topiramate and Brain-Neoplasms

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

Medical management of brain tumor-related epilepsy is complicated by interactions between antiepileptic and chemotherapeutic drugs. We studied the effect of temozolomide therapy on the disposition of the new antiepileptic drugs topiramate (TPM) or oxcarbazepine (OXC).. Fifteen patients chronically treated with TPM or OXC in monotherapy starting a chemotherapeutic treatment with temozolomide were enrolled in the study, of which ten were available for the final analyses. Blood samples were collected before temozolomide treatment (T(0)), at its end (T(7)) and after further 1-3 weeks (T(14)-T(28)). For each patient, more than one treatment cycle was studied. Topiramate and OXC mono-10-hydroxy derivative (MHD) plasma concentrations were determined by hplc coupled with ion spray mass spectrometer (TPM) or ultraviolet (MHD) detection.. Mean TPM concentrations were 5.4 +/- 2.4 microg/ml at T(0) vs. 5.5 +/- 2.4 microg/ml at T(7) (n = 14), and 5.4 +/- 2.4 microg/ml at T(0) vs. 5.6 +/- 2.8 microg/ml at T(14)-T(28) (n = 14). Mean MHD concentrations were 16.4 +/- 7.6 microg at T(0) vs. 18.5 +/- 9.0 microg/ml at T(7) (n = 5), and 16.8 +/- 7.0 microg/ml at T(0) vs. 18.0 +/- 8.7 microg/ml at T(14)-T(28) (n = 8) (all comparisons not statistically significant; Student's t-test for paired samples).. Temozolomide treatment did not affect TPM plasma concentrations in chronically treated patients. Data for MHD in OXC-treated patients were similar, but, due to the small sample size, results should be interpreted cautiously.These findings confirm that TPM (and possibly OXC) are a reasonable choice of antiepileptic drug in patients with brain tumor-related epilepsy.

Topics: Adult; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Carbamazepine; Dacarbazine; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Oxcarbazepine; Temozolomide; Topiramate; Young Adult

Epilepsy in brain tumor patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients. We conducted a prospective, observational study. The aim of this study was to investigate the efficacy and tolerability of topiramate (TPM) in brain tumor associated epilepsy. We studied 47 patients with brain tumors and epilepsy. The entire group was administered AEDs. TPM was the first therapeutic choice in 14 patients, while in the remaining 33 patients previous AEDs were modified and TPM was introduced due to side effects or inefficacy of the first drug. Follow-up ranged from 3 to 48 months (mean 16.5 months). Considering the final follow-up of each patient who assumed TPM for at least 3 months, we observed 45 patients: 25 were seizure free (55.6%), 9 had a reduction of seizure frequency (SF) higher than 50% (20%) and 11 were stable (24.4%). TPM responder rate was 75.6%. Three patients (6.4%) discontinued TPM for severe side effects (1 after 4 months and 2 after 1 month) and 4 (8.5%) had mild and reversible side effects. In the group of patients who had been in therapy with other AEDs prior to entering the study (n = 33), 19 patients had side effects (57.6%). During follow-up, the haematological parameters were in the normative ranges. Tumor-related seizures are difficult to control with AEDs; the precise reasons for this difficulty are not yet clear. Using TPM, we obtained good seizure control with a low incidence of side effects.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Drug Evaluation; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Retrospective Studies; Time Factors; Topiramate

Brain edema is a common complication of brain metastases (BM) and associated treatment. The extent to which cytotoxic edema, the first step in the sequence that leads to ionic edema, vasogenic edema, and brain swelling, contributes to radiation-induced brain edema during BM remains unknown. This study aimed to determine whether radiation-associated treatment of BM induces cytotoxic edema and the consequences of blocking the edema in preclinical models of breast-cancer brain metastases (BCBM).. Using in vitro and in vivo models, we measured astrocytic swelling, trans-electric resistance (TEER), and aquaporin 4 (AQP4) expression following radiation. Genetic and pharmacological inhibition of AQP4 in astrocytes and cancer cells was used to assess the role of AQP4 in astrocytic swelling and brain water intake. An anti-epileptic drug that blocks AQP4 function (topiramate) was used to prevent cytotoxic edema in models of BM.. Radiation-induced astrocytic swelling and transient upregulation of AQP4 occurred within the first 24 hours following radiation. Topiramate decreased radiation-induced astrocytic swelling and loss of TEER in astrocytes in vitro, and acute short-term treatment (but not continuous administration), prevented radiation-induced increase in brain water content without pro-tumorigenic effects in multiple preclinical models of BCBM. AQP4 was expressed in clinical BM and breast-cancer cell lines, but AQP4 targeting had limited direct pro-tumorigenic or radioprotective effects in cancer cells that could impact its clinical translation.. Patients with BM could find additional benefits from acute and temporary preventive treatment of radiation-induced cytotoxic edema using anti-epileptic drugs able to block AQP4 function.

Topics: Aquaporin 4; Astrocytes; Brain; Brain Edema; Brain Neoplasms; Breast Neoplasms; Edema; Female; Humans; Topiramate

This is the first case report of the safety of therapeutic repetitive transcranial magnetic stimulation (rTMS) in a patient with an intracranial space-occupying lesion who had recurrent major depression. In this case, the intracranial space-occupying lesion was a mixed cystic and solid enhancing pineal region mass measuring approximately 16.9 × 12.2 × 15.5 mm. The patient remitted from depression with 36 sessions of dorsolateral prefrontal cortex rTMS treatments over a 6-week period. During the rTMS treatment course, patient's medication list included bupropion that potentially can increase the risk for a seizure and topiramate that potentially can reduce the risk for seizure associated with the treatment. The patient tolerated the rTMS treatment well, reporting only transient headache and discomfort at the site of stimulation after the treatment. She tolerated the procedure well and had no incidental seizure activity throughout her treatment sessions.

Topics: Anticonvulsants; Antidepressive Agents, Second-Generation; Brain Neoplasms; Bupropion; Depressive Disorder, Major; Female; Fructose; Humans; Magnetic Resonance Imaging; Middle Aged; Pinealoma; Recurrence; Topiramate; Transcranial Magnetic Stimulation

Topics: Agenesis of Corpus Callosum; Anticonvulsants; Brain Neoplasms; Carbamazepine; Corpus Callosum; Epilepsy, Tonic-Clonic; Fructose; Humans; Lipoma; Magnetic Resonance Imaging; Male; Oxcarbazepine; Topiramate; Young Adult

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 investigate breakthrough mania secondary to a right temporal lobe neoplasm in a bipolar patient previously stabilized on sodium divalproex.. Right hemispheric brain tumors involving the orbitofrontal or basotemporal cortex are a rare cause of secondary mania. In such cases, early neurologic signs may be difficult to distinguish from bipolar symptoms. Breakthrough mania secondary to brain neoplasm in a bipolar patient stabilized on medication is an extremely rare phenomena which has not been previously reported.. The clinical course of a bipolar subject stabilized on valproate who developed mania secondary to a right temporal lobe astrocytoma is described. Serial brain magnetic resonance imaging (MRI), baseline electroencephalogram (EEG), and neuropsychiatric evaluations were used to examine the relationship between the patient's brain mass and behavioral disturbances.. Symptoms were those that accompanied prior episodes of mania. In addition, signs of temporal lobe dysfunction were evident including periods of detachment, déjà vu experiences, and olfactory hallucinations. In the context of mania, depersonalization was initially attributed to bipolar symptoms. Only several months later, when olfactory hallucinations and alterations in consciousness became evident, was a temporal lobe lesion suspected. Neuropsychiatric abnormalities responded to a combination of surgical intervention, radiation therapy, and topiramate, however the tumor was advanced and invasive at diagnosis resulting in a poor prognosis.. This case suggests that clinicians examining unexplained cases of breakthrough mania should be vigilant for early signs of temporal lobe dysfunction, which could aid in detecting treatable lesions.

Topics: Anticonvulsants; Antimanic Agents; Astrocytoma; Bipolar Disorder; Brain Neoplasms; Disease Progression; Electroencephalography; Female; Fructose; Hallucinations; Humans; Magnetic Resonance Imaging; Middle Aged; Temporal Lobe; Topiramate; Valproic Acid