topiramate and Nervous-System-Diseases

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

Topiramate (TPM) is an O-alkyl sulfamate derivative of the naturally occurring monosaccharide D-fructose with an epileptic activity. However, it has been suggested that, in addition to its use in epilepsy, TPM could also be used in the treatment of neurological disorders, psychiatric conditions and hyperkinetic movement disorders. The clinical applications of TPM in hyperkinetic movement disorders is consistent with the multiple pharmacodynamic mechanisms e.g., the modulation of both γ-aminobutyric acidergic or glutamatergic neurotransmission and the modulation of voltage-gated ion channels or intracellular signalling pathways. The purpose of the present review is to describe the mechanisms of action of TPM and its clinical efficacy in patients with hyperkinetic movement disorders.

Topics: Animals; Fructose; Humans; Hyperkinesis; Movement Disorders; Nervous System Diseases; Neuroprotective Agents; Topiramate

Nervous system adverse drug reactions (NS-ADRs), such as cognitive complaints and paresthesia, are among the most frequent and clinically important ADRs of topiramate. Studying ADR profiles across disorders is clinically relevant because treatment decision-making in neuropsychiatry is highly guided by ADR profiles.. We used medline searches (until July 2009) to review the NS-ADRs of topiramate across the most investigated topiramate indications: alcohol dependence, essential tremor, binge-eating disorder, bulimia nervosa, migraine and epilepsy. We compared NS-ADRs between these disorders but did not carry out meta-analysis.. ADR profiles greatly differed between disorders. Drop-outs due to ADRs highly varied between disorders: from 2% in the bulimia nervosa group to 29% in the migraine group. Paresthesia was the most common NS-ADR for all disorders but frequencies also differed between disorders. Cognitive complaints were frequent and were reported in comparable proportions.. When prescribing topiramate in neuropsychiatry, physicians should be aware that NS-ADR profiles have been found to differ between disorders. Differences in drop-out rates due to ADRs and in frequencies of specific NS-ADRs across disorders must be taken into account when evaluating the potential harm of topiramate in clinical practice.

Topics: Brain Diseases; Fructose; Humans; Mental Disorders; Nervous System Diseases; Neuroprotective Agents; Paresthesia; Randomized Controlled Trials as Topic; Topiramate

Initially synthesized as an oral hypoglycemic agent, topiramate was approved for use as an anticonvulsant in 1996. Its broad spectrum efficacy in epilepsy, including as monotherapy and in children, is well established. Topiramate has also been used in the management of nonepileptic neurologic and psychiatric conditions, including migraine prophylaxis (with firmly established efficacy), obesity (with some evidence of long-term maintenance of weight loss), substance dependence, bipolar disorder and neuropathic pain, and it has been investigated as a possible neuroprotective agent. Paresthesias and cognitive side effects are the most common troublesome adverse effects. Recent trends towards lower doses may help achieve the best combination of efficacy and tolerability.

Topics: Clinical Trials as Topic; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Expert Testimony; Fructose; Humans; Nervous System Diseases; Neuroprotective Agents; Topiramate

Topiramate is a drug that has shown efficacy in the treatment of epilepsy. A survey of MEDLINE, EMBASE and the American Academy of Neurology Abstracts reveals there is now evidence that topiramate is also effective in the treatment of neuropathic pain. The dose that has been studied ranges from 25 mg to 800 mg with a suggested dose of 400 mg daily. However, further randomized, double blind studies are needed to confirm this new use of topiramate and explore the proper dose and mechanism of action. Topiramate is conspicuous amongst the antiepileptic drugs for being well tolerated and having fewer drug interactions. Thus, it might offer an advantage over such drugs.

Topics: Clinical Trials as Topic; Dose-Response Relationship, Drug; Fructose; Humans; Nervous System Diseases; Neuroprotective Agents; Pain; Topiramate

Neuropathic cranial pain, i.e. pain due to central or peripheral nervous system damage localized in cranial area, is a clinical challenge for the neurologist. Despite major advances in knowledge of physiology and biochemistry of pain, relief for many patients suffering from neuropathic pain remains incomplete. Adjuvant analgesics play a key role in the management of neuropathic pain. The introduction in the therapeutical armamentarium of antiepileptic drugs and the results derived from clinical studies indicate that some of these compounds show promise in the treatment of neuropathic pain.

Topics: Acetates; Amines; Analgesics; Analgesics, Non-Narcotic; Anticonvulsants; Antidepressive Agents, Tricyclic; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Fructose; Gabapentin; gamma-Aminobutyric Acid; Headache; Humans; Lamotrigine; Nervous System Diseases; Phenytoin; Topiramate; Triazines

The aim of this study was to examine the efficacy and safety of topiramate as an adjunct to diet and exercise in drug-naive, obese subjects with type 2 diabetes.. Drug-naive individuals with type 2 diabetes, body mass index (BMI) of > or =27 and <50 kg/m(2) and haemoglobin A(1c) (HbA(1c)) of <10.5% were enrolled into the study. All the individuals participated in a non-pharmacologic weight loss program (Pathways to Change((R)); Johnson & Johnson Healthcare Systems, Piscataway, NJ, USA) throughout the trial. After a 6-week placebo run-in, the subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Subjects were scheduled for 8-week titration and 52-week maintenance phases. The study was ended early; efficacy data were reported for a predefined modified intent-to-treat (MITT) population (n = 229), with 40 weeks of treatment. All the subjects who provided any safety data were included in the safety population (n = 535).. Baseline mean weight was 103.7 kg, BMI 36 kg/m(2) and HbA(1c) 6.7% across all treatment groups. By the end of week 40, the placebo, the topiramate 96 mg/day and topiramate 192 mg/day groups lost 2.5, 6.6 and 9.1% of their baseline body weight respectively (p < 0.001 vs. placebo, MITT population using last observation carried forward). The decrease in HbA(1c) was 0.2, 0.6 and 0.7% respectively (p < 0.001 vs. placebo, MITT). Topiramate significantly reduced blood pressure and urinary albumin excretion; a weight-loss-independent HbA(1c) improving effect of topiramate was demonstrated. Adverse events were predominantly related to central nervous system (CNS).. Topiramate as an add-on treatment to lifestyle improvements produced significant weight loss and improved glucose homeostasis in obese, drug-naive subjects with type 2 diabetes. These treatment advantages should be balanced against the occurrence of adverse events in the CNS.

Topics: Albuminuria; Anti-Obesity Agents; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Fructose; Glycated Hemoglobin; Humans; Lipid Metabolism; Male; Middle Aged; Nervous System Diseases; Obesity; Topiramate; Treatment Outcome; Weight Loss

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

We conducted a multicenter, double-blind, randomized, parallel, placebo-controlled trial in 190 patients to evaluate the safety and efficacy of three dosages of topiramate (600, 800, and 1,000 mg/day) as adjunctive therapy for patients with refractory partial epilepsy. During an 18-week double-blind treatment period, median percent reductions from baseline in average monthly seizure rates were 1% for placebo, 41% for topiramate 600 mg/day and topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. There was a 50% or greater reduction from baseline in seizure frequency in 9% of patients in the placebo group and in 44% for topiramate 600 mg/day, 40% for topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. No placebo patients were improved by 75 to 100% in seizure frequency, whereas 20% of the topiramate patients were improved to this degree. All intent-to-treat drug-placebo comparisons including seizure reduction, percent responders, and investigator and patient global evaluations significantly (p < or = 0.02) favored topiramate. Treatment-emergent adverse events consisted mainly of neurologic symptoms commonly observed during antiepileptic drug (AED) therapy. Sixteen percent of patients on topiramate discontinued therapy due to adverse events. Results of this study indicate that topiramate is a highly efficacious and generally well tolerated new AED. When large groups of patients are compared, incremental efficacy in the add-on setting is not observed at topiramate dosages above 600 mg/day; however, higher doses may prove beneficial to individual patients who tolerate them.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Carboplatin; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Fructose; Headache; Humans; Male; Middle Aged; Nervous System Diseases; Phenytoin; Safety; Topiramate; Treatment Outcome

We conducted a randomized double-blind comparison of three doses of the novel antiepileptic drug (AED) topiramate (200, 400, and 600 mg/day) and placebo as adjunctive therapy in patients with refractory partial onset epilepsy receiving one or two other AEDs at therapeutic concentrations. A total of 181 patients completed the 12-week baseline phase and were randomized to double-blind therapy. Median percent reductions from baseline in average monthly seizure rate, the principal efficacy evaluation, were 13% for placebo, 30% for topiramate 200 mg/day, 48% for topiramate 400 mg/day, and 45% for topiramate 600 mg/day. For the seizure rate comparison of active drug to placebo p values were: topiramate 200 mg/day, p = 0.051; topiramate 400 mg/day, p = 0.007; topiramate 600 mg/day, p < 0.001. Percent responders ( > or = 50% reduction in seizure rates) were 18% for placebo, 27% for topiramate 200 mg/day, 47% for topiramate 400 mg/day (p = 0.013), and 46% for topiramate 600 mg/day (p = 0.027). A significant (p = 0.003) reduction in secondarily generalized seizures compared with placebo treatment was also documented with topiramate. Topiramate plasma concentrations were closely related to dosage, and there were no significant interactions between topiramate and other AEDs. The minimal effective dose of topiramate in this study population was approximately 200 mg/day. Mild or moderate CNS symptoms were the primary treatment-emergent adverse events, but treatment-limiting adverse events occurred in only 9% of patients given topiramate compared with 7% given placebo. Results of this initial well-controlled study in patients indicate that topiramate is a very promising new AED.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsies, Partial; Female; Fructose; Headache; Humans; Male; Middle Aged; Nervous System Diseases; Safety; Topiramate; Treatment Outcome

Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of AHC remain unknown. The long-term effects of flunarizine or topiramate on patients with AHC are still not clear.. Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated.. Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreoathetotic movements, dystonia, and ataxia. However, seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy.. The findings from the present study support flunarizine or topitamate as the rational treatment for AHC.

Topics: Adolescent; Anticonvulsants; Asian People; Child; Child, Preschool; Female; Flunarizine; Fructose; Hemiplegia; Humans; Intelligence; Longitudinal Studies; Male; Movement Disorders; Nervous System Diseases; Retrospective Studies; Surveys and Questionnaires; Topiramate

The aim of this study is to investigate the neuroprotective effects of the anticonvulsant topiramate in a new model of traumatic brain injury in rats. A new model of traumatic brain injury, based on the weight-drop technique, was developed for the purpose of this study. Seventy-five male Wistar rats weighing 320-470 g were studied. All rats were anesthetized, subsequently submitted to a round craniectomy in the left parietal region and a weight of 50 g was used for the production of a cortical contusion. In study I, 44 rats were randomized in three groups to receive either topiramate 40 mg/kg (n=13), topiramate 60 mg/kg (n=14), or water for injection (n=17) i.p. 30 min after the injury and every 12 h thereafter for 3 days. The rats were tested clinically 24 h, 72 h, 10 days and 20 days after the injury. On day 21 the animals were sacrificed and the brains were removed and prepared for histopathological analysis. In study II, 19 rats were randomized to receive either topiramate 60 mg/kg (n=10) or water for injection (n=9) i.p. 30 min after the injury and every 12 h (four doses in total). 48 h after the injury the animals were sacrificed and the brains were rapidly removed and analyzed for water content with the dry-wet weight technique. The animals that received topiramate performed significantly better in neurological tests compared to the animals that received vehicle ten (P<0.05) and 20 (P<0.001) days after the injury. There was no difference between the high and the low dose of the drug. Topiramate had no effect on the anatomic volume of the lesion. The animals that received topiramate had a tendency to present with less cerebral edema formation, but the difference was not statistically significant (P>0.05). These findings suggest that topiramate promotes neurological recovery in rats after traumatic brain injury without affecting the final size of the traumatic lesion and that it might play a role in the reduction of post-traumatic cerebral edema.

Topics: Animals; Brain Edema; Brain Injuries; Disease Models, Animal; Fructose; Functional Laterality; Male; Multivariate Analysis; Nervous System Diseases; Neurologic Examination; Neuroprotective Agents; Rats; Rats, Wistar; Recovery of Function; Time Factors; Topiramate

To characterize weight changes in patients with neurodevelopmental disabilities who received topiramate.. Retrospective, observational study.. State-supported developmental center.. Fifteen patients with neurodevelopmental disabilities who received topiramate therapy. Monthly weights for 1 year after the start of topiramate therapy were recorded. Mean body weight at drug initiation differed significantly compared with the nadir weight during the next 12 months (52.2+/-7.5 vs 49.9+/-7.2 kg, p<0.02). Twelve patients who were receiving ad libitum oral diets demonstrated a significant decrease in body weight (52.1+/-7.5 vs 49.0+/-7.3 kg, p<0.01), whereas the three patients who received enteral nutrition through enterostomy did not experience significant weight loss.. Weight loss is common in patients with neurodevelopmental disabilities who receive topiramate. Since patients who received oral diets lost weight whereas those receiving enteral nutrition did not, decreased nutrient intake is the likely cause of weight loss.

Topics: Adult; Enteral Nutrition; Female; Fructose; Humans; Male; Middle Aged; Nervous System Diseases; Retrospective Studies; Seizures; Statistics, Nonparametric; Topiramate; Weight Loss