topiramate and Epilepsy--Temporal-Lobe

The amygdala, a temporal lobe structure that is part of the limbic system, has long been recognized for its central role in emotions and emotional behavior. Pathophysiological alterations in neuronal excitability in the amygdala are characteristic features of certain psychiatric illnesses, such as anxiety disorders and depressive disorders. Furthermore, neuronal excitability in the amygdala, and, in particular, excitability of the basolateral nucleus of the amygdala (BLA) plays a pivotal role in the pathogenesis and symptomatology of temporal lobe epilepsy. Here, we describe two recently discovered mechanisms regulating neuronal excitability in the BLA, by modulating GABAergic inhibitory transmission. One of these mechanisms involves the regulation of GABA release via kainate receptors containing the GluR5 subunit (GluR5KRs). In the rat BLA, GluR5KRs are present on both somatodendritic regions and presynaptic terminals of GABAergic interneurons, and regulate GABA release in an agonist concentration-dependent, bidirectional manner. The relevance of the GluR5KR function to epilepsy is suggested by the findings that GluR5KR agonists can induce epileptic activity, whereas GluR5KR antagonists can prevent it. Further support for an important role of GluR5KRs in epilepsy comes from the findings that antagonism of GluR5KRs is a primary mechanism underlying the antiepileptic properties of the anticonvulsant topiramate. Another mechanism regulating neuronal excitability in the BLA by modulating GABAergic synaptic transmission is the facilitation of GABA release via presynaptic alpha1A adrenergic receptors. This mechanism may significantly underlie the antiepileptic properties of norepinephrine. Notably, the alpha1A adrenoceptor-mediated facilitation of GABA release is severely impaired by stress. This stress-induced impairment in the noradrenergic facilitation of GABA release in the BLA may underlie the hyperexcitability of the amygdala in certain stress-related affective disorders, and may explain the stress-induced exacerbation of seizure activity in epileptic patients.

Topics: Adrenergic alpha-Agonists; Amygdala; Animals; Anticonvulsants; Anxiety Disorders; Depression; Dose-Response Relationship, Drug; Epilepsy, Temporal Lobe; Fructose; GABA Agonists; gamma-Aminobutyric Acid; Humans; Neurons; Norepinephrine; Rats; Receptors, Adrenergic, alpha-1; Receptors, Kainic Acid; Synaptic Transmission; Topiramate

To evaluate the efficacy and tolerability of topiramate (TPM) as monotherapy for patients with temporal lobe epileptic seizures based on an observational study.. We evaluated 41 patients (20 female, mean age 54+18 years) with temporal lobe epilepsy (TLE) referred to the Epilepsy Unit, University of Catanzaro, Italy. Patients received TPM as monotherapy directly or after having taken other antiepileptic drugs. Seizure frequency changes and adverse events were recorded. Follow-up was conducted for a period of at least two years after treatment.. Patients received TPM, 50-600 mg/day, de novo (n=29) or initially as add-on therapy before the switch (n=12). In total, 28 of 41 patients achieved seizure freedom, whereas 10 showed a ≥ 50% reduction of seizure frequency. Two patients did not respond well and one patient discontinued TPM due to adverse effects.. Our results confirm that TPM as either monotherapy or add-on therapy at doses of 50-600 mg/day effectively reduces seizure frequency in TLE. TPM is particular effective and very well tolerated in patients with mild TLE.

Topics: Adult; Age of Onset; Aged; Anticonvulsants; Drug Resistance; Electroencephalography; Epilepsy, Temporal Lobe; Female; Fever; Follow-Up Studies; Fructose; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Seizures; Topiramate

The specific effects of antiseizure medications (ASMs) on cognition are a rich field of study, with many ongoing questions. The aim of this study was to evaluate these effects in a homogeneous group of patients with epilepsy to guide clinicians to choose the most appropriate medications.. We retrospectively identified 287 refractory patients with medial temporal lobe epilepsy associated with hippocampal sclerosis. Scores measuring general cognition (global, verbal and performance IQ), working memory, episodic memory, executive functions, and language abilities were correlated with ASM type, number, dosage and generation (old vs. new). We also assessed non-modifiable factors affecting cognition, such as demographics and epilepsy-related factors.. Key parameters were total number of ASMs and specific medications, especially topiramate (TPM) and sodium valproate (VPA). Four cognitive profiles of the ASMs were identified: (i) drugs with an overall detrimental effect on cognition (TPM, VPA); (ii) drugs with negative effects on specific areas: verbal memory and language skills (carbamazepine), and language functions (zonisamide); (iii) drugs affecting a single function in a specific and limited area: visual denomination (oxcarbazepine, lacosamide); and (iv) drugs without documented cognitive side effects. Non-modifiable factors such as age at testing, age at seizure onset, and history of febrile seizures also influenced cognition and were notably influenced by total number of ASMs.. We conclude that ASMs significantly impact cognition. Key parameters were total number of ASMs and specific medications, especially TPM and VPA. These results should lead to a reduction in the number of drugs received and the avoidance of medications with unfavorable cognitive profiles.

Topics: Anticonvulsants; Cognition; Epilepsy; Epilepsy, Temporal Lobe; Fructose; Humans; Memory, Short-Term; Retrospective Studies; Topiramate

Epilepsy is a widespread neurological disorder frequently associated with a lot of comorbidities. The present study aimed to evaluate the effects of the antiseizure medication topiramate (TPM) on spontaneous motor seizures, the pathogenesis of comorbid mood and cognitive impairments, hippocampal neuronal loss, and oxidative stress and inflammation in a rat model of temporal lobe epilepsy (TLE). Vehicle/TPM treatment (80 mg/kg, p.o.) was administered 3 h after the pilocarpine (pilo)-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. The chronic TPM treatment caused side effects in naïve rats, including memory disturbance, anxiety, and depressive-like responses. However, the anticonvulsant effect of this drug, administered during epileptogenesis, was accompanied by beneficial activity against comorbid behavioral impairments. The drug treatment suppressed the SE-induced neuronal damage in limbic structures, including the dorsal (CA1 and CA2 subfield), the ventral (CA1, CA2 and CA3) hippocampus, the basolateral amygdala, and the piriform cortex, while was ineffective against the surge in the oxidative stress and inflammation. Our results suggest that neuroprotection is an essential mechanism of TPM against spontaneous generalized seizures and concomitant emotional and cognitive impairments.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Epilepsy, Temporal Lobe; Hippocampus; Inflammation; Neuroprotection; Pilocarpine; Rats; Rats, Wistar; Seizures; Status Epilepticus; Topiramate

Epilepsy is a complex network phenomenon that, as yet, cannot be prevented or cured. We recently proposed network-based approaches to prevent epileptogenesis. For proof of concept we combined two drugs (levetiracetam and topiramate) for which in silico analysis of drug-protein interaction networks indicated a synergistic effect on a large functional network of epilepsy-relevant proteins. Using the intrahippocampal kainate mouse model of temporal lobe epilepsy, the drug combination was administered during the latent period before onset of spontaneous recurrent seizures (SRS). When SRS were periodically recorded by video-EEG monitoring after termination of treatment, a significant decrease in incidence and frequency of SRS was determined, indicating antiepileptogenic efficacy. Such efficacy was not observed following single drug treatment. Furthermore, a combination of levetiracetam and phenobarbital, for which in silico analysis of drug-protein interaction networks did not indicate any significant drug-drug interaction, was not effective to modify development of epilepsy. Surprisingly, the promising antiepileptogenic effect of the levetiracetam/topiramate combination was obtained in the absence of any significant neuroprotective or anti-inflammatory effects as indicated by multimodal brain imaging and histopathology. High throughput RNA-sequencing (RNA-seq) of the ipsilateral hippocampus of mice treated with the levetiracetam/topiramate combination showed that several genes that have been linked previously to epileptogenesis, were significantly differentially expressed, providing interesting entry points for future mechanistic studies. Overall, we have discovered a novel combination treatment with promise for prevention of epilepsy.

Topics: Animals; Anticonvulsants; Brain; Drug Therapy, Combination; Epilepsy, Temporal Lobe; Levetiracetam; Male; Mice; Proof of Concept Study; Protein Interaction Mapping; Topiramate; Transcriptome

We report the case of a 25-year-old woman who developed temporal lobe epilepsy associated with systemic lupus erythematosus (SLE). Serum and cerebrospinal fluid samples showed high titers of anti-ribosomal P (anti-P) antibodies with negative anti-NMDAR antibodies. She was receiving prednisone and azathioprine, with normalization of SLE serum markers, but without changes in titers of anti-P antibodies. No seizure control was achieved using valproic acid, levetiracetam and lamotrigine. However, she had a selective response to topiramate, an AMPAR blocker, maintained during 6 years of follow-up. We discuss the pathophysiology of this autoimmune epilepsy associated with high titer anti-P antibodies.

Topics: Adult; Anticonvulsants; Autoantibodies; Autoantigens; Drug Resistant Epilepsy; Epilepsy, Temporal Lobe; Female; Humans; Lupus Vasculitis, Central Nervous System; Ribosomal Proteins; Topiramate

Mammalian central neurons regulate their intracellular pH (pHi) strongly and even slight pHi-fluctuations can influence inter-/intracellular signaling, synaptic plasticity and excitability.. For the first time, we investigated topiramate´s (TPM) influence on pHi-behavior of human central neurons representing a promising target for anticonvulsants and antimigraine drugs.. In slice-preparations of tissue resected from the middle temporal gyrus of five adults with intractable temporal lobe epilepsy, BCECF-AM-loaded neocortical pyramidal-cells were investigated by fluorometry. The pHi-regulation was estimated by using the recovery-slope from intracellular acidification after an Ammonium-Prepulse (APP).. Among 17 pyramidal neurons exposed to 50 μM TPM, seven (41.24%) responded with an altered resting-pHi (7.02±0.12), i.e., acidification of 0.01-0.03 pH-units. The more alkaline the neurons, the greater the TPM-related acidifications (r=0.7, p=0.001, n=17). The recovery from APPacidification was significantly slowed under TPM (p<0.001, n=5). Further experiments using nominal bicarbonate-free (n=2) and chloride-free (n=2) conditions pointed to a modulation of the HCO3 -- driven pHi-regulation by TPM, favoring a stimulation of the passive Cl-/HCO3 --antiporter (CBT) - an acid-loader predominantly in more alkaline neurons.. TPM modulated the bicarbonate-driven pHi-regulation, just as previously described in adult guinea-pig hippocampal neurons. We discussed the significance of the resulting subtle acidifications for beneficial antiepileptic, antimigraine and neuroprotective effects as well as for unwanted cognitive deficits.

Topics: Acid-Base Equilibrium; Adult; Anticonvulsants; Bicarbonates; Chloride-Bicarbonate Antiporters; Epilepsy, Temporal Lobe; Female; Fluorometry; Hippocampus; Humans; Hydrogen-Ion Concentration; Male; Malformations of Cortical Development; Neocortex; Neurons; Pyramidal Cells; Sclerosis; Temporal Lobe; Topiramate; Young Adult

Topics: Anticonvulsants; Electroencephalography; Epilepsy, Temporal Lobe; Humans; Hyperhidrosis; Male; Middle Aged; Topiramate

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS.. Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS.. Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia.. Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS.

Topics: Adolescent; Adult; Aged; Amines; Anticonvulsants; Ataxia; Benzodiazepines; Carbamazepine; Clobazam; Cyclohexanecarboxylic Acids; Databases, Factual; Diplopia; Dizziness; Epilepsy, Temporal Lobe; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Hippocampus; Humans; Lamotrigine; Lethargy; Male; Middle Aged; Oxcarbazepine; Pregabalin; Retrospective Studies; Sclerosis; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Vertigo; Vigabatrin; Vision Disorders; Young Adult

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.

Topics: Adult; Aged; Anticonvulsants; Brain-Derived Neurotrophic Factor; DNA Methylation; Epilepsy, Temporal Lobe; Exons; Female; Fructose; Hippocampus; Humans; Male; Middle Aged; Promoter Regions, Genetic; RNA, Messenger; Sertraline; Topiramate; Young Adult

Topiramate (TPM) is a newer antiepileptic drug with high efficacy in treating various neurological disorders, especially epilepsy and migraine. The adverse effects of TPM therapy are mainly central nervous system-related somnolence and dizziness. There are rare reports about the role of TPM on sexual effects, but with inconsistent results. In this report, we describe a 31-year-old man who developed erectile dysfunction after several months of TPM use. Complete urological and sexual psychiatric evaluations were done. There was lack of an identifiable organic basis and psychiatric pathology in this patient. The erectile dysfunction improved only after the termination of TPM, documenting the temporal relationship. We reviewed and discussed the clinical aspect of TPM use in erectile dysfunction. This case and the rare cases of erectile dysfunction in TPM use reported in the literature show that TPM is worth to be paid attention to whenever it is prescribed in a wide range of neurological disorders.

Topics: Adult; Anticonvulsants; Epilepsy, Temporal Lobe; Erectile Dysfunction; Fructose; Humans; Male; Topiramate

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

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative

Topics: Adult; Anticonvulsants; Brain; Brain Mapping; Cognition; Epilepsy, Temporal Lobe; Female; Fructose; Functional Laterality; Humans; Image Processing, Computer-Assisted; Language Disorders; Magnetic Resonance Imaging; Male; Middle Aged; Names; Neuropsychological Tests; Oxygen; Topiramate; Young Adult

Lamotrigine (LTG) and topiramate (TPM), two of the most commonly used new-generation antiepileptic drugs (AEDs), have been shown to produce no adverse and impaired cognitive effects in patients with epilepsy, respectively. As seizure-induced neurogenesis might contribute to cognitive deficits that are associated with status epilepticus (SE), we examined whether these two drugs produce differential effects on seizure-induced neurogenesis in the hippocampus of adult rats. Lithium pilocarpine model was used to mimic human temporal-lobe epilepsy. Five hours after SE, LTG and TPM were administered intragastrically twice daily throughout the entire length of the experiment with total daily dose of 20 and 80 mg/kg, respectively. The hippocampal neurogenesis was examined using 5-bromodeoxyuridine and doublecortin immunohistochemistry. Both LTG and TPM treatments significantly inhibited seizure-induced proliferation of neural progenitors in the hippocampus, but did not affect the neuronal differentiation of newborn cells. Long-term treatment with both AEDs decreased the number of spontaneous recurrent seizures after SE and alleviated chronic seizure-induced neuronal injury in the dentate hilus. Eventually, TPM significantly increased the number of newborn neurons in the dentate granular cell layer after seizures likely by promoting the survival of newborn neurons. In contrast, LTG treatment significantly reduced the number of ectopic hilar newborn neurons after seizures. Neither of them prevented the formation of hilar basal dendrites of newborn neurons in the epileptic hippocampus. These results indicate that TPM but not LTG promotes aberrant neuron regeneration in the hippocampus after SE, which might be partially related to their differential effects on cognitive function.

Topics: Adult Stem Cells; Animals; Anticonvulsants; Cell Proliferation; Cell Survival; Chronic Disease; Dendrites; Dentate Gyrus; Disease Models, Animal; Doublecortin Protein; Epilepsy, Temporal Lobe; Fructose; Hippocampus; Lamotrigine; Male; Neurogenesis; Neurons; Rats; Rats, Sprague-Dawley; Seizures; Topiramate; Triazines

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 205 patient with age of seizure onset before 16 years with a undoubted diagnosis of medial temporal lobe epilepsy, who had received treatment according to ILAE recommendations, and observation time since the last treatment change was from 2 to 5 years. The groups of patient receiving CBZ, VPA small i, Cyrillic 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 medial temporal lobe epilepsy was higher compared with CBZ (79% vs 61%; p< or =0,05) and TPM (79% vs 53%; p< or =0.001). CBZ caused seizure aggravation more frequently than VPA (10% vs 1%; p< or =0,001). In case of presence of clinico-electroencephalografic signs of significant organic brain damage and in patient with seizure onset before age of 1 year CBZ was not effective while TPM showed efficacy of 20%, (p< or =0,05) and VPA was the most effective drug in this case (50%; p< or =0,001). In case of focal cortical dysphasia or the states after periventricular leucomalacia the efficacy of CBZ was lower than VPA (0% for CBZ vs 89% for VPA - p< or =0,01 and 40% for CBZ vs 77% for VPA - p< or =0,05, respectively) and TPM (0% for CBZ vs 100% for TPM - p< or =0,01 and 40% for CBZ vs 100% for TPM - p< or =0,01, respectively). In MRI-negative cases VPA was most effective (90% vs 53% for CBZ; p< or =0,001 and 67% for TPM; p< or =0,05). Efficacy CBZ reduces proportionally the number of previously used antiepileptic drugs (AEDs) (52% as a first AED vs 17% as a second AED; p< or =0,01), this tendency is noted also for TPM but in less extend (80% vs 46%, respectively p< or =0,05), but not for VPA (77% vs 75%; p>0,05, respectively). Adverse effects were more frequent during treatment with CBZ, than VPA (19% vs 5%; p< or =0,001) and TPM (19% vs 9%; p< or =0,05).

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy, Temporal Lobe; Female; Fructose; Humans; Infant; Male; Retrospective Studies; Topiramate; Treatment Outcome; Valproic Acid

Wicket spikes (WS) are a normal variant EEG pattern that sometimes can be mistaken for epileptiform activity. We present a patient with WS and idiopathic generalized epilepsy who had been wrongly diagnosed with focal epilepsy, which leads to the prescription of carbamazepine with severe aggravation of generalized tonic-clonic seizures. She was referred for presurgical assessment of refractory focal epilepsy but long-term video-EEG showed sharp theta waves over the temporal regions during awakening, with a typical aspect of WS during drowsiness, nREM sleep stages I-II, and rapid eye movements (REM) sleep. There were a few generalized spike-waves during sleep but interictal changes were increased in frequency at awakening with bursts of fast-generalized spike-waves. Carbamazepine was progressively withdrawn and the patient was progressively switched to zonisamide. The patient no longer complained of generalized tonic-clonic seizures. At one year follow-up, this patient receives zonisamide with valproate. She has remained seizure-free.

Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Clobazam; Clonazepam; Diagnostic Errors; Drug Therapy, Combination; Electroencephalography; Epilepsy, Temporal Lobe; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Isoxazoles; Middle Aged; Remission Induction; Sleep Stages; Temporal Lobe; Theta Rhythm; Topiramate; Valproic Acid; Zonisamide

Anticonvulsant and psychotropic effects of "Topamax capsules"(TC) were compared to a traditional form of topiramate (TFT) and some other anticonvulsant drugs (ACD). Thirty-six patients (12 men and 24 women) with partial temporary epilepsy were examined. Sixteen patients received TFT in tablets and 20 patients received ACD before the beginning of the study. Drug effect was assessed by frequency of seizures and some neuropsychiatric parameters. The results revealed that TC was comparable to TFT and ACD in the reduction of seizures of any semiotics. After 3 months of therapy, total MMSE scores increased from 27 to 28. There were less perseverant errors and more right responses in the WCST. Verbal fluency and memory measured with Sunderland test improved as well. TC led to decreased latencies of negative responses in the WCST and increased verbal fluency compared to TFT. Patients who received TFT prior to TC did fewer errors in the WCST than patients who received ACD prior to TC. Verbal fluency improved compared to patients who received other ACD. At the same time, a somewhat increase of paranoid signs on the scale SCL-90 was noted in the group treated with topiramate only. It has been concluded that TC has an activating effect on frontal brain areas.

Topics: Administration, Oral; Adult; Anticonvulsants; Capsules; Dose-Response Relationship, Drug; Epilepsy, Temporal Lobe; Female; Follow-Up Studies; Fructose; Humans; Male; Psychometrics; Topiramate; Treatment Outcome

To study a character of topiramate (TPM) effect on psychopathological and neurocognitive processes in patients with temporal partial epilepsy, 83 patients (33 men and 50 women, mean age 29.1 +/- 10.6 years) were examined. Fifty-three patients were diagnosed with temporal cryptogenic epilepsy and 20 with temporal symptomatic epilepsy. Thirty-three patients received TPM (124 +/- 35.6 mg daily), 26--carbamazepine (819 +/- 274.2 mg daily), 15--phenobarbital (154.6 +/- 95.1 mg daily) and 11 patients received no therapy. The statistically significant difference between the groups treated with TPM and phenobarbital were found only for cognitive traits (total MMT scores, total scores on the executive functions scale, latencies of positive and negative answers in WCST, verbal fluency). TPM was more effective than phenobarbital for all traits, with the exception of verbal fluency. The comparison of patients by some parameters before and during the treatment with TPM revealed the favorable effect of the drug in the reduction of obsessive symptoms, aggressiveness and social isolation on the SCL-90 as well as higher scores on the executive functions scale and the lower latency of positive answer in WCST. The monotherapy with TPM leads to the improvement of executive functions, reduction of aggressive and obsessive symptoms that may be explained by the improvement of prefrontal brain function in epilepsy.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Cognition; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Temporal Lobe; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Psychometrics; Topiramate; Treatment Outcome; Young Adult

A 48-year-old woman with temporal lobe epilepsy and no prior history of psychiatric illness was started on topiramate (TPM). The dose was titrated up to 150 mg twice daily over 14 weeks and led to a significant reduction in seizure frequency. Upon reaching this dose, she developed intense pruritus and the firm belief that her skin was infected by parasites. She was diagnosed with delusional parasitosis (DP). Consequently, her TPM was weaned off and her DP settled completely without the use of antipsychotic medication. DP is characterized by the unshakeable conviction that small organisms infest the body despite the absence of confirmatory medical evidence. DP can occur in a wide variety of organic and psychiatric disorders or as an isolated delusional disorder. Rarely DP can be drug-induced. While psychiatric symptoms are a well recognized side-effect of TPM, this is, to our knowledge, the first reported case of TPM-induced DP.

Topics: Anticonvulsants; Delusions; Ectoparasitic Infestations; Epilepsy, Temporal Lobe; Female; Fructose; Humans; Middle Aged; Topiramate

Turner's syndrome (TS), resulting from deletion of one X chromosome in women, is associated with cerebral development abnormalities, particularly in the temporal lobes. Symptomatic epilepsy is described only in cases with extensive malformations. Here, we report the first case of bilateral temporal epilepsy without macroscopic cerebral malformation in a woman with TS mosaicism. Bitemporal dysfunction was confirmed by the ictal and interictal EEG, PET, MR-spectroscopy and the neuropsychological examination, other causes than TS mosaicism were excluded. In rare cases, TS mosaicism may underlie non-lesional temporal lobe epilepsy, probably in relation to microanatomic structural and functional cerebral abnormalities. Further studies are needed to determine the frequency of this association.

Topics: Adult; Anticonvulsants; Drug Resistance; Electroencephalography; Epilepsy, Temporal Lobe; Female; Fructose; Humans; Magnetic Resonance Spectroscopy; Mosaicism; Positron-Emission Tomography; Topiramate; Turner Syndrome

Kleptomania, defined in the American Psychiatric Association's Diagnostic and Statistical Manua of Mental Disorders, Text Revision: DSM-IV-TR, as the inability to resist the impulse to steal objects that are not needed for personal use or for their monetary value, may reflect a form of obsessive-compulsive spectrum disorder and/or affective spectrum disorder. We report on a patient who developed kleptomania and left temporal lobe epilepsy around the same time; both disorders were completely resolved in this patient with topiramate.

Topics: Adult; Anticonvulsants; Disruptive, Impulse Control, and Conduct Disorders; Epilepsy, Temporal Lobe; Female; Fructose; Humans; Topiramate

To try to identify the critical structures during epileptogenesis, we used the lithium-pilocarpine model that reproduces most clinical and neuropathological features of temporal lobe epilepsy (TLE). We used imaging techniques as well as a disease modifying approach and pharmacological strategy. With [14C]-2-deoxyglucose autoradiography, we assessed changes in cerebral glucose utilization. T2-weighted magnetic resonance imaging (MRI, 4.7 T) allowed follow-up of structures involved in epileptogenesis. A potential disease-modifying effect was studied using preconditioning with brief seizures (amygdala kindling, maximal electroshocks) and pharmacological strategies including vigabatrin (250 mg/kg), caffeine (0.3 g/L in drinking water), topiramate (10-60 mg/kg), pregabalin (50 mg/kg followed by 10 mg/kg), or RWJ-333369 (10-120 mg/kg). In adult and PN21 rats that became epileptic, entorhinal, and piriform cortices were the initial structures exhibiting significant signal changes on MRI scans, from 6 h after status epilepticus (SE) onset, reflecting neuronal death. In PN21 rats that did not become epileptic, no signal occurred in parahippocampal cortices. In hippocampus, MRI signal change appeared 36-48 h after SE, and progressively worsened to sclerosis. During the latent and chronic phases, the metabolic level in the hilus of adult and PN21 epileptic rats was normal although neuronal loss reached 60-75%. Protection limited to CA1 and/or CA3 (caffeine, topiramate, vigabatrin, amygdala kindling) did not affect the latency to spontaneous seizures. Protection limited to the entorhinal and piriform cortices (pregabalin) delayed epileptogenesis. The combined protection of Ammon's horn and parahippocampal cortices (RWJ-333369) prolonged the latency before the onset of seizures in a dose-dependent manner or, in some cases, prevented the epilepsy. The entorhinal and piriform cortices are critically involved in the early phase of the epileptogenesis while the hilus may initiate and/or maintain epileptic seizures. Pharmacological protection of the basal cortices is necessary for a beneficial disease-modifying effect but this must be combined with protection of the hippocampus to prevent epileptogenesis in this model of TLE.

Topics: Animals; Animals, Newborn; Anticonvulsants; Autoradiography; Cell Count; Cerebral Cortex; Deoxyglucose; Disease Models, Animal; Electroencephalography; Electroshock; Entorhinal Cortex; Epilepsy, Temporal Lobe; Fructose; Glucose; Hippocampus; Kindling, Neurologic; Lithium Chloride; Magnetic Resonance Imaging; Olfactory Pathways; Pilocarpine; Rats; Rats, Sprague-Dawley; Status Epilepticus; Topiramate; Vigabatrin

Overexpression of the multiple drug resistance gene 1 (MDR1) was quantified in brain tissue from Coriaria lactone (CL)-kindled Sprague-Dawley (SD) rats after treatment with lamotrigine (LTG) or topiramate (TPM) and compared with that found in rats treated with carbamazepine (CBZ) and valproate (VPA).. Twenty-five CL-kindled SD rats were randomized into five groups (n = 5 for each group) to receive once-daily feeding of CBZ, VPA, TPM, and LTG as the monotherapy equivalent of maximum human adult dosage, or normal saline (NS control) for 1 month. The expression of P-gp in brain tissues of all rats was quantified by using an image analysis and measuring system (Image Pro-plus 4.0). Mean area and mean integrated optical density (mean IOD) of P-gp expression were calculated. In addition, the changes in seizure severity were analyzed via video-camera monitoring.. A significant decrease in the number and duration of seizures with antiepileptic drug (AED) treatment was observed in the TPM and LTG groups. The mean area and mean IOD of P-gp expression were highest in the CBZ group and next highest in the VPA group; much lower values were measured in the TPM and LTG groups, and the lowest in the NS control group (p < 0.05).. TPM and LTG significantly inhibited seizures in this CL model. The expression of P-gp was not significantly increased by TPM or LTG treatment in this study.

Topics: Animals; Anticonvulsants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Brain; Carbamazepine; Disease Models, Animal; Drug Resistance; Epilepsy, Temporal Lobe; Fructose; Gene Expression; Genes, MDR; Humans; Immunohistochemistry; Kindling, Neurologic; Lactones; Lamotrigine; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Topiramate; Triazines; Valproic Acid

Lithium-pilocarpine induces status epilepticus (SE), leading to extensive damage and spontaneous recurrent seizures (SRS). Neuroprotective and antiepileptogenic effects of topiramate (TPM) associated with diazepam (DZP) were investigated in this model. SE was induced by LiCl and pilocarpine. TPM (10, 30 or 60 mg/kg) was injected at the onset of SE and 10h later and DZP (2.5 and 1.25mg/kg) at 2 and 10h after SE. TPM treatment was continued twice daily for 6 days. Other rats received two injections of DZP on the day of SE. Cell counting was performed on thionine-stained sections 14 days after SE and after 2 months of epilepsy. Occurrence and frequency of SRS were video-recorded. The MRI T2-weighted signal was quantified in hippocampus and ventral cortices. DZP-TPM treatment induced partial neuroprotection in CA1 and hilus, and tended to increase the percentage of rats with protected neurons in layer III/IV of the ventral entorhinal cortex. The latency to and frequency of SRS were not modified by DZP-TPM. T2-weighted signal was decreased in hippocampus 3 days after SE at all TPM doses and in ventral hippocampus after epilepsy onset. In conclusion, although DZP-TPM treatment was able to partially protect two areas critical for epileptogenesis, the hippocampus and ventral entorhinal cortex, it was not sufficient to prevent epileptogenesis.

Topics: Animals; Anticonvulsants; Diazepam; Disease Models, Animal; Drug Therapy, Combination; Electroencephalography; Epilepsy, Temporal Lobe; Fructose; Hippocampus; Lithium; Magnetic Resonance Imaging; Male; Pilocarpine; Rats; Rats, Sprague-Dawley; Status Epilepticus; Topiramate

Topics: Adult; Anticonvulsants; Epilepsy; Epilepsy, Frontal Lobe; Epilepsy, Temporal Lobe; Erectile Dysfunction; Fructose; Humans; Male; Topiramate

We evaluated the effects of topiramate (TPM) on memory function in the intracarotid amobarbital (Wada) test in nine patients with mesial temporal lobe epilepsy (MTLE) whose antiepileptic drugs (AEDs) included TPM and compared their scores with those of 16 patients with MTLE on AEDs not including TPM. Sodium amobarbital was injected first into the hemisphere ipsilateral to the seizure focus and then into a contralateral site, and the patients were tested for naming and memorization. There was no statistical difference in percentage memory scores between the two patient groups following the contralateral injection. After the ipsilateral injection, however, TPM patients had significantly lower percentage memory scores compared with non-TPM patients (P < 0.02). We conclude that a possible adverse effect of TPM on memory performance should be considered when evaluating the Wada test memory scores of patients on TPM therapy.

Topics: Adolescent; Adult; Amobarbital; Anterior Temporal Lobectomy; Anticonvulsants; Dominance, Cerebral; Drug Therapy, Combination; Epilepsy, Temporal Lobe; Female; Fructose; Humans; Injections, Intra-Arterial; Male; Mental Recall; Middle Aged; Neuropsychological Tests; Psychometrics; Recognition, Psychology; Retention, Psychology; Topiramate; Verbal Learning; Wechsler Scales

To clarify the role of hippocampal sclerosis (HS) in developing psychiatric and cognitive adverse events during therapy with topiramate (TPM) in patients with temporal lobe epilepsy (TLE).. We analyzed the data of 70 patients with TLE and HS and 128 patients with cryptogenic TLE matched for age, sex, starting dose, and titration schedule of TPM. They were selected from the first consecutive 431 patients started on TPM between 1995 and 1999.. Patients with HS were more likely to develop cognitive adverse events (CAEs; p = 0.002) and depression (p = 0.018) and to be receiving a polytherapy regimen (p = 0.007). However, regression analysis demonstrated that only HS was a predictive factor for the occurrence of CAEs (OR = 2.4; p < 0.001) and depression (OR = 2.3; p = 0.02).. Patients with TLE and HS were more prone to develop CAEs and depression than were patients with cryptogenic TLE, during TPM therapy, despite the same titration schedule. The presence of HS and not duration of epilepsy or polytherapy regimen represented the main risk factor.

Topics: Adult; Anticonvulsants; Cognition Disorders; Depressive Disorder; Drug Therapy, Combination; Epilepsy, Temporal Lobe; Female; Fructose; Hippocampus; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Sclerosis; Topiramate

Topics: Anticonvulsants; Bipolar Disorder; Epilepsy, Temporal Lobe; Female; Fructose; Humans; Middle Aged; Topiramate

Topics: Adult; Anticonvulsants; Bipolar Disorder; Epilepsy, Temporal Lobe; Fructose; Humans; Male; Topiramate

We measured the intrinsic optical signals (IOSs) generated by rat hippocampus-entorhinal cortex (EC) slices in response to single shock electrical stimuli delivered in the EC deep layers during application of the convulsant drug 4-aminopyridine (50 microM). With field potential recordings the stimulus-induced responses had duration = 35 +/- 6.3 s mean +/- SEM, n = 7 slices) and characteristics resembling electrographic seizures. IOS changes reflecting an increase in light transmittance occurred in the EC and hippocampus following similar stimuli (n = 45). IOSs increased progressively to reach peak values 20-30 s after the stimulus and returned slowly to prestimulus values within 100 s, thus outlasting the field potential discharge. IOS changes initiated in the medial EC, near to the stimulation site, and spread to the lateral EC, the dentate, and the CA3/CA1 areas. IOS spread from EC to hippocampus was not seen after perforant path cut (n = 5). Moreover, field potential and IOS responses were markedly decreased by excitatory amino acid receptor antagonists (n = 12). The antiepileptic drugs topiramate (10-100 microM, n = 16) or lamotrigine (100-400 microM, n = 12) reduced the IOS changes in the EC and their spread to distant areas. These effects were reversible and dose-dependent (IC50 = 48 microM and 210 microM for topiramate and lamotrigine, respectively). Thus, in 4AP-treated hippocampus-EC slices, IOS changes accompany and outlast the field potential epileptiform responses, depend on glutamatergic transmission and are characterized by temporal and spatial distributions consistent with propagation through established anatomical pathways. We also propose that IOSs may represent a reliable tool for screening the effects of neuroactive compounds such as antiepileptic drugs.

Topics: 4-Aminopyridine; Action Potentials; Animals; Anticonvulsants; Axotomy; Electric Stimulation; Electroencephalography; Electrophysiology; Entorhinal Cortex; Epilepsy, Temporal Lobe; Excitatory Amino Acid Antagonists; Fructose; GABA Antagonists; Hippocampus; Lamotrigine; Neurons; Optics and Photonics; Organ Culture Techniques; Perforant Pathway; Potassium Channel Blockers; Rats; Rats, Wistar; Reaction Time; Seizures; Signal Processing, Computer-Assisted; Synaptic Transmission; Topiramate; Triazines

A 46-year-old man experienced intractable seizures since childhood. Due to lack of response to antiepilepsy drugs (AEDs), he underwent a surgical evaluation that was consistent with seizure onset in the left medial temporal lobe. While on topiramate and carbamazepine, his preoperative neuropsychological scores and sodium amytal (Wada) scores were low and may have excluded him from surgery. Repeat testing on lamotrigine and carbamazepine showed improvement in his scores, allowing him to undergo surgery. Physicians must therefore be cautious in evaluating such test scores while a patient is on topiramate.

Topics: Amobarbital; Anticonvulsants; Carbamazepine; Carotid Artery, Internal; Drug Therapy, Combination; Epilepsy, Temporal Lobe; Fructose; Functional Laterality; Humans; Injections, Intra-Arterial; Lamotrigine; Male; Memory Disorders; Neuropsychological Tests; Topiramate; Triazines

Topiramate (TPM) is a novel antiepileptic medication (AED) with at least three mechanisms of action. A possible fourth mechanism, that of a carbonic anhydrase inhibitor, also may contribute to its antiepileptic properties. We report a patient with intractable epilepsy and normal renal function who developed a normal anion gap metabolic acidosis, which worsened during elective surgery for temporal lobectomy. We believe this side effect of TPM can become clinically significant during surgery, concomitant use of another carbonic anhydrase inhibitor, and potentially with the ketogenic diet.

Topics: Acidosis; Anticonvulsants; Carbonic Anhydrase Inhibitors; Epilepsy; Epilepsy, Temporal Lobe; Fructose; Humans; Male; Middle Aged; Temporal Lobe; Topiramate