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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.

Graph theory models a network by its nodes (the fundamental unit by which graphs are formed) and connections. 'Degree' hubs reflect node centrality (the connection rate), while 'connector' hubs are those linked to several clusters of nodes (mainly long-range connections). Here, we compared hubs modeled from measures of interdependencies of between-electrode resting-state eyes-closed electroencephalography (rsEEG) rhythms in normal elderly (Nold) and Alzheimer's disease dementia (ADD) participants. At least 5 min of rsEEG was recorded and analyzed. As ADD is considered a 'network disease' and is typically associated with abnormal rsEEG delta (<4 Hz) and alpha rhythms (8-12 Hz) over associative posterior areas, we tested the hypothesis of abnormal posterior hubs from measures of interdependencies of rsEEG rhythms from delta to gamma bands (2-40 Hz) using eLORETA bivariate and multivariate-directional techniques in ADD participants versus Nold participants. Three different definitions of 'connector' hub were used. Convergent results showed that in both the Nold and ADD groups there were significant parietal 'degree' and 'connector' hubs derived from alpha rhythms. These hubs had a prominent outward 'directionality' in the two groups, but that 'directionality' was lower in ADD participants than in Nold participants. In conclusion, independent methodologies and hub definitions suggest that ADD patients may be characterized by low outward 'directionality' of partially preserved parietal 'degree' and 'connector' hubs derived from rsEEG alpha rhythms.

BackgroundEpilepsy and hypertension are common chronic conditions, both showing high prevalence in older age groups. This review outlines current experimental and clinical evidence on both direct and indirect role of hypertension in epileptogenesis and discusses the principles of drug treatment in patients with hypertension and epilepsy.MethodsWe selected English-written articles on epilepsy, hypertension, stroke, and cerebrovascular disease until December, 2018.ResultsRenin-angiotensin system might play a central role in the direct interaction between hypertension and epilepsy, but other mechanisms may be contemplated. Large-artery stroke, small vessel disease and posterior reversible leukoencephalopathy syndrome are hypertension-related brain lesions able to determine epilepsy by indirect mechanisms. The role of hypertension as an independent risk factor for post-stroke epilepsy has not been demonstrated. The role of hypertension-related small vessel disease in adult-onset epilepsy has been demonstrated. Posterior reversible encephalopathy syndrome is an acute condition, often caused by a hypertensive crisis, associated with the occurrence of acute symptomatic seizures. Chronic antiepileptic treatment should consider the risk of drug-drug interactions with antihypertensives.ConclusionsCurrent evidence from preclinical and clinical studies supports the vision that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms. In both post-stroke epilepsy and small vessel disease-associated epilepsy, chronic antiepileptic treatment is recommended. In posterior reversible encephalopathy syndrome blood pressure must be rapidly lowered and prompt antiepileptic treatment should be initiated.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients’ representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September–October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

Previous evidence showed a 75.5% best accuracy in the classification of 120 Alzheimer's disease (AD) patients with dementia and 100 matched normal elderly (Nold) subjects based on cortical source current density and linear lagged connectivity estimated by eLORETA freeware from resting state eyes-closed electroencephalographic (rsEEG) rhythms (Babiloni et al., 2016a). Specifically, that accuracy was reached using the ratio between occipital delta and alpha1 current density for a linear univariate classifier (receiver operating characteristic curves). Here we tested an innovative approach based on an artificial neural network (ANN) classifier from the same database of rsEEG markers. Frequency bands of interest were delta (2-4 Hz), theta (4-8 Hz Hz), alpha1 (8-10.5 Hz), and alpha2 (10.5-13 Hz). ANN classification showed an accuracy of 77% using the most 4 discriminative rsEEG markers of source current density (parietal theta/alpha 1, temporal theta/alpha 1, occipital theta/alpha 1, and occipital delta/alpha 1). It also showed an accuracy of 72% using the most 4 discriminative rsEEG markers of source lagged linear connectivity (inter-hemispherical occipital delta/alpha 2, intra-hemispherical right parietal-limbic alpha 1, intra-hemispherical left occipital-temporal theta/alpha 1, intra-hemispherical right occipital-temporal theta/alpha 1). With these 8 markers combined, an accuracy of at least 76% was reached. Interestingly, this accuracy based on 8 (linear) rsEEG markers as inputs to ANN was similar to that obtained with a single rsEEG marker (Babiloni et al., 2016a), thus unveiling their information redundancy for classification purposes. In future AD studies, inputs to ANNs should include other classes of independent linear (i.e., directed transfer function) and non-linear (i.e., entropy) rsEEG markers to improve the classification.

To date, no data have been published in literature regarding either a “model” or systematic approach to caring for patients with brain tumor-related epilepsy (BTRE). In Italy, there are numerous dedicated centers for epilepsy. Study aims: to investigate how many BTRE patients were followed by these specialized centers, independent of histological grade; to have a national snapshot of the range of care issues concerning these patients, with surveys completed by Italian centers adhering to the Italian League Against Epilepsy (LICE) study group for BTRE. Each participating Italian center received a survey requesting: description of organizational structure/service model for diagnosis and treatment of epilepsy; number of patients followed (from 1/2010 to 12/2011); services offered, within the same institution or in close proximity; degree of access to colleagues from other disciplines for discussion of cases, with indication of departments/areas of specialization were sought. Thirty out of the 35 centers adhering to LICE study group completed the survey indicating total of 2,528 patients with BTRE had been treated with 940 new patients/year. Data regarding the care model, service offerings, referral sources were collected. This study is a first collaborative project of epilepsy centers throughout Italy, aimed at collecting data on a national scale. Results indicate: (1) 2,528 patients had been followed by participating centers and account for 21 % of estimated patients with BTRE in Italy (2) difficulties in organizing meetings with other specialists (e.g. for discussion of cases/patient briefings); (3) need for multidisciplinary integration with other specialists as a priority area for intervention.

Despite the vast amount of literature on non-specific immune mechanisms in Alzheimer’s disease (AD), little is known about the role of antigen-specific immune responses. We investigated T cell reactivity to fragment 1–42 of amyloid-β (Aβ) and to N-terminal peptides of human mitochondrial and control microbial proteins. Thirty subjects with a diagnosis of probable AD according to NINCDS-ADRDA criteria and 30 sex- and age-matched healthy controls were enrolled. T cell responses to Aβ fragment showed no significant differences between AD patients and controls. By contrast, the mean number of positive T cell responses to both human mitochondrial and microbial peptides was significantly decreased in AD patients compared to control subjects. No significant correlation was found between T cell responses and both the severity of cognitive impairment and duration of the disease. Our results suggest that antigen-specific immune responses are impaired in AD. Protective immune responses to harmful amyloidogenic substances may also be impaired, thus favoring their accumulation in the brain.

To the Editor: Ascherio et al. (Feb. 1 issue) 1 report that they found no association between hepatitis B vaccination and the onset of multiple sclerosis. Vaccination was confirmed only in the respondents who said they had been vaccinated. Exclusions involved only the women with multiple sclerosis or the controls who had potentially been vaccinated, not those stating they had not been vaccinated. Similar rates of exclusion are cited for the women with multiple sclerosis and the controls, but with the wrong denominator, which should have referred to the positive cases and controls. Rather than exclude 35 percent of the women . . .