topiramate and Intellectual-Disability

Topics: Female; Humans; Intellectual Disability; Pregnancy; Topiramate

Topics: Anticonvulsants; Blood Coagulation Disorders; Cerebral Palsy; Chemical and Drug Induced Liver Injury; Child; Combined Modality Therapy; Drug Monitoring; Epilepsy; Fructose; Humans; Hyperammonemia; Intellectual Disability; Liver; Liver Failure, Acute; Male; Topiramate; Treatment Outcome

2q23.1 microdeletion syndrome is a recently characterized chromosomal aberration disorder uncovered through array comparative genomic hybridization (array CGH). Although the cardinal feature is intellectual disability (ID), neurodevelopmental features of the syndrome have not been systematically reviewed. We present a 5-year-old boy with severe psychomotor developmental delay/ID, progressive microcephaly with brain atrophy, growth retardation, and several external anomalies. He manifested intractable epilepsy, effectively treated with combined antiepileptic drug therapy including topiramate. Array CGH demonstrated a de novo interstitial deletion of approximately 1 Mb at 2q23.1-q23.2, involving four genes including MBD5. Nineteen patients have been reported to have the syndrome, including present patient. All patients whose data were available had ID, 17 patients (89%) had seizures, and microcephaly was evident in 9 of 18 patients (50%). Deletion sizes ranged from 200 kb to 5.5 Mb, comprising 1-15 genes. MBD5, the only gene deleted in all patients, is considered to be responsible for ID and epilepsy. Furthermore, the deletion junction was sequenced for the first time in a patient with the syndrome; and homology of three nucleotides, identified at the distal and proximal breakpoints, suggested that the deletion might have been mediated by recently-delineated genomic rearrangement mechanism Fork Stalling and Template Switching (FoSTeS)/microhomology-mediated break-induced replication (MMBIR).

Topics: Abnormalities, Multiple; Child, Preschool; Chromosomes, Human, Pair 2; Comparative Genomic Hybridization; Developmental Disabilities; DNA-Binding Proteins; Fructose; Humans; Intellectual Disability; Male; Microcephaly; Oligonucleotide Array Sequence Analysis; Seizures; Sequence Deletion; Topiramate

On the basis of the relevance of adequate epilepsy treatment (antiepileptic drugs, surgery and vagus nerve stimulation) for people with intellectual disabilities, all articles, published from the beginning of 2005 to March 2006 and searched by MEDLINE, on this topic were reviewed.. On pharmacological treatment of epilepsy in people with intellectual disabilities, there were two articles on topiramate and one on levetiracetam. Two studies described the effect of surgical interventions, one of epilepsy surgery in the narrow sense and one of vagus nerve stimulation. Two papers were published on clinical conditions and therapeutic aspects of Angelman syndrome. They highlight the importance of gamma-aminobutyric acidergic mechanism in Angelman syndrome and the antiepileptic drug effects in this syndrome.. A contradiction exists between the relevance of epilepsy treatment in people with intellectual disabilities and the small number of published studies on pharmacological treatment. Some of the reasons are addressed and some alternatives are proposed.

Topics: Anticonvulsants; Brain; Electric Stimulation Therapy; Epilepsy; Fructose; Humans; Intellectual Disability; Levetiracetam; Neurosurgical Procedures; Piracetam; Postoperative Complications; Topiramate; Vagus Nerve

Tuberous sclerosis complex is characterized by hamartomatous lesions involving skin, brain, kidneys, eyes and heart. Pathologically, tuberous sclerosis is a disorder of cell migration, proliferation and differentiation. Cell lineage and cell migration disorders in the developing cortex of tuberous sclerosis complex patients might produce very different neurological phenotypes including epilepsy, cognitive impairment and autism. Cortical tubers constitute the hallmark of the disease and are pathognomonic of cerebral tuberous sclerosis. Epilepsy is the most common neurological feature, occurring in 96% of patients. Seizures often begin in the first months of life and are frequently severe and intractable. The treatment of seizures has recently benefited from the advent of the new anti-epileptic drugs. Selected drug-resistant patients with tuberous sclerosis complex could be considered for surgical treatment. Clear localization of the most active epileptogenic focus and the zone of the cortical abnormality may lead to tuberectomy and improved seizure control in selective drug-resistant patients. The finding of multiple areas of cerebral involvement should not automatically preclude epilepsy surgery in a child with intractable seizures and a well defined seizure origin.

Topics: Anticonvulsants; Brain; Cell Movement; Diagnosis, Differential; Electroencephalography; Epilepsy; Fructose; Humans; Intellectual Disability; Topiramate; Tuberous Sclerosis

The aim of the present study was to assess the behavioral and cognitive effects following treatment with topiramate in children and adolescents with epilepsy with mild to profound mental retardation. The study group comprised 29 children, 16 males and 13 females, aged 3 to 19 years, affected by partial (4) and generalized (25) crypto/symptomatic epilepsy and mental retardation (7 mild, 5 moderate, 15 severe, 2 profound), who were administered topiramate (TPM) as add-on therapy to their baseline antiepileptic treatment. At baseline, 3 months, 6 months, and 12 months, parents or caregivers of each patient were administered a questionnaire based on the Holmfrid Quality of Life Inventory. After a 3-month follow-up, the add-on topiramate caused overall mild to moderate cognitive/behavioral worsening in about 70% of children and adolescents with mental retardation and epilepsy. After 6 and 12 months of follow-up, global worsening persisted in 31 and 20.1% of cases, respectively. In conclusion, this trial confirms that TPM can have significant adverse cognitive and behavioral side effects, even in mentally disabled children and adolescents.

Topics: Adolescent; Adult; Anticonvulsants; Behavior; Child; Child, Preschool; Cognition Disorders; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Male; Mental Disorders; Prospective Studies; Severity of Illness Index; Statistics, Nonparametric; Topiramate; Treatment Outcome

To study the effectiveness of topiramate (TPM) in refractory epilepsy in patients who have intellectual disability (ID).. A representative population sample of 57 patients with ID (age range 2-61, mean 32.8) was administered add-on TPM for drug-refractory epilepsy.. Seizure freedom for at least for 6 months was attained by 10 (17%), and seizure reduction of > or = 50% by further 26 (46%). Less than 50% decrease in seizure frequency was found in 16 (29%). TPM was more efficacious in localisation-related than in generalised epilepsies (81% vs. 50%, P=0.019). An at least 50% decrease in seizure frequency was achieved by patients with temporal lobe epilepsy in 100%, continuous spike-waves during sleep syndrome in 75%, Lennox-Gastaut syndrome in 52%, and those with infantile spasms in 25% of cases. As great decrease in seizure frequency was found in most patients with cortical dysplasia (83%), acquired encephalopathy with mesial temporal sclerosis (MTS) (75%), and genetic disease associated with MTS (66%). Adverse effects occurred in 10% including two (3%) with seizure aggravation and three (5%) necessitating discontinuation.. TPM is an effective antiepileptic drug which is of value in treating people with seizures that are resistant to other antiepileptic medication. As a broad-spectrum drug it may substitute for polypharmacy and, at the same time decrease adverse effects and costs of therapy.

Topics: Adult; Anticonvulsants; Brain; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Middle Aged; Periodicity; Retrospective Studies; Topiramate

This randomized, double-blind, placebo-controlled UK trial evaluated the effect of topiramate as add-on therapy on seizure frequency, seizure severity, and quality of life in patients with epilepsy and intellectual disability. There were three phases: 4 weeks baseline, 18 weeks titration to 200-400 mg topiramate/day (adults) or 5-9 mg/kg/day (children), 12 weeks maintenance. Recruitment was low (88/120); analyses were underpowered. Seizure frequency varied enormously (median 17.7, maximum 1706.2). There was no significant difference in reduction in mean total seizure frequency or number of responders between the groups. Topiramate reduced seizure frequency by >30% from baseline (placebo 1%); post hoc analyses showed a trend toward significance (R ratio, P=0.052). There were no significant differences between the groups with respect to mean seizure severity or other outcome measures. Topiramate was generally well tolerated; body weight (P=0.015) and systolic blood pressure (P=0.043) were reduced. The study suggests that topiramate reduces seizure frequency in patients with epilepsy and intellectual disability without the added burden of behavior effects, and was potentially advantageous to physical well-being.

Topics: Adaptation, Psychological; Adult; Anticonvulsants; Body Weight; Double-Blind Method; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Intelligence Tests; Male; Neuropsychological Tests; Quality of Life; Seizures; Sex Characteristics; Topiramate

We aimed to analyze the genotype-phenotype correlations of STXBP1 pathogenic variants, prognostic factors and the treatment choices in a case-series of STXBP1-related disorders from China.. The clinical data and genetic results of the children diagnosed with STXBP1-related disorders at Xiangya hospital from 2011 to 2019 were collected retrospectively, and analyzed. We divided our patients into groups for comparison purposes: patients with missense variants and nonsense variants, patients who are seizure-free and not seizure-free, patients with mild to moderate intellectual disability (ID) and severe to profound global developmental delay (GDD).. Nineteen patients were enrolled: 17 (89.5%) unrelated and 2 (10.5%) familial. Twelve (63.2%) were females. Developmental epileptic encephalopathy (DEE) was observed in 18 (94.7%) patients and ID alone in 1 (5.3%) individual. Thirteen patients (68.4%) had profound ID/GDD, 4 (23.53%) severe, 1 (5.9%) moderate and 1 (5.9%) mild. Three patients (15.8%) with profound ID died. A total of 19 variants were detected: pathogenic (n = 15) and likely pathogenic (n = 4). Seven were novel variants: c.664-1G>-, M486R, H245N, H498Pfs*44, L41R, L410del, and D90H. Of the 8 previous reported variants, 2 were recurrent: R406C and R292C. Anti-seizure medications were used in combinations, and 7 patients became seizure-free, and most of them achieved seizure freedom within the first 2 years of life irrespective of the type of the mutation. Effective medications for the seizure-free individuals included adrenocorticotropic (ACTH) and/or levetiracetam and/or phenobarbital and/or sodium valproate and/or topiramate and/or vigabatrin and/or nitrazepam. There was no correlation between the types of pathogenic variants and the phenotypes.. Our case-series showed that there is no genotype-phenotype correlation in patients with STXBP1-related disorders. This study adds 7 novel variants which expand the spectrum of STXBP1-related disorders. Combinations of levetiracetam and/or sodium valproate and/or ACTH and/or phenobarbital and/or vigabatrin and/or topiramate and/or nitrazepam were more often associated with seizure freedom in our cohort within 2 years of life.

Topics: Adrenocorticotropic Hormone; China; Female; Genetic Association Studies; Humans; Intellectual Disability; Levetiracetam; Male; Munc18 Proteins; Nitrazepam; Phenobarbital; Phenotype; Retrospective Studies; Topiramate; Valproic Acid; Vigabatrin

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by mutations in TCF4. Seizures have been found to vary among patients with PTHS. We report the case of a PTHS patient with a novel missense mutation in the gene TCF4, presenting with two types of early epileptic encephalopathy.. The patient was a Japanese boy. His first seizure was reported at 17 days of age, with twitching of the left eyelid and tonic-clonic seizures on either side of his body. An ictal electroencephalogram (EEG) showed epileptic discharges arising independently from both hemispheres, occasionally resembling migrating partial seizures of infancy (MPSI) that migrated from one side to the other. Brain magnetic resonance imaging revealed agenesis of the corpus callosum. His facial characteristics included a distinctive upper lip and thickened helices. His seizures were refractory, and psychomotor development was severely delayed. At the age of 10 months, he developed West syndrome with spasms and hypsarrhythmia. After being prescribed topiramate (TPM), his seizures and EEG abnormalities dramatically improved. Also, psychomotor development progressed. Whole-exome sequencing revealed a novel de novo missense mutation in exon 18 (NM_001083962.2:c.1718A > T, p.(Asn573Ile)), corresponding to the basic region of the basic helix-loop-helix domain, which may be a causative gene for epileptic encephalopathy.. To our knowledge, this is the first report of a patient with PTHS treated with TPM, who presented with both MPSI as well as West syndrome. This may help provide new insights regarding the phenotypes caused by mutations in TCF4.

Topics: Anticonvulsants; Facies; Humans; Hyperventilation; Infant; Intellectual Disability; Male; Mutation, Missense; Spasms, Infantile; Topiramate; Transcription Factor 4

Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain.. To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders.. The Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED) is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2017; analysis performed February 2022). From 4 702 774 alive-born children with available mother-child identities and maternal prescription data, this study included 4 494 926 participants. Children from a multiple pregnancy or with chromosomal disorders or uncertain pregnancy length were excluded (n = 207 848).. Prenatal exposure to ASM determined from maternal prescription fills between last menstrual period and birth.. We estimated cumulative incidence at age 8 years in exposed and unexposed children. Cox regression adjusted for potential confounders yielded adjusted hazard ratios (aHRs) with 95% CIs for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID).. A total of 4 494 926 children were included; 2 306 993 (51.3%) were male, and the median (IQR) age at end of follow-up was 8 (4.0-12.1) years. Among 21 634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% (numerators were not available because of personal data regulations in Denmark) of ID by age 8 years. In same-aged children of mothers with epilepsy exposed to topiramate and valproate monotherapy, 4.3% and 2.7%, respectively, had ASD, and 3.1% and 2.4% had ID. The aHRs for ASD and ID after topiramate exposure were 2.8 (95% CI, 1.4-5.7) and 3.5 (95% CI, 1.4-8.6), respectively, and after valproate exposure were 2.4 (95% CI, 1.7-3.3) and 2.5 (95% CI, 1.7-3.7). The aHRs were elevated with higher ASM doses compared with children from the general population. The duotherapies levetiracetam with carbamazepine and lamotrigine with topiramate were associated with increased risks of neurodevelopmental disorders in children of women with epilepsy: levetiracetam with carbamazepine: 8-year cumulative incidence, 5.7%; aHR, 3.5; 95% CI, 1.5-8.2; lamotrigine with topiramate: 8-year cumulative incidence, 7.5%; aHR, 2.4; 95% CI, 1.1-4.9. No increased risk was associated with levetiracetam with lamotrigine (8-year cumulative incidence, 1.6%; aHR, 0.9; 95% CI, 0.3-2.5). No consistently increased risks were observed for neurodevelopmental disorders after prenatal exposure to monotherapy with lamotrigine, levetiracetam, carbamazepin, oxcarbazepine, gapapentin, pregabalin, clonazepam, or phenobarbital.. In this cohort study, prenatal exposure to topiramate, valproate, and several duotherapies were associated with increased risks of neurodevelopmental disorders.

Topics: Anticonvulsants; Autism Spectrum Disorder; Autistic Disorder; Carbamazepine; Child; Cohort Studies; Epilepsy; Female; Humans; Intellectual Disability; Lamotrigine; Levetiracetam; Male; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Topiramate; Valproic Acid

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Depression; Female; Humans; Intellectual Disability; Lithium; Olanzapine; Pica; Topiramate

Intellectual disability (ID) is associated with weight gain caused by antiepileptic drugs such as valproic acid. The present study analyzed the relationship between ID and weight loss caused by topiramate (TPM).. Seventy-eight patients with epilepsy (35 women, aged 18 to 70years) were enrolled in this prospective study. Body weight was measured before and 1, 6, 12, and 18months after initiation of TPM treatment. Both patients and caregivers were provided information about TPM-related weight loss. The patients were divided into the group with no or mild ID (intelligence quotient >50) and the group with moderate to profound ID (intelligence quotient ≤50).. Body weight of both groups significantly decreased until 6months but stabilized after 12months. Weight loss at 6, 12, and 18months was significantly greater in the group with no or mild ID than in the group with moderate to profound ID. Body weight change at 18months was correlated with intellectual levels (β=0.274, p=0.011) and baseline body mass index (β=-0.322, p=0.002) by multiple linear regression analysis.. The present study suggests that the pattern of weight loss during TPM administration differs according to intellectual levels. Patients with ID maintained their body weight. Weight loss due to TPM might be weakened by caregiver control of food intake or inactivity.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Body Mass Index; Body Weight; Cohort Studies; Epilepsy; Female; Humans; Intellectual Disability; Male; Middle Aged; Prospective Studies; Topiramate; Weight Gain; Weight Loss; Young Adult

Topiramate (TPM) is an effective antiepileptic drug (AED). A high proportion of patients, however, experiences cognitive adverse events (CAEs), especially in verbal fluency, memory spans, and working memory. To our knowledge, CAEs of TPM have not been studied systematically in patients with intellectual disability (ID). This may be due to the fact that many of those patients are not able to follow test instructions properly and that neuropsychological instruments are not validated for that group. Cognitive deterioration in patients with ID may thus easily be overlooked. Topiramate is in frequent use in persons with ID. We included 26 consecutive patients with epilepsy and ID in this observational study who had undergone neuropsychological examinations as part of clinical routine before and after the introduction of TPM into the therapeutic regimen (n=4) or before and after the withdrawal of TPM (n=22). Examinations under TPM showed reduced cognitive speed, reduced verbal memory, reduced verbal fluency, and reduced flexibility compared to examinations without TPM. Despite some limitations (especially small sample size, high interindividual variation of the results dependent on the degree of ID, effects of other - limited - changes in the therapeutic regimen), our study indicates that TPM in persons with epilepsy and ID may lead to CAEs comparable to those in persons with normal intelligence. Neuropsychological testing is mandatory in order not to miss CAEs that might severely impair quality of life.

Topics: Adult; Aged; Anticonvulsants; Cognition Disorders; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Topiramate; Young Adult

Lennox-Gastaut syndrome (LGS) is a well-defined epileptic encephalopathy highly drug resistant. The first-line treatment option is valproate (VPA), usually in combination with lamotrigine. VPA has been linked to serious hepatotoxicity. We report a 22-year-old liver transplanted patient with LGS successfully treated with VPA in combination with phenobarbital (100 mg/d; blood level: 36 mg/l), lamotrigine (125 mg/d; blood level: 4.81 mg/l) and topiramtate (175 mg/d), as well as immunosuppressive, antiviral, anti-anemic, hypo-phosphoric and alkaline medication. On VPA 1000 mg/d, the seizure frequency decreased significantly. Taking into consideration the patient's good tolerance and the normal liver function, VPA was increased to 1500 mg/d. At this dose the daily drop attacks and generalized tonic-clonic seizures totally ceased. The patient presented only some tonic seizures around awakening. During many years, VPA was avoided in this patient because of its potential hepatotoxicity. However the good functioning of the transplanted liver permitted its introduction. VPA can be used safely in liver transplanted patients under the strict control of the hepatic function.

Topics: Anticonvulsants; Chemical and Drug Induced Liver Injury; Electroencephalography; Female; Fructose; Humans; Immunosuppressive Agents; Intellectual Disability; Lamotrigine; Lennox Gastaut Syndrome; Liver Function Tests; Liver Transplantation; Phenobarbital; Seizures; Spasms, Infantile; Topiramate; Triazines; Valproic Acid; Young Adult

A 42-year-old patient with cognitive deficits due to childhood meningitis suffered from recurrent episodes of familial hemiplegic migraine. Additionally, he developed concomitant psychotic episodes requiring subsequent in-patient psychiatric treatment. Following combined neurological and psychiatric treatment he always recovered from the episodes within a few weeks time. Prophylactic treatment of migraine using topiramate and acetazolamide (off-label) prevented attacks for several months. When off-label compensation was refused and, as a consequence, the drug discontinued, hemiplegia relapsed within a few days. Hence, acetazolamide was prescribed again and the family paid for the medication. Since that time, the patient did not show severe attacks for at least 8 months apart from a transient attack induced by acute flu-like illness.

Topics: Acetazolamide; Adult; Anticonvulsants; Carbonic Anhydrase Inhibitors; Comorbidity; Drug Costs; Drug Therapy, Combination; Financing, Personal; Fructose; Germany; Humans; Insurance, Pharmaceutical Services; Intellectual Disability; Male; Migraine with Aura; National Health Programs; Off-Label Use; Psychotic Disorders; Topiramate; Treatment Outcome

Lennox-Gastaut syndrome (LGS) is a catastrophic childhood form of epilepsy. The syndrome is characterized by mental impairment, frequent seizures of multiple types that are particularly resistant to treatment, and high rates of seizure-related injury. With the introduction of newer, but more costly, antiepileptic drugs (AEDs), it is important that decision makers are able to assess their value in the management of this rare and difficult-to-treat condition. To evaluate the cost effectiveness, from the UK NHS perspective, of rufinamide in patients with LGS. An individual patient-simulation model was developed to estimate the total treatment-related costs and clinical benefits of rufinamide compared with topiramate and lamotrigine over a 3-year time horizon. The model examines the treatment scenarios of adding rufinamide, lamotrigine or topiramate to older AEDs (standard therapy), or standard therapy alone within a primary-care or community setting. Three placebo-controlled clinical trials of adjunctive AED treatment for children with LGS were analysed. There are no head-to-head comparator studies. Between 98 and 139 patients were randomized in each study and the mean age in each study was 10, 11 and 14 years. A mixed-treatment comparison using a random-effects model was carried out on the number of patients in each response category, using the placebo arms of the respective trials. The primary outcome measure was the percentage of successfully treated patients, defined as >50% reduction in the frequency of total seizures and drop attacks. The hypothesis being tested was formulated after data collection. Costs ( pound, year 2006/07 values) of patient monitoring, switching treatments, hospitalization due to seizure, treatment of adverse effects, and personal and social services were included in the analysis. Results of 10,000 Monte Carlo simulations were bootstrapped to conduct probabilistic sensitivity analysis. Over 3 years, adjunctive rufinamide resulted in higher total costs than topiramate and lamotrigine; however, with more patients being treated successfully, this leads to acceptable incremental cost-effectiveness ratios. If society is prepared to pay at least 250 pounds for a 1% increase in the number of successfully treated LGS patients, in terms of a 50% reduction in the frequency of drop attacks, the probability of the treatment with rufinamide being cost effective is >80%. This cost-effectiveness analysis suggests that rufinamide results in more

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Computer Simulation; Cost-Benefit Analysis; Epilepsy, Absence; Fructose; Health Care Costs; Humans; Infant; Intellectual Disability; Lamotrigine; Models, Economic; Randomized Controlled Trials as Topic; Syndrome; Time Factors; Topiramate; Treatment Outcome; Triazines; Triazoles; United Kingdom

To assess the long-term usefulness of 'new anti-epileptic drugs (AEDs)' (lamotrigine, topiramate, levetiracetam, gabapentin and pregabalin) in institutionalized intellectually disabled patients. Information from RCTs is lacking in this population with severe intellectual and behavioural disabilities.. Retrospective study. Data from the medical files and the pharmacy databases of 118 institutionalized intellectually disabled patients who had ever used at least one of the new AEDs were analyzed. The main evaluation parameters were the duration of use (using Kaplan-Meier survival estimates) and the reason for discontinuation (lack of efficacy, occurrence of adverse events, or both) of the new AEDs. Drug continuation was based on the evaluation of treatment results by experienced epileptologists, and not on fixed criteria.. New AEDs were generally tried only after a substantial number of other regimens (with classic AEDs) had failed. The most frequently used new AEDs were lamotrigine (68%) and levetiracetam (58%), followed by topiramate (28%) and gabapentin (8%). The 3-year retention rates were 70% (lamotrigine), 52% (levetiracetam), 51% (topiramate) and 33% (gabapentin). Discontinuation due to "lack of efficacy" occurred in 61% (topiramate), 60% (lamotrigine) and 42% (levetiracetam) of the cases. Discontinuation due to adverse events occurred in 42% (levetiracetam), 33% (topiramate) and 28% (lamotrigine).. Treatment of epilepsy with new AEDs was quite often successful in this very therapy-resistant population.

Topics: Adolescent; Adult; Amines; Anticonvulsants; Child; Cyclohexanecarboxylic Acids; Drug Utilization Review; Epilepsy; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Institutionalization; Intellectual Disability; Lamotrigine; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Topiramate; Triazines

This noninterventional single-arm study explored effectiveness and behavioral outcomes in intellectually disabled patients treated with topiramate for epilepsy. Data from 21 patients diagnosed with cerebral palsy were available for evaluation. Behavioral changes were assessed using the validated Aberrant Behavior Checklist and Matson Evaluation of Social Skills for Individuals with Severe Retardation (MESSIER) scales. Some improvement in nearly all behavioral aspects was observed under concomitant topiramate therapy; for example, the Aberrant Behavior Checklist total score changed from 33.7+/-25.8 to 25.3+/-19.1 (P=0.047). In addition, seizure frequency decreased from 16.1+/-22.2/4 weeks to 12.2+/-17.0/4 weeks (N=21, P=0.164). Fifty-two percent of the patients experienced at least 50% seizure reduction during the 24-week treatment period. The safety profile is in accordance with the current Summary of Product Characteristics of Topiramate. Two unexpected deaths were attributed to sudden unexpected death in epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Behavior; Cerebral Palsy; Data Interpretation, Statistical; Drug Resistance; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotropic Drugs; Seizures; Social Behavior; Topiramate; Treatment Outcome; Young Adult

Urolithiasis occurs infrequently in the pediatric population, where metabolic factors play a primary role in the pathogenesis of stone formation. Topiramate, an antiepileptic drug, is associated with a kidney stone in 1.5% of patients in published clinical trials. However, this risk may be much higher in certain populations with multiple preexisting risk factors. We performed a retrospective review of all nonambulatory and neurologically impaired individuals in a long-term care facility. Three groups were involved: those with no exposure to antiepileptic drugs, those on antiepileptic drugs other than topiramate, and those who had been treated with topiramate. Thirteen of 24 (54%) individuals on topiramate monotherapy or polytherapy developed clinical evidence of urolithiasis after a mean duration of 36.4 months. Our results suggest that nonambulatory and neurologically impaired individuals in a long-term care facility appear to be at higher risk of developing kidney stones with topiramate than previously reported.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Citrates; Developmental Disabilities; Female; Fructose; Humans; Intellectual Disability; Male; Middle Aged; Retrospective Studies; Topiramate; Urolithiasis; Young Adult

Congenital bilateral perisylvian syndrome (CBPS) is a rare neurological disorder characterised by pseudobulbar palsy, cognitive deficits and epilepsy associated with bilateral perisylvian cortical dysplasia on neuroimaging studies. We report a long-term follow-up of a 18-years girl diagnosed with CBPS according to the typical clinical and magnetic resonance imaging (MRI) features. The patient showed faciopharyngoglossomasticatory diplegia, severe dysarthria, ataxia, spastic quadriparesis and severe mental retardation. Brain MRI evidenced bilateral perisylvian cortical dysplasia. Since early life she suffered from complex febrile seizures and epilepsy consisting of complex partial attacks with affective manifestations associated with centro-temporal EEG abnormalities. During 18 years of follow-up she was treated with phenobarbital, carbamazepine, lamotrigine, gabapentin but did not show any significant clinical improvement. Subsequently, monotherapy with phenytoin (PHT) was followed by a significant clinical improvement. At age 17, because of adverse effects, PHT was gradually substituted by topiramate (TPM). Full control of seizures was obtained at the age of 17 years with TPM. EEG abnormalities throughout the years have been reduced according to the clinical course. These findings emphasised the importance of long-term follow-up, suggesting that the prognosis for epilepsy may not be predicted based on the early response to treatment or on the presence of structural encephalic abnormalities, as reported in the literature.

Topics: Adolescent; Cerebral Cortex; Electroencephalography; Epilepsies, Partial; Female; Follow-Up Studies; Fructose; Globus Pallidus; Humans; Intellectual Disability; Magnetic Resonance Imaging; Nervous System Malformations; Phenytoin; Pseudobulbar Palsy; Quadriplegia; Syndrome; Topiramate; Treatment Outcome

There is little knowledge about the effects of topiramate in intellectually impaired epileptic patients. This open prospective study compares seizure frequencies during a 3-month period of topiramate add-on therapy (after 3 months of titration) compared with a 3-month baseline period. An intention-to-treat analysis was made on the first 24 consecutive topiramate-treated adult patients (residents of the Bethel epilepsy centre, therapy-resistant epilepsy, intellectual impairment of different degrees, one half with neurological deficits). The responder rate (at least a 50% reduction in seizure frequency) was 37.5%. One patient became completely seizure-free during post-evaluation (up to 24 months). Efficacy was not different between different epileptic syndromes or seizure types (case number too small). Responders had topiramate dosages above 200 mg/day and serum concentrations above 2.2 micrograms/ml. Six patients (25%) experienced serious neuropsychiatric complications such as confusion and severe deceleration of thinking and acting, up to complete helplessness (at topiramate dosages from 50 mg/day to 900 mg/day and serum concentrations from 2.2 micrograms/ml to 8.0 micrograms/ml). Preexisting brain damage may enhance the risk of unwanted central nervous effects.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Fructose; Humans; Intellectual Disability; Male; Middle Aged; Neuropsychological Tests; Topiramate; Treatment Outcome

The efficacy and safety of topiramate in patients with intractable mixed seizures, mental retardation (MR), and developmental disabilities (DD) were investigated. Twenty patients (eight females and 12 males) aged 21-57 years old with intractable epilepsy with mixed seizures, MR [profound (five), severe (three), moderate (two), mild (eight) and borderline (two)], and DD were treated with adjunctive topiramate 25 mg per day for 1 week followed by titration to clinical response (range 50-350 mg per day). Other antiepileptic drugs (AEDs) were decreased simultaneously. Topiramate therapy was discontinued in four patients for adverse events consisting of disorientation, unsteadiness, and pneumonia (one patient); anaphylactic shock from a tuna fish allergy (one); patient choice (one); and loss to follow-up (one). Seizures improved by gt-or-equal, slanted 50% in 11 of 16 patients (69%). Two patients (13%) were seizure free, including one patient who prior to topiramate therapy was seizure free but experiencing an intolerable adverse effect during therapy with another AED. Seizure duration and/or severity decreased in seven patients (44%). An increase in alertness was observed in 11 patients (59%). Topiramate was associated with improvement in seizure severity and alertness in this series and may be useful as adjunctive therapy in patients with mixed seizures, MR, and DD.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Anticonvulsants; Child; Comorbidity; Developmental Disabilities; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Female; Fructose; Humans; Intellectual Disability; Male; Middle Aged; New York; Topiramate; Treatment Outcome

Topics: Adult; Anticonvulsants; Epilepsy; Fructose; Humans; Intellectual Disability; Male; Topiramate; Vomiting

The novel anticonvulsant topiramate has been shown to have efficacy across a range of seizure types including both generalized and partial seizures in several well-designed randomized controlled trials. It has also been shown to be effective in atonic seizures associated with Lennox-Gastaut syndrome. Tolerability data show a tendency to neuropsychiatric side-effects, such as confusion and word finding difficulties, when topiramate is used in polytherapy; these side-effects are reduced in monotherapy usage. The efficacy and spectrum of seizures treated by topiramate suggests that it has an important role in managing epilepsy in people with intellectual disability. The predictable side-effects can be monitored in clinical practice and possibly reduced by slow dose increments. The data set of patients with intellectual disability is still too small to rule out idiosyncratic drug reaction.

Topics: Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Epilepsies, Partial; Fructose; Humans; Intellectual Disability; Topiramate; Treatment Outcome