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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with epilepsy, particularly infants, differ from adults not only in the clinical manifestations of their seizures but also in the presence of unique electroencephalographic patterns, etiologies, and response to antiepileptic drugs (AEDs). There is a growing list of newer AEDs and nonpharmacologic therapies available to manage childhood epilepsy. These newer AEDs may not be overall more efficacious than the older drugs, but they do appear to be safer, better tolerated, and to have fewer drug-drug interactions. Selection of the AED for initial therapy must be based upon clinical judgment and patient-specific circumstances, such as the specific epilepsy syndrome being treated, anticipated duration of treatment, presence of comorbidities, ability to use certain formulations, and overall cost effectiveness. In some cases, seizures may be aggravated by the use of certain AEDs. Overall, oxcarbazepine is the first-line treatment for localization-related epilepsy with partial-onset seizures. For generalized epilepsies, the AED choice is highly dependent upon which specific syndrome is being treated. For generalized epilepsies with primarily absence seizures, lamotrigine is the AED of first choice. For mixed generalized epilepsies such as Lennox-Gastaut syndrome or juvenile myoclonic epilepsy, zonisamide or topiramate are the first-line agents. For infants with West syndrome, treatment is based upon the underlying etiology: vigabatrin for tuberous sclerosis; adrenocorticotropic hormone for children with no specific etiology uncovered (cryptogenic); and zonisamide for those with a severe symptomatic etiology other than tuberous sclerosis. Single drug therapy (monotherapy) is the goal of epilepsy treatment because this is associated with better compliance, fewer adverse effects, and lower cost. If the seizures prove intractable or adverse effects are encountered with the first AED, then a second monotherapy trial is undertaken. Once three appropriate medications at therapeutic doses have failed, other modalities should be considered, including epilepsy surgery, vagus nerve stimulation, and the ketogenic diet.
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PMID:Use of the newer antiepileptic drugs in pediatric epilepsies. 1758 6

We describe a case of West syndrome with the balanced translocation t(X;18)(p22;p11.2). Treatment with high-dose vitamin B6, adrenocorticotropic hormone, thyrotropin-releasing hormone, and antiepileptic compounds was not effective, and the patient exhibited persistent refractory seizures and severe developmental delays. Although no mutation analysis and X chromosome inactivation were performed, we suggest that the chromosomal abnormality in the present patient is the main etiologic factor responsible for the infantile spasms and severe developmental delay.
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PMID:West syndrome in a patient with balanced translocation t(X;18)(p22;p11.2). 1762 26

From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before (group A: eight patients), simultaneously (group B: eight patients), and after (group C: six patients) a diagnosis of human CMV (HCMV) infection and antiviral treatment. In 11 patients, DNA CMV [corrected] was found in cerebrospinal fluid by nested-polymerase chain reaction method (neuroinfection). All infants excreted CMV in urine. DNA CMV [corrected] and specific immunoglobulin M and immunoglobulin G antibodies were present in blood. Ten patients, including four with neuroinfection, have been seizure-free for at least the past 18 months. In two patients with neuroinfection, vigabatrin monotherapy was withdrawn after a 2 year 6 month seizure-free period. Eighteen patients required antiepileptic drugs polytherapy, four of whom required additional adrenocorticotropic hormone (ACTH). Six patients on polytherapy were seizure-free on follow-up, two of whom were treated with ACTH, but one patient [corrected] who required ACTH [corrected] was seizure-free on follow-up. In five patients, psychomotor development was normal, 16 had tetraplegia (Gross Motor Function Classification System [GMFCS] Level V), and one had diplegia (GMFCS Level III). Early antiviral and antiepileptic therapy could result in the long-term cessation of seizures.
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PMID:Infantile spasms and cytomegalovirus infection: antiviral and antiepileptic treatment. 1771 25

Vitamin B(12) deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B(12) deficiency can be difficult when the typical macrocytic anaemia is absent. We report the case of a 10-month-old female diagnosed with West syndrome associated with vitamin B(12) deficiency but without macrocytic anaemia caused by nutritional inadequacy in the mother. The patient's motor skills and cognitive development were normal until she was 9 months old, when she began to exhibit a series of sudden flexions of the head, trunk, arms, and legs. She was exclusively breast-fed and had received no vitamin supplementation. Results of electroencephalography (EEG) indicated modified hypsarrhythmia and the patient was diagnosed as having West syndrome. Synthetic adrenocorticotropic hormone was administered and although her spasms had resolved, the patient remained apathic and could not sit without assistance. EEG results indicated generalized slow activity. After she was diagnosed as having vitamin B(12) deficiency, parenteral treatment with vitamin B(12) was initiated. Her symptoms resolved and EEG was completely normal. When she was 20 months old she exhibited an age-appropriate developmental and neurological profile. To our knowledge, this is the first report of West syndrome as a presenting symptom of vitamin B(12) deficiency.
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PMID:West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia. 1875 25

Genetic variation in G protein-coupled receptors (GPCRs) results in the disruption of GPCR function in a wide variety of human genetic diseases. In vitro strategies have been used to elucidate the molecular pathologies that underlie naturally occurring GPCR mutations. Various degrees of inactive, overactive, or constitutively active receptors have been identified. These mutations often alter ligand binding, G protein coupling, receptor desensitization, and receptor recycling. The role of inactivating and activating calcium-sensing receptor (CASR) mutations is discussed with respect to familial hypocalciuric hypercalemia (FHH) and autosomal dominant hypocalemia (ADH). Among ADH mutations, those associated with tonic-clonic seizures are discussed. Other receptors discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone, luteinizing hormone, gonadotropin-releasing hormone (GnRHR), adrenocorticotropic hormone, vasopressin, endothelin-beta, purinergic, and the G protein associated with asthma (GPRA). Diseases caused by mutations that disrupt GPCR function are significant because they might be selectively targeted by drugs that rescue altered receptors. Examples of drug development based on targeting GPCRs mutated in disease include the calcimimetics used to compensate for some CASR mutations, obesity therapeutics targeting melanocortin receptors, interventions that alter GnRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor in a rare bleeding disorder. The discovery of GPRA suggests that drug screens against variant GPCRs may identify novel drugs. This review of the variety of GPCRs that are disrupted in monogenic disease provides the basis for examining the significance of common pharmacogenetic variants.
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PMID:G protein-coupled receptors disrupted in human genetic disease. 1837 Feb 33

To determine a management strategy for the epilepsy in children with bilateral cortical malformations, clinical data of 23 patients (age, 3-23 years, M:F=7:16) were retrospectively reviewed. Among these patients, 15 were bedridden and 16 were profoundly retarded and could not even smile. The patients were categorized into the following five groups based on the findings of neuroimaging, seizure types, and electroencephalographic patterns. Group 1: Diffuse cortical malformation with epileptic spasms and secondarily generalized tonic seizures, group 2: diffuse cortical malformation with erratic twitches, group 3: bilaterally extended but not diffuse cortical malformations, group 4: bilateral polymicrogyria with persistent epileptic spasms (Aicardi syndrome), and group 5: bilateral cortical malformation with drop attacks (subcortical band heterotopia and congenital bilateral perisylvian syndrome). Eleven patients suffered from infantile spasms; adrenocorticotropic hormone was effective in group 1 but ineffective in group 4. Treatment of tonic seizures in groups 1-3 and erratic twitching in group 3 with phenobarbital, zonisamide and potassium bromide was beneficial. Epileptic spasms and tonic seizures were prominent in group 4 and were refractory to medical treatment, except that zonisamide, clobazam, and a ketogenic diet were partially or transiently effective. Complex partial and astatic/atonic seizures in group 5 were refractory to medications other than that carbamazepine and clobazam provided limited benefits. Total callosotomy resulted in better seizure control for three patients in group 5, and functional hemispherectomy was effective for one patient in group 4. These results provide the basis for the appropriate choice of medical and surgical treatment for managing bilateral, widespread cortical malformations.
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PMID:Treatment of epilepsy in severely disabled children with bilateral brain malformations. 1903 89

This commentary discusses a retrospective study by Muzykewicz et al. that details EEG results from children with infantile spasms in the setting of tuberous sclerosis complex (TSC). In this study, several factors were identified as being predictive of poor cognitive outcome, including worsening degree of hypsarrhythmia, abnormalities in EEG background activity, and incomplete response to vigabatrin. Notably, the majority of patients had a poor outcome, experiencing cognitive impairment and intractable epilepsy irrespective of whether they were treated with adrenocorticotropic hormone (corticotropin) or vigabatrin, despite the fact that vigabatrin has shown promise in previous studies. However, among the entire cohort a third of patients enjoyed greater than 1 year of seizure freedom and about a quarter had either mild or no cognitive impairment at follow-up. Overall, these findings underscore the great challenges that are faced in the treatment of infantile spasms in patients with TSC. I suggest that, while vigabatrin has been shown to have impressive short-term efficacy, the intractable seizures and cognitive impairment in many patients with TSC strongly indicate that new therapies and treatment strategies are urgently needed.
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PMID:Treatment of infantile spasms in tuberous sclerosis complex: dismal outcomes but future hope? 1910 7

Both seizures and antiepileptic drugs may induce disturbances in hormonal system. Regarding endocrine effects of anticonvulsants, an interaction of these drugs with gonadal, thyroid, and adrenal axis deserves attention. Since majority of antiepileptic drugs block voltage dependent sodium and calcium channels, enhance GABAergic transmission and/or antagonize glutamate receptors, one may expect that similar neurochemical mechanisms are engaged in the interaction of these drugs with synthesis of hypothalamic neurohormones such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH). Moreover some antiepileptic drugs may affect hormone metabolism via inhibiting or stimulating cytochrome P-450 iso-enzymes. An influence of antiepileptic drugs on hypothalamic-pituitary-gonadal axis appears to be sex-dependent. In males, valproate decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but elevated dehydroepiandrosterone sulfate (DHEAS) concentrations. Carbamazepine decreased testosterone/sex-hormone binding globulin (SHBG) ratio, whereas its active metabolite--oxcarbazepine--had no effect on androgens. In females, valproate decreased FSH-stimulated estradiol release and enhanced testosterone level. On the other hand, carbamazepine decreased testosterone level but enhanced SHBG concentration. It has been reported that carbamazepine, oxcarbazepine or joined administration of carbamazepine and valproate decrease thyroxine (T4) level in patients with no effect on thyrotropin (TSH). While valproate itself has no effect on T4, phenytoin, phenobarbital and primidone, as metabolic enzyme inducers, can decrease the level of free and bound thyroxine. On the other hand, new antiepileptics such as levetiracetam, tiagabine, vigabatrine or lamotrigine had no effect on thyroid hormones. With respect to hormonal regulation of metabolic processes, valproate was reported to enhance leptin and insulin blood level and increased body weight, whereas topiramate showed an opposite effect. In contrast to thyroid and gonadal hormones, only a few data concern antiepileptic drug action in HPA axis. To this end, no effect of antiepileptic drugs on adrenocorticotropic hormone (ACTH)/cortisol circadian rhytmicity was found. Valproate decreased CRH release in rats, whereas lamotrigine stabilized ACTH/cortisol secretion. Moreover, felbamate was found to inhibit stress-induced corticosterone release in mice. Interestingly, recent data suggest that felbamat and some other new antiepileptic drugs may inhibit transcriptional activity of glucocorticoid receptors. Summing up, the above data suggest that traditional antiepileptic drugs may cause endocrine disturbances, especially in gonadal hormones.
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PMID:[Endocrine effects of antiepileptic drugs]. 1920 63

Smith-Magenis syndrome is characterized by multiple congenital anomalies and mental retardation caused by the heterozygous deletion of chromosomal region 17p11.2. We present a long-term follow-up study of a girl with Smith-Magenis syndrome and West syndrome. West syndrome became apparent at 7 months of age. Since then, mental retardation, particularly in terms of language development, became increasingly more obvious. The patient's spasms and hypsarrhythmia disappeared after a course of adrenocorticotropic hormone therapy, but focal seizures reappeared at the age of 3 years and 3 months. Her craniofacial dysmorphia and mental retardation became increasingly evident compared to her condition at the onset of West syndrome. Chromosome analysis detected the characteristic 17p deletion, which was then confirmed via fluorescent in situ hybridization analysis. This is the second report of a patient with Smith-Magenis syndrome and West syndrome; taken together, these results suggest that Smith-Magenis syndrome may be a further cause of West syndrome.
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PMID:Smith-Magenis syndrome with West syndrome in a 5-year-old girl: a long-term follow-up study. 1926 35

We describe two cases of a non-epileptic florid movement disorder presenting as status epilepticus. Both patients presented with florid jerking of the limbs and eyes. Convulsive status epilepticus related to presumed meningitis or encephalitis was suspected in both cases. The patients received treatment for seizures, without resolution of the abnormal movements, resulting ultimately in anaesthetic, intubation and ventilation. EEGs showed no epileptic discharges. The diagnosis was opsoclonus myoclonus syndrome in both. One patient was treated with adrenocorticotropic hormone (40 IU/day), the other with prednisolone (4 mg/kg/day) with rapid resolution of symptoms. Neither patient had an underlying neoplasm or infectious agent identified. To date, neither patient has suffered a relapse of symptoms nor does either show any sign of developmental delay. These cases show that the movements in opsoclonus myoclonus syndrome can be sufficiently florid to mimic convulsive status epilepticus. Video footage of both patients at the time of diagnosis is presented online.
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PMID:Opsoclonus myoclonus: a non-epileptic movement disorder that may present as status epilepticus. 1984


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