levetiracetam and Brain-Neoplasms

Epilepsy is the most common symptom in patients with brain tumors. The shared genetic, molecular, and cellular mechanisms between tumorigenesis and epileptogenesis represent 'two sides of the same coin'. These include augmented neuronal excitatory transmission, impaired inhibitory transmission, genetic mutations in the BRAF, IDH, and PIK3CA genes, inflammation, hemodynamic impairments, and astrocyte dysfunction, which are still largely unknown. Low-grade developmental brain tumors are those most commonly associated with epilepsy. Given this strict relationship, drugs able to target both seizures and tumors would be of extreme clinical usefulness. In this regard, anti-seizure medications (ASMs) are optimal candidates as they have well-characterized effects and safety profiles, do not increase the risk of developing cancer, and already offer well-defined seizure control. The most important ASMs showing preclinical and clinical efficacy are brivaracetam, lacosamide, perampanel, and especially valproic acid and levetiracetam. However, the data quality is low or limited to preclinical studies, and results are sometimes conflicting. Future trials with a prospective, randomized, and controlled design accounting for different prognostic factors will help clarify the role of these ASMs and the clinical setting in which they might be used. In conclusion, brain tumor-related epilepsies are clear examples of how close, multidisciplinary collaborations among investigators with different expertise are warranted for pursuing scientific knowledge and, more importantly, for the well-being of patients needing targeted and effective therapies.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsy; Humans; Levetiracetam; Valproic Acid

Levetiracetam (LEV) is an anti-epileptic drug (AED) that sensitizes glioblastoma (GBM) to temozolomide (TMZ) chemotherapy by inhibiting O. A search of CINAHL, Embase, PubMed, and Web of Science from inception to May 2021 was performed to identify relevant articles. Hazard ratios (HR), median overall survival, and adverse events were pooled using random-effect models. Meta-regression, funnel plots, and the Newcastle-Ottawa Scale were utilized to identify sources of heterogeneity, bias, and statistical influence.. From 20 included studies, 5804 GBM patients underwent meta-analysis, of which 1923 (33%) were treated with LEV. Administration of LEV did not significantly improve survival in the entire patient population (HR 0.89, p = 0.094). Significant heterogeneity was observed during pooling of HRs (I. Levetiracetam treatment may not be effective for all GBM patients. Instead, LEV may be better suited for treating specific molecular profiles of GBM. Further studies are necessary to identify optimal GBM candidates for LEV.

Topics: Brain Neoplasms; Glioblastoma; Humans; Levetiracetam; Survival Analysis; Treatment Outcome

A concise review of recent findings in brain tumor-related epilepsy (BTRE), with focus on the effect of antitumor treatment on seizure control and the management of antiepileptic drugs (AEDs).. Isocitrate dehydrogenase mutation and its active metabolite d -2-hydroxyglutarate seem important contributing factors to epileptogenesis in BTRE. A beneficial effect of antitumor treatment (i.e. surgery, radiotherapy, and chemotherapy) on seizure control has mainly been demonstrated in low-grade glioma. AED prophylaxis in seizure-naïve BTRE patients is not recommended, but AED treatment should be initiated after a first seizure has occurred. Comparative efficacy randomized controlled trials (RCTs) are currently lacking, but second-generation AED levetiracetam seems the preferred choice in BTRE. Levetiracetam lacks significant drug-drug interactions, has shown favorable efficacy compared to valproic acid in BTRE, generally causes no hematological or neurocognitive functioning adverse effects, but caution should be exercised with regard to psychiatric adverse effects. Potential add-on AEDs in case of uncontrolled seizures include lacosamide, perampanel, and valproic acid. Ultimately, in the end-of-life phase when oral intake of medication is hampered, benzodiazepines via nonoral administration routes are potential alternatives.. Management of seizures in BTRE is complex and with currently available evidence levetiracetam seems the preferred choice. Comparative efficacy RCTs in BTRE are warranted.

Topics: Anticonvulsants; Benzodiazepines; Brain Neoplasms; Epilepsy; Humans; Isocitrate Dehydrogenase; Lacosamide; Levetiracetam; Seizures; Valproic Acid

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

A 26-year-old female presented with vision loss accompanied by migraine-like headaches. A contrast-enhanced magnetic resonance imaging of the brain was performed which revealed findings suggestive of stroke-like migraine attacks after radiation therapy (SMART) syndrome. SMART syndrome is a delayed complication of brain radiation characterized by neurologic symptoms including migraine-like headaches, seizures, and hemispheric impairment. The purpose of this article is to make the readers aware of this rare complication of brain irradiation. Appropriate diagnosis of SMART syndrome is essential to avoid invasive tests.

Topics: Adult; Brain Neoplasms; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Migraine Disorders; Nootropic Agents; Piracetam; Radiation Injuries; Syndrome

Treatment options for recurrent glioma of the brain include chemotherapy, radiotherapy, surgery, and palliation. Temozolomide appears to be effective in patients with recurrent high-grade gliomas.. A middle-aged woman presented with a high-grade glioma of corpus callosum. The tumor, a grade 3 anaplastic oligodendroglioma, was excised, and chemoradiotherapy was administered. The patient presented with significant recurrence 5 years later. Repeat surgery and radiation were suggested but refused. She was given temozolomide and dexamethasone intermittently, and levetiracetam was continued. Magnetic resonance imaging performed at 10-month follow-up showed 90% remission.. There are a few reports in the literature of similar response to temozolomide and levetiracetam. Similar reports give more hope in the treatment of recurrent high grade glioma.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chemoradiotherapy; Corpus Callosum; Craniotomy; Dacarbazine; Decompression, Surgical; Dexamethasone; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Oligodendroglioma; Piracetam; Remission Induction; Temozolomide; Tomography, X-Ray Computed

In neurological malignancies, antiepileptic drugs (AEDs) are frequently used to control the seizure activity that accompanies the disorder. There is a growing body of evidence on the importance of AED selection for reasons other than pharmacokinetics (PK) properties. Epigenetic modifications may occur in glioblastomas, such as changes in gene methylation and histone acetylation states. Secondary mechanisms of AED drug action which impact these epigenetic modifications could play a significant role in patient survival outcomes. Both valproic acid (VPA) and carbamazepine have histone deacetylase (HDAC) inhibitory activities, and levetiracetam and VPA reduce the activity of O6-methylguanine-DNA methyltransferase (MGMT), a DNA-repair molecule implicated in resistance to alkylating agents used for chemotherapy. The use of AEDs for purposes other than seizure prophylaxis and their selection based on non-PK properties present a potential paradigm shift in the field of neuro-oncology.

Topics: Animals; Anticonvulsants; Brain Neoplasms; Carbamazepine; Humans; Levetiracetam; Piracetam; Seizures; Valproic Acid

Seizures are common complications for patients with brain tumors. No clear evidence exists regarding the use of antiepileptic agents for prophylactic use yet newer agents are being favoured in many clinical settings. The objective of this systematic review was to determine the efficacy of levetiracetam for preventing seizures in patients with brain tumors. A literature search was completed using the databases PubMed (1948 to December 2015), EMBASE (1980 to December 2015), Cochrane Database of Systematic Reviews, and Google Scholar. Studies were included if they reported seizure frequency data pertaining to levetiracetam use in patients with brain tumors as either monotherapy or as an add on agent. The literature search produced 21 articles (3 randomized controlled trials, seven prospective observational studies, and 11 retrospective observational studies). All studies were found to be at high risk of bias. Overall, studies show levetiracetam decreased seizure frequency in brain tumor patients with or without craniotomy. Safety outcomes were also favourable. As such, levetiracetam appears effective for reducing seizures in patients with brain tumors and may be considered a first-line agent. However, there is an urgent need for more high quality prospective data assessing levetiracetam and other antiepileptic drugs in this population.

Topics: Anticonvulsants; Brain Neoplasms; Humans; Levetiracetam; Observational Studies as Topic; Piracetam; Prospective Studies; Randomized Controlled Trials as Topic; Reproducibility of Results; Retrospective Studies; Seizures; Treatment Outcome

This review provides management recommendations for medical and neurologic problems in patients with brain tumors, including vasogenic edema, infections, seizures, prophylaxis and treatment of venous thromboembolism, drug interactions, cognitive and emotional problems, palliative symptom management, and long-term sequelae of brain tumors and their therapy.. Non-enzyme-inducing antiepileptic drugs are the preferred category of seizure medication for patients with brain tumors, and levetiracetam is emerging as the drug of choice. Select groups of patients, such as those with cortically based hemorrhagic melanoma metastases, may benefit from prophylactic antiepileptic drug use. Antiangiogenic agents can reduce the steroid requirement of patients with vasogenic edema. Patients with brain tumors remain at risk for infections from the perioperative period through many months after treatment, and steroids may mask signs of infection. Few studies have been done on management of common cognitive issues such as short-term memory deficits and fatigue, but memantine may help delay cognitive deficits in patients receiving whole-brain radiation therapy. Palliative care conversations should begin early in the course of treatment.. Meticulous medical management begins at diagnosis of brain tumors and continues through the active treatment course and into either palliative care strategies or management of long-term sequelae of treatment. During the active treatment phase, problems such as vasogenic edema, seizures, and venous thromboembolism predominate, whereas late complications include the continuing risk of infections; sequelae of radiation such as vascular disease, cavernous angiomas, and cognitive decline; and secondary tumors. Attention to symptom palliation is an important part of the neurologist's role throughout the course of a brain tumor patient's illness.

Topics: Angiogenesis Inhibitors; Anticonvulsants; Brain Edema; Brain Neoplasms; Cognition Disorders; Dopamine Agents; Humans; Levetiracetam; Memantine; Palliative Care; Piracetam; Seizures

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

Seizures are a common symptom of brain tumours. The mainstay of treatment for seizures is medical therapy with antiepileptic drugs.. To evaluate the relative effectiveness and tolerability of antiepileptic drugs commonly used to treat seizures in adults with brain tumours.. We searched CENTRAL (Issue 2 of 4, The Cochrane Library 2011), MEDLINE (1948 to May week 3, 2011) and EMBASE (1980 to 31 May 2011) databases. In addition, we handsearched articles published since 2000 in the following journals selected by the authors: Epilepsia; The Lancet Neurology and Neuro-Oncology.. Controlled clinical trials with random allocation of the use of antiepileptic drugs to treat seizures in adults with brain tumours.. Both review authors screened the search results and reviewed the abstracts of potentially relevant articles before retrieving the full text of eligible articles.. Only one trial met the inclusion criteria for this review which was a small, open-label, unblinded, randomised trial of the safety and feasibility of switching from phenytoin to levetiracetam monotherapy or continuing phenytoin for glioma-related seizure control following craniotomy (Lim 2009). Levetiracetam (a non enzyme-inducing antiepileptic drug) appears to have been at least as well tolerated and as effective as phenytoin (an enzyme-inducing antiepileptic drug) for the treatment of seizures in people with brain tumours. Eighty-seven per cent of participants treated with levetiracetam were free of seizures at six months compared with 75% of participants treated with phenytoin. There is one ongoing study of levetiracetam versus pregabalin for the treatment of seizures in adults undergoing chemotherapy, radiotherapy,or both for primary brain tumours. No data from this study were available at the time of preparing this review.. There is a lack of robust, randomised, controlled evidence to support the choice of antiepileptic drug for the treatment of seizures in adults with brain tumours. While some authors support the use of non enzyme-inducing antiepileptic drugs, reliable, comparative evidence to provide clinical justification for this is limited. There is a need for further large, randomised, controlled trials in this area.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Drug Substitution; Humans; Levetiracetam; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures

Epileptic seizures are a common clinical problem in children with brain tumors. The conventional antiepileptic drugs (AEDs) permit a good seizure control in most of these children. An emerging problem is the possible interactions between AEDs and chemotherapeutic drugs, because many of these drugs are metabolized by the cytochrome P450. The aim of this article is to propose a novel therapeutic approach for new-onset epilepsy in children with brain tumors. Among the new AEDs not metabolized by the P450 system, levetiracetam seems to be a promising AED owing to its pharmacokinetic features, efficacy, and safety.

Topics: Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Child; Child, Preschool; Drug Interactions; Drug Therapy, Combination; Humans; Levetiracetam; Piracetam; Seizures

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

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with a structural brain lesion, and a role for multidrug resistance proteins has been suggested. Until now, the medical treatment of epilepsy in brain tumor patients has only been studied retrospectively. Therefore, the optimal seizure management by antiepileptic drugs (AEDs) in this patient category is essentially unsure. Choices depend on the outcome of retrospective studies, a few nonrandomized series, extrapolation from other studies in symptomatic epilepsy, and anticipated interactions, most notably between AEDs and anticancer agents. The newly developed AEDs levetiracetam and gabapentin are recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents. The use of prophylactic AEDs in brain tumor patients is disputable and generally not advised.

Topics: Amines; Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Cyclohexanecarboxylic Acids; Drug Interactions; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Piracetam; Retrospective Studies; Seizures

Levetiracetam is commonly used as a prophylactic antiseizure medication in patients undergoing surgical resection of brain tumors.. To quantitate side effects experienced in patients treated with 1 week vs 6 weeks of prophylactic levetiracetam using validated measures for neurotoxicity and depression.. Patients undergoing surgical resection of a supratentorial tumor with no seizure history were randomized within 48 hours of surgery to receive prophylactic levetiracetam for the duration of either 1 or 6 weeks. Patients were given oral levetiracetam extended release 1000 mg during the first part of this study. Owing to drug backorder, patients enrolled later in this study received levetiracetam 500 mg BID. The primary outcome was the change in the neurotoxicity score 6 weeks after drug initiation. The secondary outcome was seizure incidence.. A total of 81 patients were enrolled and randomized to 1 week (40 patients) or 6 weeks (41 patients) of prophylactic levetiracetam treatment. The neurotoxicity score slightly improved in the overall cohort between baseline and reassessment. There was no significant difference between groups in neurotoxicity or depression scores. Seizure incidence was low in the entire cohort of patients with 1 patient in each arm experiencing a seizure during the follow-up period.. The use of prophylactic levetiracetam did not result in significant neurotoxicity or depression when given for either 1 week or 6 weeks. The incidence of seizure after craniotomy for tumor resection is low regardless of duration of therapy.

Topics: Anticonvulsants; Brain Neoplasms; Humans; Levetiracetam; Prospective Studies; Seizures

An open-label single-arm phase 2 study was conducted to evaluate the role of levetiracetam as a sensitizer of concurrent chemoradiotherapy (CCRT) for patients with newly diagnosed glioblastoma. This study aimed to determine the survival benefit of levetiracetam in conjunction with the standard treatment for glioblastoma.. Major eligibility requirements included histologically proven glioblastoma in the supratentorial region, patients 18 years or older, and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Levetiracetam was given at 1,000-2,000 mg daily in two divided doses during CCRT and adjuvant chemotherapy thereafter. The primary and the secondary endpoints were 6-month progression-free survival (6mo-PFS) and 24-month overall survival (24mo-OS), respectively. Outcomes of the study group were compared to those of an external control group.. Between July 2016 and January 2019, 76 patients were enrolled, and 73 patients were included in the final analysis. The primary and secondary outcomes were improved in the study population compared to the external control (6mo-PFS, 84.9% vs. 72.3%, p = 0.038; 24mo-OS, 58.0% vs. 39.9%, p = 0.018), but the differences were less prominent in a propensity score-matched analysis (6mo-PFS, 88.0% vs. 76.9%, p = 0.071; 24mo-OS, 57.1% vs. 38.8%, p = 0.054). In exploratory subgroup analyses, some results suggested that patients with ages under 65 years or unmethylated MGMT promoter might have a greater survival benefit from the use of levetiracetam.. The use of levetiracetam during CCRT in patients with newly diagnosed glioblastoma may result in improved outcomes, but further investigations are warranted.

Topics: Adult; Aged; Brain Neoplasms; Chemoradiotherapy; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioblastoma; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Progression-Free Survival; Propensity Score; Republic of Korea; Tumor Suppressor Proteins

Temozolomide is applied as the standard chemotherapy agent in patients with glioblastoma (GBM) after surgery. However, the benefit of this treatment for patients is limited by the invasive growth of gliomas and drug resistance. There are indications from fundamental experimental and retrospective studies that levetiracetam has the potential to improve the survival rate of patients with GBM. However, it has yet to be determined whether the combination of temozolomide and levetiracetam is more effective than standard temozolomide chemotherapy. Therefore, we designed a randomized clinical trial to investigate the therapeutic effect of the new combined regime for treating GBM.. This is a double-blind and randomized clinical trial conducted in a single center. One hundred forty-two patients will be recruited and screened for the inclusion and exclusion criteria. Then, eligible participants will be randomly assigned to an experimental group or a control group in a 1:1 ratio. Based on the administration of radiation therapy (RT), participants in the experimental group will be prescribed levetiracetam plus temozolomide chemotherapy for 34 weeks while participants in the control group will receive placebo tablets plus temozolomide for the same duration. A 3-year follow-up will be conducted on all patients after intervention. Accordingly, the primary outcome will be progression-free survival (PFS). The secondary endpoints include overall survival (OS), the Karnofsky Performance Status (KPS), the objective response rate (ORR), and adverse event incidence.. It is expected that the results of this trial will provide high-level evidence regarding the clinical benefits of levetiracetam and temozolomide combined in the treatment of GBM.. Chinese Clinical Trial Registry, ChiCTR2100049941 . Registered on 14 August 2021.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Glioblastoma; Humans; Levetiracetam; Randomized Controlled Trials as Topic; Retrospective Studies; Temozolomide

Phenytoin (PHT) is routinely used for seizure prophylaxis in patients with brain tumours during and after craniotomy, despite incomplete evidence. We performed a prospective, randomised study to investigate the significance of prophylactic use of levetiracetam (LEV), in comparison with PHT, for patients with supratentorial tumours in the perioperative period.. Patients were randomised to receive LEV, 500 mg/body every 12 h until postoperative day 7, or PHT, 15-18 mg/kg fosphenytoin followed by 125 mg PHT every 12 h until postoperative day 7. The primary end point was the occurrence of seizures, and secondary end points included the occurrence of haematological and non-haematological adverse events.. One hundred and forty-six patients were randomised to receive LEV (n=73) or PHT (n=73). The incidence of seizures was significantly less in the LEV group (1.4%) compared with the PHT group (15.1%, p=0.005), suggesting benefit of LEV over PHT. The observed OR for being seizure free in the LEV prophylaxis group relative to the PHT group was 12.77 (95% CI 2.39 to 236.71, p=0.001). In a subgroup analysis of patients who did not have seizures before craniotomy, similar results were demonstrated: the incidence of seizures was 1.9% (LEV) and 13.8% (PHT, p=0.034), and OR was 8.16 (95% CI 1.42 to 154.19, p=0.015). LEV was completed in all cases, although PHT was withdrawn in five patients owing to liver dysfunction (1), skin eruption (2) and atrial fibrillation (2).. Prophylactic use of LEV in the perioperative period is recommended because it is safe and significantly reduces the incidence of seizures in this period.. UMIN13971.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Cohort Studies; Craniotomy; Female; Humans; Levetiracetam; Male; Middle Aged; Neurosurgical Procedures; Phenytoin; Piracetam; Postoperative Complications; Prospective Studies; Seizures; Treatment Outcome; Young Adult

In patients with brain tumors, the choice of antiepileptic medication is guided by tolerability and pharmacokinetic interactions. This study investigated the effectiveness of levetiracetam (LEV) and pregabalin (PGB), 2 non-enzyme-inducing agents, in this setting.. In this pragmatic, randomized, unblinded phase II trial (NCT00629889), patients with primary brain tumors and epilepsy were titrated to a monotherapy of LEV or PGB. Efficacy and tolerability were assessed using structured questionnaires. The primary composite endpoint was the need to discontinue the study drug, add-on of a further antiepileptic treatment, or occurrence of at least 2 seizures with impaired consciousness during 1 year follow-up.. Over 40 months, 25 patients were randomized to LEV, and 27 to PGB. Most were middle-aged men, with a high-grade tumor and at least one generalized convulsion. Mean daily doses were 1125 mg (LEV) and 294 mg (PGB). Retention rates were 59% in the LEV group, and 41% in the PGB group. The composite endpoint was reached in 9 LEV and 12 PGB patients-need to discontinue: side effects, 6 LEV, 3 PGB; lack of efficacy, 1 and 2; impaired oral administration, 0 and 2; add-on of another agent: 1 LEV, 4 PGB; and seizures impairing consciousness: 1 in each. Seven LEV and 5 PGB subjects died of tumor progression.. This study shows that LEV and PGB represent valuable monotherapy options in this setting, with very good antiepileptic efficacy and an acceptable tolerability profile, and provides important data for the design of a phase III trial.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Follow-Up Studies; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Piracetam; Pregabalin; Prognosis; Survival Rate

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

We performed a case series analysis to evaluate the effects of levetiracetam (LEV) monotherapy on seizures, adverse events, cognitive functioning and quality of life (QoL) in patients with brain tumor-related epilepsy (BTRE). We also explored the possible effects of systemic therapies on the efficacy of LEV. Twenty-nine patients were followed (13 female, 16 male; age 24-75 years) with 12 months of follow-up. Patients were evaluated by QoL and neuropsychological tests. At final follow-up, mean LEV dosage was 1991.4 mg/day. Among patients who reached the final follow-up of 12 months (n = 15), 1 patient had ≥50% reduction of seizure frequency (SF), and 14/15 were seizure free. The difference in presence/absence of seizures between baseline and final follow-up was significant (p < 0.001). Responder rate was 100%. We observed five side-effects: four mild (reversible) and one severe. Logistic regression revealed that chemotherapy and radiotherapy did not affect the efficacy of LEV in seizure outcome (p = 0.999). The following statistically significant observations emerged by tests' evaluation: less worry about seizures, effects of antiepileptic, and ability to maintain social functions. Our data suggest that seizure occurrence can be an important warning sign that the clinician should heed throughout the duration of the illness. Patients with BTRE represent a unique patient population that presents difficulties regarding management of two very different pathologies: epilepsy on the one hand, and brain tumor on the other. Our data indicate that LEV, in patients with BTRE, is safe and efficacious, with positive impact on QoL.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Quality of Life; Statistics, Nonparametric; 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

Epilepsy is a common clinical problem in patients with brain tumours, strongly affecting patients' quality of life. Tumour-related seizures are often difficult to control, and the clinical picture is complicated by frequent interactions between antiepileptic drugs (AEDs) and antineoplastic agents. We studied the safety and efficacy of levetiracetam (LEV), a new AED with a different pharmacological profile from traditional anticonvulsants, in 19 patients (6 females; age range 28-70 years, mean 48 years) with supratentorial gliomas and epilepsy. Seizure types were simple partial in four patients, complex partial in 4, complex partial with secondary generalization in 7, and generalized tonic-clonic in 4. LEV was added to the existing AED treatment on account of persisting seizures, and titrated at dosages of 1,000-3,000 mg/day. Patients were seen at the Outpatient's Centre every 1-3 months, and followed-up for 7-50 months (mean 25 months, median 20 months). At the end of the observation period, nine patients were seizure free (seizure free period ranging from 7 to 33 months, mean 16, median 12) and five patients reported an improvement in seizure-frequency from daily to weekly (n=1) or from weekly to monthly (n=3). Seizure frequency was unmodified in four patients and increased (from monthly to weekly) in one. No LEV-related adverse effects were observed. LEV plasma concentrations monitored in 12 subjects ranged from 11.9 to 82.1 microg/ml. Our preliminary open data indicate that add-on treatment with LEV in patients with brain tumours is safe and appears to be effective in reducing seizure frequency. Controlled studies on larger populations are warranted to confirm these open observations.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam

The association between levetiracetam and survival with isocitrate dehydrogenase (. In this observational single-institution cohort study (2010-2018), inclusion criteria were (1) age ≥18 years; (2) newly diagnosed supratentorial tumor; (3) histomolecular diagnosis of. A total of 460 patients were included. The median OS was longer in the 116 patients with levetiracetam use during the whole duration of the standard chemoradiation protocol (21.0 months; 95% confidence interval [CI] 17.2-24.0) than in the 126 patients with part-time levetiracetam use (16.8 months; 95% CI 12.4-19.0) and in the 218 patients who never received levetiracetam (16.0 months; 95% CI 15.5-19.4;. Levetiracetam use during the whole standard chemoradiation protocol possibly improves OS of patients with. This study provides Class III evidence that in individuals with

Topics: Adolescent; Adult; Brain Neoplasms; Cohort Studies; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Prognosis; Retrospective Studies; Survival Rate

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation; Prognosis; Retrospective Studies

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation; Prognosis; Retrospective Studies

Glioblastoma multiforme (GBM) is an aggressive brain tumor, often occurring with seizures managed with antiepileptic drugs, such as levetiracetam (LEV). This study is aimed at associating progression-free survival (PFS) and overall survival (OS) of GBM patients with LEV plasma concentration, MGMT promoter methylation, and sex. In this retrospective, non-interventional, and explorative clinical study, GBM patients underwent surgery and/or radiotherapy and received LEV during adjuvant temozolomide (TMZ) treatment. A high-performance liquid chromatography with UV-detection was used for therapeutic drug monitoring of LEV plasma concentrations. Follow-up average drug concentration was related to patients' clinical characteristics and outcomes. Forty patients (42.5 % female; mean age=54.73 ± 11.70 years) were included, and GBM MGMT methylation status was assessed. All were treated with adjuvant TMZ, and LEV for seizure control. Patients harboring methylated MGMT promoter showed a longer median PFS (460 vs. 275 days, log-rank p < 0.001). The beneficial effect of MGMT promoter methylation was more evident for females (p < 0.001) and in patients with LEV concentration ≤ 20.6 µg/mL (562 days vs. 274.5 days, p = 0.032). Female patients also showed longer OS (1220 vs. 574 days, p = 0.03). Also, higher LEV concentration (>20.6 µg/mL) synergized with MGMT promoter methylation by extending the OS (1014 vs. 406 days of patients with no methylation and low LEV average concentration, p = 0.021). Beneficial effect of higher LEV plasma levels was more evident in males (p = 0.024). Plasma concentrations of LEV may support better outcomes for chemoradiotherapy when other positive prognostic factors are lacking and may promote overall survival by synergizing with MGMT promoter methylation and male sex.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Dacarbazine; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Prognosis; Retrospective Studies; Seizures; Temozolomide; Tumor Suppressor Proteins

In seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively.. Fortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4-6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up).. No significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up (p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning (p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients).. A significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients.. This study was registered prospectively (Date: 25/11/2015; EudraCT: 2015-003,916-19).

Topics: Anticonvulsants; Brain Neoplasms; Humans; Levetiracetam; Piracetam; Prospective Studies; Quality of Life; Seizures; Supratentorial Neoplasms

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation; Prognosis

Topics: Adult; Brain Neoplasms; Glioblastoma; Humans; Isocitrate Dehydrogenase; Levetiracetam; Mutation

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

Glioblastoma multiforme is the most common malignant primary brain tumor in adults. Despite new treatments developed including immunomodulation using vaccines and cell therapies, mortality remains high due to the resistance mechanisms presented by these tumor cells and the function of the blood-brain barrier that prevents the entry of most drugs. In this context of searching for new glioblastoma therapies, the study of the existing drugs to treat neurological disorder is gaining great relevance. The aim of this study was to determine, through a preliminary in vitro study on human glioblastoma (A172, LN229), anaplastic glioma (SF268) and neuroblastoma (SK-N-SH) cell lines, the possible antitumor activity of the active principles of several drugs (levomepromazine, haloperidol, lacosamide, valproic acid, levetiracetam, glatiramer acetate, fingolimod, biperiden and dextromethorphan) with the ability to cross the blood-brain barrier and that are commonly used in neurological disorders. Results showed that levetiracetam, valproic acid, and haloperidol were able to induce a relevant synergistic antitumor effect when associated with the chemotherapy currently used in clinic (temozolomide). Regarding the mechanism of action, haloperidol, valproic acid and levomepromazine caused cell death by apoptosis, while biperiden and dextromethorphan induced autophagy. Fingolimod appeared to have anoikis-related cell death. Thus, the assayed drugs which are able to cross the blood-brain barrier could represent a possibility to improve the treatment of neural tumors, though future in vivo studies and clinical trials will be necessary to validate it.

Topics: Adult; Apoptosis; Biperiden; Brain Neoplasms; Cell Line, Tumor; Dextromethorphan; Fingolimod Hydrochloride; Glioblastoma; Haloperidol; Humans; Levetiracetam; Methotrimeprazine; Valproic Acid

Patients with brain tumor-related epilepsy (BTRE) are at a higher risk of significant morbidity, lower quality of life, and increased risk of mortality. We surveyed providers regarding anti-seizure medication (ASM) management in pediatric BTRE to determine if practices are standard or markedly variable.. An anonymous voluntary online survey was sent to members of the Child Neurology Society. Providers were asked specific questions regarding initiation and wean of ASMs and if this was dependent on multiple factors. Demographic information was collected.. Fifty-one providers responded to the survey. Ninety-four percent of providers would start an ASM after a second seizure. Eighty-four percent chose levetiracetam as the preferred ASM. Management was variable when based on tumor location, extent of surgical resection, pathology, and tumor prognosis. Statistically significant differences in responses regarding management were identified when comparing neurologists and epileptologists, providers with formal neuro-oncology or epilepsy training, providers at large institutions, and years of experience. For patients who underwent a gross total resection of the tumor, neuro-oncology and epilepsy-trained providers were more likely to wean off ASMs (p < 0.049). Providers without formal training in neuro-oncology or epilepsy were more likely to get an EEG prior to making a decision about weaning off ASMs (p < 0.016).. These results suggest that ASM management in BTRE varies greatly according to sub-specialty and experience. Further studies and potential development of guidelines are needed to identify the most appropriate management of ASMs for BTRE.

Topics: Anticonvulsants; Brain Neoplasms; Child; Epilepsy; Humans; Levetiracetam; Quality of Life

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

Brain metastases originate from other primary cancers within the body, most commonly lung, breast, and melanoma. Because patients with brain metastasis, stroke, or intracranial hemorrhage may present with similar acute neurologic symptoms, clinicians must have a high suspicion for brain metastasis and perform an immediate workup to rule out life-threatening conditions. This case report focuses on the clinical symptoms, diagnostics, and treatment options for brain metastasis in a patient with multiple malignancies.

Topics: Brain Neoplasms; Cranial Irradiation; Dexamethasone; Esophageal Neoplasms; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Melanoma; Neoplasms, Multiple Primary; Nervous System Diseases; Prostatic Neoplasms; Radiosurgery; Scalp; Seizures; Skin Neoplasms; Tomography, X-Ray Computed

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

Awake craniotomy is an established procedure for resecting brain tumors in eloquent lesions, and intraoperative seizure is one of the most important complications. Phenytoin is normally used to control intraoperative seizures. Recently, phenytoin was replaced with levetiracetam at our institution because the latter has fewer side effects. While the phenytoin dose is calibrated in accordance with the serum concentration, there is currently no consensus on a method of monitoring the serum concentration of levetiracetam or the effective concentration range needed to control intraoperative seizures during awake craniotomy. The present study therefore aimed to determine whether monitoring the serum levetiracetam concentration is useful for controlling intraoperative seizures during awake craniotomy. The intraoperative serum concentration of levetiracetam during awake craniotomy was measured in 34 patients and compared with that of phenytoin in 33 patients undergoing the same procedure. The levetiracetam concentration inversely correlated with body surface area (BSA) and estimated glomerular filtration rate (eGFR). Levetiracetam was superior to phenytoin in terms of the correlation between the serum concentration and the dose adjusted for BSA and eGFR (correlation coefficient, 0.49 vs 0.21). Furthermore, the serum levetiracetam concentration in patients with intraoperative seizures was below the 95% confidence interval (CI) of the regression line whereas the serum phenytoin concentration of two patients with seizures was within the 95% CI, indicating that evaluating the serum levetiracetam concentration against the BSA and eGFR-adjusted dosage may be useful in preventing intraoperative seizures during awake craniotomy by allowing prediction of the seizure risk and enabling more accurate dosage calibration.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Craniotomy; Humans; Levetiracetam; Middle Aged; Phenytoin; Seizures; Wakefulness

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

Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely unknown beyond survey data.. To describe patterns and predictors of postoperative AED prophylaxis following intracranial tumor surgery.. The MarketScan Database was used to analyze pharmacy claims data and clinical characteristics in a national sample over a 5-year period.. Among 5895 patients in the cohort, levetiracetam was the most widely used AED for prophylaxis (78.5%) followed by phenytoin (20.5%). Prophylaxis was common but highly variable for patients who underwent open resection of supratentorial intraparenchymal tumors (62.5%, reference) or meningiomas (61.9%). In multivariate analysis, biopsies were less likely to receive prophylaxis (44.8%, OR 0.47, 95% CI 0.33-0.67), and there was near consensus against prophylaxis for infratentorial (9.7%, OR 0.07, CI 0.05-0.09) and transsphenoidal procedures (0.4%, OR 0.003, CI 0.001-0.010). Primary malignancies (52.1%, reference) and secondary metastases (42.2%) were more likely to receive prophylaxis than benign tumors (23.0%, OR 0.63, CI 0.48-0.83), as were patients discharged with home services and patients in the Northeast. There was a large spike in duration of AED use at approximately 30 days.. Use of seizure prophylaxis following intracranial biopsies and supratentorial resections is highly variable, consistent with a lack of guidelines or consensus. Current practice patterns do not support a clear standard of care and may be driven in part by geographic variation, availability of post-discharge services, and electronic prescribing defaults rather than evidence. Given uncertainty regarding effectiveness, indications, and appropriate duration of AED prophylaxis, well-powered trials are needed.

Topics: Adolescent; Adult; Anticonvulsants; Brain Neoplasms; Craniotomy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neurosurgical Procedures; Phenytoin; Practice Patterns, Physicians'; Prognosis; Retrospective Studies; Seizures; Supratentorial Neoplasms; Young Adult

BACKGROUND Phenytoin is an antiepileptic drug that is usually prescribed as a prevention treatment for tonic-clonic seizures or partial seizures, and as a prophylaxis for the neurosurgical related seizures. Phenytoin administration has several drawbacks; one drawback phenytoin-induced thrombocytopenia, which is a rare and significant adverse event. We report a rare adverse event after phenytoin prophylaxis therapy after a brain tumor debulking surgery, which resulted in severe unpredicted thrombocytopenia. CASE REPORT A 40-year-old male with no known health problems started to have an on/off headaches and loss of memory. Clinical investigations revealed a right frontal brain lesion. On the first day of admission, the patient was managed on neurosurgical seizure prophylaxis therapy of 100 mg intravenous phenytoin every 8 hours and 4 mg oral dexamethasone every 6 hours. On the fifth day of hospital admission, the patient underwent tumor debulking surgery. Twenty-four hours post-surgery, the patient's platelet level dropped to 26×10⁹/L. Severe thrombocytopenia was managed first by transfusion of 17 units of platelets and by cessation of intravenous phenytoin plus the starting of 500 mg levetiracetam orally twice daily. Further management included infusion of 34 grams (0.4 g/kg) intravenous immunoglobulin (IVIG) over 5 days. Five days later, the patient gradually recovered with a platelet count of 239×10⁹/L. CONCLUSIONS Phenytoin-induced thrombocytopenia is considered a rare event, but it has life-threatening consequences. The first and cornerstone management of this event is the cessation of phenytoin, followed by consideration of appropriate management based on the level of thrombocytopenia severity, and avoiding concomitant therapy of phenytoin and the use of dexamethasone as neurosurgical-related seizure prophylaxis.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Cytoreduction Surgical Procedures; Humans; Immunoglobulins, Intravenous; Levetiracetam; Male; Phenytoin; Postoperative Complications; Thrombocytopenia

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

Nearly 75% of patients with metastatic melanoma develop brain metastases. We here report the case of an 83 year-old woman hospitalized for secondarily generalized clonic seizures of the left leg with partial convulsive seizures in the Resuscitation Department. Melanoma resection of the left ankle had been performed 6 months before her admission. Neurological examination showed left ataxic crural monoparesis. Electro-encephalogram showed central and right frontal focus with left-sided dissemination. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain showed multiple supratentorial and subtentorial encephalic lesions with varying size and shape, with T1 hypersignal (A and A'), haemorrhage on T2*-weighted sequences (B and B'), gadolinium-enhancing T1 with perilesional edema on Flair sequences. Positron emission tomography (PET) showed multiple lymph node and bone metastases. Lymph node biopsy was negative for VE1 antibody with no BRAFV600E mutation by immunohistochemistry. An increase in the number of metastatic lesions was observed during control brain CT scan despite 10 brain radiotherapy sessions motivating palliative care. Epileptic seizures were controlled with levetiracetam. In patient with multiple hemorrhagic and spontaneous brain lesions, it is essential to obtain informations on patient's history of melanoma and to perform a thorough dermatologic examination in order to investigate its cause and to establish adequate therapeutic treatment.

Topics: Aged, 80 and over; Anticonvulsants; Bone Neoplasms; Brain Neoplasms; Female; Humans; Levetiracetam; Lymphatic Metastasis; Magnetic Resonance Imaging; Melanoma; Positron-Emission Tomography; Seizures; Skin Neoplasms

Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported.. A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs.. To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Chorea; Female; Glioblastoma; Humans; Levetiracetam; Seizures; Spinal Cord Neoplasms

Glioblastoma multiforme (GBM) is a lethal and aggressive malignant tumor of the central nervous system. The World Health Organization classifies it as a grade IV astrocytoma. Controlling seizures is essential during GBM treatment because they are often present and closely associated with the quality of life of GBM patients. Some antiepileptic drugs (AEDs) exhibit antitumor effects and could decrease the mortality of patients with GBM. In this retrospective cohort study, we examined 418 patients treated with surgery, radiotherapy, and chemotherapy with temozolomide (TMZ) at Severance Hospital in South Korea, per the current protocol. Median overall survival (OS) was 21 months [95% confidence interval (CI): 18.1-23.9] in the levetiracetam (LEV) treatment group, whereas it was 16 months [95% CI: 14.1-17.9] in the group without LEV, exhibiting a statistically significant difference between the two groups (P < 0.001). Of nine AED groups, only LEV treatment [P = 0.001; hazard ratio (HR), 0.65; 95% CI: 0.51-0.83] exhibited a statistically significant difference in the OS, in the univariate analysis. In the risk analysis of the baseline characteristics, age, administration of LEV, and O6-methylguanine-DNA methyltransferase (MGMT) promoter status correlated with OS. The use of LEV in the group with a methylated MGMT promoter resulted in a positive impact on the OS [P = 0.006; HR, 0.174; 95% CI: 0.050-0.608], but the effect of LEV on the OS was not statistically significant in the unmethylated MGMT promoter group (P = 0.623). This study suggests that, compared with other AEDs, the administration of LEV may prolong the survival period in GBM patients with methylated MGMT promoters, who are undergoing chemotherapy with TMZ.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Child; Child, Preschool; Dose Fractionation, Radiation; Female; Follow-Up Studies; Glioblastoma; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Quality of Life; Republic of Korea; Retrospective Studies; Risk Factors; Seizures; Temozolomide; Time Factors; Treatment Outcome; Young Adult

The efficacy of levetiracetam (LEV) in controlling seizures in patients with brain tumor-related epilepsy (BTRE) depends on tumoral expression of synaptic vesicle protein 2A (SV2A). Although LEV is generally well tolerated, neuropsychiatric adverse events (NPAEs) might occur, limiting compliance and seizure control. We aimed to assess the influence of tumoral SV2A expression on the occurrence of LEV-related NPAEs in patients with glioma.. Specimens from patients enrolled in the multicenter COMPO study, with glioma and BTRE treated with LEV, undergoing neurosurgery were retrieved. Immunohistochemistry-based expression of SV2A in tumoral and peritumoral tissue was scored in a four-point scale from absent (score = 0) to strong (score = 3). Low immunoreactivity (IR) corresponded to scores < 2. Staining ratios (tumoral SV2A IR/peritumoral SV2A IR) were grouped into low (≤ 0.5) and high (> 0.5). NPAEs were assessed longitudinally with the Neuropsychiatry Inventory 12 test (NPI-12).. Overall, 18 patients were eligible for analysis. All received LEV monotherapy, with 67% developing NPAEs. Patients with NPAEs had significantly lower median SV2A intensity score compared to patients without NPAEs (score 1 vs 0, p = 0.025). Low staining ratio (≤ 0.5) associated with higher NPAE occurrence compared to SR > 0.5 (85.7% vs 0%, p < 0.01). A SR ≤ 0.5 predicted a consistent increase in risk of NPAEs (OR 45.0; 95% CI 1.8-1128; p = 0.02).. Our results suggest that SV2A expression in tumoral and peritumoral tissue correlates with the occurrence of LEV-related NPAEs. Thus, considering that SV2A expression also influences LEV effectiveness, SV2A staining might help in tailoring treatment to patients.

Topics: Adult; Aged; Anticonvulsants; Biomarkers; Brain Neoplasms; Epilepsy; Female; Gene Expression; Humans; Levetiracetam; Male; Membrane Glycoproteins; Mental Disorders; Middle Aged; Nerve Tissue Proteins; Predictive Value of Tests; Prospective Studies

Postoperative blindness is a devastating surgical complication. Although usually associated with prolonged cardiac and prone spinal operations, it may follow other procedures as well. Postoperative blindness is most commonly caused by a vascular etiology, but it can more rarely be caused by status epilepticus. We have previously reported a case of this phenomenon following a staged spinal deformity surgery.. Here we report 2 additional cases following a skull base procedure and a single stage lumbar spine surgery. In all instances, rapid recognition that the patients' blindness was due to occipital seizures resulted in acute antiepileptiform treatment and full restoration of vision.. Although a rare phenomenon, this syndrome, first recognized and described by Tarik F. Ibrahim, should be considered in any patient with postoperative visual impairment.

Topics: Aged; Anticonvulsants; Blindness; Brain Neoplasms; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Lumbar Vertebrae; Occipital Lobe; Postoperative Complications; Skull Base; Spinal Stenosis; Status Epilepticus

Epilepsy is a common symptom in patients with glioblastoma (GB). 213 patients with GB from RedLANO follow-up registry were included. All patients underwent surgery, if feasible, followed by chemoradiation based on temozolomide (Stupp platform). Information was recorded regarding demographics, seizure timing, anti-epileptic drugs (AEDs), dosage, time to next seizure, total seizures in 6 months, and main side effects of AEDs. The relationship between epilepsy treatment and overall survival (OS) was evaluated. Mean age was 53 years old and 56.8% were male. Seventy-eight patients (37%) were treated with levetiracetam (LEV), 27% were given another AED and 36% did not require any AED. Choice of AED was not associated with age (p = 0.67), performance status (p = 0.24) or anatomic tumor site (p = 0.34). Seizures and AED requirement were greater in those having primary GB (p = 0.04). After starting an AED, the mean time until next crisis was 9.9 days (SD ± 6.3), which was shorter in those receiving LEV (p = 0.03); mean number of seizures during the first 3 and 6 months were 2.9 and 4, respectively. Most patients treated with LEV (n = 46) required less than two medication adjustments compared to those treated with other AEDs (p = 0.02). Likewise, less patients exposed to LEV required a coadjuvant drug (p = 0.04). Additionally, patients receiving LEV had significantly less adverse effects compared to patients treated with another AED. OS was significantly higher in the group treated with LEV compared to other AEDs (25.5 vs. 17.9 months; p = 0.047). Patients treated with LEV had better seizure control and longer OS compared to other AEDs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Glioblastoma; Hispanic or Latino; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Prospective Studies; Young Adult

Topics: Anticonvulsants; Astrocytoma; Brain Neoplasms; Epilepsy, Generalized; Female; Humans; Italy; Levetiracetam; Middle Aged; Rhabdomyolysis

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

To explore possible correlations among brain lesion location, development of psychiatric symptoms and the use of antiepileptic drugs (AEDs) in a population of patients with brain tumor and epilepsy. The medical records of 283 patients with various types of brain tumor (161 M/122 F, mean age 64.9 years) were analysed retrospectively. Patients with grade III and IV glioma, previous history of epileptic seizures and/or psychiatric disorders were excluded. Psychiatric symptoms occurring after initiation of AED therapy were considered as treatment emergent psychiatric adverse events (TE-PAEs) if they fulfilled the following conditions: (1) onset within 4 weeks after the beginning of AED therapy; (2) disappearance on drug discontinuation; (3) absence of any other identified possible concurrent cause. The possible influence of the following variables were analysed: (a) AED drug and dose; (b) location and neuroradiologic features of the tumor, (c) location and type of EEG epileptic abnormalities, (d) tumor excision already or not yet performed; (e) initiation or not of radiotherapy. TE-PAEs occurred in 27 of the 175 AED-treated patients (15.4%). Multivariate analysis showed a significant association of TE-PAEs occurrence with location of the tumor in the frontal lobe (Odds ratio: 5.56; 95% confidence interval 1.95-15.82; p value: 0.005) and treatment with levetiracetam (Odds ratio: 3.61; 95% confidence interval 1.48-8.2; p value: 0.001). Drug-unrelated acute psychiatric symptoms were observed in 4 of the 108 AED-untreated patients (3.7%) and in 7 of the 175 AED-treated patients (4%). The results of the present study suggest that an AED alternative to levetiracetam should be chosen to treat epileptic seizures in patients with a brain tumor located in the frontal lobe to minimize the possible onset of TE-PAEs.

Topics: Aged; Anticonvulsants; Brain Neoplasms; Cohort Studies; Electroencephalography; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Piracetam; Psychiatric Status Rating Scales; ROC Curve

Lacosamide (LCM) due to no known drug interaction and the absence of metabolic enzyme induction is a good candidate for an add-on medication, especially in combination with lamotrigine, levetiracetam (LEV), oxcarbazepine, topiramate, and valproic acid (VPA). Here we report for the first time, to our knowledge, that LCM can lower VPA and LEV serum levels. At present, there are no known explicable mechanisms of action of LCM, which lowers VPA and LEV. Here observed drug interaction of LCM is of clinical significance, which might be useful for other colleagues in the field.

Topics: Acetamides; Adolescent; Anticonvulsants; Brain Neoplasms; Drug Interactions; Epilepsies, Partial; Humans; Lacosamide; Levetiracetam; Neoplasms, Neuroepithelial; Piracetam; Seizures; Valproic Acid

Brain tumor-related epilepsy (BTRE) is often drug resistant and patients can be forced to take polytherapy that can adversely affect their quality of life (QoL). Lacosamide (LCM) is a new antiepileptic drug (AED) used as adjunctive therapy in patients with partial seizures with or without secondary generalization, with a favorable pharmacokinetic profile that seems to be effective and well tolerated. Therefore it represents a possible therapeutic choice for patients with BTRE. We propose a prospective study with a historical control group to evaluate the effect of LCM as add-on therapy on seizure control and quality of life in patients with BTRE. This study has been designed to test the superiority of Lacosamide over Levetiracetam as an add-on. We compared a prospective cohort of 25 patients treated with Lacosamide with a historical control group (n=19) treated with Levetiracetam as an add-on.. We recruited 25 adult patients (M 18, F 7; mean age 41.9) affected by BTRE with uncontrolled partial-onset seizures treated with AED polytherapy. We added LCM as an add-on. Patients were evaluated at baseline, after 3months and at 6months. This population has been compared with a historical control group of 19 BTRE adult patients (M 13, F 6; median age 48.0, range: 28-70) with uncontrolled partial-onset seizures treated with LEV as add-on. The patients underwent QoL, mood and adverse events tests (Adverse Event Profile-AEP) and evaluation of seizure frequency.. Twelve patients had high grade gliomas, and thirteen had low grade gliomas. During follow-up, thirteen patients underwent chemotherapy, three radiotherapy and five patients had disease progression. Nine patients had simple partial seizures, eight had complex partial seizures, and eight had secondary generalized seizures. Fifteen patients were in monotherapy and ten in polytherapy with AEDs. LCM was added up to reach the maximum dosage of 400mg/die (mean final dose 300mg/die). Four patients dropped out due to poor compliance and 1 for inefficacy. In the historical control group treated with LEV (mean final dose 2000mg/die) 12 patients had high-grade gliomas, and 7 had low grade gliomas. Thirteen patients were in monotherapy and 6 in polytherapy with AEDs. In the 22 patients evaluable of 25 patients treated with LCM, we observed at final follow-up 7 patients seizure free, 12 with a significant reduction of seizures≥50%, 2 stable and 1 patient with number of seizures increased. Mean seizure frequency at baseline compared with baseline period: the mean number of seizures significantly decreased from baseline (9.4) to final follow-up (1.2) (P=0.005). The Responder Rate was 86.4%. Comparing responder rate of 22 evaluable patients with LCM with responder rate of 19 patients with LEV we didn't observe significant differences (p=0.31). In our patients treated with LCM we didn't observe significant difference at 3 and 6months in QoL tests results; we observe a significant reduction in the mean score of Karnofsky Performance Status (KPS) and Barthel Index (BI) between baseline and 6months of follow-up (KPS p=0.003; BI p=0.007). No clinical side effects were observed.. Comparing the LCM with the historical group treated with LEV in add-on, we observed that LCM seems to have a higher clinical efficacy than LEV. In our patients, we did not observe any significant changes in QoL tests, indicating stability in all quality of life domains explored, despite the objective worsening in their functional status. Although this is a small series with a relatively short follow-up, our data indicates that LCM in add-on in patients with BTRE appears to be as effective as LEV in add-on, without impact on mood and quality of life.

Topics: Acetamides; Adult; Affect; Aged; Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Female; Historically Controlled Study; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Outcome Assessment, Health Care; Piracetam; Prospective Studies; Quality of Life

We assessed the prevalence and magnitude of neuropsychiatric adverse events (NPAEs) associated with antiepileptic drugs (AEDs) among patients with brain tumour-related epilepsy (BTRE).. This observational, prospective, multicentre study enrolled 259 patients with BTRE after neurosurgery. All patients received AED monotherapy. Efficacy was assessed through clinical diaries, whereas NPAEs were collected using the Neuropsychiatric Inventory Test-12 questionnaire at baseline and after 5 months.. Tumour localization in the frontal lobe was associated with a higher prevalence of NPAEs (odds ratio, 7.73; P < 0.001). Independent of tumour localization, levetiracetam (LVT) treatment was associated with higher prevalence and magnitude of NPAEs (odds ratio, 7.94; P < 0.01) compared with other AEDs. Patients with oligodendroglioma reported more NPAEs than patients with other tumour types. NPAEs were not influenced by chemotherapy, radiotherapy or steroid treatment. Evaluating non-neurobehavioural adverse events of AEDs, no significant differences were found among AEDs, although patients treated with old AEDs had a higher prevalence of adverse events than those treated with new AEDs.. Both tumour localization in the frontal lobe and LVT treatment are associated with a higher risk of NPAEs in patients with BTRE. LVT is regarded as a first-line option in patients with BTRE because of easy titration and few significant drug-to-drug interactions. Thus, as NPAEs lead to poor compliance and a high dropout rate, clinicians need to accurately monitor NPAEs after AED prescription, especially in patients with frontal lobe tumours receiving LVT.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Epilepsy; Female; Humans; Italy; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Treatment Outcome; Young Adult

Topics: Anticonvulsants; Brain Neoplasms; Epilepsy; Humans; Levetiracetam; Piracetam

Levetiracetam may induce serious behavioral disturbances, especially after surgical resection of frontal lobe low-grade glioma. Two patients, treated with levetiracetam, developed serious psychiatric complications postoperatively which completely resolved after switching to valproate. We aim to create awareness for this serious but reversible adverse effect of levetiracetam in this specific patient category.

Topics: Anticonvulsants; Brain Neoplasms; Craniotomy; Epilepsy; Frontal Lobe; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Mental Disorders; Middle Aged; Oligodendroglioma; Piracetam; Postoperative Complications; Valproic Acid

Temozolomide (TMZ) is an alkylating agent used for treatment of brain neoplasms and levetiracetam (LEV) is a commonly used antiepileptic. When administered separately each medication has few negative side effects impacting the liver.. We sought to determine the risk of liver injury associated with the co-administration of TMZ and LEV.. A case-control study was performed comparing patients who received combination therapy of TMZ and LEV (group A) with matched controls (group B) who received monotherapy with one of either TMZ or LEV. We assessed patient demographics, laboratory results including presence of liver injury, and mortality.. Twenty-six patients were included in group A and 68 patients were included in group B. Both groups were similar with respect to demographics and baseline liver function tests (P>0.05). There was a significant elevation in liver enzymes in 73%, 46%, 19%, 31% and 27% of ALT, AST, ALK-P, GGT and bilirubin, respectively, in group A, as compared to elevations of 10.3%, 19%, 1.5%, 7% and 1.5%, respectively in group B (P<0.05). One patient in group A died as a result of acute liver failure while no deaths from acute liver failure occurred in group B (P=0.05). Univariate analysis identified combination therapy as a risk factor for liver injury. Multivariate regression showed that only co-treatment with TMZ and LEV was an independent risk factor for liver injury with an odds ratio of 19.1 (95 CI, 2.16-160).. Combination therapy with TMZ and LEV may precipitate acute liver injury and even death.

Topics: Adult; Aged; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Case-Control Studies; Chemical and Drug Induced Liver Injury; Dacarbazine; Drug Therapy, Combination; Female; Humans; Israel; Levetiracetam; Liver Function Tests; Male; Middle Aged; Multivariate Analysis; Piracetam; Regression Analysis; Retrospective Studies; Temozolomide

We report the case of a man who developed seizures on a background of recurrent metastatic squamous cell carcinoma with intracranial involvement. Initial seizure control with enteral levetiracetam was achieved, and when enteral and intravenous (i.v.) access was no longer available, a continuous subcutaneous infusion (CSCI) of levetiracetam successfully controlled his seizures without the need for sedating anticonvulsants. As a result, end-of-life care was able to be given with the patient retaining the ability to communicate with his family and healthcare staff. This report adds to the sparse but growing evidence base for the use of subcutaneous levetiracetam to manage seizures in palliative and end-of-life care.

Topics: Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Infusions, Subcutaneous; Levetiracetam; Male; Palliative Care; Piracetam; Quality of Life; Scalp; Seizures; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck; Terminal Care; Treatment Outcome

Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma.. To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV).. VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use.. The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Clinical Trials as Topic; Dacarbazine; Epilepsy; Female; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prognosis; Survival Analysis; Temozolomide; Valproic Acid

Topics: Acyclovir; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antiviral Agents; Brain Neoplasms; Ceftriaxone; Dexamethasone; Diagnosis, Differential; Electroencephalography; Emergency Service, Hospital; Encephalitis, Herpes Simplex; Fever; Humans; Hypnotics and Sedatives; Infarction; Levetiracetam; Male; Massachusetts; Middle Aged; Phenytoin; Piracetam; Propofol; Status Epilepticus; Temporal Lobe; Tomography, X-Ray Computed; Unconsciousness; Vancomycin

Patients with grade IV astrocytoma or glioblastoma multiforme (GBM) have a median survival of <12 months, increased to 14.6 months by maximal safe resection with radiation and temozolamide. In the absence of chemotherapy, radiotherapy or chemoradiotherapy, spontaneous regression of GBM or regression while only being on dexamethasone (DEX) and levetiracetam (LEV) have seldom been reported. Here, we present a case of a patient who had significant regression of the GBM with DEX and LEV alone. In this study, we hypothesise a plausible antineoplastic role of DEX and or LEV in GBM and highlight molecular, preclinical and clinical studies supporting this role.

Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Cognition Disorders; Dacarbazine; Dexamethasone; Glioblastoma; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Regression, Spontaneous; Neoplasms, Second Primary; Piracetam; Temozolomide

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

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity.

Topics: Adult; Aged; Anticonvulsants; Blood Cell Count; Blood Cells; Brain Neoplasms; Chemoradiotherapy; Female; Glioblastoma; Hemoglobins; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Valproic Acid; Young Adult

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

Transcranial electrical motor-evoked potential (tceMEP) monitoring is used in complex intracranial and spinal surgeries to detect and prevent neurological injury. We present a case of transient, reproducible loss of tceMEPs after an infusion of levetiracetam during craniotomy and tumor resection in a child. Cessation of the infusion resulted in restoration of baseline tceMEPs. When the infusion was resumed at the end of the procedure, a similar decrease in tceMEPs was seen as before, after the infusion was stopped. The surgery and postoperative course proceeded without incident, and the patient experienced a full recovery.

Topics: Anticonvulsants; Astrocytoma; Brain Neoplasms; Child; Craniotomy; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Female; Humans; Infusions, Intravenous; Levetiracetam; Monitoring, Intraoperative; Piracetam

A chemosensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O-6 methylguanine-DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. The objective of this study was to assess the survival benefit of LEV compared with other antiepileptic drugs as a chemosensitizer to temozolomide for patients with glioblastoma.. In total, 103 consecutive patients with primary glioblastoma who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and 58 patients (56%) received LEV during temozolomide chemotherapy for at least 3 months. A Cox regression survival analysis was performed to adjust for confounding factors, including age, extent of lesion, Karnofsky performance scale score, extent of removal, and MGMT promoter methylation status.. The median progression-free survival (PFS) and overall survival (OS) for patients who received LEV in combination with temozolomide (PFS: median, 9.4 months; 95% confidence interval [CI], 7.5-11.3 months; OS: median, 25.7 months; 95% CI, 21.7-29.7 months) were significantly longer than those for patients who did not receive LEV (PFS: median, 6.7 months; 95% CI, 5.8-7.6 months; OS: median, 16.7 months; 95% CI, 12.1-21.3 months; P = .010 and P = .027, respectively). In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (hazard ratio [HR], 0.37; P = .016), MGMT promoter methylation (HR, 0.30; P = .002), and receipt of LEV (HR, 0.31; P < .001.. LEV may provide a survival benefit in patients with glioblastoma who receive temozolomide-based chemotherapy. A prospective randomized study may be indicated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chemoradiotherapy; Chemotherapy, Adjuvant; Dacarbazine; Female; Glioblastoma; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Piracetam; Proportional Hazards Models; Retrospective Studies; Temozolomide; Young Adult

Brain metastases occur in about 30% of patients with non-small-cell lung carcinoma; seizures occur in approximately 20% of them. Antiepileptic drugs are commonly given for postoperative prophylaxis after brain or metastasis tumor surgery. The incidence of seizures following supratentorial craniotomy is estimated to be 15%-20%. Postoperative seizures are more common in the first month after cranial surgery. However, the use of antiepileptic drugs postoperatively has been investigated in randomized controlled trials. In case of seizures, the recommendations are continuing antiepileptic drugs after a 1- to 4-year seizure-free interval. This decision must weigh the risk of seizure recurrence against the possible benefits of the drug. Some antiepileptic drugs have been known to cause blood dyscrasias, including neutropenia, but this is a rare occurrence.. We report a case of neutropenia related to the use of levetiracetam at first exposure. After drug administration, neutropenia was detected. Additional tests were performed.. By exclusion, it was decided to withdraw the drug, and the patient had a reversal of neutropenia.. Levetiracetam-induced neutropenia is infrequent but possible. It is an exclusion diagnosis.

Topics: Adenocarcinoma; Anticonvulsants; Brain Neoplasms; Craniotomy; Drug Administration Schedule; Humans; Levetiracetam; Lung Neoplasms; Male; Middle Aged; Neutropenia; Piracetam; Seizures

Topics: Aged; Antineoplastic Agents; Brain Neoplasms; DNA-Binding Proteins; Female; Frontal Lobe; Humans; Immunocompetence; Levetiracetam; Lymphoma; Magnetic Resonance Imaging; Nootropic Agents; Piracetam; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6; Spasm

Topics: Aged; Anticonvulsants; Brain Neoplasms; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Injections, Subcutaneous; Levetiracetam; Palliative Care; Piracetam; Treatment Outcome

To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation.. A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months. Cox-regression survival analysis was performed on 165 patients receiving chemoradiation with temozolomide of whom 108 receiving this in combination with VPA for at least 3 months.. Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on monotherapy. Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status.. Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Drug Therapy, Combination; Female; Follow-Up Studies; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Neoplasm Recurrence, Local; Piracetam; Prognosis; Retrospective Studies; Seizures; Survival Rate; Temozolomide; Valproic Acid; Young Adult

Topics: Anticonvulsants; Brain Neoplasms; Female; Glioblastoma; Humans; Levetiracetam; Male; Neoplasm Recurrence, Local; Piracetam; Seizures; Valproic Acid

Antiepileptic drugs are commonly given for perioperative prophylaxis after brain tumor surgery, and there has been growing interest in levetiracetam, a second-generation antiepileptic drug. This retrospective study compared the seizure outcomes, side effects and durability of levetiracetam with valproic acid after a craniotomy for supratentorial brain tumors.. Between 2009 and 2012, 282 consecutive patients with a supratentorial brain tumor underwent a craniotomy at Seoul National University Bundang Hospital. Of these patients, 51 (18.1%) and 231 (81.9%) were pre-operatively administered levetiracetam and valproic acid, respectively. The postoperative seizure outcomes (within 1 month after surgery) and the long-term side effects of both drugs were evaluated.. Of the 51 patients in the levetiracetam group, 4 (7.8%) experienced postoperative seizures after brain tumor surgery, and 15 (6.5%) of the 231 patients in the valproic acid group experienced postoperative seizures (p = 0.728). The long-term complication rate of the valproic acid group (26.8%; 62/231) was significantly higher than that of the levetiracetam group (9.8%; 5/51) [p = 0.010]. In the valproic acid group, 10 hepatotoxicities, 20 hyperammonemias and 10 hematologic abnormalities (6 thrombocytopenias, 3 pancytopenias, and 1 leucopenia) occurred. Moreover, 89 patients (38.5%) in the valproic acid group changed or added other anticonvulsants because of side effects or uncontrolled seizures, whereas only 9 patients (17.6%) in the levetiracetam group changed or added other anticonvulsants (p = 0.005).. The postoperative seizure control rates of levetiracetam and valproic acid were not statistically significantly different; however, levetiracetam may be superior to valproic acid in terms of its safety and durability after supratentorial tumor surgery.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Supratentorial Neoplasms; Treatment Outcome; Valproic Acid; Young Adult

To identify risk factors for the development of tumor-associated epilepsy (TAE) and potential benefit of newer generation AEDs in seizure prevention.. We performed an IRB approved retrospective study of newly diagnosed GBM patients at the University of Rochester between 1/1/05 and 5/13/11. Records were reviewed to describe demographics, seizure incidence, occurrence of status epilepticus, and AED use and toxicity.. 172 patients with newly diagnosed GBM were included in the study. 53.4% developed TAE. 31.4% had seizure prior to diagnosis. 118 patients were seizure-free at diagnosis: 32.2% developed post-diagnosis TIE (PostTAE) and 60.2% remained seizure-free. 70 seizure-free patients received an AED peri-operatively. 36 were weaned off AEDs and 31 were continued. Incidence of PostTAE and time to first seizure were comparable in AED-treated and untreated patients. 4 PostTAE patients presented with status epilepticus (SE), all were not AED treated. AEDs were withdrawn in 10 patients due to toxicity: 9 from phenytoin and 1 from levetiracetam.. There is a high incidence of PostTAE in GBM. Prophylactic AED therapy did not reduce PostTAE but may have prevented SE. Minimal toxicity was observed on 2nd generation AEDs. The high burden of epilepsy in this population and tolerability of newer AEDS suggest that AAN guidelines should be revisited.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Risk Factors; Seizures; Status Epilepticus; Treatment Outcome

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

There were nearly 700,000 patients in the United States in 2010 living with brain tumor diagnoses. The incidence of seizures in this population is as high as 70% and is historically difficult to control. Approximately 30-40% of brain tumors patients who present with status epilepticus (SE) will not respond to typical therapy consisting of benzodiazepines and phenytoin (PHT), resulting in patients with refractory status epilepticus (RSE). RSE is usually treated with anesthetic doses of propofol or midazolam infusions. This therapy can have significant risk, particularly in patients with cancer.. A retrospective chart review was performed on 23 patients with primary or metastatic brain tumors whose SE was treated with intravenous PHT, levetiracetam (LEV), and oral pregabalin (PGB).. In all the patients under study, PHT or LEV was used as first-line therapy. PGB was typically used as third-line treatment. The median daily dose of PGB was 375 mg (usually divided BID or TID), and the median daily dose of LEV 3000 mg (usually divided BID). Cessation of SE was seen in 16/23 (70%) after administration of PHT, LEV, and PGB. SE was aborted, on average, 24 h after addition of the third antiepileptic drug. Only one patient in the responder group required intubation. Mortality rate was zero in the responder group. No adverse reactions to this medication regimen were observed.. Our study suggests that the administration of PHT, LEV, and PGB in brain tumor patients with RSE is safe and highly effective.

Topics: Acute Disease; Aged; Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pregabalin; Retrospective Studies; Status Epilepticus; Treatment Outcome

A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline.

Topics: Acute Kidney Injury; Anticonvulsants; Astrocytoma; Brain Neoplasms; Humans; Levetiracetam; Male; Middle Aged; Nephritis, Interstitial; Piracetam; Seizures

Anticonvulsant drugs are frequently given after craniotomy. Phenytoin (PHT) is the most commonly used agent; levetiracetam (LEV) is a new anticonvulsant drug with fewer side effects. To compare the incidence of seizures in patients receiving either prophylactic PHT or LEV perioperatively, 971 patients undergoing a craniotomy were analysed retrospectively during a 2-year period. PHT was used routinely and LEV was administered when PHT was contraindicated. Seizures documented during the first 7 days after craniotomy were considered. A total of 235 patients were treated with an antiepileptic drug: 81 patients received LEV, and 154 patients, PHT. Two patients receiving LEV (2.5%) and seven receiving PHT (4.5%) had a seizure despite this treatment. No patient had a documented side effect or drug interaction. The data show that LEV may be an alternative option in patients with contraindications to PHT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Child; Contraindications; Craniotomy; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Postoperative Complications; Retrospective Studies; Seizures; Young Adult

Topics: Aged; Amygdala; Anticonvulsants; Astrocytoma; Brain Neoplasms; Electroencephalography; Hippocampus; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Piloerection; Piracetam; Seizures; Temporal Lobe; Valproic Acid

An open pilot study to evaluate the effect of pregabalin (PGB) as add-on therapy on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy (BTRE).. We recruited 25 consecutive patients with BTRE and uncontrolled seizures. At baseline and during follow-up, patients underwent a complete physical and neurological examination and were evaluated using the QOLIE 31P (V2), EORTC QLQ C30, Adverse Events Profile, and Hamilton Anxiety Rating Scale (HAM-A). At baseline, a seizure diary was given.. During follow-up, 17 patients underwent chemotherapy, none underwent radiotherapy, 9 had disease progression, and 3 died. Mean duration of follow-up was 4.1 months. Mean PGB dosage was 279 mg/day. At baseline, mean weekly seizure frequency was 5.3 (±10) and at last available follow-up visit was 2.8±5. This difference was statistically significant (p=0.016). The responder rate was 76%. Ten patients dropped out; 4 as a result of seizure worsening, 1 as a result of unchanged seizure frequency, 3 as a result of a lack of compliance, and 2 as a result of side effects. Based on the QOLIE-31-P, a significant improvement of the subscale "seizure worry" (p=0.004) and a significant decrease in distress scores related to AEDs and social life (p=0.009 and p=0.008, respectively) were observed. A significant decrease in HAM-A score (p=0.002) was documented. CONCLUSIONS; These data indicate that PGB may represent a valid alternative as add-on treatment in this patient population, based on its efficacy on seizure control and anxiety.

Topics: Adult; Aged; Anticonvulsants; Anxiety; Benzodiazepines; Brain Neoplasms; Carbamazepine; Clobazam; Drug Therapy, Combination; Epilepsy; Female; Fructose; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenobarbital; Pilot Projects; Piracetam; Pregabalin; Quality of Life; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

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

Breakthrough seizure activity has been reported with conversion from brand name to generic anticonvulsants. This has prompted several organizations to support physician notification of generic substitution and patient consent. Recently, a generic formulation of levetiracetam has become available. Risk of seizures with generic levetiracetam has yet to be reported. Literature was reviewed regarding risk of generic substitution. Four cases of seizure activity in primary brain tumor patients after conversion from Keppra to generic levetiracetam are reported. In all cases, there was no evidence of tumor growth or concurrent illness that would increase the risk of seizures. In three cases, the patients have remained seizure free with conversion back to Keppra. The final patient required an increased dose of levetiracetam. As has been described with generic substitution of other anticonvulsants, patients switched to generic levetiracetam may be at risk for breakthrough seizure activity.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Drugs, Generic; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures

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

Topics: Brain Neoplasms; Humans; Levetiracetam; Nootropic Agents; Piracetam; Prospective Studies

Rare cases of levetiracetam-induced thrombocytopenia have been reported in the literature. We report a case of glioblastoma multiforme and partial epilepsy treated with levetiracetam with subsequent development of thrombocytopenia. After ruling out all other possible causes of a decreased platelet count, we conclude that levetiracetam was the cause of this adverse event.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsies, Partial; Female; Frontal Lobe; Glioblastoma; Humans; Levetiracetam; Middle Aged; Piracetam; Platelet Count; Thrombocytopenia; Treatment Outcome

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

Children with brain tumors and other cancers can suffer from seizures. Unfortunately, most antiepileptic therapies are metabolized by the hepatic cytochrome P450 (CYP) system. Levetiracetam, a newer anticonvulsant, does not undergo CYP metabolism and does not alter the pharmacokinetics of chemotherapy, antiemetics, and corticosteroids, which are metabolized by the liver. We studied 23 patients with cancer and seizures treated with levetiracetam. Over 95% of patients had fewer seizures, with 65.2% becoming seizure free; only one patient experienced an adverse reaction. Levetiracetam is effective and well tolerated in children with brain tumors and other cancers, who are often on multiple enzyme-inducing drugs.

Topics: Adolescent; Anticonvulsants; Brain Neoplasms; Child; Drug Evaluation; Female; Humans; Levetiracetam; Male; Neoplasms; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Topics: Anticonvulsants; Benzodiazepines; Brain Neoplasms; Cell Phone; Clobazam; Electroencephalography; Epilepsy, Complex Partial; Female; Frontal Lobe; Glioblastoma; Humans; Levetiracetam; Magnetic Resonance Imaging; Middle Aged; Piracetam; Status Epilepticus; Tomography, X-Ray Computed

The aim of this pilot study was to investigate the effects of levetiracetam monotherapy on seizure control, quality of life and neurocognitive performance in patients with brain tumor-related epilepsy. We present here preliminary data from 18 patients with follow-up of 6 months. We evaluated seizure frequency at baseline. We used administered Mini Mental State Examination (MMSE), Karnofsky Performance Status (KPS), Barthel index (BI), QOLIE 31P (V2), EORTC QLQ-C30 and Adverse Events Profile. After 6 months, 16 patients were seizure free (88.9%), 2 (11.1%) had reduction in seizure frequency >50%. Compared to baseline, we observed a worsening of performance (KPS p = 0.011; BI = 0.008) and global lower cognitive performance (MMSE p = 0.011); distress related to seizure frequency (p = 0.003) and medication effects (p = 0.046) were significantly lower. Levetiracetam caused mild and reversible side effects. These preliminary data on LEV monotherapy in patients with brain tumor-related epilepsy show that this antiepileptic drug is efficacious and well tolerated.

Topics: Activities of Daily Living; Adult; Aged; Anticonvulsants; Blood Cell Count; Brain Neoplasms; Combined Modality Therapy; Epilepsy; Female; Humans; Karnofsky Performance Status; Levetiracetam; Logistic Models; Male; Middle Aged; Neuropsychological Tests; Personal Autonomy; Piracetam; Quality of Life; Seizures; Surveys and Questionnaires; Young Adult

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

We report on a case of epilepsia partialis continua with rapid response to intravenous bolus administration of levetiracetam. A 60-year-old woman presented with continuous jerking of the right foot and hallux persisting for more than two days. She had a 9-year history of epilepsy due to a left temporoparietal oligodendroglioma with occasional focal seizures clinically presenting as speech arrest, which was treated with levetiracetam and oxcarbazepine administered orally. After hospital admission, the twitching of the foot and toe was refractory to add-on treatment with lorazepam and diazepam but stopped within 15 min after intravenous bolus administration of 2000 mg levetiracetam. This observation suggests that intravenous bolus administration of levetiracetam may be an effective therapeutic option in epilepsia partialis continua.

Topics: Anticonvulsants; Brain Neoplasms; Epilepsies, Partial; Female; Humans; Injections, Intravenous; Levetiracetam; Middle Aged; Oligodendroglioma; Piracetam; Speech Disorders

Topics: Aged; Anticonvulsants; Brain Neoplasms; Female; Humans; Levetiracetam; Papilloma, Choroid Plexus; Piracetam; Vomiting

Topics: Age Factors; Anticonvulsants; Antiemetics; Antineoplastic Agents; Brain Neoplasms; Glioblastoma; Humans; Levetiracetam; Logistic Models; Nausea; Piracetam; Retrospective Studies; Vomiting

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

Seizures are a common complication of metastatic brain tumors (MBT), affecting approximately 27-50% of all patients during the course of their illness. Treatment of tumor-induced seizures is often inadequate with traditional antiepileptic drugs (AED) due to a variety of factors, including activation of glutamatergic NMDA receptors, alterations of neuronal input pathways, and tumor growth. Levetiracetam (LEV) is a 2nd generation non-enzyme inducing AED with a novel mechanism of action, binding to neuronal synaptic vesicle protein SV2A, that has been previously shown to reduce seizure activity in patients with primary brain tumors. Due to its unique mechanism of action, it has been postulated that LEV may also be effective in controlling seizures from MBT. A retrospective chart review was performed of all Neuro-Oncology Center patients with MBT who had received LEV for seizure control. Thirteen patients were reviewed with a median age of 55.1 years (range: 34-70). Six patients had breast cancer, five had lung cancer, and two had melanoma. LEV was used as an add-on AED in seven patients (54%) and as monotherapy in six patients (46%), with a median dose of 1,000 mg/day (range: 500-3,000). The baseline median seizure frequency was one ictal event every other day. After the addition of LEV, the median seizure frequency was reduced to 0 per week. The seizure frequency was reduced to less than 50% of the pre-LEV baseline in 100% of patients (P=0.0002, Sign test), with 10 patients (77%; confidence interval: 46-95%) noting complete seizure control. The most common adverse event was somnolence and headache, noted in 3 of 13 patients (23%). LEV was very effective and well tolerated in MBT patients with seizures and should be considered for add-on therapy or as a substitute AED for monotherapy.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures

Levetiracetam (LEV) is used in the setting of acute brain injury for seizure treatment or prophylaxis but its safety and efficacy in this setting is unknown.. We retrospectively analyzed the patterns of use and safety/efficacy of LEV in 379 patients treated in the neuroscience intensive care unit (NSICU). We extracted from the charts clinical data including diagnosis, AED therapy before and during stay in the NSICU, complications of treatment, length of stay, and clinical outcomes (improvement, Glasgow Coma Scale, and death). We analyzed the data using binary and ordered (multi-category) logistic regression.. Overall, our findings are that phenytoin used prior to the NSICU admission was frequently replaced with LEV monotherapy (P < 0.001). Patients treated with LEV monotherapy when compared to other AEDs had lower complication rates and shorter NSICU stays. Older patients and patients with brain tumors or strokes were preferentially treated with LEV for prevention and/or management of seizures (all P < or = 0.014).. The results of this study suggest that LEV is a frequently used AED in the setting of acute brain injury and that it may be a desirable alternative to phenytoin. Prospective studies evaluating the long-term safety, efficacy and outcomes of LEV in this setting are indicated.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Diseases; Brain Neoplasms; Cerebral Hemorrhage; Comorbidity; Critical Illness; Epilepsy; Humans; Intensive Care Units; Length of Stay; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Stroke; Treatment Outcome

Seizures are a common complication of primary (PBT) and metastatic (MBT) brain tumors, affecting approximately 50% of all patients during the course of their illness. Anti-convulsant therapy of these tumor-induced seizures is often inadequate with conventional anti-epileptic drugs (AEDs), due to a variety of factors, including activation of glutaminergic NMDA receptors, immune-mediated neuronal damage, and anatomic alterations of neuronal input pathways. Levetiracetam (LEV) is a new AED with a novel mechanism of action, which includes reducing the Ca++ current through neuron-specific, high voltage activated Ca++ channels (n-type). Because of this unique mechanism, it has been postulated that LEV may be effective in controlling tumor-induced seizures. A retrospective chart review was performed of all patients who had received LEV for seizure control. Forty-one patients were reviewed (22 female, 19 male), with a median age of 47.5 years (range 25-81). There were 34 patients with PBT and 7 with MBT. LEV was used as an add-on AED in 33 patients and as monotherapy in eight patients, with a median dose of 1500 mg/day (range 500-3500). The baseline median seizure frequency for the cohort was 1 per week. After the addition of LEV and follow-up for a minimum of 4 weeks, the median seizure frequency was reduced to 0 per week (59% of patients noted complete seizure control). Overall, the seizure frequency was reduced in 90% of patients (P<0.0001; Sign test). The most common toxicity was somnolence, noted in 37% of patients. LEV was very effective and well tolerated in brain tumor patients with seizures, and should be considered for add-on therapy to current AEDs, or as a substitute anti-convulsant for monotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures

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