levetiracetam and Glioma

Seizures are common in patients with brain tumours, even though prophylactic anti-seizure treatment for all patients with brain tumours is not recommended. Newer anti-epileptic drugs have shown benefits that outweigh the side effects of treatment and can also be given in combination with traditional anti-epileptic drugs. The authors have reviewed the literature on the various combinations of anti-epileptics in patients with seizures and brain tumours.

Topics: Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Epilepsy; Gabapentin; Glioma; Humans; Lamotrigine; Levetiracetam; Neoplasm Grading; Phenytoin; Survival Rate; Topiramate; Valproic Acid; Zonisamide

Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%-2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. Hence, effective management of seizures is a major priority for patients with LGG. Evidence-based guidelines suggest that levetiracetam is the best first-line agent for treatment of seizures in this population due to both its efficacy and tolerability. An important consideration in the field of neuro-oncology is that levetiracetam has very few drug interactions. Unfortunately, approximately one-third of patients with LGG have refractory epilepsy where additional agents such as valproic acid, or lacosamide, lamotrigine and nonpharmacologic therapies such as diet-based interventions, epilepsy surgery, and devices are considered.

Topics: Anticonvulsants; Brain Neoplasms; Glioma; Humans; Lamotrigine; Levetiracetam; Piracetam; Seizures; Triazines

To determine the safety and tolerability of IV and oral levetiracetam monotherapy for seizures in brain tumor patients following resection. Brain tumor patients undergoing neurosurgery with >or=1 seizure within the preceding month prior to surgery were enrolled to receive intravenous levetiracetam for a minimum of 48 h, transitioned to oral levetiracetam at the same dose, and followed for 1-month after discharge. Patients were assessed daily in the hospital, provided with a seizure diary, and supplied with 30 days of levetiracetam upon discharge. Study patients were telephoned weekly to assess their cognitive status and seizure frequency. Of the 17 patients enrolled, the baseline seizure types were tonic clonic, partial, and complex partial with secondary generalization. The most common type of tumor was glioblastoma multiforme. Levetiracetam was well tolerated with no medication discontinuation during the study period. Adverse effects reported were somnolence, nausea/vomiting, headache, and insomnia. Eleven patients were evaluable for TICS scores (64.7%) with an average score of 33.3. Two patients were deemed to be cognitively impaired (18.2%). Eleven of twelve patients (91.7%) that completed the study period achieved a >or=50% reduction in their number of seizures. A total of 92 drug interactions were avoided (P = 0.0016) with dexamethasone, acetaminophen, and fentanyl being the most common. Levetiracetam monotherapy was found to be safe and tolerable in this patient population. Nearly all patients achieved a >or=50% reduction in seizure frequency post-op with levetiracetam monotherapy. Levetiracetam also has the potential for less drug interactions compared to phenytoin in these patients.

Topics: Administration, Oral; Adult; Aged; Anticonvulsants; Brain Neoplasms; Dose-Response Relationship, Drug; Drug Interactions; Female; Follow-Up Studies; Glioma; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Seizures; Survival Rate; Treatment Outcome

Levetiracetam (LEV) is a newer anticonvulsant with a favorable safety profile. There seem to be no relevant drug interactions, and an intravenous formulation is available. Therefore, LEV might be a suitable drug for the perioperative anticonvulsive therapy of patients with suspected brain tumors undergoing neurosurgery.. In this prospective study (NCT00571155) patients with suspected primary brain tumors and tumor-related seizures were perioperatively treated with oral and intravenous LEV up to 4 weeks before and until 4 weeks after a planned neurosurgical procedure.. Thirty patients with brain tumor-related seizures and intended neurosurgery were included. Three patients did not undergo the scheduled surgery after enrollment, and two patients were lost to follow-up. Therefore, 25 patients were fully evaluable. After initiation of therapy with LEV, 100% of the patients were seizure-free in the pre-surgery phase (3 days up to 4 weeks before surgery), 88% in the 48 h post-surgery phase and 84% in the early follow-up phase (48 h to 4 weeks post surgery). Treatment failure even after dose escalation to 3,000 mg/day occurred in three patients. No serious adverse events related to the treatment with LEV occurred.. Our data show the feasibility and safety of oral and intravenous LEV in the perioperative treatment of tumor-related seizures. Although this was a single arm study, the efficacy of LEV appears promising. Considering the side effects and interactions of other anticonvulsants, LEV seems to be a favorable option in the perioperative treatment of brain tumor-related seizures.

Topics: Administration, Oral; Adult; Aged; Anticonvulsants; Brain Neoplasms; Chemotherapy, Adjuvant; Electroencephalography; Feasibility Studies; Female; Follow-Up Studies; Glioma; Humans; Infusions, Intravenous; Levetiracetam; Male; Meningioma; Middle Aged; Monitoring, Physiologic; Neurosurgery; Neurosurgical Procedures; Pilot Projects; Piracetam; Prospective Studies; Seizures; Treatment Outcome; Young Adult

Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently used to control tumor-related seizures. PHT, however, has many undesirable side effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV) is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug interactions. We performed a pilot study testing the safety and feasibility of switching patients from PHT to LEV monotherapy for postoperative control of glioma-related seizures. Over a 13-month period, 29 patients were randomized in a 2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT therapy. 6 month follow-up data were available for 15 patients taking LEV and for 8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43), mood instability (7/0). The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma. A large-scale, double-blinded, randomized control trial of LEV versus PHT is required to determine seizure control equivalence and better assess differences in SEs.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Craniotomy; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Pilot Projects; Piracetam; Seizures

This study aimed to directly compare the effectiveness of first-line monotherapy levetiracetam (LEV) versus enzyme-inducing antiseizure medications (EIASMs) in glioma patients.. In this nationwide retrospective observational cohort study, Grade 2-4 glioma patients were included, with a maximum duration of follow-up of 36 months. Primary outcome was antiseizure medication (ASM) treatment failure for any reason, and secondary outcomes were treatment failure due to uncontrolled seizures and due to adverse effects. For estimation of the association between ASM treatment and ASM treatment failure, multivariate cause-specific cox proportional hazard models were estimated, adjusting for potential confounders.. In the original cohort, a total of 808 brain tumor patients with epilepsy were included, of whom 109 glioma patients were prescribed first-line LEV and 183 glioma patients first-line EIASMs. The EIASM group had a significantly higher risk of treatment failure for any reason compared to LEV (adjusted hazard ratio [aHR] = 1.82, 95% confidence interval [CI] = 1.20-2.75, p = .005). Treatment failure due to uncontrolled seizures did not differ significantly between EIASMs and LEV (aHR = 1.32, 95% CI = .78-2.25, p = .300), but treatment failure due to adverse effects differed significantly (aHR = 4.87, 95% CI = 1.89-12.55, p = .001).. In this study, it was demonstrated that LEV had a significantly better effectiveness (i.e., less ASM treatment failure for any reason or due to adverse effects) compared to EIASMs, supporting the current neuro-oncology guideline recommendations to avoid EIASMs in glioma patients.

Topics: Anticonvulsants; Epilepsy; Glioma; Humans; Levetiracetam; Retrospective Studies; Seizures

The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma.. This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n = 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan-Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n = 101) is used as first line.. Treatment with levetiracetam as a first-line ASM resulted in a significant increase in the probability of seizure freedom (p < .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic-clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p < .05) and 132% more likely to fail treatment by 5 years (p < .01) when compared to individuals who had seizures with progression to bilateral tonic-clonic activity. ASM choice did not significantly affect treatment failure rates.. More than two-thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first-choice agent. Experiencing mainly focal seizures without progression infers a significant long-term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.

Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy; Freedom; Glioma; Humans; Levetiracetam; Seizures; Treatment Failure; World Health Organization

Epilepsy is a major symptom in patients with glioma. Levetiracetam (LEV) is recognized as a first-line treatment for glioma-related epilepsy. Increasing the LEV dose is allowed into patients with seizure occurrence against its initial dose. However, the therapeutic efficacy of increasing the LEV dose in response to seizure occurrence remains unclear.. We retrospectively analyzed 236 glioma patients who were treated with antiseizure medications (ASMs) internally at our institute between September 2010 and December 2017. Of these, the analysis focused on 156 patients treated with LEV who had a clear history of administration.. Seizure occurrences were observed in 21 of 75 patients (26.7%) who received LEV as first-line therapy and in 33 of 81 patients (40.7%) who received LEV as non-first-line treatment. The seizure control rate for seizure occurrence with LEV as first-line treatment was significantly higher in patients treated with addition of other ASMs (72.7%) than in those treated with increasing dose of LEV (20.0%) (p = 0.016). The seizure control rate for seizure occurrence with LEV as non-first-line treatment did not differ significantly between patients with addition of other ASMs (58.3%) and those treated with increasing dose of LEV (47.6%) (p = 0.554).. Adding other ASMs was more effective than increasing the LEV dose for seizure control in patients treated with LEV as first-line treatment, but they demonstrated comparable efficacy in patients treated with LEV as non-first-line treatment.

Topics: Epilepsy; Glioma; Humans; Levetiracetam; Patients; Retrospective Studies

Antiseizure drug (ASD)-induced skin rash remains the main side effect of seizure management in patients with glioma. New generations of ASDs, such as levetiracetam (LEV) and lacosamide (LCM) are associated with less frequent skin rashes than conventional ASDs. However, there are few reports regarding the incidence of skin rashes by LEV and LCM in patients with glioma. Therefore, the aim of this study was to investigate the incidence and risk factors of LEV- and LCM-associated skin rashes in patients with glioma.. We compared the incidence of ASD-associated skin rash between 353 patients with glioma and 125 patients with meningioma, who received LEV or LCM and underwent surgery between 2017 and 2019 at our institution. Furthermore, to evaluate the association between potential risk factors and ASD-associated skin rashes, univariate and multivariate analyses were performed.. The incidence of ASD-associated skin rash in patients with glioma was higher (11 %) than in those with meningiomas (1.6 %). The multivariate regression analysis showed that adjuvant treatment with radiotherapy (p = 0.023) and a history of drug allergy (p = 0.023) were significant risk factors for ASD-associated skin rash. The rate of ASD-related skin rashes in patients with glioma was also higher than the previously reported rates of 1-3 % in patients with epilepsy.. Our results indicate that adjuvant treatment with radiotherapy and a history of drug allergy correlated with a high incidence of ASD-related skin rashes in patients with glioma who receive LEV and LCM. Patients with these two factors should be carefully checked for skin rashes.

Topics: Anticonvulsants; Drug Hypersensitivity; Exanthema; Glioma; Humans; Incidence; Lacosamide; Levetiracetam; Risk Factors

Seizures are a common presenting symptom among patients with low- and high-grade glioma. However, the impact and inter-relationship between the presence of seizures, anti-seizure medication (ASM) and survival are unclear. We retrospectively analyzed the incidence of seizures and identified the pattern and relationship of anti-seizure medication on survival in our cohort of patients with glioma.. We evaluated all glioma patients who underwent treatment at the University of Malaya Medical Centre (UMMC) between 2008 and 2020. Demographic and clinical data of seizures and pattern of ASM administration in comparison to overall survival were analyzed.. A total of 235 patients were studied, with a minimum of one year clinical follow-up post-treatment. The median survival for low-grade glioma was 38 months whereas high-grade glioma was 15 months. One-third of our glioma patients (n = 74) presented with seizures. All patients with seizures and a further 31% of patients without seizures were started on anti-seizure medication preoperatively. Seizure and Levetiracetam (LEV) were significantly associated with OS on univariate analysis. However, only LEV (HR 0.49; 95% CI 0.23-0.87; p=0.02) was significantly associated with improving overall survival (OS) on multivariate analysis. Once ASM was adjusted for relevant factors and each other, LEV was associated with improved survival in all grade gliomas (HR 0.52; 95% CI 0.31-0.88; p=0.02) and specifically high-grade gliomas (HR 0.53; 95% CI 0.30-0.94; p=0.03).. Pre-operative seizures among patients with glioma indicated a better overall prognosis. The administration of ASM, specifically LEV was associated with a  significant survival advantage in our retrospective cohort of patients.

Topics: Anticonvulsants; Brain Neoplasms; Glioma; Humans; Levetiracetam; Retrospective Studies

About 30% of patients with glioma need an add-on antiseizure medication (ASM) due to uncontrolled seizures on ASM monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV + VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in patients with glioma.. In this multicenter retrospective observational cohort study, treatment failure (i.e., replacement by, addition of, or withdrawal of an ASM) for any reason was the primary outcome. Secondary outcomes included (1) treatment failure due to uncontrolled seizures and (2) treatment failure due to adverse effects. Time to treatment failure was estimated from the moment of ASM duotherapy initiation. Multivariable cause-specific Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months.. A total of 1,435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received ASM duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV + VPA was prescribed in 66% (236/355) and other ASM duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy vs LEV + VPA had a higher risk of treatment failure for any reason (cause-specific adjusted hazard ratio [aHR] 1.50 [95% CI 1.07-2.12],. This observational cohort study suggests that LEV + VPA has better efficacy than other ASM combinations. Similar toxicities were experienced in the 2 groups.. This study provides Class III evidence that for patients with glioma with uncontrolled seizures on ASM monotherapy, LEV + VPA has better efficacy than other ASM combinations.

Topics: Anticonvulsants; Cohort Studies; Glioma; Humans; Levetiracetam; Piracetam; Retrospective Studies; Seizures; Valproic Acid

Patients with glioblastoma frequently suffer epileptic seizures and often require anticonvulsant therapy during the treatment course. The present study investigated four common antiepileptic drugs, perampanel, carbamazepine (CBZ), sodium valproate (VPA) and levetiracetam (LEV), which are expected to have antitumor effects, and determined the most beneficial drug for the treatment of malignant glioma by comparing antitumor effects such as inhibition of cell proliferation and suppression of migration and invasion (using Transwell assays). The inhibition of cell growth was investigated using six malignant glioma cell lines (A‑172, AM‑38, T98G, U‑138MG, U‑251MG and YH‑13). Significant inhibition of cell proliferation was observed in all six cell lines treated with perampanel, three cell lines treated with CBZ, four cell lines treated with VPA and two cell lines treated with LEV at the therapeutic blood concentration levels for the drugs to be used as antiepileptics. Further antitumor effects in combination with temozolomide were investigated using T98G and U‑251MG cell lines, and were confirmed in both cell lines with perampanel and in T98G cells with LEV, but not observed with CBZ and VPA. Cell migration was significantly suppressed in both T98G and U‑251MG cell lines with perampanel, but not with CBZ, VPA or LEV. To investigate the mechanisms by which perampanel suppresses the migration of malignant glioma cells, the expression of mRNA related to epithelial‑mesenchymal transition following perampanel treatment was analyzed using reverse transcription‑quantitative PCR in the T98G and U‑251MG cell lines. The expression of

Topics: Anticonvulsants; Cadherins; Carbamazepine; Glioma; Humans; Levetiracetam; Matrix Metalloproteinase 2; RNA, Messenger; Temozolomide; Valproic Acid

Topics: Anticonvulsants; Brain Neoplasms; Cerebral Cortex; Constriction, Pathologic; Electrodes, Implanted; Electroencephalography; Epilepsy; Glioma; Humans; Laryngeal Diseases; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Seizures

We analyzed the resting state functional magnetic resonance images to investigate the alterations of neural networks in patients with glioma-related epilepsy (GRE).. Fifty-six patients with right temporal lower-grade glioma were divided into GRE (n = 28) and non-GRE groups. Twenty-eight healthy subjects were recruited after matching age, sex, and education level. Sensorimotor, visual, language, and left executive control networks were applied to generate functional connectivity matrices, and their topological properties were investigated.. No significant alterations in functional connectivity were found. The least significant discovery test revealed differences only in the language network. The shortest path length, clustering coefficient, local efficiency, and vulnerability were greater in the non-GRE group than in the other groups. The nodal efficiencies of two nodes (mirror areas to Broca and Wernicke) were weaker in the non-GRE group than in the other groups. The node of degree centrality (Broca), nodal local efficiency (Wernicke), and nodal clustering coefficient (temporal polar) were greater in the non-GRE group than in the healthy group.. Different tumor locations alter different neural networks. Temporal lobe gliomas in the right hemisphere altered the language network. Glioma itself and GRE altered the network in opposing ways in patients with right temporal glioma.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Glioma; Humans; Language; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Temporal Lobe

This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.. In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow-up was 36 months.. In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%-38%] vs 50% [95% CI 45%-55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%-19%] vs 28% [95% CI 23%-32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%-18%] vs 15% [95% CI 11%-18%]; P = .636).. Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first-line AED treatment in patients with glioma.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Retrospective Studies; Seizures; Treatment Outcome; Valproic Acid

After introduction of levetiracetam (LEV), treatment of seizures in patients with malignant brain tumors has prominently improved. On the other hand, we still experience some cases with LEV-uncontrollable epilepsy. Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate acid receptor antagonist that has recently been approved for treating focal epilepsy as a secondary drug of choice. Available literature reporting PER medication in patients with gliomas is still sparse. Here, we report our initial experience with glioma patients and report efficacy of adding low dose 2-4 mg PER to LEV in patients whose seizure were uncontrollable with LEV monotherapy. Clinical outcome data of 18 consecutive patients were reviewed. This included nine males and nine females aged 24-76 years (median, 48.5 years), treated for glioma between June 2009 to December 2018. We added PER to patients with LEV-uncontrollable epilepsy. Adverse effects, irritability occurred in two patients, but continuous administration was possible in all cases. Though epileptic seizures occurred in four cases receiving 2 mg PER, 17 cases achieved seizure freedom by dose increments; final dose, 2-4 mg PER added to LEV 500-3000 mg. Our study revealed anti-epileptic efficacy of low dose PER 2-4 mg as first add-on therapy to LEV in glioma patients who have failed or intolerable to LEV monotherapy. Low dose PER added on to LEV may have favorable efficacy with tolerable adverse effects in glioma patients with LEV-uncontrollable epilepsy.

Topics: Adult; Aged; Anticonvulsants; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Combined Modality Therapy; Drug Resistance; Drug Resistant Epilepsy; Female; Follow-Up Studies; Glioma; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Neurosurgical Procedures; Nimustine; Nitriles; Pyridones; Radiotherapy, Adjuvant; Receptors, AMPA; Retrospective Studies; Temozolomide; Young Adult

Glioma, especially glioblastoma (GBM), is the most aggressive malignant brain tumor and its standard therapy is often ineffective because of temozolomide (TMZ) resistance. Reversal of the TMZ resistance might improve the prognosis of glioma patients. We previously found that interferon-α (IFN-α) and anti-epileptic drug levetiracetam (LEV) could sensitize glioma to TMZ, respectively. In this study, we further investigated the efficiency of combining of LEV and IFN-α for improving the efficacy of TMZ.. We evaluated whether LEV and IFN-α could increase TMZ efficacy using colony formation assay and cell viability assay with MGMT-positive and MGMT-negative glioma cell lines in vitro. Subcutaneous xenografts and orthotopic xenografts mice models were used in vivo to observe the tumor growth and mice survival upon treatments with TMZ, TMZ + IFN-α, TMZ + LEV, or TMZ + LEV + IFN-α. The expression levels of MGMT, markers of pro-apoptotic and anti-apoptotic in tumor samples were analyzed by Western blotting.. The combinational use of IFN-α, LEV, and TMZ showed the best anti-tumor activity in MGMT-positive cell lines (U138, GSC-1, U118, and T98 G). TMZ + LEV + IFN-α further obviously increased TMZ + LEV or TMZ + IFN-α efficiency in MGMT-positive cell lines, while not in negative cell lines (SKMG-4, U87, U373, and U251) in vitro, which were also observed in subcutaneous mice models (U138, GSC-1 compared to SKMG-4, U87) and orthotopic models (GSC-1) in vivo. Strikingly, the combination of LEV and IFN-α together with TMZ significantly prolonged the survival of mice with orthotopic GSC-1 glioma. Furthermore, we confirmed that the combination of LEV and IFN-α enhanced the inhibition of MGMT and the activation of apoptosis in U138 tumor on the basis of TMZ treatment.. The combination use of LEV and IFN-α could be an optimal method to overcome TMZ resistance through obvious MGMT inhibition in MGMT-positive glioma.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Line, Tumor; DNA Modification Methylases; DNA Repair Enzymes; Drug Resistance, Neoplasm; Drug Synergism; Female; Glioma; Humans; Interferon-alpha; Levetiracetam; Mice; Temozolomide; Tumor Suppressor Proteins; Xenograft Model Antitumor Assays

Glioma is the most common intracranial primary brain tumor. Patients with glioma often suffer from epilepsy, anxiety and depression. Aims of this study were to identify risk factors for drug-treated anxiety and depression, and to determine the use of psychiatric medication in a national glioma cohort.. Data from the Cancer Registry of Norway on all persons diagnosed with glioma WHO grade II-IV 2004-2010 were linked with data from the Norwegian Prescription Database. Cox regression analysis was used to assess risk factors for drug-treated anxiety and depression. Standardized incidence ratios were calculated for psychiatric medication dispensed to glioma patients and compared to the general population.. The glioma cohort consisted of 1056 males and 772 females. Of the 1828 patients, 565 had glioma grade II-III, and 1263 had grade IV. The patients with glioma grade II-III who were treated with levetiracetam had an increased risk for drug-treated anxiety compared to patients without levetiracetam; hazard ratio 2.8 (95% confidence interval 1.7-4.9). Female gender increased the risk for drug-treated anxiety compared to males in patients with glioma grade IV; hazard ratio 1.5 (95% confidence interval 1.2-2.0). Antidepressants were less frequently dispensed to patients with glioma grade II-III and epilepsy than to the general population.. Patients with glioma grade II-III on levetiracetam had an increased risk for drug-treated anxiety. The subgroup of patients with glioma grade II-III and epilepsy received less antidepressants than the general population.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Antidepressive Agents; Anxiety; Brain Neoplasms; Cohort Studies; Depression; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Registries; Risk Factors; Treatment Outcome; Young Adult

Gap junctions (GJs) in astrocytes and glioma cells are important channels for cell-to-cell communication that contribute to homo- and heterocellular coupling. According to recent studies, heterocellular gap-junctional communication (H-GJC) between glioma cells and their surrounding environment enhances glioma progression. Therefore, we developed a new in vitro model to examine H-GJC between glioma cells, astrocytes and microglia. Consequently, F98 rat glioma cells were double-labeled with GJ-impermeable (CM-DiI) and GJ-permeable dye (calcein AM) and were seeded on unlabeled astrocyte-microglia co-cultures. Dual whole cell voltage clamp recordings were carried out on selected cell pairs to characterize the functional properties of H-GJC in vitro. The expression of four types of connexins (Cxs), including Cx32, Cx36, Cx43 and Cx45, and microglial phenotypes were analyzed by immunocytochemistry. The H-GJC between glioma cells and astrocytes/microglia increased after a longer incubation period with a higher number of glioma cells. We provided evidence for the direct GJ coupling of microglia and glioma cells under native in vitro conditions. In addition, we exploited this model to evaluate H-GJC after incubation with levetiracetam (LEV) and/or dexamethasone (DEX). Previous in vitro studies suggest that LEV and DEX are frequently used to control seizure and edema in glioma. Our findings showed that LEV and/or DEX decrease the number of heterocellular coupled cells significantly. In conclusion, our newly developed model demonstrated H-GJC between glioma cells and both astrocytes and microglia. The reduced H-GJC by LEV and DEX suggests a potential effect of both drugs on glioma progression.

Topics: Animals; Antineoplastic Agents; Astrocytes; Cell Communication; Cell Line, Tumor; Connexin 43; Connexins; Dexamethasone; Gap Junction beta-1 Protein; Gap Junction delta-2 Protein; Gap Junctions; Glioma; In Vitro Techniques; Levetiracetam; Microglia; Neuroglia; Piracetam; Rats; Tumor Cells, Cultured

Brain tumor-related epilepsy (BTRE) is a unique condition that is distinct from primary epilepsy. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution. From a database of 121 consecutive patients with supratentorial gliomas treated at Chiba Cancer Center from 2006-2012, the incidence and control of seizures before and after surgery were retrospectively evaluated. Epilepsy occurred in 33.9% of patients before surgery. All patients received prophylactic anti-epileptic drugs (AED) during surgery; however, seizures occurred in 9.1% of patients within the first postoperative week. During follow-up, seizures occurred in 48.3% of patients. The overall incidence of seizures was 73.7% in patients with World Health Organization Grade II gliomas, 66.7% in those with Grade III and 56.8% in those with Grade IV gliomas. Levetiracetam was very well tolerated. However, carbamazepine and phenytoin were poorly tolerated because of adverse effects. AED were discontinued in 56 patients. Fifteen of these patients (26.8%) had further seizures, half occurring within 3 months and 80% within 6 months of AED withdrawal. No clinical factors that indicated it was safe to discontinue AED were identified. The unpredictable epileptogenesis associated with gliomas and their excision requires prolonged administration of AED. To maintain quality of life and to safely and effectively control the tumor, it is necessary to select AED that do not adversely affect cognitive function or interact with other drugs, including anti-cancer agents.

Topics: Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Carbamazepine; Female; Glioma; Humans; Incidence; Japan; Levetiracetam; Male; Middle Aged; Neoplasm Grading; Phenytoin; Piracetam; Retrospective Studies; Seizures

We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l-carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration.

Topics: Anesthesia, General; Anesthesia, Local; Anticonvulsants; Aphasia; Benzodiazepines; Brain Diseases; Brain Mapping; Brain Neoplasms; Carnitine; Clobazam; Conscious Sedation; Consciousness Disorders; Craniotomy; Dominance, Cerebral; Frontal Lobe; Glioma; Humans; Hyperammonemia; Hypnotics and Sedatives; Intraoperative Complications; Language; Levetiracetam; Male; Middle Aged; Piperidines; Piracetam; Propofol; Remifentanil; Seizures; Temporal Lobe; Valproic Acid

Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of older and newer AEDs on cognitive performance in postoperative HGG patients.. We selected HGG patients from 3 separate cohorts for use of older, newer, or no AEDs, as they represented distinct treatment eras and provided the opportunity to compare older and newer AEDs. In all 3 cohorts, patients were included within 6 weeks following neurosurgery before the start of postoperative treatment. Cognitive functioning was evaluated by an extensive neuropsychological assessment, executed in 6 cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed).. One hundred seventeen patients met the inclusion criteria; 44 patients used no AED, 35 were on monotherapy with a newer AED (all levetiracetam), and 38 were on monotherapy with an older AED (valproic acid or phenytoin). Patients on older and newer AEDs performed equally well as patients not on an AED, and patients on levetiracetam performed even better on verbal memory tests than patients not on an AED. Post-hoc analyses revealed that within the group using older AEDs, patients on valproic acid performed better than patients on phenytoin.. Neither levetiracetam nor valproic acid was associated with additional cognitive deficits in HGG patients. Both AEDs even appeared to have a beneficial effect on verbal memory in these patients.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Brain Neoplasms; Cognition Disorders; Female; Glioma; Humans; Levetiracetam; Male; Memory Disorders; Middle Aged; Neoplasm Grading; Neuropsychological Tests; Piracetam; Prognosis; Prospective Studies; Psychomotor Performance; Quality of Life; Verbal Learning; Young Adult

Epileptic seizures are among the presenting clinical signs of malignant glioma patients, frequently necessitating treatment with antiepileptic drugs (AEDs). The efficacy of 5-aminolevulinic acid (5-ALA)-based intraoperative fluorescence-guided surgery and photodynamic therapy (PDT) in glioblastoma multiforme (GBM) patients depends on the specific accumulation and total amount of intracellularly synthesized protoporphyrin IX (PpIX) in tumour cells. In this study, we investigated the effect of the AEDs phenytoin (PHY) and levetiracetam (LEVE) on 5-ALA-induced PpIX accumulation in two glioma cell lines (U373 MG and U-87 MG) and primary GBM cells isolated from a human biopsy. After treatment with PHY and LEVE for three days cells were incubated with 1 mM: 5-ALA for 4 h and PpIX accumulation was determined by fluorescence measurement. We observed a decrease in PpIX synthesis of up to 55 ± 12 % in primary GBM cells after incubation with phenytoin. This reduction was dose-dependent for all tested cell lines and primary GBM cells. LEVE on the other hand did not alter PpIX concentration in GBM cells. PDT was performed in vitro by irradiating the GBM cells with light doses from 0.5 to 10 J cm(-2) at 627 nm after AED and 5-ALA treatment. Although less PpIX accumulated in PHY-treated cells, efficacy of PDT was not affected. We assume that damage to the mitochondrial membrane by PHY inhibits PpIX synthesis in vitro, because we showed mitochondrial dysfunction as a result of reduced mitochondrial membrane potential in PHY-treated cells. No change in glutathione status was observed. To evaluate further the effect of PHY on PpIX fluorescence, and to establish its significance in clinical practice, animal and clinical studies are required, because the results presented here imply PHY may reduce intracellular accumulation of PpIX in patients with high-grade gliomas.

Topics: Aminolevulinic Acid; Anticonvulsants; Fluorescence; Glioma; Glutathione; Humans; Levetiracetam; Membrane Potential, Mitochondrial; Phenytoin; Photochemotherapy; Photosensitizing Agents; Piracetam; Protoporphyrins; Tumor Cells, Cultured

To correlate SV2A expression in surgically removed tumor and peritumoral tissue of glioma patients with epilepsy with the clinical response to levetiracetam in a prospective cohort.. Forty glioma patients with epilepsy were recruited. All patients had undergone surgery and were on levetiracetam monotherapy. Clinical characteristics were documented. Follow-up visits were scheduled at 3 and 6 months. Patients who responded to levetiracetam were compared to those who did not respond. Expression of SV2A was determined by means of immunohistochemistry in the surgically removed tumor and peritumoral tissue. Optical density (OD) was used to measure SV2A expression.. In total, 34 patients were eligible for analysis. Patients with a good response to treatment had significantly stronger SV2A expression as demonstrated by OD in tumor tissue (mean 44.5, SD 17.3) as well as in peritumoral tissue (mean 67.5, SD 7.8) than patients who did not show such a response (mean 8.1, SD 7.7, p < 0.01 and 45.6, SD 11.2, p < 0.01). SV2A expression predicted efficacy of levetiracetam monotherapy with an accuracy of 91%.. Our results suggest that expression of SV2A in tumor and peritumoral tissue is correlated to the clinical response to levetiracetam and predicts levetiracetam efficacy.

Topics: Adult; Aged; Blotting, Western; Brain Neoplasms; Cohort Studies; Epilepsy; False Positive Reactions; Female; Follow-Up Studies; Glioma; Humans; Immunohistochemistry; Levetiracetam; Male; Membrane Glycoproteins; Middle Aged; Nerve Tissue Proteins; Nootropic Agents; Piracetam; Predictive Value of Tests; Prospective Studies; Treatment Outcome; Young Adult

To evaluate the efficacy and safety of levetiracetam in the management of epilepsy in patients with glioma.. A prospective study in hospitalized patients with a new diagnosis of glioma.. Department of Neurological Sciences and Visions, Spedali Civili of Brescia.. From March 1, 2006, until January 1, 2009, 176 consecutive patients (101 men and 75 women) with a first diagnosis of glioma were enrolled in the study. All patients with a diagnosis of epilepsy were treated with levetiracetam.. Clinical, histological, and magnetic resonance imaging findings were analyzed.. Age at the diagnosis of glioma ranged from 22 to 79 years (mean [SD], 57 [15] years; median, 59 years). Duration of the disease ranged from 27 days to 2(1/2) years (mean [SD], 13.7 [7.8] months; median, 13 months). Eighty-two patients received levetiracetam because of a diagnosis of epilepsy. At the last evaluation (May 1, 2009), 75 of 82 patients (91%) treated with levetiracetam were seizure free; in 2 of these patients, levetiracetam was withdrawn because of intolerable adverse effects. Prompt and long-lasting control of seizures was obtained in 49 of 82 patients (60%) with a dose of levetiracetam that ranged from 1500 to 3000 mg/d, and 9 (11%) of the treated patients needed an increase of levetiracetam dosage to 4000 mg/d to become seizure free. No laboratory abnormalities were observed in patients with concomitant chemotherapy.. The results of this study provide good evidence that levetiracetam is efficacious and safe in patients with epilepsy due to glioma.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Dose-Response Relationship, Drug; Epilepsy; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Severity of Illness Index

Second-generation antiepileptic drugs (AEDs) are increasingly used in the care of patients with glioma. There is little data on how this practice compares with the use of traditional AEDs in this population. This noninferiority analysis compares seizure outcomes and side effects in patients with glioma treated with phenytoin and levetiracetam monotherapy.. The authors retrospectively reviewed the records of 500 consecutive patients with glioma who were treated in clinical trials from 2001 to 2008 at 3 Mayo Clinic campuses. To be eligible for the study, these patients had to have had at least 1 clinical seizure and to have undergone follow-up for at least 6 months. Seizure outcomes, defined by the occurrence of a second seizure, time to second seizure, and seizure frequency, along with AED side effects, were compared between cohorts treated with phenytoin or levetiracetam. Seventy-six patients were identified, 25 treated with phenytoin and 51 with levetiracetam. Sixty-four percent of the patients had a Grade 4 astrocytoma. There was no difference in seizure outcome between the phenytoin and levetiracetam groups when comparing time to second seizure (p=0.584), second seizure rates (p=0.561), and average seizures per month (p=0.776). When adjusting for age, sex, type of seizure, type of glioma, and dosage using univariate and multivariate models, there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values>0.05). The incidence of side effects in the levetiracetam group was 6% versus 20% in the phenytoin group (p=0.106). Additionally, 36% of the patients in the phenytoin group had dose adjustments unrelated to breakthrough seizures compared with only 10% in the levetiracetam group (p=0.010). In this study, patients with glioma treated with levetiracetam and phenytoin had similar seizure control. Patients treated with levetiracetam experienced fewer side effects and required fewer nonseizure-related dose adjustments than patients treated with phenytoin. Levetiracetam is a safe, effective, and preferred alternative for seizure management in patients with glioma.

Topics: Adult; Aged; Anticonvulsants; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Seizures

Topics: Brain Neoplasms; Convulsants; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Glioma; Humans; Levetiracetam; Piracetam; Time Factors

Although seizures in brain tumor patients are common, the knowledge on optimal anti-seizure therapy in this patient group is limited. An observational study was carried out using a database of all patients from the neuro-oncology service during the period 2000-2005, with data on seizure characteristics, therapy with AEDs, the underlying brain tumor and its treatment. A total of 140 brain tumor patients were studied of whom 23.6% had a low-grade glioma, 53.6% a high-grade glioma, and 22.8% belonged to a mixed group existing of ependymoma, meningioma, and brain metastasis. Epilepsy as the presenting sign was more frequent in low-grade vs. high-grade gliomas (69.7 vs. 52%, P = 0.087), and a total of 75.8% of patients developed seizures with low-grade and of 80.0% with high-grade gliomas. Of all 99 patients with seizures, 80.1% received valproic acid (VPA) as first choice, and either levetiracetam (LEV), carbamazepine (CBZ) or lamotrigine (LMT) as the most frequent next choice. Patients treated with a combination of VPA and LEV showed the highest percentage of responders (81.5%), with a decline in seizure frequency of more than two categories in 55.6% and seizure freedom in 59%. No correlation was found between the use of VPA and survival. A combination of VPA and LEV seems effective, if seizure control cannot be achieved by VPA alone. This indicates that adding levetiracetam may be preferable over sequential trials of AED monotherapy in treatment-resistant seizures in patients with brain tumors.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Carbamazepine; Drug Therapy, Combination; Female; Follow-Up Studies; Glioma; Humans; Kaplan-Meier Estimate; Lamotrigine; Levetiracetam; Male; Middle Aged; Neoplasm Staging; Piracetam; Seizures; Time Factors; Treatment Outcome; Triazines; Valproic Acid

Antiepileptic drugs are frequently used in children with brain tumors. This retrospective study reviewed chronic use of antiepileptic drugs in children with brain tumors at two children's hospitals between 2000 and 2007. Antiepileptic drugs were used in 32/334 pediatric brain tumor patients (10%). Almost all (94%) had supratentorial tumors, of which 78% were glial tumors. The most common localization was temporal (70%). The most frequently used initial antiepileptic drugs were phenytoin (n = 14) and oxcarbazepine (n = 7). Initial antiepileptic drugs were frequently changed, because of lack of efficacy and adverse effects, as well as concerns about possible drug interactions. At last follow-up, the most common antiepileptic drugs were oxcarbazepine (n = 11) and levetiracetam (n = 10). Levetiracetam was more likely to be used in children who received chemotherapy or radiation therapy (8/14, or 57%) than in those who did not receive adjuvant therapies (3/18, or 17%) (P = 0.03). The patients started on newer-generation antiepileptic drugs (levetiracetam, oxcarbazepine, lamotrigine) tended to remain on the same antiepileptic drugs more than did patients on older-generation antiepileptic drugs (valproic acid, phenytoin, phenobarbital) (73% vs 28%) (P = 0.04). Newer antiepileptic drugs, especially those without significant drug-drug interactions, may be a more appropriate first choice in children with brain tumors and seizures.

Topics: Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Carbamazepine; Child; Drug Interactions; Follow-Up Studies; Glioma; Humans; Levetiracetam; Oxcarbazepine; Phenytoin; Piracetam; Retrospective Studies; Seizures; Supratentorial Neoplasms; Treatment Outcome

Efficacy of keppra was studied in 52 patients, aged 10-55 years, after the surgical treatment of gliomas of the brain hemispheres. The medication was used (in combination with other anticonvulsant drugs and hormones) during the radiotherapy. In 30 (57,8%) of cases epileptic seizures were before the surgery. In 22 (42,2%) of patients they developed during the radiotherapy. Keppra was used in the regiment of "urgent aid" in relation to the appearance of seizures and increase of their frequency during the radiotherapy. Doses of keppra varied from 500 to 2500 mg (30-50 mg/kg/day) in a single dose. Then patients received the drug 2 times daily under the control of clinical and EEG presentations. A clinical effect, including the decrease of seizures frequency by 48,3% (p<0,001), positive changes of quality of seizures (more simple structure, reduced time of seizures), was observed for the first 24 h and in future the state of patients was stable. All patients have completed the course of radiotherapy. The choice of dose was depended on age, body mass and dynamics of clinical and EEG data.

Topics: Administration, Oral; Adolescent; Adult; Anticonvulsants; Brain Neoplasms; Child; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Glioma; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Postoperative Period; Treatment Outcome; Young Adult

Topics: Brain Neoplasms; Follow-Up Studies; Glioma; Humans; Levetiracetam; Piracetam; Prospective Studies; Seizures