the treatment with these two molecules, in addition to standard therapeutic options.

Glioblastoma is characterized by a high proliferative rate and drug resistance. The standard of care includes maximal safe surgery, followed by radiotherapy and temozolomide chemotherapy. The expression of glutamate receptors has been previously reported in human glioma cell lines. The aim of this study was to examine the cellular effects of perampanel, a broad-spectrum antiepileptic drug acting as an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) glutamate receptor antagonist, alone or in combination with temozolomide. Four human glioma cell lines were exposed to different concentrations of perampanel and temozolomide, alone or in combination. The type of drug interaction was assessed using the Chou-Talalay method. Apoptosis, cell cycle perturbation, and glutamate receptors (GluRs) subunit expression were assessed by flow cytometry. Perampanel significantly inhibited the growth, inducing high levels of apoptosis. A strong synergistic effect of the combination of perampanel with temozolomide was detected in U87 and A172, but not in U138. Treatment with perampanel resulted in an increased GluR2/3 subunit expression in U87 and U138. Perampanel displays a pro-apoptotic effect on human glioblastoma cell lines when used alone, possibly due to increased GluR2/3 expression. The observed synergistic effect of the combination of temozolomide with perampanel suggests further investigation on the impact of this combination on oncologic outcomes in glioblastoma.

Cerebral amyloid angiopathy (CAA) is a small vessel disease, causing spontaneous intracerebral hemorrhage (ICH) in the elderly. It is strongly associated with Alzheimer disease (AD), as most CAA patients show deposition of Aβ—i.e. the basic component of parenchymal Alzheimer amyloid deposits—in the cerebral vessels. Iatrogenic early-onset CAA has been recently identified in patients with a history of traumatic brain injury or other cerebral as well as extra-cerebral lesions that led to neurosurgery or other medical procedures as intravascular embolization by cadaveric dura mater extracts many years before the first ICH event. In those patients, a transmission of Aβ seeds from neurosurgical instruments or from cadaveric dura mater exposure was suggested. We report a 51-year-old woman with unremarkable family history who presented abruptly with aphasia and right hemiparesis. A cerebral left lobar haemorrhagic stroke was documented by neuroimaging. Accurate anamnesis revealed a neurosurgical procedure with cadaveric dura mater graft at the age of 2 years for an arachnoid cyst. The neuropathological examination of the cerebral parietal biopsy showed severe amyloid angiopathy in many leptomeningeal and cortical vessels, as well as abundant parenchymal Aβ deposits, neurofibrillary tangles and neuropil threads. The mechanism involved in the human-to-human transmission of the Aβ proteinopathy remains to be clarified. In our patient the cadaver derived dura used for grafting is a very strong candidate as the source of the transmission. A systematic monitoring of individuals who have had neurosurgical procedures in early life, especially those involving cadaveric dural grafts, is required to determine the ratio of those affected by CAA many years later and unaffected. Moreover, our report confirms that in addition to vascular and parenchymal Aβ pathology, neurofibrillary changes indistinguishable from AD may develop in specific conditions with long latency period from the neurosurgical or embolization procedure.

Phagocytosis and inflammation within the lungs is crucial for host defense during bacterial pneumonia. Triggering receptor expressed on myeloid cells (TREM)-2 was proposed to negatively regulate TLR-mediated responses and enhance phagocytosis by macrophages, but the role of TREM-2 in respiratory tract infections is unknown. Here, we established the presence of TREM-2 on alveolar macrophages (AM) and explored the function of TREM-2 in the innate immune response to pneumococcal infection in vivo. Unexpectedly, we found Trem-2(-/-) AM to display augmented bacterial phagocytosis in vitro and in vivo compared to WT AM. Mechanistically, we detected that in the absence of TREM-2, pulmonary macrophages selectively produced elevated complement component 1q (C1q) levels. We found that these increased C1q levels depended on peroxisome proliferator-activated receptor-δ (PPAR-δ) activity and were responsible for the enhanced phagocytosis of bacteria. Upon infection with S. pneumoniae, Trem-2(-/-) mice exhibited an augmented bacterial clearance from lungs, decreased bacteremia and improved survival compared to their WT counterparts. This work is the first to disclose a role for TREM-2 in clinically relevant respiratory tract infections and demonstrates a previously unknown link between TREM-2 and opsonin production within the lungs.

Epilepsy is the most common comorbidity in patients with brain tumors. To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.

This study analyzed the subjective facets of quality of life (QoL) and their relation to the type of brain tumor (BT) and phase of disease. Two hundred and ninety-one patients with pinealoblastoma, medulloblastoma, low-grade glioma, anaplastic astrocytoma, or glioblastoma were evaluated. With respect to 110 healthy controls, patients in the phases of radiotherapy/chemotherapy, stable disease, or tumor recurrence were significantly more anxious and depressed compared with patients in the early postoperative period. All patients were impaired in mental flexibility and memory, with preservation of abstract reasoning. The Functional Living Index-Cancer (FLIC), previously validated in cancer and BT patients, yielded six subjective factors (disease perception, affective well-being, role and leisure, personal base, nausea, sharing). None of the FLIC factors were predicted by tumor type, which only related to the physical and cognitive performances and mood scores. Affective well-being, role and leisure, and sharing were predicted by the phase of disease. Personal base, including self-perception and confidence, was independent on tumor progression and treatment. To conclude, QoL encompasses different subjective aspects, which vary in relation to the phase of disease and clinical burden. However, some person-related facets appear independent on tumor progression and treatment, indicating individual resources. Knowing this may guide tailored interventions supporting QoL.