topiramate and Developmental-Disabilities

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

We systematically reviewed the files of 51 infants presenting with infantile spasms and hypsarrhythmia in order to study the initial treatment strategies and the long term outcome. 80% of the infants were classified as symptomatic. In the nine participating centres, different treatment protocols were used, but the large majority of the children received vigabatrin as first line treatment. Second line options included hormonal treatment, topiramate and valproate. The time to reach cessation of infantile spasms was significantly shorter in the cryptogenic group than in the symptomatic group (50% at 13 days versus 66 days respectively) and was irrespective of the treatment used. The late follow up data (>2 years) showed that 60% of the children had epilepsy and that 75% of the children had a delay in their psychomotor development. Again, outcome in the cryptogenic group was better than in the symptomatic group, but also in the cryptogenic group, 50% of the children had a clear developmental delay, even if spasms were controlled early in the course of the disease. Our retrospective study illustrates that not only the underlying brain dysfunction is the major determinant for later outcome in infantile spasms (symptomatic group) but also even a short period of infantile spasms can be responsible for later developmental delay (cryptogenic group).

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anticonvulsants; Developmental Disabilities; Follow-Up Studies; Fructose; Humans; Infant; Retrospective Studies; Spasms, Infantile; Topiramate; Treatment Outcome; Valproic Acid; Vigabatrin

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

We describe four children with Dravet syndrome treated with the combination of valproic acid (VPA) and topiramate (TPM) who developed transient liver toxicity. The time-interval between fever, administration of acetaminophen, epileptic status and liver enzyme disturbances in our four cases suggests that accumulation of toxic acetaminophen-metabolites is possibly responsible for liver toxicity. If acetaminophen and its metabolites cause those liver problems in children treated with the combination of VPA and TPM, the advice to use acetaminophen for treating fever in children using this combination, should be changed. Only future clinical observations and research can solve this clinical dilemma.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anticonvulsants; Chemical and Drug Induced Liver Injury; Developmental Disabilities; Drug Therapy, Combination; Enzymes; Female; Fructose; Humans; Infant; Influenza, Human; Liver Function Tests; Male; Myoclonic Epilepsy, Juvenile; NAV1.1 Voltage-Gated Sodium Channel; Nerve Tissue Proteins; Sodium Channels; Syndrome; Topiramate; Valproic Acid

Topics: Anticonvulsants; Brain; Child; Developmental Disabilities; Dose-Response Relationship, Drug; Dystonia; Female; Fructose; Hemiplegia; Humans; Migraine with Aura; Nystagmus, Pathologic; Recovery of Function; Syndrome; Topiramate; Treatment Outcome

Topics: Anticonvulsants; Antipsychotic Agents; Autistic Disorder; Caregivers; Child; Developmental Disabilities; Epilepsy; Female; Foster Home Care; Fructose; Humans; Impulsive Behavior; Mental Status Schedule; Psychological Tests; Risperidone; Status Epilepticus; Topiramate; Valproic Acid

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