topiramate and Brain-Injuries

For a retrospective observational investigation based on real clinical practice of relative efficacy of valpoic acid (VPA), carbamazepine (CBZ) and topiramate (TPM) we have selected 106 patients with age of seizure onset before 17 years with a undoubted diagnosis of symptomatic or cryptogenic occipital lobe epilepsy (OLE), who had received treatment according to ILAE recommendations, and observation time since the last treatment change was from 2 to 10 years. Patients suspicious for idiopathic epilepsies were excluded. The groups of patient receiving CBZ, VPA and TPM did not differ significantly in presenting unfavorable prognostic factors and dose regimes that allowed to conduct direct comparison of efficacy of the investigated drugs. Efficacy of VPA in children with OLE was higher compared with CBZ (69% vs 36%, p < 0.01) and TPM (69% vs 8%, p < 0.001). CBZ and TPM caused seizure aggravation more frequently than VPA (12% and 13% respectively vs 1%, p < 0.001). In case of presence of clinico-electroencephalografic and MRI signs of significant organic brain damage and in patients with seizure onset under 11 years TPM was not effective. In case of focal cortical dysphasia the efficacy of CBZ was lower than VPA (20% vs 63%, p < 0.05). In MRI-negative cases VPA was most effective (79% vs 44% for CBZ, p < 0.001 and 29% for TPM, p < 0.01). Efficacy of CBZ and TPM reduces proportionally the number of previously used antiepileptic drugs (AEDs), this tendency is noted also for VPA but as a second AED it was more effective than CBZ and TPM (56% vs 15%, p < 0.01 and 14%, p < 0.05, respectively); as a first AED VPA was also most effective (82% vs 37%, p < 0.001 for CBZ and 82% vs 33%, p < 0.01 for TPM). Adverse effects were more frequent during treatment with CBZ and TPM, than VPA (21% vs 6%, p < 0.001 and 17% vs 6%, p < 0.05).

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Brain Injuries; Carbamazepine; Child; Epilepsies, Partial; Epilepsy; Fructose; Humans; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Valproic Acid

Despite recent advances in our understanding of human traumatic brain injury (TBI) pathophysiology, we still need effective neuroprotective agents. The lack of rigorous drug pharmacokinetic studies in the "living" brain is an important cause of neuroprotection trials failure in human TBI research. In the past, several drugs have been labeled as inefficient, and even withdrawn from expensive trials, without knowing their actual penetration in the traumatized human brain. The injured brain is characterized by an increased diffusion distance, due to edema, and reduced blood flow that modulates drug transport across the blood-brain barrier (BBB). In the study reported in this paper, we used cerebral microdialysis to provide a safe and efficient tool for continuous in vivo evaluation of bioavailability and pharmacologic efficacy of topiramate, a glutamate release inhibitor. Topiramate crossed the BBB in neuroprotective concentrations, and showed a lowering effect on glutamate levels, thereby modifying the natural history of glutamate release after TBI. The use of cerebral microdialysis in phase II drug studies will allow the detection of the appropriate therapeutic window and dosage for the neuroprotective agent. This strategy represents a clear improvement compared to traditional clinical trial design, and will reduce the trial costs.

Topics: Blood-Brain Barrier; Brain Injuries; Fructose; Glutamic Acid; Humans; Microdialysis; Neuroprotective Agents; Time Factors; Topiramate

Topics: Adolescent; Adult; Aged; Anticonvulsants; Brain Injuries; Dose-Response Relationship, Drug; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Retrospective Studies; Time Factors; Topiramate; Treatment Outcome; Young Adult

Early treatment of epilepsy is warranted to avoid possible severe consequences. This study aimed to assess the value of treatment in a patient who developed epilepsy after major brain surgery.. Case description. A 51 years-old man had a history of putative petit mal seizures since adolescence and left frontotemporal lobectomy after a major traffic accident at age 17. He subsequently developed quickly generalizing partial complex seizures, associated with severe behavioural alterations and personality changes; the condition was left untreated. A further seizure-related loss of consciousness led to another traffic accident at age 47.. The patient was administered 200 mg/day topiramate, 600 mg/day quetiapine, 1000 mg/day valproate, 1200 mg/day gabapentin and 800 mg/day carbamazepine.. The instituted anti-epileptic treatment reduced seizure frequency and severity, but did not affect psychiatric symptomatology, which even worsened. An association between anti-epileptic drugs with mood stabilizing properties and an atypical anti-psychotic dramatically improved psychiatric symptoms, but did not prevent the patient from needing long-term healthcare.. Long-term untreated epilepsy may expose to accident proneness and further psychiatric deterioration. Early diagnosis and treatment of epilepsy may help in avoiding a potentially lethal vicious circle.

Topics: Accidents, Traffic; Aggression; Amines; Anterior Temporal Lobectomy; Anticonvulsants; Brain Injuries; Carbamazepine; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Disease Progression; Early Diagnosis; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Italy; Male; Middle Aged; Personality Disorders; Quetiapine Fumarate; Time Factors; Topiramate; Treatment Outcome; Valproic Acid

The effect of anticonvulsant drugs on posttraumatic convulsive reactions and the stability of the brain with respect to complete ischemia and hypoxia upon brain injury has been studied in animals with model contact craniocerebral trauma. It is established that lamotrigine, topiramate, and sodium valproate produce a strong effect on convulsive reactions, while magnesium sulfate and gabapentin produce a moderate action. The antiishemic and antihypoxic action of lamotrigine and sodium valproate is stronger than that of topiramate and gabapentin.

Topics: Amines; Animals; Animals, Outbred Strains; Anticonvulsants; Brain; Brain Injuries; Brain Ischemia; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Electric Stimulation; Fructose; Gabapentin; gamma-Aminobutyric Acid; Lamotrigine; Magnesium Sulfate; Mice; Rats; Seizures; Topiramate; Triazines; Valproic Acid

The aim of this study is to investigate the neuroprotective effects of the anticonvulsant topiramate in a new model of traumatic brain injury in rats. A new model of traumatic brain injury, based on the weight-drop technique, was developed for the purpose of this study. Seventy-five male Wistar rats weighing 320-470 g were studied. All rats were anesthetized, subsequently submitted to a round craniectomy in the left parietal region and a weight of 50 g was used for the production of a cortical contusion. In study I, 44 rats were randomized in three groups to receive either topiramate 40 mg/kg (n=13), topiramate 60 mg/kg (n=14), or water for injection (n=17) i.p. 30 min after the injury and every 12 h thereafter for 3 days. The rats were tested clinically 24 h, 72 h, 10 days and 20 days after the injury. On day 21 the animals were sacrificed and the brains were removed and prepared for histopathological analysis. In study II, 19 rats were randomized to receive either topiramate 60 mg/kg (n=10) or water for injection (n=9) i.p. 30 min after the injury and every 12 h (four doses in total). 48 h after the injury the animals were sacrificed and the brains were rapidly removed and analyzed for water content with the dry-wet weight technique. The animals that received topiramate performed significantly better in neurological tests compared to the animals that received vehicle ten (P<0.05) and 20 (P<0.001) days after the injury. There was no difference between the high and the low dose of the drug. Topiramate had no effect on the anatomic volume of the lesion. The animals that received topiramate had a tendency to present with less cerebral edema formation, but the difference was not statistically significant (P>0.05). These findings suggest that topiramate promotes neurological recovery in rats after traumatic brain injury without affecting the final size of the traumatic lesion and that it might play a role in the reduction of post-traumatic cerebral edema.

Topics: Animals; Brain Edema; Brain Injuries; Disease Models, Animal; Fructose; Functional Laterality; Male; Multivariate Analysis; Nervous System Diseases; Neurologic Examination; Neuroprotective Agents; Rats; Rats, Wistar; Recovery of Function; Time Factors; Topiramate

Nowhere is it more important to maintain peek mental functioning than in a combat zone. Conditions ranging from pain to head injury to post-traumatic stress disorder can cause impairments in neuropsychological function and place service members at risk. Medications can sometimes help alleviate these problems, but also have the risk of further slowing cognitive function or impairing reaction time. Standard methods of neuropsychological testing are often not available in a combat environment. New technologies are being advanced that can allow portable, computerized neuropsychological testing to be performed at almost any location. We present a case that demonstrates how the use of such handheld technology can assist a military physician in assessing the influence of medication on reaction time and in determining if and when a service member is ready to return to combat.

Topics: Brain Injuries; Cognition; Fructose; Headache; Humans; Iraq War, 2003-2011; Male; Mental Competency; Military Medicine; Military Personnel; Neuropsychological Tests; Physical Fitness; Stress Disorders, Post-Traumatic; Topiramate; Young Adult

Recent studies have shown that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. Besides its antiepileptic effects, topiramate exerts neuroprotective effects in animal models of stroke, hypoxia ischemia, excitotoxic insults, and status epilepticus. In the present study, we investigated the effects of topiramate against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+phosphate buffered saline treated group and hyperoxia+topiramate treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in plexiglas chambers in which the oxygen concentration was monitored twice daily from birth until postnatal day five. The hyperoxia+topiramate group received an intraperitoneal injection of topiramate at a dose of 80 mg/kg/day. At postnatal day 5, all animals were killed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that topiramate significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus. Topiramate may offer a therapeutic potential for neuroprotection under conditions of hyperoxic brain injury.

Topics: Analysis of Variance; Animals; Animals, Newborn; Brain Injuries; Cell Death; Disease Models, Animal; DNA; Enzyme-Linked Immunosorbent Assay; Fructose; Hippocampus; Histones; Hyperoxia; In Situ Nick-End Labeling; Neuroprotective Agents; Parietal Lobe; Rats; Rats, Wistar; Topiramate

Topics: Accidents; Benzodiazepines; Brain Injuries; Craniocerebral Trauma; Electroconvulsive Therapy; Fructose; Humans; Male; Memantine; Middle Aged; Pilot Projects; Pyridines; Topiramate; Valproic Acid; Zolpidem

Topics: Adult; Awards and Prizes; Brain Injuries; Case-Control Studies; Cohort Studies; Cyclosporine; Fructose; Glucose; Glutamic Acid; Humans; Lactic Acid; Microdialysis; Neuroprotective Agents; Oxygen Inhalation Therapy; Pyruvic Acid; Topiramate

Topiramate is an antiepileptic drug known to have effects on weight. In order to use this as a tool to treat eating disorders, it is useful to examine whether these effects can be predicted in certain patients.. To report the effects of topiramate, initiated for the treatment of epilepsy, on top of ongoing treatment, on eating patterns and weight of 17 patients with traumatic brain injury (TBI) with post-traumatic epilepsy and weight gain of various etiologies.. Patients were followed up according to their usual treatment plan. Topiramate was added on top of current and stable treatment. Dose was titrated based on the patients' neurological status. Patients were asked to report side effects. No other changes were made.. Of the 17 patients included, one patient dropped out. Six patients with binge eating disorder (BED) demonstrated the most pronounced effects, with marked attenuation of binges and normalizing body mass index. Less noticeable were the effects in patients with mood disorders. Topiramate was ineffective in patients whose overweight was a side effect of their medication. Side effects were rated as mild and included somnolence, paresthesias, mild cognitive disturbances and some gastrointestinal disturbances.. In this report of the actual effects of topiramate in a clinical setting on weight and eating habits of 17 patients with TBI and obesity of various etiologies, topiramate seemed to be a safe intervention. Topiramate appeared to be differentially effective, with particular effects on primary pathological eating patterns.

Topics: Adult; Anticonvulsants; Body Weight; Brain Injuries; Bulimia; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Feeding Behavior; Female; Fructose; Humans; Male; Middle Aged; Neuroprotective Agents; Obesity; Psychiatric Status Rating Scales; Psychotic Disorders; Topiramate

The efficacy of topiramate, a novel therapeutic agent approved for the treatment of seizure disorders, was evaluated in a model of traumatic brain injury (TBI). Adult male rats were anesthetized (sodium pentobarbital, 60 mg/kg, i.p.), subjected to lateral fluid percussion brain injury (n = 60) or sham injury (n = 47) and randomized to receive either topiramate or vehicle at 30 min (30 mg/kg, i.p.), and 8, 20 and 32 h postinjury (30 mg/kg, p.o.). In Study A, memory was evaluated using a Morris water maze at 48 h postinjury, after which brain tissue was evaluated for regional cerebral edema. In Study B, animals were evaluated for motor function at 48 h and 1, 2, 3, and 4 weeks postinjury using a composite neuroscore and the rotating pole test and for learning ability at 4 weeks. Brains were analyzed for hemispheric tissue loss and hippocampal CA3 cell loss. Topiramate had no effect on posttraumatic cerebral edema or histologic damage when compared to vehicle. At 48 h, topiramate treatment improved memory function in sham but not brain-injured animals, while at one month postinjury it impaired learning performance in brain-injured but not sham animals. Topiramate significantly improved composite neuroscores at 4 weeks postinjury and rotating pole performance at 1 and 4 weeks postinjury, suggesting a potentially beneficial effect on motor function following TBI.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain Edema; Brain Injuries; Fructose; Male; Maze Learning; Memory; Rats; Rats, Sprague-Dawley; Recovery of Function; Time Factors; Topiramate; Treatment Outcome