topiramate and Syndrome

We report a 16-year-old adolescent with 2 episodes of focal neurological deficits, pseudomigrainous headache, and lymphocytic pleocytosis due to the syndrome of transient headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL), also known as pseudomigraine with CSF pleocytosis. Review of the literature identifies 13 additional cases of HaNDL in the pediatric population. These cases are reviewed and evidence for possible etiopathogenesis is discussed. This syndrome may mimic much more common conditions such as complicated or hemiplegic migraine, aseptic meningitis, meningoencephalitis, or stroke. However, HaNDL differs from complicated or hemiplegic migraine and stroke since CSF pleocytosis is uniformly present. There are many infectious conditions that can present with neurological deficits, headache, and CSF pleocytosis, but the transient nature of the deficits and lack of a consistently identifiable infectious etiology despite extensive evaluations typify HaNDL. This clinical syndrome is underrecognized and underreported. HaNDL remains a diagnosis of exclusion.

Topics: Adolescent; Diagnosis, Differential; Electroencephalography; Fructose; Headache; Humans; Lymphocytosis; Magnetic Resonance Imaging; Male; Nervous System Diseases; Neuroprotective Agents; Syndrome; Tomography, X-Ray Computed; Topiramate

Dravet syndrome (DS) is one of the most pharmacoresistant epilepsy syndromes. Valproate is used as a first-line agent to prevent the recurrence of febrile seizures and oral/nasal/rectal benzodiazepine is used for any long-lasting seizures, but these agents are most often insufficient. Lamotrigine, carbamazepine, and high doses of intravenous phenobarbital should be avoided because they may worsen seizures. Topiramate, levetiracetam, bromide, and the ketogenic diet may provide substantial efficacy as adjunctive therapy/procedure. Stiripentol is the only compound that proved its efficacy in DS through two independent randomized placebo-controlled trials, when combined with valproate and clobazam. Their dose has to be decreased to minimize the side effects (mostly loss of appetite) resulting from pharmacokinetic interactions of stiripentol powerfully inhibiting cytochromes P450. Stiripentol acts as a γ-aminobutyric acid (GABA)ergic agent, mainly via the α3 subunit of GABA(A) receptors. Stiripentol (Diacomit) was approved as an orphan drug in 2007 in Europe for adjunctive therapy in DS. Up to now, >500 children have been safely treated, and recent experiment in Japan confirmed stiripentol benefit in DS children with comedications other than valproate and clobazam. Because early status epilepticus is likely to negatively impact cognitive outcome, we recommend the introduction of stiripentol as soon as the diagnosis of DS is clinically confirmed. Topiramate and the ketogenic diet are alternatives in pharmacoresistant cases.

Topics: Anticonvulsants; Diet, Ketogenic; Epilepsies, Myoclonic; Fructose; Humans; Syndrome; Topiramate; Treatment Outcome

As a group, idiopathic generalized epilepsies (IGEs) have the highest rates of complete seizure control with medication. However, there are little evidence-based data to guide drug choice for treatment. Examples of IGE include absence epilepsy, generalized tonic-clonic epilepsy, and juvenile myoclonic epilepsy. Generalized epilepsies seem to be particularly vulnerable to seizure aggravation, and medications that are primarily effective against partial seizures are more commonly involved in seizure aggravation than other medications. A review of current research has shown that only a few medications can control IGE without potentially causing seizure aggravation. Broad-spectrum antiepileptic drugs such as valproate (VPA), lamotrigine, and topiramate are extremely effective at controlling a variety of seizures without causing excessive seizure aggravation. Among these drugs, VPA has the longest clinical experience history and the largest body of published data.

Topics: Adult; Anticonvulsants; Child; Clinical Trials as Topic; Epilepsy, Generalized; Fructose; Humans; Lamotrigine; Syndrome; Topiramate; Treatment Outcome; Triazines; Valproic Acid

To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox-Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.

Topics: Anticonvulsants; Child; Child Behavior Disorders; Child, Preschool; Epilepsy; Female; Fructose; Gastrointestinal Diseases; Humans; Infant; Male; Nervous System Diseases; Prospective Studies; Syndrome; 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

Acute encephalitis with refractory repetitive partial seizure (AERRPS) is a peculiar type of post-encephalitic/encephalopathic epilepsy. Here we report an analysis of AERRPS in a series of children and propose an effective treatment option for seizure control in these children.. We retrospectively reviewed cases of AERRPS treated in a pediatric intensive care unit, between February 2002 and June 2006. Clinical characteristics were systemically assessed. Burst suppression coma was induced by high-dose suppressive therapy; 24-h electroencephalogram (EEG) monitoring was performed on each patient. The goal of treatment was to achieve complete clinical seizure control or burst-suppression pattern on EEG, aiming for an interburst interval of >5s. Brain imaging was done for each patient.. There were nine patients (seven boys), aged 5-15 years. Clinical symptoms included fever (100%), upper respiratory symptoms (66.7%) and altered consciousness (66.7%). All patients received multiple high-dose suppressive drugs and were intubated with/without inotropic agents. Seizures in three patients were stopped after high-dose lidocaine infusion (6-8 mg/kg/h) in the acute stage and three patients were stopped after high dose phenobarbital (serum level 60-80 ug/mL) combined with high-dose oral topiramate (15-20 mg/kg/day). Follow-up for this study was 16-61 months. Two subjects died while seven developed epilepsy and/or neurologic deficits; none returned to baseline. All survivors were discharged and continued multiple antiepileptic medications.. Our data indicates that children with AERRPS have high mortality and morbidity rates. High-dose topiramate combined with high-dose lidocaine infusion or high-dose phenobarbital in the acute stage might be an effective treatment option for children with AERRPS.

Topics: Acute Disease; Adolescent; Anticonvulsants; Child; Drug Therapy, Combination; Electroencephalography; Encephalitis; Epilepsies, Partial; Female; Fructose; Humans; Lidocaine; Magnetic Resonance Imaging; Male; Phenobarbital; Radiography; Severity of Illness Index; Syndrome; Topiramate; Treatment Outcome

Dyke-Davidoff-Masson syndrome is a disorder involving hemiatrophy or hypoplasia of 1 cerebral hemisphere secondary to an insult in the developing brain. Often this will manifest with seizures, hemiparesis, mental retardation, and facial changes. Associated with this pathology are the radiologically evident changes, such as thickening of the calvarium, hyperpneumatization of the sinuses, and dilation of the ipsilateral lateral ventricle among others. The following is a case presentation of an 18-year-old female emigrating from Ghana who presented to the emergency department with complaints of seizures diagnosed as being caused by cerebral malaria at 13 years of age. We hypothesize that the cerebral malaria and related vascular occlusion are the causes of her acquired cerebral changes. Included are computed tomography images.

Topics: Adolescent; Anticonvulsants; Atrophy; Cerebral Cortex; Epilepsy; Female; Frontal Sinus; Fructose; Ghana; Humans; Hyperostosis; Lateral Ventricles; Malaria, Cerebral; Skull; Syndrome; Tomography, X-Ray Computed; Topiramate; Treatment Outcome

SUNCT Syndrome (short-lasting unilateral neuralgiform headache with conjuntival injection and tearing) combines neuralgic, migraineus and autonomic headaches, three of four primary ones described in the International Classification of the IHS (International Headache Society). This work describes a paediatric case evaluated under MIDAS score in which a new therapeutic approach with topiramate (TPM) was used.

Topics: Adolescent; Conjunctiva; Fructose; Humans; Male; Migraine Disorders; Neuralgia; Syndrome; Tears; Topiramate

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

The cerebellar cognitive affective syndrome (CCAS) represents a spectrum of cerebellar-induced neurocognitive and affective disturbances. In this report a patient is described who developed CCAS under a treatment with standard daily dose of the anti-epileptic drug topiramate (TPM). Cognitive disturbances consisted of impaired visuo-spatial memory, concentration deficits and executive dysfunctions. Behavior and affect were characterized by marked mood-swings and several disinhibited symptoms. After a gradual discontinuation of treatment with topiramate, a complete remission of the cognitive and affective symptoms was observed within 6 weeks. Functional neuroimaging studies by means of SPECT were conducted 2 weeks and 8 months following TPM discontinuation. This case report seems to suggest that functional disruption of the cerebello-cerebral circuitry, leading to CCAS, can follow treatment with topiramate.

Topics: Amines; Anticonvulsants; Carbamazepine; Cerebellar Diseases; Cerebellum; Cognition Disorders; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Middle Aged; Mood Disorders; Neuropsychological Tests; Oxcarbazepine; Syndrome; Topiramate; Treatment Outcome

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

Cyclic vomiting syndrome is a disorder characterized by recurrent attacks of vomiting and intervals of normal health between vomiting episodes averaging 2-4 weeks. It has been described by a variety of names such as abdominal migraine, abdominal epilepsy, and periodic syndrome but now has been classified in the subgroup of childhood periodic syndromes that are commonly precursors of migraine. Topiramate is an antiepileptic drug used both in the treatment of epilepsy and in migraine prophylaxis. This report presents a child with cyclic vomiting syndrome with generalized epileptiform discharges who responded to topiramate therapy. The common features of epilepsy, migraine, and cyclic vomiting syndrome are discussed.

Topics: Anticonvulsants; Brain; Child; Electroencephalography; Female; Fructose; Humans; Periodicity; Syndrome; Topiramate; Vomiting

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

A 15-year-old boy with inverted duplication of chromosome 15 was admitted for acute onset of irritability, increasing sleepiness, and worsening of seizures. He had been on valproate and other anti-convulsants. However, he was found to have hyperammonemia within 2 weeks after the addition of low-dose topiramate to valproate. He recovered within 7 days after discontinuation of valproate. Topiramate was tailed off. The reintroduction of valproate monotherapy caused hyperammonemia again without clinical features of encephalopathy. He also developed anticonvulsant hypersensitivity syndrome following the use of phenytoin. We propose the term topiramate-valproate-induced hyperammonemic encephalopathy syndrome to include the following features: excessive sleepiness or somnolence, aggravation of seizures, hyperammonemia, and absence of triphasic waves on electroencephalography in any individual on simultaneous topiramate-valproate therapy. The ammonia level ranged from 1.5 to 2 times normal. The serum valproate level might be within the therapeutic range. The possible mechanism is topiramate-induced aggravation of all the known complications of valproate monotherapy. This condition is reversible with cessation of either valproate or topiramate.

Topics: Adolescent; Anticonvulsants; Brain Diseases; Chromosome Inversion; Chromosomes, Human, Pair 15; Drug Therapy, Combination; Epilepsy; Fructose; Humans; Hyperammonemia; Male; Syndrome; Topiramate; Valproic Acid

Two cases of paroxysmal hemicrania (PH) associated with trigeminal neuralgia are reviewed. The paroxysmal hemicrania component in one patient was episodic, while it was chronic in the other. Each headache type responded completely to separate treatment, highlighting the importance of recognizing this association. We review the six other cases of chronic paroxysmal hemicrania-tic (CPH-tic) reported, and suggest that the term paroxysmal hemicrania-tic syndrome (PH-tic) be used to describe this association.

Topics: Aged; Carbamazepine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fructose; Humans; Indomethacin; Male; Middle Aged; Syndrome; Topiramate; Trigeminal Neuralgia; Vascular Headaches; Verapamil

Topics: Acute Disease; Anticonvulsants; Choroid; Ciliary Body; Fructose; Glaucoma, Angle-Closure; Humans; Myopia; Syndrome; Topiramate; Uveal Diseases

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Drug Approval; Fructose; Humans; Seizures; Syndrome; Topiramate; United States; United States Food and Drug Administration

Topics: Central Nervous System Vascular Malformations; Conjunctival Diseases; Drug Resistance; Fructose; Headache Disorders; Humans; Male; Middle Aged; Migraine with Aura; Neuroprotective Agents; Refractory Period, Electrophysiological; Syndrome; Topiramate

Several epileptic syndromes that occur during childhood are characterized by severe treatment-resistant seizures, progressive loss of higher intellectual functions, and characteristic electroencephalographic abnormalities. These catastrophic epileptic syndromes include epileptic encephalopathy with diffuse slow spike waves (Lennox-Gastaut syndrome), West syndrome, progressive myoclonic epilepsies, and electrical status epilepticus during sleep. This article summarizes each syndrome and reviews the most recent information concerning the effectiveness of topiramate with respect to each condition. Suggestions are offered to help clinicians maximize topiramate's efficacy and tolerability in patients suffering with these syndromes. Overall, topiramate is a valuable antiepileptic medication in the treatment of catastrophic pediatric epileptic syndromes.

Topics: Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy; Fructose; Humans; Randomized Controlled Trials as Topic; Syndrome; Topiramate; Treatment Outcome