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Rational treatment of refractory epilepsy in childhood.

A multifaceted study on childhood refractory epilepsy disclosed an insufficient classification of epilepsies and epileptic seizures, and inappropriate polypharmacy as the most important factors preventing appropriate therapy. By means of an adjustment of AEDs based on the accurate classification of epilepsies and epileptic seizures, the number of AEDs could be reduced in 37.5% and monotherapy was successful in 13.8% of refractory cases. Most of the latter were those of partial epilepsy and generalized epilepsy with the monoseizure type. The exacerbation of seizures due to AEDs was also mentioned as one of the important side effects of AEDs.

Adolescent↗

Psychopathology in epilepsy: relationship of seizure type to age at onset.

Study of patients with temporal lobe epilepsy and generalized epilepsy revealed no overall seizure type differences, nor overall age-at-onset effects, on MMPI measures of psychopathology. However, statistically significant interactions between seizure type and age at onset were obtained on several MMPI measures, and subsequent analyses revealed that patients with adolescent-onset temporal lobe epilepsy are at higher risk of developing psychological dysfunctions.

Adolescent↗

Recognition impairment correlated with short bisynchronous epileptic discharges.

The occurrence of transitory cognitive impairment during diffuse subclinical electroencephalographic (EEG) discharges has been widely documented but the role of the parameters influencing the cognitive performance and the involvement of motor or verbal response in the tasks used is still under debate. Fifteen patients suffering from primary generalized epilepsy with frequent bisynchronous EEG epileptic bursts underwent a shape recognition task during EEG monitoring. The test sequence was as follows: memorandum, pause, and multiple choice set. After pressing the response button, the patient was asked to confirm the choice verbally. The following parameters were considered: geometrical complexity of the shape, chronological position of the burst occurring during the single test, and the duration of discharge ranging from 1 to 3 s. Results showed a significant increase in incorrect responses during the test when discharges occurred, with more errors occurring for difficult than for easy shapes. Neither the discharge position nor the duration of the epileptic burst influenced the performance. Diffuse epileptic activity of short duration produced selective effects on the cognitive process regardless of the motor component of the response.

Adolescent↗

Effects of generalized interictal EEG discharges on sleep stability: assessment by means of cyclic alternating pattern.

Generalized interictal EEG discharges are influenced by a biphasic (phase A and B) modality of arousal control during non-rapid eye movement (REM) sleep termed cyclic alternating pattern (CAP). Each phase A and the following phase B compose a CAP cycle. The percentage ratio of total CAP time to total non-REM sleep time is the CAP rate, a sleep parameter that measures the instability and fragmentation of sleep. Since CAP exerts a powerful influence on generalized interictal EEG discharges during sleep, the polysomnograms of seven epileptic patients affected by a clinically active form of primary generalized epilepsy were matched with those of seven healthy volunteers of the same age and sex to assess the influence of interictal discharges on sleep organization. No remarkable differences emerged when the traditional polysomnographic parameters were compared between the two groups. However, the epileptic patients showed significantly higher CAP rate values (52.7 vs. 34.6%; p less than 0.003), indicating a greater arousal instability in the sleep records of these subjects. Within the epileptic group, the CAP cycles that included at least one interictal paroxysm were significantly longer than those without EEG discharges (31.2 vs. 25.4 s; p less than 0.007). The selective lengthening of CAP cycles is likely due to an exaggeration of the natural activating power of phase A when coupled with EEG paroxysms and an intensification of the inhibitory properties of the following phase B. The dynamic relationships and differences between spindles in animals, k-complexes, and slow-wave bursts in humans may have a functional linkage with epileptic phenomena during sleep.

Adolescent↗

Absence seizures and carbamazepine in adults.

Carbamazepine (CBZ) therapy was associated with development of absence seizures in 4 adults with generalized epilepsy. Two patients had new appearance of absence seizures and 2 patients had recrudescence of remote absence seizures. The seizures abated after discontinuation of CBZ therapy or addition of ethosuximide (ESM) in 1 patient intolerant of valproate (VPA).

Adult↗

Benzodiazepine-GABAA receptor binding during absence seizures.

The role of benzodiazepine (BZD)-gamma-aminobutyric acidA (GABAA) receptors in the pathogenesis of absence seizures is uncertain. In this study, we examined the effect of absence seizures on the binding of flumazenil to the BZD binding site of the GABAA receptor. Five patients with idiopathic generalized epilepsy (IGE) were studied at rest and during absence seizures with [11C]flumazenil and positron emission tomography (PET). Normalized regional cerebral time-activity curves from the resting and ictal scans were compared with each other and with computed simulations showing the effects of changes in cerebral blood flow (CBF) and [11C]flumazenil binding. No evidence was found for a change in [11C]flumazenil binding with absence seizures. This result, together with those of a recent study showing no abnormality of [11C]flumazenil binding interictally in patients with childhood and juvenile absence epilepsy (JAE) does not support a primary role for the BZD binding site of the GABAA receptor in the pathogenesis of absence seizures.

Adolescent↗

Typical absence status in adults: diagnostic and syndromic considerations.

PURPOSE: To study the electroclinical features of typical absence status (TAS) in adults with syndromes of idiopathic generalized epilepsies (IGEs). METHODS: Twenty-one patients with one or more spells of TAS were identified among 136 consecutive adult patients with IGEs. All patients with TAS had comprehensive electroclinical investigations and EEG or video-EEG recorded absences. RESULTS: TAS occurred in 24.4% of 86 patients who had IGEs with typical absences alone or in combination with other seizures presisting in adult life. The prevalence of TAS appeared to be syndrome related, ranging from as high as 57.1% in perioral myoclonia with absences and 46.2% in "phantom" absences with GTCS to as low as 6.7% in juvenile myoclonic epilepsy. A varying degree of impairment of cognition was the cardinal clinical symptom shared in all TAS, but corresponding syndromes of IGE were often betrayed by other symptoms such as eyelid or perioral myoclonia. In phantom absences with GTCS, TAS was more numerous (p < or = 0.05) and more frequently the first overt seizure type (p = 0.006) than in any other IGE. Only in the syndrome of eyelid myoclonia with absences, TAS was always situation related, mainly as a result of antiepileptic drug discontinuation. CONCLUSIONS: The clinical EEG semiology and prevalence of TAS appear to be syndrome related with the highest prevalence in the syndromes of perioral myoclonia with absences and phantom absences with GTCS (p = 0.0024).

Adult↗

Evolutional changes and outcome of West syndrome: correlation with magnetic resonance imaging findings.

The prognosis and evolutional changes of 77 patients with West syndrome (WS) were studied after patients were classified into four groups on the basis of their magnetic resonance imaging (MRI) findings: anomaly, perinatal injury, normal, and the other groups. The average age at onset of spasms was earliest in the patients with anomalies and latest in patients with normal MRI findings. Patients with normal MRI findings had the shortest duration of spasms, and patients with anomalies had the longest duration of spasms. Antecedent seizures were observed in 6 patients (3 patients with anomalies, 1 patient with normal MRI findings, and 2 patients with other abnormalities). Thirty-five patients had subsequent seizures. Patients with anomalies often had partial seizures and patients with perinatal injuries often had generalized seizures. Seizures were infrequent in patients with normal MRI findings. Developmental outcome was best in the patients with normal MRI findings and worst in patients with perinatal injuries. Various types of epileptic syndromes occurred subsequent to WS in patients with anomalies, although nonspecific symptomatic generalized epilepsy was common in patients with perinatal injuries. These results suggest that seizure prognosis, evolutional changes in seizures, and developmental outcome are different among the types of brain lesions.

Adolescent↗

A case of extended spectrum GEFS+.

A 10-year-old boy developed febrile convulsions at age 2 years, and multiple types of nonfebrile generalized seizures over the ensuing months and years. Gestation, birth, and early development were normal, as were initial EEG and brain imaging studies. By age 5 years, he had developed behavioral difficulties, and the EEG demonstrated both interictal and ictal generalized epileptiform patterns, as well as mild background slowing. Seizures were poorly controlled with multiple medication trials. There was a strong family history of clinically benign febrile seizures in the maternal lineage. Genetic analysis revealed a novel mutation in the voltage-gated neuronal sodium channel SCN1A. This patient's relatively malignant clinical course is consistent with "extended spectrum" generalized epilepsy with febrile seizures plus (GEFS+), and along with the family history illustrates the phenotypic variability of this disease.

Child↗

Lamotrigine-induced rash--worth a rechallenge.

OBJECTIVES: The only serious adverse event associated with lamotrigine (LTG) treatment is a hypersensitivity reaction primarily presenting as a rash. Despite this concern, LTG is an antiepileptic drug (AED) with one of the most favorable efficacy/tolerability ratio compared with the new as well as the old AEDs. Thus, this study aimed to evaluate the results of rechallenge with LTG after the initial rash. MATERIAL AND METHODS: A total of 688 patients (350 as monotherapy, and 338 as add-on therapy) with either idiopathic generalized epilepsy or focal epilepsy were treated with LTG. The patients with LTG-induced rash were rechallenged to LTG. The dosage schedule was: 5 mg every day or every second day for 14 days, increased by 5 mg every 14th day to 25 mg a day. After achieving the daily dosage of 25 mg/day, the up-titration was completed following the current guidelines. RESULTS: A total of 52 patients developed a rash. The LTG-induced rash occurred in 6%, where 12 (1.8%) developed a rash shown to be coincidentally associated with the initiation of LTG therapy. In their cases LTG was continued with success without intermission. Nineteen (38%) of the initial cohort were rechallenged with LTG, with a success rate of 84%. CONCLUSION: This study is the first one to provide a successful recipe verified in time for the rechallenge with LTG after the initial drug-induced rash. Importantly, the concurrent use of valproate (VPA) was not found in this study to represent an additional risk factor for the occurrence of the rash during rechallenge with LTG. Our results agree with previous findings that women are more likely to develop the rash (P < 0.009).

Anticonvulsants↗

Sex hormones, gonadotropins and prolactin in male epileptic subjects in remission: role of the epileptic syndrome and of antiepileptic drugs.

Sex steroid peripheral pattern, pulsatile luteinizing hormone (LH) secretion, gonadotropin and prolactin responses to LH-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) were studied in 35 male epileptics treated with phenobarbital (PB), carbamazepine (CBZ), or phenytoin (PHT), and in age-matched healthy males. Idiopathic generalized epilepsy (IGE) was diagnosed in 12 cases and partial epilepsy (PE) in 23 cases. Patients were seizure-free and did not show EEG abnormalities at repeated controls in the last 5 years, so that interfering effects of seizures were possibly excluded. The aim of the study was to evaluate both the role of epileptic syndromes and of anti-epileptic drugs on the endocrine function. Changes in sex hormone binding globulin, total and free testosterone, dihydrotestosterone and delta 4-androstenedione were found to be independent of the epileptic syndrome type. The LH response to LHRH was lower in PB-treated PE than in IGE subjects on the same drug regimen. An impairment of LH pulsatility with respect to controls was found in PE but not in IGE patients taking PB. Among antiepileptic drugs, PHT is associated with higher sex hormone binding globulin and estradiol and lower free testosterone and dihydrotestosterone levels. PB and CBZ, but not PHT, blunt the LH response to exogenous LHRH in PE. Prolactin responses to TRH were consistently enhanced in PE subjects treated with CBZ or PHT.

Adult↗

Attitudes towards epilepsy in general practice.

Little is known about the attitudes of general practitioners (GPs) towards epilepsy or of the attitudes they attribute to laypersons. Postal questionnaires returned by 50 GPs permitted an analysis of the main sources of their knowledge of epilepsy, the role of GPs in treating patients with epilepsy, the personalities and behaviour of people with epilepsy, and the psychological and social consequences of having epilepsy. The results were compared with a recent Australian survey and the implications for care discussed.

Adult↗

Ion channels and the genetic contribution to epilepsy.

Recent application of genetic analysis to rare, hereditary epilepsies has resulted in the identification of mutations in genes encoding ion channels or functionally related proteins in several human and animal syndromes. Reviewed here are selected human and murine epilepsies that result from ion channel mutations. In humans, three autosomal-dominant disorders--benign familial neonatal convulsions, nocturnal frontal lobe epilepsy, and "generalized epilepsy with febrile seizures plus"--result from mutations affecting voltage-sensitive potassium channels, a central nicotinic acetylcholine receptor, and a voltage-sensitive sodium channel, respectively. In mice, four genetically distinct, autosomal-recessive models of absence epilepsy are caused by mutations in genes encoding three types of calcium channel subunits and a sodium-hydrogen ion exchanger. These findings suggest that variation in genes encoding ion channels could determine susceptibility to common human epilepsies.

Chromosome Aberrations↗

Epileptic syndromes in children with somatosensory evoked spikes.

We studied 186 children with frequent EEG paroxysms evoked by tapping of the feet or hands (ES). Seventy-five (40.3%) patients had a history of epileptic seizures. Febrile convulsions alone occurred in 31 (16.7%) of the children and nonfebrile in 44 cases (23.7%). Non-febrile seizures occurred in a greater proportion among patients with ES than in a control group with normal EEG. Spontaneous epileptiform activity was recorded in 39.6% of the patients without epileptic seizures but in a great percentage of the children with seizures (85.3%). The non-febrile seizures were partial in 26 cases and generalized in 18. In 39 of these cases the EEG also showed spontaneous focal spikes, which occurred predominantly in the parietal regions in 24 cases. ES were observed in different types of partial and generalized epilepsies of childhood. Our findings also suggest that in an important proportion of cases there is a benign condition of a functional nature that is age-dependent, involving mainly the parietal lobe but in which seizure type does not so easily permit definition as a clearly characterized epileptic entity compared to other recognized idiopathic partial childhood epilepsies.

Adolescent↗

Structural changes in patients with primary generalized tonic and clonic seizures.

We conducted MR volumetry and voxel-based morphometry in 19 patients who had idiopathic generalized epilepsy (IGE) with tonic clonic seizures as the only seizure type and 52 control subjects. Patients exhibited elevated frontal lobe fraction of CSF and reduced fraction of gray matter in the frontal, parietal, temporal cortex, thalamus, and cerebellum. The thalamus and cerebellum also showed reduced volumes, as did the caudate and putamen. Contrary to current diagnostic criteria, regional tissue abnormalities may be present in IGE.

Adult↗

Zonisamide: newer antiepileptic agent with multiple mechanisms of action.

Zonisamide (Zonegran, Eisai, Inc.) is a broad spectrum antiepileptic drug indicated for use as adjunctive therapy in the treatment of partial seizures. Zonisamide has multiple mechanisms of action, which may explain widespread reports of its utility in focal epilepsy and generalized epilepsy, and for nonseizure disorders such as headache and neuropathic pain. Zonisamide has been available in Japan since 1989 and became available in the USA in 2002. The rights to this drug in North America and Europe were recently acquired by Eisai Co. A review of the chemical properties, pharmacokinetics, metabolism, potential mechanisms of action, efficacy in seizure and nonseizure disorders, and tolerability was therefore thought to be timely.

Animals↗

[Occipital epileptiform activity with or without blockade with eye opening: a comparative clinico-electroencephalographic study].

Occipital epileptiform activity blocked by eyes opening (OEAB) is primarily observed in childhood epilepsy with occipital paroxysms but may be also found in cases of benign childhood epilepsy with centrotemporal spikes, cryptogenic/symptomatic partial epilepsies, idiopathic generalized epilepsies and in patients with no seizures. We studied comparatively EEG and clinical features of 20 patients with OEAB and 120 patients with occipital epileptiform activity not suppressed by eyes opening (OEA). Epileptiform activity (OEA or OEAB) was registered until the 7 years of age in 67.5% of the patients with OEA and in 45% of the patients with OEAB. Epileptic seizures began before 4 years of age in 44.4% of the cases with OEA and in 14.2% in the group OEAB. Febrile convulsions alone occurred only in the OEA group (12.5%). Developmental retardation was referred in 27 patients with OEP. The occurrence of spike and wave complexes was statistically more frequent among patients with OEAB (80.0%) as opposed to patients with OEA (17.5%). Our findings suggest clinical and electroencephalographic differences between children with OEA and OEAB.

Adolescent↗

Wavelength dependency of photoparoxysmal responses in photosensitive nonepileptic subjects.

Using specially made optical filters, we analyzed the wavelength dependency of photoparoxysmal responses (PPRs) in five photosensitive nonepileptic subjects. The wavelength spectrum around 700 nm (680-700 nm) was estimated as the only visible spectrum essential for eliciting PPRs in two normal trichromat nonepileptic subjects, although the effect of some wavelength spectra (360-400 nm and 520-580 nm) was uncertain. The wavelength dependency of PPRs in two photosensitive nonepileptic subjects was the same as that found in some patients with photosensitive idiopathic generalized epilepsy.

Adolescent↗