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Genome-wide linkage scan of epilepsy-related photoparoxysmal electroencephalographic response: evidence for linkage on chromosomes 7q32 and 16p13.

Photoparoxysmal response (PPR) is an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. It is an epilepsy-related electroencephalographic trait with high prevalence in idiopathic epilepsies, especially in common idiopathic generalized epilepsies (IGEs), such as childhood absence epilepsy and juvenile myoclonic epilepsy. This degree of co-morbidity suggests that PPR may be involved in the predisposition to IGE. The identification of genes for PPR would, therefore, aid the dissection of the genetic basis of IGE. Sixteen PPR-multiplex families were collected to conduct a genome-wide linkage scan using broad (all PPR types) and narrow (exclusion of PPR types I and II and the occipital epilepsy cases) models of affectedness for PPR. We found an empirical genome-wide significance for parametric (HLOD) and non-parametric (NPL) linkage (Pgw(HLOD)=0.004 and Pgw(NPL)=0.01) for two respective chromosomal regions, 7q32 at D7S1804 (HLOD=3.47 with alpha=1, P(NPL)=3.39x10(-5)) and 16p13 at D16S3395 (HLOD=2.44 with alpha=1, P(NPL)=7.91x10(-5)). These two genomic regions contain genes that are important for the neuromodulation of cortical dynamics and may represent good targets for candidate-gene studies. Our study identified two susceptibility loci for PPR, which may be related to the underlying myoclonic epilepsy phenotype present in the families studied.

Chromosome Mapping↗

Mutation screen of GABRA1, GABRB2 and GABRG2 genes in Japanese patients with absence seizures.

Absence seizures are classified into typical and atypical absences according to clinical and EEG characteristics. Although missense mutations in the GABA(A) receptor gamma2 subunits (GABRG2) gene have recently been detected in two families with typical absence seizures, no study has been carried out to clarify the relationship between atypical absence and GABA(A) receptors. We performed mutation analysis of all the coding exons of GABA(A) receptor alpha1, beta2 and gamma2 subunit (GABRA1, GABRB2 and GABRG2) genes by direct sequencing to clarify whether there was common molecular biological mechanism underlying both typical and atypical absences. We recruited 52 unrelated Japanese patients, thirty-eight with typical absences and 14 with atypical absences. They consisted of 38 with childhood absence epilepsy, three with Lennox-Gastaut syndrome, two with epilepsy with myoclonic-astatic seizures and nine with epilepsy with continuous spike-waves during slow wave sleep. All of the subjects were idiopathic or cryptogenic cases without any organic brain lesions or underlying diseases. We detected five polymorphisms (T156C in GABRA1, C1194T in GABRB2, and C315T, T588C and C1230T in GABRG2), and they are silent mutations. In conclusion, mutations in GABRA1, GABRB2 and GABRG2 do not seem to be a major genetic cause of epilepsy with typical and atypical absences in Japanese subjects.

DNA Mutational Analysis↗

Valproic acid therapy inducing absence status evolving into generalized seizures.

The authors herein present two children with mild absence epilepsy, having intermittent absences, who developed absence status evolving into atonic generalized seizures and drop attacks along with progressive disorientation induced by relatively small doses of valproic acid. Consciousness and awareness were intact before the introduction of valproic acid. Both children, after the first dose of valproic acid, developed prolonged and recurrent clusters of absences, which became prolonged, with drop attacks occurring in one patient associated with progressive disorientation. The electroencephalogram concurrently demonstrated prolonged spike-wave discharges, along with disturbance of background activity. Discontinuation of valproic acid resulted in immediate cessation of the prolonged and repetitive clusters of absence episodes and disappearance of drop attacks, along with sensorium clearing. In conclusion, although uncommon, a possible induction of absence status and even atonic seizures by valproic acid should be taken into account and properly managed by abrupt discontinuation of the drug.

Anticonvulsants↗

A study of newly diagnosed epilepsy in Malaysia.

BACKGROUND/AIM OF STUDY: To determine the characteristics of newly diagnosed epilepsy in the multiracial population of Malaysia. METHODS: This is a prospective study of 165 consecutive newly diagnosed cases of epilepsy presenting to the neurology laboratory of the University Hospital, Kuala Lumpur. The inclusion criteria were: two or more seizures with interval of > 24 hours, age > 1 month, residents of Klang Valley. All the patients underwent an awake and sleep EEG. RESULTS: One hundred and sixty-five cases were collected over 1992-1994. Their ethnic origin was: Chinese (36%), Indian (35%), Malay (29%). The mean age of onset of epilepsy was 18.7 years. Localisation related epilepsies accounted for 57.6% of cases while the remaining 42.4% were generalised epilepsies. Of the generalised epilepsies, subclassification was as follows: idiopathic generalised epilepsy 28.5%, juvenile myoclonic epilepsy 5.5%, childhood absence epilepsy 3.6%, West syndrome 3%, Lennox Gastaut syndrome 1.2% and photosensitive epilepsy 0.6%. Twenty-two percent of the cases were symptomatic and 78% were cryptogenic/idiopathic. The patients had a mean of 3.9 other siblings. Only 0.76% of the close relatives (parents and siblings) had a history of epilepsy. CONCLUSION: The characteristics of epilepsy in Malaysia is largely similar to those reported elsewhere. Genetic factors may be playing a relatively minor role in causing epilepsy in this community.

Adolescent↗

A prevalence study of epilepsy in Hong Kong.

OBJECTIVES: To examine epidemiological data on epilepsy for the Hong Kong west region. DESIGN. Descriptive study. SETTING: Epilepsy clinic, university teaching hospital, Hong Kong. PATIENTS AND METHODS: The epilepsy clinic of Queen Mary Hospital manages the majority of adult patients (aged 15 years or older) with chronic seizure disorders resident in the Hong Kong west area with an adult population of 475,900. All patients underwent electroencephalography examination and each subject was independently assessed by two epileptologists for diagnosis and classified according to the International League Against Epilepsy recommendations. RESULTS: Seven hundred and thirty-six patients (female, 42.9%; male, 57.1%; mean age, 40.8 years; standard deviation, 13.6 years) with epilepsy were enrolled in the study. The prevalence rate of active epilepsy in the population 15 years or older was estimated at 1.54 per 1000 on 1 January 2002. Two hundred and eighty-five (38.7%) patients had idiopathic epilepsy syndromes, 100 (13.6%) had cryptogenic epilepsy, and 285 (38.7%) had a remote symptomatic aetiology. Seizure type was partial in 408 (55.4%) patients and generalised in 285 (38.7%). Thirty-one (4.2%) patients had a positive family history. Idiopathic generalised epilepsy syndromes described as common in the literature, such as juvenile myoclonic epilepsy and childhood absence epilepsy, were infrequently seen at 0.68% and 0.95% of cases, respectively. CONCLUSIONS: This study provides baseline data for epilepsy service development and research in Hong Kong. The prevalence rate of active epilepsy in this Chinese, adult population was low compared with that reported in other developed countries. Further population-based epidemiological research is indicated to confirm the prevalence of seizure disorders in this locality.

Adolescent↗

[Genetics and genetic counselling in childhood epilepsy (author's transl)].

According to electroencephalographical studies on the pathogenesis of epilepsy a hereditary predisposition plays a greater role than believed before. It is far more frequent than the manifest disease. The phenomenon of cerebral excitability is influenced by different genetically determined, differently age- and sexdependent but amongst each other independent factors. When defining the risk of epilepsy for siblings and descendents in practice, one is forced to proceed from the statistical empirical value with all its uncertainty. During the past few years, the figures have become more exact for special types of epilepsy as absence-epilepsy, myoclonic astatic Petit mal, and Impulsiv-Petit mal. Details of these results and their consequences for genetic advice are discussed.

Adolescent↗

Sleep and epilepsy: A key role for nitric oxide?

PURPOSE: It has been suggested that nitric oxide (NO) is involved in sleep mechanisms and in the pathophysiology of epilepsy. Data are, however, controversial because it is not clear whether NO facilitates sleep or waking, or whether it exerts pro-or antiepileptic influences. METHODS: The question was considered through NO voltammetric measurements and electroencephalographic recordings performed in GAERS rats (Genetic Absence Epilepsy Rat from Strasbourg): an experimental model of "petit-mal" human disease. Regulatory processes of sleep and epilepsy were studied after administration of a NO synthase inhibitor [l-arginine-p-nitroanilide (l-ANA) 100 mg/kg i.p.], a NO donor (SIN-1 100 ng/2 microl i.c.v.), and the antiepileptic drugs used in clinic [valproate (VPA 200 mg/kg i.p.) and ethosuximide (ESM 100 mg/kg i.p.)]. RESULTS: In GAERS rats, spontaneous circadian organizations of spike-wave discharges and paradoxical sleep (PS) occur in an opposite way; spontaneous NO concentrations are higher during seizures than during wakefulness, slow-wave sleep, and PS, respectively. l-ANA induces a disappearance of NO peak, an epileptic induction, and a loss of PS while SIN-1 induces opposite effects. Antiepileptic effects of VPA and ESM are associated with a PS increase and a significant release of NO. CONCLUSIONS: These results indicate that NO could be, in GAERS rats, a central piece in the reciprocal inhibitory mechanisms regulating the induction of PS and spike-wave discharges. NO could prevent absence epilepsy and act as an antiepileptic substance in facilitating PS. Antiepileptic efficiency of VPA and ESM may work through their ability to release NO. A track for a new treatment of petit-mal disease in children can be envisioned.

Animals↗

Absences in juvenile myoclonic epilepsy: a clinical and video-electroencephalographic study.

We report a prospective clinical and electroencephalographic study of 19 patients with juvenile myoclonic epilepsy and absence seizures. Absences began 1 to 9 (4.5 +/- 2.5) years before myoclonic jerks and generalized tonic-clonic seizures. Clinical manifestations during the absence ictus showed great variation, ranging from subtle or no overt features to severe impairment of consciousness, and severity was age related. Simple and complex absence seizures can occur in the same patient. The electroencephalographic features were distinct, with many interictal discharges, fragmentation of the paroxysms, and frequent polyspikes of varying numbers and amplitude for each spike-slow wave component. The combined clinical-electroencephalographic manifestations were characteristic and allow differentiation of absences in juvenile myoclonic epilepsy from typical absence seizures in other epileptic syndromes.

Adolescent↗

Experimental absence seizures: potential role of gamma-hydroxybutyric acid and GABAB receptors.

We have investigated whether the pathogenesis of spontaneous generalized non-convulsive seizures in rats with genetic absence epilepsy is due to an increase in the brain levels of gamma-hydroxybutyric acid (GHB) or in the rate of its synthesis. Concentrations of GHB or of its precursor gamma-butyrolactone (GBL) were measured with a new GC/MS technique which allows the simultaneous assessment of GHB and GBL. The rate of GHB synthesis was estimated from the increase in GHB levels after inhibition of its catabolism with valproate. The results of this study do not indicate significant differences in GHB or GBL levels, or in their rates of synthesis in rats showing spike-and-wave discharges (SWD) as compared to rats without SWD. Binding data indicate that GHB, but not GBL, has a selective, although weak affinity for GABAB receptors (IC50 = 150 microM). Similar IC50 values were observed in membranes prepared from rats showing SWD and from control rats. The average GHB brain levels of 2.12 +/- 0.23 nmol/g measured in the cortex and of 4.28 +/- 0.90 nmol/g in the thalamus are much lower than the concentrations necessary to occupy a major part of the GABAB receptors. It is unlikely that local accumulations of GHB reach concentrations 30-70-fold higher than the average brain levels. After injection of 3.5 mmol/kg GBL, a dose sufficient to induce SWD, brain concentrations reach 240 +/- 31 nmol/g (Snead, 1991) and GHB could thus stimulate the GABAB receptor. Like the selective and potent GABAB receptor agonist R(-)-baclofen, GHB causes a dose-related decrease in cerebellar cGMP. This decrease and the increase in SWD caused by R(-)-baclofen were completely blocked by the selective and potent GABAB receptor antagonist CGP 35348, whereas only the increase in the duration of SWD induced by GHB was totally antagonized by CGP 35348. The decrease in cerebellar cGMP levels elicited by GHB was only partially antagonized by CGP 35348. These findings suggest that all effects of R(-)-baclofen are mediated by the GABAB receptor, whereas only the induction of SWD by GHB is dependent on GABAB receptor mediation, the decrease in cGMP being only partially so. Taken together with the observations of Marescaux et al. (1992), these results indicate that GABAB receptors are of primary importance in experimental absence epilepsy and that GABAB receptor antagonists may represent a new class of anti-absence drugs.

4-Butyrolactone↗

Physiological and pathological spindling phenomena have similar regional EEG power distributions.

Sleep spindles in human and in rat are known to have a thalamocortical substrate. It has also been suggested that absence epilepsy spike and wave discharges may be generated by a similar mechanism. In addition, we have previously reported a possible thalamocortical origin of the EEG spindling rhythmic discharges associated with myoclonic jerks in the picrotoxin rat model of primary generalised epilepsy. To investigate whether pathological and physiological brain rhythms have common mechanisms of generation, we analysed four electroencephalographic (EEG) spindling activities in the rat. These were the non-convulsive spindle discharges induced by picrotoxin (picrotoxin spindles), naturally occurring absence epilepsy spike and wave discharges (absence spindles), spindle discharges during natural sleep (sleep spindles) and spindling activity that occurs under barbiturate anaesthesia (barbiturate spindles). We used power spectral analysis to define and compare the strength and brain distribution of EEG power during the spindling activities in 12 forebrain and 7 brainstem regions. There were brain-wide differences in power for each of the different spindle types with the pathological rhythms of the epilepsies containing more power than the physiological rhythms. There were also similar differences in the expression of spindles related to the region examined and no thalamic emphasis. These results provide evidence for a similar regional EEG power distribution for all four types of spindling activity and thus for the different spindles being expressions of a single phenomenon.

Analysis of Variance↗

Changes in blood flow of the middle cerebral artery during absence seizures.

Blood flow velocities (BFVs) of the middle cerebral artery were measured by transcranial Doppler blood flowmeter in 2 patients with childhood absence epilepsy; a total of 8 absence seizures were recorded. BFV began to decrease 7-9 sec after the appearance of diffuse bilateral 3 Hz spike-and-wave bursts on electroencephalography, reaching the trough 0-8 sec after the disappearance of spike-and-wave bursts which was followed by BFV recovery with rebound phenomenon. BFV then returned to the pre-ictal value within 1 min after the seizure ended. Pulsatility index increased in accordance with BFV decrease.

Adolescent↗

A dissociation of gamma-butyrolactone-induced absence seizure and CRE- and AP-1 DNA-binding activities in the developing rat brain.

Generalized absence epilepsy is a neurological childhood disorder which is characterized by behavioral arrest with staring and by 3 Hz spike and wave discharges (SWDs) in the electroencephalogram (EEG). In the present study, we investigated the correlation between behavioral and EEG changes and nuclear cAMP-responsive element (CRE)- and activator protein-1 (AP-1) DNA-binding activities during gamma-butyrolactone (GBL)-induced absence seizure in the developing rat brain. In the adult postnatal day 60 (P60) rat brain, both the transcription factor activation and absence seizure in behavior and EEG were simultaneously induced 15 min after GBL injection. In the infant P20 rat or young P40 rat, a higher sensitivity to GBL induced absence epilepsy in behavior and EEG 10-15 min after injection compared with that of adult rat. By contrast, no significant increase of CRE- and AP-1 DNA-binding activities could be seen in the infant thalamus. A significant increase in CRE- and AP-1 DNA-binding activities first occurred in the P30-40 young thalamus at 30 and 90 min, respectively, after GBL injection. Such a dissociation of high inducibility of behavior and EEG changes and low inducibility of CRE- and AP-1 DNA-binding activities in the infant or young rat clearly indicates that the activation of nuclear CRE- and AP-1 DNA-binding activities is a late occurring phenomenon with a different developmental maturation of thalamocortical circuit compared with absence seizure.

4-Butyrolactone↗

Epilepsy with myoclonic absences.

The cases are described of eight children, five of them girls, who had epilepsy with myoclonic absences. The mean age of onset was 4.9 years. Brief episodes of loss of awareness with bilateral clonic jerking of the upper limbs were associated with rhythmic 3 cycles/second spike-wave discharges on electroencephalogram. Generalised tonic-clonic or astatic seizures, or both, also occurred in seven patients. All now have learning difficulties, and seven have behavioural problems. Conventional treatment for absences was effective in only two children. Of six patients treated with lamotrigine, five have improved substantially, but only one is in sustained complete remission. One recently diagnosed patient continues to have frequent myoclonic absences. As the response to treatment and long term outcome are much poorer, it is important to differentiate myoclonic absences from typical childhood absence epilepsy.

Anticonvulsants↗

Association of mu-opioid receptor subunit gene and idiopathic generalized epilepsy.

OBJECTIVE: To replicate and extend the previously reported association between the opioid receptor mu subunit gene (OPRM1) and idiopathic absence epilepsy (IAE), using a sample of 230 probands with idiopathic generalized epilepsy (IGE). BACKGROUND: In humans and in animal models, several lines of evidence implicate opioid receptors with seizures. The G118 allele of OPRM1 was associated with IAE (p = 0.019). METHODS: Three single nucleotide polymorphisms (SNP) of OPRM1 were investigated by association studies with IGE using a case/control design, one of which also used a within-family design. RESULTS: Association was found for G118 with IGE (p = 0.00027, odds ratio [OR] = 1.86), replicating the previous association. Within-family tests of linkage and association (haplotype-based haplotype relative risk and transmission disequilibrium test) confirmed this result. Further evidence for involvement of OPRM1 in IGE was provided by an association with G-172T, located in the 5' untranslated region (p = 0.0015, OR = 2.36). Haplotypes of the two SNPs were associated with IGE with a greater level of significance (p = 0.000087) suggesting that both SNPs might be in linkage disequilibrium with a single functional variant. Analysis of the results by subgroups of IGE showed association with all subgroups tested. CONCLUSIONS: These results confirm the previous association and support the hypothesis of a role for OPRM1 in IGE, including absence syndromes. However, the authors found no evidence for a specific association between OPRM1 and idiopathic absence epilepsy. The data suggest that the functional variant predisposing to IGE is located within 60kb of exon 1.

Adult↗

Spike-and-wave epilepsy in rats: sex differences and inheritance of physiological traits.

Spontaneously occurring spike-and-wave patterns were examined in seven to eight-month-old rats of the inbred Fischer 344 and Brown Norway strains and their F1 and F2 hybrids. Neocortical activity and movement were monitored for 12 night h. Spike-and-wave episodes were identified by a three-layer back-propagation neural network. The incidence, average duration and total duration of spike-and-wave episodes were significantly higher in F1 males and F2 hybrids than in the parental strains. Male rats of the Brown Norway strain had significantly more and longer episodes than females, whereas no sex differences were present in Fischer rats. The average intraepisodic frequency of spike-and-wave patterns was significantly lower in Fischer rats than in the other groups and significantly higher in males than females. Tremor (myoclonic movements) associated with spike-and-wave episodes was absent or of very small amplitude in Fischer rats but frequent and of large amplitude in Brown Norway rats and their F1 and F2 descendants. Most of the interstrain differences were limited to male rats. Spike-and-wave episodes recurred at predictable short-term (10-30 s) and long-term (15-30 min) periods. The long-term oscillation corresponded to a similar fluctuation of motor activity. The maximum probability of spike-and-wave patterns occurred at a relatively narrow range of delta power (0-3.1 Hz) of the background EEG activity. Systemic administration of the adrenergic alpha-2 agonist, clonidine, increased the incidence of spike-and-wave episodes several-fold. The total duration of spike-and-wave episodes in the clonidine sessions (15 min) and night sessions (12 h test) correlated significantly. We suggest that several genes interact with maturational, environmental and endocrine factors, resulting in sex differences, and produce the variety of EEG and behavioral findings encountered. In addition, we submit that the clonidine test may be useful in genetic investigations of human absence epilepsies. The findings of this work demonstrate that genetic manipulation of rodents is a promising method for producing analogous models for the various forms of human absence epilepsies.

Animals↗

Focal cortical-subcortical calcifications (FCSCs) and epilepsy in the Indian subcontinent.

PURPOSE: A focal cortical-subcortical calcification (FCSC) is a common finding on computed tomography (CT) in individuals with focal or generalized seizures in the Indian subcontinent. We sought to determine the relation of FCSCs to epilepsy by comparing the lobe of seizure origin by electroclinical and CT evaluations and to study the nature and severity of epilepsy associated with FCSCs. METHODS: The relation of these FCSCs to epilepsy/seizures was studied in 40 patients, seen for the first time to the neurology outpatient department of a tertiary care hospital. An attempt was made to classify seizures and determine their lobe of origin based on clinical-electroencephalographic (EEG) criteria of the International League Against Epilepsy (ILAE). The clinical lobe of origin was compared with the location of the FCSC on CT scan. In addition, records of the CT unit of the same hospital were reviewed retrospecitvely, to identify cases with an FCSC and their referral diagnoses. RESULTS: Thirty-one (77.5%) patients with FCSCs were considered to have localization-related epilepsy (frontal lobe epilepsy, 20; temporal lobe epilepsy, three; parietal lobe epilepsy, one; occipital lobe epilepsy, three; and definitely localization related but having ambiguous localization features, four) based on ictal semiology and EEG studies. Other ILAE categories in the cohort included epilepsy without unequivocal focal or generalized features (four patients; 10%), isolated seizures (one patient; 2.5%), juvenile absence epilepsy (one patient; 2.5%), and insufficient data to classify epilepsy (three patients; 7.5%). Radiologic sites for FCSCs included frontal (20; 50%), temporal (six; 15%), parietal (seven; 17.5%), and occipital (seven; 17.5%). Electroclinical and radiologic data were congruent in localizing and lateralizing seizures in 22 (55%) patients. The FCSC was truly incidental in one patient with juvenile absence epilepsy. Discordance between the clinical and radiologic localizations was noted in five (12.5%) instances. Magnetic resonance imaging (MRI) did not reveal additional lesions corresponding to lobes of origin as determined by electroclinical analysis. Discordance was surmised to be a result of seizure spread from a silent region to symptomatic cortex. In 12 (30%) patients, electroclinical and radiologic congruence could not be ascertained because ictal descriptions were either inadequate or ambiguous, and EEG findings were noncontributory. Review of 4,452 CT scans of brain performed in the CT unit revealed 29 (0.65%) cases with FCSCs in individuals with nonseizure disorders, that could be labeled as incidental. CONCLUSIONS: An FCSC is an important radiologic finding in localization-related epilepsy in the Indian subcontinent. The severity of epilepsy ranges from asymptomatic cases to daily seizures.

Adolescent↗

Treatment of pediatric epilepsy: expert opinion, 2005.

BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that differ in diagnostic criteria and management and have dramatically different outcomes. Despite increasing data on treatment of epilepsy, research findings on childhood epilepsy are more limited and many clinical questions remain unanswered, so that clinicians must often rely on clinical judgment. In such clinical situations, expert opinion can be especially helpful. METHODS: A survey on pediatric epilepsy and seizures (33 questions and 645 treatment options) was sent to 41 U.S. physicians specializing in pediatric epilepsy, 39 (95%) of whom completed it. In some questions, the experts were asked to recommend overall treatment approaches for specific syndromes (the order in which they would use certain strategies). Most of the questions asked the experts to rate options using a modified version of the RAND 9-point scale for medical appropriateness. Consensus was defined as a non-random distribution of scores by chi-square test, with ratings used to assign a categorical rank (first line/usually appropriate, second line/equivocal, and third line/usually not appropriate) to each option. RESULTS: Valproate was treatment of choice for symptomatic myoclonic and generalized tonic-clonic seizures except in the very young, with lamotrigine and topiramate also first line (usually appropriate). Zonisamide was first line only if the child also has myoclonic seizures. For initial monotherapy for complex partial seizures, oxcarbazepine and carbamazepine were treatments of choice, with lamotrigine and levetiracetam also first line. As initial therapy for infantile spasms caused by tuberous sclerosis, viagabatrin was treatment of choice, with adrenocorticotropic hormone (ACTH) also first line. As initial therapy for infantile spasms that are symptomatic in etiology, ACTH was treatment of choice, with topiramate also first line. As initial therapy for Lennox-Gastaut syndrome, valproate was treatment of choice, with topiramate and lamotrigine also first line. For acute treatment of a prolonged febrile seizure or cluster of seizures, rectal diazepam was treatment of choice. For benign childhood epilepsy with centro-temporal spikes, oxcarbazepine and carbamazepine were treatments of choice, with gabapentin, lamotrigine, and levetiracetam also first line. For childhood absence epilepsy, ethosuximide was treatment of choice, with valproate and lamotrigine also first line. For juvenile absence epilepsy, valproate and lamotrigine were treatments of choice. For juvenile myoclonic epilepsy in adolescent males, valproate and lamotrigine were treatments of choice, with topiramate also first line; for juvenile myoclonic epilepsy in adolescent females, lamotrigine was treatment of choice, with topiramate and valproate other first-line options. As initial therapy for neonatal status epilepticus, intravenous phenobarbital was treatment of choice, with intravenous lorazepam or fosphenytoin also first line. As initial therapy for all types of pediatric status epilepticus, lorazepam was treatment of choice, with intravenous diazepam also first line. For generalized tonic-clonic status epilepticus, rectal diazepam and fosphenytoin were also first line; for complex partial status epilepticus, fosphenytoin was also first line; and for absence status epilepticus, intravenous valproate was also first line. CONCLUSION: The expert panel reached consensus on many treatment options. Within the limits of expert opinion and with the understanding that new research data may take precedence, the experts' recommendations provide helpful guidance in situations where the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.

Adolescent↗