Correction to: Phase II study of weekly carboplatin in pretreated adult malignant gliomas.

In the original article, the names of authors Mariantonia Carosi and Tatiana Koudriavtseva were incorrectly captured, and author Francesco Cognetti's affiliation was incorrect. The information is correctly shown here.

Perampanel in patients with brain tumor-related epilepsy in real-life clinical practice: a retrospective analysis.

INTRODUCTION: Epilepsy occurs in 35-70% of patients with gliomas; glutamate plays a central role via AMPA-receptor activation, which is involved both in seizure activity and tumor growth. We conducted a retrospective study on brain tumor-related epilepsy patients (BTRE) treated with perampanel in add-on (PER) for 12 months, to evaluate efficacy and tollerability, according to real-life clinical practice. MATERIALS AND METHODS: Medical records of eleven patients (9 males, mean age 54 years) with glioma and epilepsy treated with PER in add-on, for inadequate seizure control or adverse events (AEs) from previous antiepileptic drugs (AEDs) therapy, were reviewed. Data collected included: tumor history, molecular factors, systemic therapy, type and number of seizures and concomitant AEDs, and AEs. RESULTS: After 12 months of PER therapy, five patients were seizure-free, 4 had a seizure reduction ≥50% and the seizure frequency was unchanged in 2 patients. Responder rate was 81.8%. Two patients reported AEs; PER dose was reduced only in the one case. The final median dose of PER was 7.3 mg/day. We didn't find statistically significant differences in the comparison between mean values pre, mean values post and the average of decreasing number of seizures related to: histology, presence/absence of chemotherapy, radiotherapy, progression disease, KPS, IDH1, MGMT. DISCUSSION: Despite the limitations due to small number of patients in a retrospective study, the high rate of responder and seizure-free patients suggest that PER could be a therapeutic option in BTRE. Prospective controlled studies are needed to confirm our data.

A predictive value of von Willebrand factor for early response to Bevacizumab therapy in recurrent glioma.

Bevacizumab (BV), a neutralizing monoclonal antibody against the vascular endothelial growth factor ligand, is recognized as a potent anti-angiogenic agent with antitumor activity. The aim of this single-center, retrospective, longitudinal study was to investigate the possible predictive value of baseline demographic, clinical and laboratory parameters for early 3-month response to BV therapy in patients with recurrent glioma. Forty-nine patients with recurrent glioma received BV at 10 mg/kg intravenously every 3 weeks alone or in association with chemotherapy were included in this study. Blood samples were collected from all patients before the first (baseline), the second and the third administration of BV. After 3 months of BV therapy, patients with partial response were defined as responders whereas patients with stable or progressive disease were defined as non-responders. The median overall follow-up was 8 months (range 1-73), the median overall survival (OS) was 8 months (95% CI 6-10) and the median progression free survival (PFS) was 4 months (95% CI 3-5). Thirty-five % of patients were responders and showed significantly lower von Willebrand factor (VWF) levels than non-responders at all sample times (p < .02 for all). Also, on multivariate analysis the baseline VWF value was the only predictor for an early response to BV therapy. Furthermore, D-dimer and prothrombin fragment 1+2 were predictive factors for OS while Karnofsky performance status resulted predictive for PFS. VWF antigen value is a possible predictive biomarker for an early 3-month response to BV therapy in recurrent glioma.

HIV and decreased risk of multiple sclerosis: role of low CD4+ lymphocyte count and male prevalence.

In this retrospective case-control study, we compared the number of circulating lymphocyte subsets among 31 healthy controls, 18 naïve and 40 antiretroviral-treated HIV patients, 28 untreated and 18 treated relapsing-remitting multiple sclerosis (MS) patients. Lymphocyte subsets were no different between untreated MS patients and controls. Untreated and treated MS had a lower CD8+ count and a higher CD4+ number compared to untreated and treated HIV patients except similar CD4+ number between treated MS and HIV patients. CD4/CD8 ratio was lower in female HIV non-responders and in relapsing MS women compared, respectively, to female HIV responders and remitting MS women, and there were no differences in men.

Interferon-ß therapy and risk of thrombocytopenia in multiple sclerosis patients.

Thrombocytopenia is a well-described adverse event of several disease-modifying therapies (DMT) in multiple sclerosis (MS). On the other hand, an increased prevalence of MS has been reported in patients with immune thrombocytopenia. In this retrospective, cross-sectional, case-control study we evaluated in a heterogeneous MS cohort: (1) the prevalence of thrombocytopenia in comparison with sex- and age-matched controls; (2) the relationship between thrombocytopenia and patients' demographic, clinical characteristics; (3) the risk for thrombocytopenia in relation to DMT. 187 consecutive MS patients [51 males, mean age (±SD) 44.5 ± 10.7 years] and 200 controls (56 males, mean age 45.5 ± 12 years) were included. Thrombocytopenia was defined as platelet count lower than normal laboratory values (130-400 × 10(9)/L). The prevalence of thrombocytopenia was significantly higher in MS patients than in controls (7 vs. 2.5 %, p = 0.04). Thrombocytopenia was present only in relapsing-remitting MS cases, and significantly associated with lower EDSS (p = 0.002) and with a trend for shorter disease duration (p = 0.06). It was more frequent in patients on high-dose interferon-ß therapy compared with those on low-dose interferon-ß therapy, other therapies or untreated patients (p = 0.02). High-dose interferon-ß therapy was associated with more than eightfold increase in the risk for thrombocytopenia (odds ratio 8.60, 95 % confidence interval: 1.01-74.48 adjusted for EDSS, disease duration and type of disease). The prevalence of thrombocytopenia was increased in MS patients treated with DMT. High-dose interferon-ß therapy is the variable most strongly associated with thrombocytopenia.

Association between anemia and multiple sclerosis.

BACKGROUND/AIMS: The relationship between multiple sclerosis (MS) and anemia has not been clarified sufficiently. In this retrospective, cross-sectional, case-control study we evaluated in MS patients: (1) prevalence of anemia relative to sex- and age-matched controls; (2) relationships between patients' demographic, clinical and drug-related characteristics and anemia; (3) effect of anemia on the risk of developing MS. METHODS: 187 consecutive MS patients (51 males, mean age (±SD) 44.5 ± 10.7 years) and 200 controls (56 males, mean age 45.5 ± 12 years) were included in the study. Anemia was defined as hemoglobin <12 g/dl for females and <13 g/dl for males. RESULTS: There was a significant difference in the prevalence of anemia between MS patients and controls (35 (18.7%) and 19 (9.5%), respectively, p = 0.009). We did not find any association between patients' characteristics and anemia. The occurrence of anemia increased more than twice the risk of developing MS (odds ratio: 2.19, 95% confidence interval 1.19-4.0). CONCLUSION: Our study showed a consistent association between anemia and MS.

High frequency of antiphospholipid antibodies in relapse of multiple sclerosis: a possible indicator of inflammatory-thrombotic processes.

The exact prevalence and pathogenic role of antiphospholipid antibodies (aPL) in multiple sclerosis (MS) remain unclear. This observational laboratory-blinded study evaluated the rate of aPL positivity in healthy controls and MS patients in different disease phases to recognize their frequency and possible pathogenic meaning. Reactivity for anti-cardiolipin, anti-ß2 glycoprotein I, anti-prothrombin, anti-annexin V (IgG and IgM) was studied by enzyme immunoassays in 60 healthy controls and 100 consecutive MS patients [58 relapsing-remitting (RR) patients in remission, 26 RR patients in relapse, and 16 secondary progressive patients]. The overall rate of positivity for at least one aPL was significantly higher in MS patients compared to controls (32 % vs. 7 %, respectively, p < 0.0001), and in relapsing phase compared to those remitting or secondary progressive (53.8, 20.7 and 37.5 %, respectively, p = 0.002). In the single aPL analysis, the rate of positivity was significantly higher in MS patients compared to controls for anti-prothrombin IgM (7 % vs. 0, p = 0.05), and in relapsing phase compared to remitting and secondary progressive phases for anti-ß2 glycoprotein I IgM (26.9, 1.7, 6.3 %, respectively, p < 0.0001), anti-prothrombin IgM (15.4, 3.4, 6.3 %, respectively, p = 0.05) and IgG (19.2, 5.2, 0 %, respectively, p = 0.05). We showed a significant aPL increase in MS patients compared to healthy controls, particularly during disease relapse which was also associated with significantly higher values of anti-ß2 glycoprotein I and anti-prothrombin. These data suggest that antiphospholipid antibody occurrence in multiple sclerosis could be related to modification of structure and function of proteins involved in the inflammatory-thrombotic processes during disease re-activation.

From high- to low-frequency administered interferon-beta for multiple sclerosis: a multicenter study.

OBJECTIVES: To investigate whether clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) who required a reduction of administration frequency of interferon-beta (IFNB) were similar to those of patients who did not. METHODS: We identified three subgroups of patients under treatment for 24 months with subcutaneous (sc) high-frequency IFNB-1a or -1b: those continuing to receive IFNB according to the drug label (recommended frequency group), those reducing the administration frequency of sc IFNB-1a or -1b (reduced frequency group), and those switched to once weekly intramuscular (im) IFNB (switched group). All patients were followed for further 24 months. The occurrence of relapse, MRI activity and disability worsening were considered as outcome measures. RESULTS: We identified 308 patients, 201 in the recommended frequency group, 70 in the reduced frequency group, and 37 in the switched group. Patients in the reduced frequency group had increased risk for relapses (HR = 1.95, p < 0.001) and MRI activity (HR = 1.41, p < 0.001), while patients in the switched group had increased risk for relapses (HR = 1.67, p = 0.012), but not for MRI activity (HR = 1.26, p = 0.08) than those in the recommended frequency group. Predictors for disease activity re-start after the reduction of IFNB administration frequency were younger age, higher pre-IFNB relapse rate, and reducing sc IFNB frequency to twice weekly rather than switching to im IFNB-1a once weekly. CONCLUSION: Our findings discourage the reduction of sc IFNB administration frequency, especially in younger patients with a higher pre-IFNB relapse rate. However, switching to im IFNB-1a may be considered in some selected cases.

Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis.

Objectives: Recent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities. Methods: We compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission (n=30; 23F/7M, 40 ± 8.14 years) or a relapse (n=30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls (n=30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis. Results: Compared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3. Conclusion: Tissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis. Clinical trial registration: ClinicalTrials.gov, identifier NCT04380220.

The importance of physician-patient relationship for improvement of adherence to long-term therapy: data of survey in a cohort of multiple sclerosis patients with mild and moderate disability.

Patient involvement in the improvement of health care is important for the best long-term treatment outcomes. Our objective is to assess patient satisfaction with offered care service and to identify parameters which influence the adherence to long-term therapy. A prospective single-center study based on the administration of a structured interview to multiple sclerosis (MS) patients attending our MS Centre with mild and moderate disabilities. The interview regarding clinical parameters, quality of life and satisfaction of care service was structured in three parts with multiple-choice answers to close- or open-ended questions. Patient satisfaction was evaluated by the concordance between the level of patient attention and judgment regarding the services offered. The impact of all variables on the adherence to therapy and on the perceived utility of treatment was evaluated. The concordance between patient attention and judgment on health care services resulted statistically significant for almost all parameters. The perceived utility of treatment was significantly correlated to patients feeling confident in the clinical staff, to their perception of being involved in therapeutic decision (p<0.05), and associated to therapy adherence (p=0.0001). In a multivariate model, the adherence to therapy resulted associated to possibility of choosing the physician (p=0.037) and inversely to therapy duration (p=0.001). Our conclusion reveals that, to improve the adherence to long-term therapy and the perceived utility of treatment, a particular attention should be devoted to physician-patient relationship.

Elevated risk of thrombotic manifestations of SARS-CoV-2 infection in cancer patients: A literature review.

Coronavirus disease 2019 (COVID-19) results in higher risks of hospitalization or death in older patients and those with multiple comorbidities, including malignancies. Patients with cancer have greater risks of COVID-19 onset and worse prognosis. This excess is mainly explained by thrombotic complications. Indeed, an imbalance in the equilibrium between clot formation and bleeding, increased activation of coagulation, and endothelial dysfunction characterize both COVID-19 patients and those with cancer. With this review, we provide a summary of the pathological mechanisms of coagulation and thrombotic manifestations in these patients and discuss the possible therapeutic implications of these phenomena.

Impact of epilepsy and its treatment on brain metastasis from solid tumors: A retrospective study.

Introduction: Retrospective observational study on medical records of patients with epilepsy related brain metastases (BM) to evaluate efficacy, safety and possible interaction with cancer treatment of different anti-seizure medications (ASMs) and the risk of seizures. Materials and methods: We consecutively reviewed all medical records of epilepsy-related BM patients from 2010 to 2020 who were followed for at least one month at the Brain Tumour-related Epilepsy Center of the IRCCS Regina Elena National Cancer Institute Rome, Italy. Results: We selected 111 cancer patients. Of these, only 42 had at least undergone a second neurological examination. In the whole population, 95 (85.2%) had seizures and 16 patients had no seizures (14.4%). The most frequently first ASM prescribed was LEV (40.5%). We observed a significant correlation between tumor site and probability of having seizures, but not between seizure type and age (>65 or <65 years). Among 42 patients, 26 were administered levetiracetam, followed by oxcarbazepine. Until the last follow-up, 19 never changed the first ASM, maintained the same dosage and remained seizure free. After a median of 7 months, 16 (38.1%) required changes in therapeutic treatment due to inefficacy. At the last follow-up, 24 patients (57.1%) were seizure free. Eighteen patients (42.8%) never achieved freedom from seizures despite had at least 2 therapy changes. Two patients changed ASM due to adverse events and 1 to phenobarbital owing to the interaction with cancer treatment. The mean daily dose of first ASM in all 42 patients was very close to the Defined Daily Dose (DDD). Conclusion: In BM patients seizure incidence could be underestimated; a team evaluation performed by oncologist and neurologist together, could guarantee an accurate taking care of both oncological illness and epilepsy, in this fragile patient population. More than 50% of our patients respond to monotherapy with new generation ASMs. Furthermore we deemed in patients receiving chemotherapy the choice of ASM should consider possible interactions with antitumor therapies, for this reason newer generation ASMs should be the preferred choice. It is necessary to get close to the DDD before considering an ASM ineffective in seizure control.

Prevention of Bortezomib-Induced Peripheral Neuropathy in Newly Multiple Myeloma Patients Using Nervonic Acid, Curcuma Rizoma, and L-Arginine Compound: A Pilot Study.

INTRODUCTION: This is a phase II pilot study to evaluate the efficacy of a nutraceutical compound composed of nervonic acid, curcuma rizoma, and l-Arginine to prevent the onset of bortezomib-induced peripheral neuropathy (BIPN) in 16 newly diagnosed multiple myeloma (MM) patients treated with bortezomib (BTZ) over 6 months. MATERIALS AND METHODS: Assessments included neurological examination and electroneurography, Common Terminology Criteria for Adverse Events (NCI-CTCAE), reduced version of Total Neuropathic Score (TNSr), pain evaluation, functional autonomy scales, self-perceived symptoms and quality of life questionnaires at baseline and after 6 months. RESULTS: No patients were symptomatic at baseline, despite neurophysiological data and TNSr evidence of peripheral neuropathy (PN) in 11 of them. After 6 months, only 9 patients completed the study. All had modifications in neurological examination with 8 out of 9 showing neurophysiological data of PN (2 of which had a NCI-CTCAE grade of neurotoxicity ≥2); 4 patients dropped out due to BIPN, 2 because of MM progression, 1 for scarce compliance. DISCUSSION: In our study, the compound was not adequate to prevent BIPN. The incidence of subclinical PN in MM patients is a risk factor for the development of severe neurotoxicity during BTZ treatment. For this reason to evaluate the efficacy of any preventive compound, as well as to manage MM patients, it should be mandatory to include neurophysiological study as a standard procedure.

Homocysteine and Inflammatory Cytokines in the Clinical Assessment of Infection in Venous Leg Ulcers.

Inflammation and biofilm-associated infection are common in chronic venous leg ulcers (VU), causing deep pain and delayed healing. Albeit important, clinical markers and laboratory parameters for identifying and monitoring persistent VU infections are limited. This study analyzed 101 patients with infected (IVU) and noninfected VUs (NVU). Clinical data were collected in both groups. The serum homocysteine (Hcys) and inflammatory cytokines from the wound fluid were measured. In addition, microbial identification, antibiotic susceptibility, and biofilm production were examined. IVU were 56 (55.4%) while NVU were 45 (44.5%). IVUs showed a significant increase in the wound's size and depth compared to NVUs. In addition, significantly higher levels of interleukin (IL)-6, IL-10, IL17A, and tumor necrosis factor-alpha (TNF-α) were found in patients with IVUs compared to those with NVUs. Notably, hyperhomocysteinemia (HHcy) was significantly more common in patients with IVUs than NVUs. A total of 89 different pathogens were identified from 56 IVUs. Gram-negative bacteria were 51.7%, while the Gram-positives were 48.3%. At the species level, Staphylococcus aureus was the most common isolate (43.8%), followed by Pseudomonas aeruginosa (18.0%). Multidrug-resistant organisms (MDROs) accounted for 25.8% of the total isolates. Strong biofilm producers (SBPs) (70.8%) were significantly more abundant than weak biofilm producers (WBP) (29.2%) in IVUs. SBPs were present in 97.7% of the IVUs as single or multispecies infections. Specifically, SBPs were 94.9% for S. aureus, 87.5% for P. aeruginosa, and 28.6% for Escherichia coli. In IVU, the tissue microenvironment and biofilm production can support chronic microbial persistence and a most severe clinical outcome even in the presence of an intense immune response, as shown by the high levels of inflammatory molecules. The measurement of local cytokines in combination with systemic homocysteine may offer a novel set of biomarkers for the clinical assessment of IVUs caused by biofilm-producing bacteria.

Case Report: Probable Cerebral Amyloid Angiopathy-Related Inflammation During Bevacizumab Treatment for Metastatic Cervical Cancer.

Bevacizumab is an anti-angiogenic monoclonal antibody targeting Vascular Endothelial Growth Factor (VEGF) that induces the proliferation and migration of vascular endothelial cells thus, promoting vasculogenesis. Bevacizumab inhibits cancer angiogenesis, which is fundamental for either tumor development, exponential growth, or metastatic spread by supplying nutrients and oxygen. We report a new possible adverse event of bevacizumab, a Cerebral Amyloid Angiopathy-Related Inflammation (CAARI), in a 72-year-old woman with metastatic cervical cancer. After six cycles every three weeks of chemotherapy (cisplatin, paclitaxel, bevacizumab) and following two maintenance bevacizumab administrations, the patient presented a worsening confusional state. The MRI scan showed bilateral asymmetric temporo-parieto-occipital hyperintensity with numerous cortical microbleeds indicative of a CAARI. After stopping bevacizumab treatment, steroid therapy was administered resulting in rapid clinical improvement. The subsequent neurological and oncological follow-up was negative for recurrence. The patient was a heterozygote carrier for apolipoprotein-E ε4 that increases the risk of sporadic Cerebral Amyloid Angiopathy (CAA), which is characterized by beta-amyloid accumulation and fibrinoid necrosis in cerebral vasculature leading to micro/macrohemorrhages and dementia. Moreover, CAA is present in 30% of people aged over 60 years without dementia. In the brains of CAA patients, there is a proinflammatory state with cerebrovascular endothelial cell alteration and elevated levels of either adhesion molecules or inflammatory interleukins that increase the blood-brain barrier permeability. Moreover, CAARI is an inflammatory form of CAA. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival effects on endothelial cells, impairs their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, bevacizumab administration may have further increased permeability of cerebral microvasculature likely impaired by an underlying, asymptomatic CAA. To our knowledge, this is the first case reporting on the development of probable CAARI during bevacizumab treatment, which should alert the clinicians in case of neurological symptom onset in older patients under anti-angiogenic therapy.

Neutrophil-to-lymphocyte ratio, Factor VIII and Antithrombin III: inflammatory-clotting biomarkers in glioma.

One of the key difficulties in glioma treatment is our limited ability to consistently assess cancer response or progression either by neuroimaging or specific blood biomarkers. An ideal biomarker could be measured through non-invasive methods such as blood-based biomarkers, aiding both early diagnosis and monitoring disease evolution. This is a single-center, case-control, 10-year retrospective, longitudinal study. We evaluated routine coagulation factors in 138 glioma patients (45 Females/93 Males; median [range] age, 56.4 [27-82] years; 64 non-recurrent/74 recurrent) and, for comparison, in 56 relapsing-remitting MS patients (41 Females/15 Males; 40.8 [25-62] years, 35 stable/21 active) and 23 controls (16 Females/7 Males; 41.7 [24-62] years) as well as Neutrophil-to-lymphocyte ratio (NLR) in subgroups of 127 glioma patients, 33 MS patients and 23 healthy controls. Secondly, we assessed whether these indicators could be predictive of overall (OS) and progression-free survival (PFS) in glioma patients. NLR, d-dimer, Antithrombin III and Factor VIII were significantly higher in glioma patients compared to both MS patients and controls (p<0.0001 for all). ROC curves confirmed that either NLR, Antithrombin III or Factor VIII were moderately accurate biomarkers (0.7

Fatal herpetic encephalitis during brain radiotherapy in a cerebral metastasized breast cancer patient.

Herpes simplex encephalitis (HSE) is a life-threatening condition with high mortality. The pathogenesis underlying the reactivation of latent herpes simplex virus (HSV) remains undefined. We present the case of a 55-year-old female who developed HSE type 1 during brain irradiation and antioedematous dexamethasone treatment for leptomeningeal metastasized breast tumor with epileptic seizures. During the radiotherapy (RT), after a total of 32 Gray administrated in 16 fractions, our patient developed cognitive impairment and partial epileptic status without fever. Two days later the patient's clinical conditions had deteriorated and high fever manifested. A diagnosis of HSE type 1 was made by a positive cerebrospinal fluid polymerase chain reaction. Antiviral therapy with high doses of acyclovir was practiced for four weeks but the comatose state persisted. The patient died 59 days after the last RT fraction. The temporal relationship of RT to the occurrence of HSE suggests that cranial irradiation may play a role in the reactivation of latent HSV. Although antiviral therapy resistance is infrequent in immunocompetent patients, it is one of the main problems in immunocompromized patients.

Perampanel in brain tumor-related epilepsy: Observational pilot study.

OBJECTIVE: Possible loss of efficacy and potential interactions between antiepileptic drugs (AEDs) and chemotherapy could complicate the management of patients with brain tumor-related epilepsy (BTRE) that may expose patients to an increased risk of adverse events. Perampanel (PER) is a highly selective, noncompetitive, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptor antagonist. This study evaluates the effectiveness, QoL, cognition, and mood of PER in add-on therapy in BTRE patients. MATERIAL AND METHODS: Observational pilot study on the effectiveness of PER as add-on therapy in BTRE patients with uncontrolled seizures with a 6-month follow-up. RESULTS: We recruited 26 BTRE patients. During the follow-up, 16 underwent chemotherapy and 11 radiotherapy; 11 had disease progression. Five patients dropped out. Mean daily PER dosage was 6.6 mg in the 21 patients who completed the follow-up and 6.4 mg in the ITT population. The mean number of seizures/month decreased from 10.8 ± 15.03 at baseline to 1.7 ± 4.34 in the 21 patients who reached the final follow-up. Responder rate was 88.4%: Eight patients were seizure-free, 15 had ≥50% seizure reduction, and 3 remained stable. Four patients (15.4%) reported AEs: 2 required PER dose reduction, and 2 dropped out. Neuropsychological, mood, and QoL questionnaires were not statistically different compared to baseline. There were no significant differences in seizure control in patients with/without IDH1 mutation and with/without MGMT methylation. CONCLUSIONS: Perampanel proved to be effective on seizure control in BRTE patients and to be well tolerated without negative effects on cognition and QoL. Perampanel could be a valid therapeutic option in BTRE.