topiramate and Epilepsy--Complex-Partial

Anti-epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE.. This was a non-randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument.. Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05).. For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.

Topics: Adolescent; Adult; Anticonvulsants; Cognition Disorders; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Psychometrics; Taiwan; Topiramate; Young Adult

A 6-year-old boy with partial complex seizures developed recurrent episodes of hyperthermia 2 months after topiramate was introduced into his antiepilepsy drug regimen. Further investigation revealed that the febrile episodes were related to environmental temperature and physical activity. A pilocarpine iontophoresis sweat test showed that the amount of sweat produced by the child was 5% that of age-matched controls. Topiramate discontinuation resulted in the disappearance of febrile episodes and normalization of sweat quantity in repeat sweat testing. Based on this observation and the previous data on zonisamide and isolated case reports on topiramate-related hyperthermia and the effect on sweat production, topiramate was suspected of causing oligohydrosis. A pilot study was carried out involving 13 additional children and young adults (age range 1-37 years) receiving topiramate. All patients were directly questioned regarding symptoms of decreased sweating and heat intolerance, went through a pilocarpine iontophoresis sweat test, and were compared with 14 age-matched controls who went through the sweat test for unrelated reasons. Nine of the patients were found to have reduced sweat quantity on the pilocarpine iontophoresis sweat test (including index case) (mean 0.089 g/30 minutes, SD 0.082; age-matched control: mean 0.21 g/30 minutes, SD 0.06). Eight of them were children (below 16 years). However, only three patients revealed symptoms related to heat intolerance. Topiramate is most likely responsible for decreased sweat production as detected by a pilocarpine iontophoresis sweat test. The effect seems to be more significant in children than in adults. There is a discrepancy between test results and clinical symptoms. Interestingly, oligohydrosis was found to be a relatively common side effect of zonisamide. Both zonisamide and topiramate share a carbonic anhydrase inhibitor activity. The significance of oligohydrosis in hot climates should not be underestimated. Its extent, the role of sweat test prediction, and clinical significance during topiramate treatment should be further estimated.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Epilepsy, Complex Partial; Female; Fever; Fructose; Humans; Hypohidrosis; Infant; Iontophoresis; Male; Muscarinic Agonists; Pilocarpine; Pilot Projects; Topiramate

Hypohidrosis is an uncommon and reversible side effect of topiramate treatment, reported mainly in children. This report presents an adult patient with complex partial seizures who was treated with topiramate and developed hypohidrosis coupled with hyperthermia, related to high environmental temperature and physical exercise. Reduced sweat response was confirmed using the Neuropad test. Signs and symptoms ceased after drug discontinuation. During topiramate treatment, it is important to recognise this side effect, although the exact causal mechanism has not yet been clarified.

Topics: Adult; Anticonvulsants; Epilepsy, Complex Partial; Fever; Fructose; Humans; Hypohidrosis; Male; Topiramate

The aim of this observational study was to obtain information regarding efficacy and safety of add-on levetiracetam (LEV; n=32) in Japanese patients with refractory partial seizures in an everyday clinical setting, relative to control AEDs (n=30). This is the first study of LEV add-on therapy conducted in Japan since approval was made. The medical charts of patients were retrospectively reviewed. The efficacy variables were seizure freedom and ≥50% reduction in seizure frequency. A significantly higher response to LEV was demonstrated in patients with all seizure types at baseline, relative to control AEDs. In patients with a duration of epilepsy of at least 10 years, significant effects in response to LEV were demonstrated with regards to efficacy variables, relative to control AEDs, thus providing meaningful results. Only two patients (6.2%) discontinued LEV treatment due to worsening of seizures, but no discontinuation was reported due to adverse events. LEV as add-on therapy to other AEDs is a promising useful treatment option for patients with refractory partial seizures without notable effects on safety, indicating that this treatment regimen might be recommended for such patients.

Topics: Adult; Anticonvulsants; Benzodiazepines; Clobazam; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy, Complex Partial; Female; Fructose; Humans; Japan; Lamotrigine; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

Drug Rash (or Reaction) with Eosinophilia and Systemic Symptoms (DRESS) is a potentially life-threatening hypersensitivity reaction to drugs characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and involvement of internal organs. Initially coined in 1996, the term is used to refer to an idiosyncratic reaction to several drugs, the most common of which are carbamazepine, allopurinol, sulfasalazine, and phenobarbital. We report the first case of DRESS related to rufinamide in a ten year old boy with a history of a complex seizure disorder.

Topics: Anti-Inflammatory Agents; Anticonvulsants; Child; Drug Hypersensitivity Syndrome; Epilepsy, Complex Partial; Fructose; Humans; Levetiracetam; Male; Piracetam; Prednisone; Topiramate; Triazoles

Reversible erectile dysfunction due to Topiramate has been linked to the effect of this antiepileptic drug on reproductive hormones levels. We described two epileptic male patients which experienced erectile dysfunction during Topiramate treatment. Serum sexual hormones were tested during treatment and at several time intervals following drug discontinuation. Topiramate did not seem to affect plasma levels of total, free and bioavailable testosterone and sex hormone-binding globulin. Since Topiramate erectile dysfunctions could not be related to changes in reproductive hormones levels, a vasogenic mechanism must be considered.

Topics: Adult; Androgens; Anticonvulsants; Epilepsy, Complex Partial; Epilepsy, Temporal Lobe; Fructose; Gonadal Steroid Hormones; Humans; Impotence, Vasculogenic; Luteinizing Hormone; Magnetic Resonance Imaging; Male; Middle Aged; Penis; Regional Blood Flow; Sex Hormone-Binding Globulin; Testosterone; Topiramate

Approximately two-thirds of the patients with newly diagnosed partial epilepsy remained on their first antiepileptic drug (AED) for 2 years in clinical practice. We aimed to analyze retention on the first AED for 2 years in newly diagnosed cryptogenic partial epilepsy patients in clinical practice and whether the presence of epileptiform discharges on the initial EEG was a predictor of the failure of retention on the first AED.. For the purpose of this study, we retrospectively reviewed epilepsy database. On the Epilepsy Database, we found 495 newly diagnosed epilepsy patients who had been followed up for at least 2 years. Of these 495 newly diagnosed epilepsy patients, 172 patients had cryptogenic partial epilepsy. The outcome of this study was the retention rate for the first AED for 2 years. In addition, we analyzed the retention on first AED according to the presence or absence of epileptiform discharges on the initial EEG using Kaplan-Meier survival analysis.. Overall, retention rate on the first AED for 2 years was 51%. The main lesion of retention failure was a lack of tolerance. The presence of epileptiform discharges on the initial EEGs was significantly related to the failure of retention on the first AED (p=0.003).. In newly diagnosed cryptogenic partial epilepsy, overall retention on the first AED was not significantly different from that in newly diagnosed partial epilepsy. In clinical practice, epileptiform discharges on the initial EEG could predict the failure of retention on the first AED for 2 years.

Topics: Adolescent; Adult; Anticonvulsants; Brain; Carbamazepine; Electroencephalography; Epilepsy, Complex Partial; Female; Fructose; Humans; Kaplan-Meier Estimate; Lamotrigine; Male; Middle Aged; Phenytoin; Retrospective Studies; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Young Adult

Topics: Adult; Antipsychotic Agents; Carbamazepine; Electroencephalography; Epilepsy, Complex Partial; Female; Fructose; Humans; Psychotic Disorders; Telemetry; Topiramate; Videotape Recording

Topics: Adult; Anticonvulsants; Cerebral Cortex; Electroencephalography; Epilepsy, Complex Partial; Face; Female; Fructose; Hallucinations; Humans; Illusions; Levetiracetam; Magnetic Resonance Imaging; Piracetam; Reflex; Topiramate; Valproic Acid

To assess the relation between seizure control and brain homocarnosine and gamma-aminobutyric acid (GABA) levels of patients with complex partial seizures taking gabapentin (GBP) or topiramate (TPM) as adjunctive therapy.. In vivo measurements of GABA and homocarnosine were made of a 14-cc volume in the occipital cortex by using (1)H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Poor seizure control was defined as more recent seizures than the median for the two groups of patients studied.. Homocarnosine levels were higher in patients with better seizure control than in those with poor control. No differences were found in the intracellular GABA levels between the patients who responded to GBP or TPM compared with those who did not.. In the visual neocortex, which is remote from the presumed seizure-onset zone, higher homocarnosine levels were associated with better seizure control in the patients taking GBP or TPM as adjunctive therapy; elevated intracellular GABA levels appeared to offer no additional protection.

Topics: Adult; Amines; Anticonvulsants; Brain Chemistry; Carnosine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Epilepsy, Complex Partial; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neocortex; Topiramate; Treatment Outcome; Visual Cortex

Topiramate is an antiepileptic drug with a beneficial clinical effect on various seizure types. Topiramate does not seem to be associated with serious adverse effects and is also well tolerated in pediatric patients. Only few cases of hypohidrosis have been described. This report presents one young patient with complex partial seizures who was medicated with topiramate when she developed fatigue, headache, intermittent hyperthermia, inability to produce sweat secretion, and dryness of the skin. Reduced sweat response was determined using the Wescor Macroduct collection procedure. Topiramate was discontinued, and within 3 weeks a repeat sweat test was completely normal. At that time, clinical signs had also disappeared. Hypohidrosis is an uncommon and reversible side effect reported in association with topiramate therapy. It is rare in patients on monotherapy. Although a definite causal relationship still needs to be established, this side effect might be attributed to an autonomic dysfunction by inhibition of isoenzymes of carbonic anhydrase localized in human eccrine sweat glands.

Topics: Anticonvulsants; Child, Preschool; Epilepsy, Complex Partial; Female; Fructose; Humans; Hypohidrosis; Sweating; Topiramate

Topics: Anticonvulsants; Child; Epilepsy, Complex Partial; Fever; Fructose; Humans; Hypohidrosis; Male; Topiramate

Profound language regression developed in three children with epilepsy 4 to 28 weeks after beginning topiramate (TPM). TPM was administered as an adjunctive antiepileptic drug at doses of 2.5 to 6.0 mg/kg/day. Language functions recovered while TPM was being reduced in dose or stopped.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy, Complex Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Language Disorders; Speech Disorders; Topiramate

The objective of this study was to evaluate the interaction of the novel antiepileptic drug (AED), topiramate (TPM), with conventional AEDs against amygdala-kindled seizures in rats and pentylenetetrazol-induced convulsions in mice.. Experiments were performed on mice and fully kindled rats. In pentylenetetrazol test, the chemoconvulsant was used at its CD97 dose of 105 mg/kg, producing clonic seizures in 97% of mice. Adverse effects were evaluated with the chimney test and passive avoidance task. Plasma levels of AEDs were measured with immunofluorescence.. TPM at 20 mg/kg exerted a significant anticonvulsant effect as regards seizure and afterdischarge durations in amygdala-kindled seizures in rats, being ineffective at lower doses. Coadministration of TPM (10 mg/kg) with valproate (VPA; at a subtherapeutic dose of 50 mg/kg) resulted in essential reductions of seizure and afterdischarge durations. TPM (10 mg/kg) combined with carbamazepine (CBZ; at a subtherapeutic dose of 15 mg/kg) significantly increased afterdischarge threshold, simultaneously decreasing the remaining seizure parameters (duration or severity of seizures and afterdischarge duration). TPM (10 mg/kg) given with phenobarbital (PB; 15 mg/kg) markedly shortened seizure severity and seizure and afterdischarge durations. Combinations of TPM with diphenylhydantoin (PHT) were ineffective against kindled seizures in rats. TPM combined with VPA and PB did not alter their plasma levels, but its combination with CBZ resulted in an increased free plasma CBZ concentration. TPM (10 and 20 mg/kg) alone and its combinations with conventional AEDs affected neither motor coordination nor long-term memory, evaluated in the chimney and passive avoidance tests, respectively, in rats. In pentylenetetrazol-evoked convulsions in mice, TPM (175 and 200 mg/kg) showed anticonvulsant effects per se. Moreover, TPM (at its subtherapeutic dose of 150 mg/kg), significantly potentiated the anticonvulsant action of ethosuximide (ESM), but not that of VPA, PB, or clonazepam (CZP) against pentylenetetrazol-induced seizures. Either TPM alone (150 mg/kg) or its combination with ESM did not result in significant undesired effects.. The experimental data indicate that except for PHT, the combinations of TPM with conventional AEDs are beneficial against amygdala-kindled seizures in rats. In the pentylenetetrazol test, this novel AED potentiated only the protection offered by ESM.

Topics: Amygdala; Animals; Anticonvulsants; Convulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Complex Partial; Fructose; Kindling, Neurologic; Male; Mice; Pentylenetetrazole; Rats; Seizures; Topiramate

The aim of this study was to determine the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with topiramate (TPM). Classification, relation to TPM dosing, and outcome were evaluated to identify a patient profile at risk of developing PAEs.. We evaluated the data of the first consecutive and prospectively collected patients in therapy with TPM.. Follow-up information was available for 431 patients. PAEs occurred in 103 (23.9%) patients; M/F ratio, 55:48; mean age (+/-SD), 36.5 +/- 11.2. In 46 (10.7%) patients, an affective disorder developed; in 16 (3.7%), a psychotic disorder; in 24 (5.6%), aggressive behavior with or without irritability; in 17 (3.9%), other behavior abnormalities such as agitated behavior, anger/hostility behavior, or anxiety. High starting dose and rapid titration schedule were relevant for the development of PAEs. Family psychiatric history and family history of epilepsy, personal history of febrile convulsions, psychiatric history, and presence of tonic-atonic seizures were found to be significant risk factors. Low seizure frequency before starting TPM and TPM/lamotrigine coadministration had a protective effect for PAEs.. We found that PAEs associated with TPM were related to the titration schedule of the drug and that a unique patient profile is suggested by the clinical history.

Topics: Adult; Affective Symptoms; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy; Epilepsy, Complex Partial; Female; Fructose; Genetic Predisposition to Disease; Humans; Male; Mental Disorders; Middle Aged; Product Surveillance, Postmarketing; Prospective Studies; Psychoses, Substance-Induced; Risk Factors; Topiramate

Hypohidrosis during topiramate (TPM) treatment was recently reported in children. We describe an adult epilepsy patient who developed inability to sweat as well as heat intolerance while undergoing treatment with TPM.. To detect the site of the sweat block, patient underwent examination of sweat gland function, cardiovascular autonomic test, and body temperature rhythm determination.. During TPM treatment, cardiovascular autonomic function and circadian rhythm of body core temperature were normal, whereas thermoregulatory sweat test (TST) showed anhydrosis. This adverse drug effect was quickly resolved after drug discontinuation.. Because of normal cardiovascular autonomic function and central and peripheral thermoregulatory mechanisms, we hypothesize that hypohidrosis during TPM treatment could be due to a carbonic anhydrases (CA) block at the level of sweat gland.

Topics: Adult; Anticonvulsants; Body Temperature Regulation; Carbonic Anhydrase Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsies, Partial; Epilepsy, Complex Partial; Fructose; Heat Exhaustion; Humans; Hypohidrosis; Male; Sweating; Topiramate

Topics: Aged; Anticonvulsants; Drug Resistance; Electroencephalography; Epilepsy, Complex Partial; Female; Fructose; Humans; Nephrectomy; Postoperative Complications; Recurrence; Topiramate

Topics: Adult; Anticonvulsants; Bulimia; Comorbidity; Epilepsy, Complex Partial; Female; Fructose; Humans; Topiramate; Treatment Outcome

The short- and long-term pharmacodynamic effects of topiramate (TPM) on brain gammay-aminobutyric acid (GABA) metabolism were studied in patients with complex partial seizures.. In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14-cc volume in the occipital cortex using 1H spectroscopy with a 2.1-Tesla magnetic resonance spectrometer and an 8-cm surface coil. Fifteen patients (four men) were studied serially after the first, oral dose (100 mg) of TPM.. The first dose of TPM increased brain GABA within 1 h. Within 4 h, GABA was increased by 0.9 mM (95% CI, 0.7-1.1). Brain GABA remained elevated for > or =24 h. Pyrrolidinone and homocarnosine increased slowly during the first day. Daily TPM therapy (median, 300 mg; range, 200-500) increased GABA (0.3 mM; 95% CI, 0.1-0.5), homocarnosine (0.4 mM; 95% CI, 0.3-0.5), and pyrrolidinone (0.15 mM; 95% CI, 0.10-0.19), compared with levels before TPM. There was no dose response evident with daily TPM doses of 200-500 mg.. TPM promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the effects of increased homocarnosine and pyrrolidinone within 24 h.

Topics: Administration, Oral; Anticonvulsants; Brain Chemistry; Carnosine; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy, Complex Partial; Fructose; gamma-Aminobutyric Acid; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Occipital Lobe; Pyrrolidinones; Stimulation, Chemical; Topiramate

In order to select a new medication for a patient with epilepsy, it would be helpful to have an idea of which drug might have the greatest overall chance for success. Since epilepsy is a chronic disorder, the long-term effectiveness and tolerability of the medications are very important. Here, we compared gabapentin, lamotrigine, topiramate and vigabatrin using Kaplan-Meier survival analysis to see how long patients chose to stay on each drug and if they stopped, why they stopped. The results seem to suggest the type of responses to be expected in a hospital seizure clinic.

Topics: Acetates; Adult; Aged; Aged, 80 and over; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Epilepsy, Complex Partial; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Male; Medical Records; Middle Aged; Retrospective Studies; Survival Analysis; Topiramate; Treatment Outcome; Triazines; Vigabatrin

Topiramate is a novel antiepileptic drug that was licensed in Norway in 1997 as adjunctive treatment for patients with partial seizures. Metaanalysis of randomized controlled studies suggest that topiramate may be the most potent of the new antiepileptic drugs and have a favourable pharmacokinetic profile. At the National Center for Epilepsy we have used topiramate since 1990. We present our clinical experience with the drug.. We have, retrospectively, assessed 114 adult patients, mainly with intractable partial seizures, who received topiramate as add-on treatment. Average follow-up was 2.3 years.. Four patients (3.5%) became seizure free. The overall seizure frequency was reduced by > 50% in 56 patients (49%). Adverse effects were observed in 82 patients (72%); in 54 patients (47%) the drug had to be withdrawn due to unacceptable side effects and/or lack of clinical effect. The most frequent side effects were weight loss, fatigue, behavioural and cognitive problems.. Our results corroborate an impression of topiramate being an effective drug used as adjuntive therapy in patients with refractory epilepsy. Side effects can be a problem, but a low starting dose, a slow dose escalation, and topiramate used alone may reduce this problem.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Epilepsy, Complex Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Myoclonic Epilepsy, Juvenile; Retrospective Studies; Topiramate

The incidence of psychosis during clinical trials of topiramate was 0.8%, not significantly different from the rate for placebo or reported rates of psychosis in patients with refractory epilepsy. We observed psychotic symptoms in five patients soon after initiation of topiramate therapy. We performed a retrospective chart review of the first 80 patients who began on topiramate after approval for clinical use, between January and April 1997. Symptoms suggestive of psychosis, including hallucinations and delusions, were sought for analysis. Cognitive effects such as psychomotor slowing, confusion, and somnolence were not included. Five patients developed definite psychotic symptoms 2 to 46 days after beginning topiramate. Dosages at symptom onset were 50-400 mg/day. Symptoms included paranoid delusions in four patients and auditory hallucinations in three. Symptoms of psychosis and other psychiatric symptoms resolved quickly with discontinuation of topiramate in three patients, dose reduction from 300 to 200 mg/day in one and with inpatient treatment and neuroleptics in another. One patient had a history of auditory hallucinations, one of aggressive and suicidal thoughts, but three had no significant psychiatric history. Physicians should be aware of the possibility of psychotic symptoms, even in patients without a previous psychiatric history, when prescribing topiramate. Symptoms resolve quickly with discontinuation.

Topics: Adult; Anticonvulsants; Delusions; Dose-Response Relationship, Drug; Epilepsy, Complex Partial; Epilepsy, Post-Traumatic; Epilepsy, Tonic-Clonic; Female; Fructose; Hallucinations; Humans; Male; Middle Aged; Patient Care Team; Prognosis; Psychoses, Substance-Induced; Retrospective Studies; Topiramate

To study the effectiveness and safety of topiramate in clinical practice, for a group of patients with childhood onset epilepsy.. All patients treated with topiramate at the three study centers between November 1995 and December 31, 1997 were analyzed retrospectively, using a standardized study protocol. Data were gathered on demographic features, seizures response and medication related adverse events.. Eighty-seven patients were treated with topiramate. Over 90% seizure reduction was achieved in 8 (9%) patients, 50%-90% in 21 (24%), < 50% in 54 (62%) patients. Four patients (5%) had a deterioration in seizure control. Adverse events required topiramate discontinuation in 36 (41%). Of these 27 (31%) complained of unacceptable cognitive dulling. The rate of dose escalation and final dose in mg/kg were similar in those who remained on topiramate and those who were intolerant because of cognitive side effects.. Although topiramate resulted in > 50% seizure reduction in 29 (33%) of this group of patients with difficult epilepsy, its usefulness was limited by a high incidence of adverse effects. Adverse events prevented ongoing therapy for 36 (41%) and cognitive dulling resulted in topiramate discontinuation by 27 (31%) of the group.

Topics: Adolescent; Age of Onset; Anticonvulsants; Child; Child, Preschool; Epilepsies, Myoclonic; Epilepsy; Epilepsy, Absence; Epilepsy, Complex Partial; Epilepsy, Generalized; Fructose; Humans; Infant; Retrospective Studies; Topiramate