Spike-wave Activity Research Articles

Three cases of right frontal megalencephaly: Clinical characteristics and long-term outcome

AimTo delineate the clinical and neuroimaging characteristics of localized megalencephaly involving the right frontal lobe. MethodData from three patients aged 14–16years at the last follow-up were retrospectively reviewed. ResultsAll the patients were normal on neurological examination with no signs of hemiparesis. Enlargement of the right frontal lobe with increased volume of subcortical and deep white matter, as well as thickening of the ipsilateral genu of the corpus callosum was common. The onset of epilepsy was 4–7years of age, with seizure types of massive myoclonus in two and generalized tonic-clonic in two, which could be eventually controlled by antiepileptics. Interictal electroencephalography showed frontal alpha-like activity in one, and abundant spike–wave complexes resulting in diffuse continuous spike–wave activity during sleep in two patients even after suppression of clinical seizures. Psychomotor development appeared unaffected or slightly delayed before the onset of epilepsy, but became mildly disturbed during follow-up period of 7–11years. ConclusionCertain patients with right frontal megalencephaly can present with a milder epileptic and intellectual phenotype among those with localized megalencephaly and holohemispheric hemimegalencephaly, whose characteristic as epileptic encephalopathy was assumed from this study.

3-(1′-Cyclobutylspiro[4H-1,3-benzodioxine-2,4′-piperidine]-6-yl)-5,5-dimethyl-1,4-dihydropyridazin-6-one (CEP-32215), a new wake-promoting histamine H3 antagonist/inverse agonist

CEP-32215 is a new, potent, selective, and orally bioavailable inverse agonist of the histamine H3 receptor (H3R) with drug-like properties. High affinity in human (hH3R Ki = 2.0 ± 0.2 nM) and rat (rH3R Ki = 3.6 ± 0.7 nM) H3R radioligand binding assays was demonstrated. Potent functional antagonism (Kb = 0.3 ± 0.1 nM) and inverse agonism (EC50 = 0.6 ± 0.2 nM) were demonstrated in [35S]guanosine 5′-O-(γ-thio)-triphosphate binding assays. Oral bioavailability and dose-related exposure was consistent among rat, dog, and monkey. After oral dosing, occupancy of H3R by CEP-32215 was estimated by the inhibition of ex vivo binding in rat cortical slices (ED50 = 0.1 mg/kg p.o.). Functional antagonism in brain was demonstrated by the inhibition of R-α-methylhistamine-induced drinking in the rat dipsogenia model (ED50 = 0.92 mg/kg). CEP-32215 significantly increased wake duration in the rat EEG model at 3–30 mg/kg p.o. Increased motor activity, sleep rebound or undesirable events (such as spike wave or seizure activity) was not observed following doses up to 100 mg/kg p.o., indicating an acceptable therapeutic index. CEP-32215 may have potential utility in the treatment of a variety of sleep disorders.This article is part of the Special Issue entitled ‘Histamine Receptors’.

Modulatory effects of inosine, guanosine and uridine on lipopolysaccharide-evoked increase in spike-wave discharge activity in Wistar Albino Glaxo/Rijswijk rats.

We showed previously that the number of spike-wave discharges (SWDs) was increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), inosine (Ino) and muscimol alone whereas i.p. guanosine (Guo), uridine (Urd), bicuculline, theophylline and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) alone decreased the SWD number in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These drugs may exert their effects on absence epileptic activity mainly via proinflammatory cytokines-evoked increase in cortical excitability (such as LPS), GABAergic system (LPS, Ino, Urd, muscimol and bicuculline), glutamatergic system (LPS, Guo and MK-801) and adenosinergic system (LPS, Ino, Guo, Urd and theophylline). Both GABAergic system and glutamatergic system are involved in the pathomechanism of absence epilepsy, the LPS-evoked increase in absence epileptic activity and the pro- or antiepileptic effects of non-adenosine (non-Ado) nucleosides Ino, Guo and Urd. Moreover, Ino, Guo and Urd have modulatory effects on inflammatory processes. Thus, we investigated whether Ino, Guo and Urd have also modulatory influence on LPS-evoked increase in SWD number using two different concentrations of each nucleoside in WAG/Rij rats. We demonstrated that Ino dose-dependently aggravated whereas Guo and Urd attenuated the LPS-evoked increase in SWD number. Our results suggest that different nucleosides have diverse effects on LPS-induced changes in absence epileptic activity.

Scalp allodynia-precipitating seizures in a girl after starting topiramate

We are reporting the case of a 9-year-old girl with left sided complex partial epilepsy who developed scalp allodynia after commencing topiramate. She first had seizures at the age of 6 weeks. Apart from having epilepsy, she is generally healthy and making normal educational progress. Her electroencephalographs have shown some bursts of irregular spike wave activity particularly in the right central region. A computerize tomography brain scan and two magnetic resonance imaging brain scans, one performed recently, have been normal. Initially her epilepsy responded to phenobarbitole and she remained seizure free for 3 years after it was stopped. At the age of 5 years, she had a recurrence of seizures. During these episodes, she turned her head to the left and had left leg jerking associated with confusion and at times loss of consciousness. Her seizures were occurring several times a week. Subsequently, she was prescribed various antiepileptic drugs (AEDs) including carbamazepine, sodium valproate and levetiracetam as monotherapies and in combination. Most of the AEDs initially did have a beneficial effect but seizure control wore of quickly. After starting topiramate, levetiracetam dose was gradually reduced and

Prognostic value of the second ictal intracranial pattern for the outcome of epilepsy surgery

ObjectiveTo investigate the prognostic value of the second ictal pattern (SIP) that follows the first ictal pattern (FIP) seen at seizure onset in order to predict seizure control after epilepsy surgery. MethodsSIPs were analysed in 344 electro-clinical and subclinical seizures recorded with intracranial electrodes in 63 patients. SIPs were classified as (a) electrodecremental event (EDE); (b) fast activity (FA); (c) runs of spikes; (d) spike-wave activity; (e) sharp waves; (f) alpha activity; (g) delta activity and (h) theta activity. Engel surgical outcome scale was used. ResultsThe mean follow-up period was 42.1months (SD=30.1). EDE was the most common SIP seen (41%), followed by FA (19%), spike-wave activity (18%), alpha activity (8%), sharp-wave activity (8%), delta activity (3%), runs of spikes (2%) and theta activity (2%). EDE as SIP was associated with favourable outcome when compared with FA (p=0.0044) whereas FA was associated with poor outcome when compared with any other pattern (p=0.0389). FA as SIP tends to occur after EDE (75%) whereas EDE tends to evolve from a FIP containing FA (77%). SIP extent was focal in 46% of patients, lobar in 24%, multilobar in 14% and bilateral in 16%. There is a gradual decrease in the proportion of Engel grade I with the extent of SIP. Focal and delayed (in temporal lobe epilepsy) SIPs appear to be associated with better outcome. ConclusionsAs SIP, EDE was associated with favourable surgical outcome whereas FA was associated with poor outcome, probably because outcome is dominated by FIP. SignificanceEDE as SIP should not discourage surgery. However, FA as SIP should be contemplated with caution. SIP focality and latency can have prognostic value in epilepsy surgery.

Sleep and epilepsy syndromes.

Sleep and epilepsy have a close relationship. About 20% of patients suffer seizures only during the night, approximately 40% only during the day and approximately 35% during the day and night. In certain epilepsy syndromes, the occurrence of seizures is strongly related to sleep or awakening. Infantile spasms appear predominately on awakening, and hypsarrhythmia is sometimes visible only in sleep. Children with Panayiotopoulos syndrome or benign epilepsy with centrotemporal spikes (BECTS) have seizures mostly when asleep, and in both syndromes interictal spike waves are markedly accentuated in slow wave sleep. Electrical status epilepticus during slow sleep/continuous spike wave discharges during sleep (ESES/CSWS), atypical benign partial epilepsy, and Landau-Kleffner syndrome are epileptic encephalopathies with substantial behavioral and cognitive deficits, various seizures, and continuous spike-wave activity during non-rapid eye movement (NREM) sleep. The hallmark of juvenile myoclonic epilepsy and grand mal seizures on awakening are seizure symptoms within 2 hours after awakening, often provoked by sleep deprivation. Nocturnal frontal lobe epilepsy is sometimes mistaken for parasomnia. Differentiation is possible when the clinical symptoms and the frequency of the paroxysmal events per night and month are carefully observed and nocturnal video electroencephalography (EEG) performed. Sleep EEG recordings may be helpful in patients with suspected epilepsy and nonconclusive awake EEG. Depending on the clinical question, sleep recordings should be performed during nap (natural sleep or drug induced), during the night, or after sleep deprivation.

Analysis of the clinical features and electroencephalogram characteristics in 24 patients with agyria-pachygy-ria

Objective To analyze the clinical manifestations and electroencephalogram (EEG)characteristics of agyria-pachygyria for its early diagnosis, treatment and prognosis judgment in clinical practice. Methods The cli-nical manifestations and EEG features of twenty-four patients with agyria-pachygyria who were diagnosed by CT or magnetic resonance imaging(MRI) at Pediatric Neurology of Children's Hospital of Chongqing Medical University from July 2004 to July 2013 were retrospectively analyzed. Results Of twenty-four patients, eighteen cases were diagnosed as diffuse agyria-pachygyria and six cases were diagnosed as partial agyria-pachygyria.The clinical features were mainly manifested as mental retardation (twenty-four patients), and motor retardation (twenty-four patients), and epilepsy (eighteen patients). All of the twenty-four patients had abnormal EEG pattern which were mainly three tapes.Type Ⅰ had diffused high amplitude alpha and beta activity in all cortical regions, frontal-central, or parietal-occipital region (fourteen patients). Type Ⅱ showed alternating high amplitude bursts with sharp and slow waves (seven patients). Type Ⅲ was characterized by high amplitude spike or sharp wave activity generalized or multifocal distribution and δ, θ wave mixing graphics (twelve patients). Nine of twenty-four patients showed two or three EEG characteristic patterns in an awake-asleep EEG recording.During the follow-up of 1-8 years old, twelve of the thirteen patients who were diagnosed as epilepsy in diffuse agyria-pachygyria had refractory epilepsy, mainly with infantile spasms or Lennox-Gastaut syndrome.One of the five patients who was diagnosed as epilepsy in focal agyria-pachygyria had refractory epilepsy, mainly for partial epilepsy secondary generalized seizures.There was a significant diffe-rence between them (P=0.008). Eighteen of twenty patients who had moderate-severe mental retardation or dyskinesia were diagnosed as diffuse a gyria-pachygyria, while two were focal agyria-pachygyria.Both of them had a significant difference (P=0.005). Conclusions Agyria-pachygyria is a brain malformation caused by neuronal migration abnormality.Diffuse agyria-pachygyria is presented with serious clinical manifestations and poor outcome while the clinical manifestation of focal agyria-pachygyria is relatively mild and epilepsy could be controlled by antiepileptic drugs or epilepsy surgery.These characteristics of EEG patterns along with clinical findings could provide important evidence for early diagnosis, timely treatment and prognosis judgment of agyria-pachygyria. Key words: Agyria-pachygyria; Clinical manifestations; Electroencephalogram characteristics

PP01.12 – 2602: Differential diagnosis of progressive myoclonic epilepsia: Five patients with Lafora disease

Objective Lafora disease (LD) is a rare, fatal, autosomal recessive hereditary disease characterized by epilepsy, myoclonus and progressive neurological deterioration. Diagnosis is made by polyglucosan inclusion bodies (Lafora bodies) shown in skin biopsy. Responsible mutations involves either the EPM2A or NHLRC1 (EPM2B) gene. Methods We report genetic mutations and clinical courses of Lafora disease in 5 adolescents with homozygote NHLRC1 mutation and homozygous EPM2A mutation. Results A total 5 patients (3 female, 2 male) were presented with progressive myoclonic epilepsy. In all cases there were no problems at birth, childhood, and their psychomotor development were normal and attended regular school. In general seizures began around at 13–14 years old. Over the time they demostrated ataxia, and significant deterioration occurred in mental functions, myoclonus of the extremities started, and 3 of all patients were unable to walk unassisted and one of them died at 15 years old. Axillary skin biopsies were performed to all and Lafora bodies in cytoplasm were demostrated. All patients parents are second-degree relatives. Routine blood test, cerebrospinal fluid analaysis were normal. In three patients cranial magnetic resonance imaging (MRI) were normal, but 2 patients had mild serebral and serebellar atrophy. There were multifocal, from time-to-time generalized spike-wave activity were observed in their electroencephalography (EEG). Genetic analaysis for Lafora was studied and 2 patients (sublings) had same mutation) homozygous (c.336 C>A) p.Y112X mutation in EPM2A gene, homozygous (c.199 G>T) p. E67X mutation (2 patient had same mutation) in NHLRC1 gene, homozygous L 180V (CTG>GTC) mutation in EPM2A gene were detected. Conclusion LD is characterized by progressive myoclonic epilepsy and neurodegenerative symptoms. Therefore early recognation is diffucult. If patient show progressive myoclonic seizures with progressive mental deterotation, as well as ataxi we should consider LD

Reduction of epileptic spike-wave activity in WAG/Rij rats fostered by Wistar dams

In WAG/Rij rat genetic model of absence epilepsy, the first spike-wave discharges (EEG hallmark of absence epilepsy) are known to appear after puberty, and their incidence increases with age. WAG/Rij rats are known to have a genetic predisposition to absence epilepsy, and further development of epilepsy might be influenced by epigenetic factors. This preliminary study examined the effect of early postnatal factors on the incidence of epileptic spike-wave discharges in adulthood. The newborn WAG/Rij rats were fostered by Wistar dams (from birth throughout the weaning age), and their EEG was examined continuously from 5 to 13 months of age. It was found that the number and duration of absence seizures was reduced in WAG/Rij rats adopted by Wistar dams as compared with the age-matched control WAG/Rij rats nursed by their own mothers. These data indicate that natural (epigenetic) factors, such as maternal care during suckling period, affect development of seizure activity in genetically prone subjects. It is suggested that improvement of primarily care-giving environment in subjects with genetic predisposition to absence epilepsy is a way to reduce epileptic activity in later life.

Reversible homonymous hemianopia secondary to occipital lobe seizures

Occipital lobe infarcts, hemorrhages, or metastatic tumors can present with complex visual hallucinations, sensory or proprioceptive abnormalities, speech dysfunction, visual loss, and homonymous hemianopia (HH). Treatment of occipital lobe seizures is by single or multiple antiepileptic drugs. We present a case of idiopathic occipital lobe epilepsy where the seizures were controlled by antiepileptic drugs, but the HH did not subside until treated with high dose intravenous (IV) steroids.

Genetics of Epilepsy: What for and How to Examine Children with Epilepsy E.D. Belousova

The paper focuses on problems of genetic examination of children with epilepsy. The major types of monogenic epilepsies in children are described; clinical and research justification of molecular-genetic examination in these patients is given. Priority in molecular diagnosis should be given to epileptic syndromes with clear phenotype. In individuals with Dravet syndrome, detection of a typical mutation allows one to clarify the diagnosis and provides important data concerning prognosis and treatment strategy. If the phenotype is less clear, diagnostic panels need to be used to determine the most frequent mutations that cause severe epilepsy (epileptic encephalopathies). Thus, genetic studies provide new insights into epileptic encephalopathies with prolonged spike-wave activity during sleep: the GRIN2A gene encoding the alpha subunit of NMDA receptors was muted in 17.6% of children with this syndrome. The need for supplementing the examination algorithm of a child with severe epilepsy with comparative genomic hybridization is emphasized. In practical terms, detection of an epilepsy-causing muta- tion allows one to refuse further expensive diagnostic procedures, to predict the disease course more accurately (in some cases), to optimize the therapeutic strategy, and to determine the prognosis of further reproductive potential in some cases. Scientifically, studies into the sequelae of the known mutations (and their effect on child's brain development) allow one to refine the key processes of epileptogenesis. These data may be used to design new therapy methods (the so-called target therapy for epilepsy) in future.

Prognostic value of intracranial seizure onset patterns for surgical outcome of the treatment of epilepsy

ObjectiveTo investigate if intracranial EEG patterns at seizure onset can predict surgical outcome. MethodsIctal onset patterns from intracranial EEG were analysed in 373 electro-clinical seizures and subclinical seizures from 69 patients. Seizure onset patterns were classified as: (a) Diffuse electrodecremental (DEE); (b) Focal fast activity (FA); (c) Simultaneous onset of fast activity and diffuse electrodecremental event (FA-DEE); (d) Spikes; (e) Spike-wave activity; (f) Sharp waves; (g) Alpha activity; (h) Delta activity. Presence of preceding epileptiform discharge (PED) was also studied. Engel and ILAE surgical outcome scales were used. ResultsThe mean follow-up period was 42.1months (SD=30.1). Fast activity was the most common seizure onset pattern seen (33%), followed by (FA-DEE) (20%), DEE (19%), spike-wave activity (12%), sharp-waves (6%), alpha activity (6%), delta activity (3%) and spikes (1%). Preceding epileptiform discharges were present in 75% of patients. FA was associated with favourable outcome (p=0.0083) whereas DEE was associated with poor outcome (p=0.0025). A widespread PED was not associated with poor outcome (p=0.9559). There was no clear association between seizure onset pattern and specific pathology, except possibly between sharp/spike waves and mesial temporal sclerosis. ConclusionsFA activity is associated with favourable outcome. DEE at onset was associated with poor surgical outcome. Widespread/bilateral PEDs were not associated with poor or good outcome. SignificanceFA appears to be the best marker for the epileptogenic zone. Surgery should be contemplated with caution if DEE is the first ictal change. However, a widespread/bilateral PED at onset is common and should not discourage surgery.

Panayiotopoulos syndrome and symptomatic occipital lobe epilepsy of childhood: a clinical and EEG study.

Panayiotopoulos syndrome (PS) is an age-related seizure susceptibility syndrome that affects the central autonomic system. Although the majority of the few ictal recordings obtained so far suggest an occipital origin, semiological and interictal EEG data appear to favour more extensive involvement. In this study, the characteristics (including those based on semiology and EEG) of children with Panayiotopoulos syndrome (n=24) and those with lesion-related, symptomatic occipital lobe epilepsy (SOLE) (n=23) were compared. Detailed semiological information and EEG parameters including the localisation, distribution, density (n/sec), reactivity, and morphological characteristics of spike-wave foci and their relationship with different states of vigilance were compared between the two groups. The age at seizure onset was significantly younger in patients with symptomatic occipital lobe epilepsy than in those with PS (mean age at onset: 3.4 versus 5.6 years, respectively; p=0.044). Autonomic seizures (p=0.001) and ictal syncope (p=0.055) were more frequent in PS than in symptomatic occipital lobe epilepsy (87.5% and 37.5% versus 43.5% and 13%, respectively). The interictal spike-wave activity increased significantly during non-rapid eye movement (non-REM) sleep in both groups. The spike waves in non-REM seen in PS tended to spread mainly to central and centro-temporal regions. The results indicate that although common features do exist, Panayiotopoulos syndrome differs from symptomatic occipital lobe epilepsy and has a unique low epileptogenic threshold related to particular brain circuits.

Variable outcome for epilepsy after neonatal hypoglycaemia.

To evaluate the electroclinical features of epilepsy secondary to neonatal hypoglycaemia. This was a retrospective study of children who had seizures beyond infancy after neonatal hypoglycaemia treated at The Royal Children's Hospital, Melbourne between 1996 and 2012. Patients with perinatal asphyxia were excluded. Clinical details were obtained from medical records. Digital electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were reviewed. Eleven patients met the inclusion criteria (six males, five females; mean age 10y 5mo, range 4-18y at the time of review). Age at seizure onset ranged from 4 months to 5 years. Seizures were focal occipital in nine and generalized tonic in two patients. MRI showed gliosis with or without cortical atrophy in the occipital lobe with or without parietal lobe in all. Predominant EEG findings were stereotyped occipital sharp-slow discharges in five, polymorphic occipital spike-wave or paroxysmal fast activity in three, and generalized slow spike-wave and fast activity in two. Seizures were infrequent or remitted in six of the nine children with focal occipital seizures, and frequent and refractory in both children with generalized seizures. Despite the common antecedent and bilateral occipital lobe injury, the seizure manifestations and course of epilepsy after neonatal hypoglycaemia were variable, with mild occipital, refractory occipital, and symptomatic generalized epilepsy recognized.

4. Familial generalized seizures due to LGI1 mutation: Importance of family history for genetic testing

Background It is well known that patients with temporal lobe epilepsy may present with generalized seizures, and the temporal localization depends on further investigation. We present a family with five individuals in three generations where the clinical pattern consisted largely of generalized seizures, but who were then shown to have epilepsy due to an LGI1 mutation. We wish to discuss the clinical and EEG findings in these patients, and to compare these with families with autosomal dominant partial epilepsy with auditory features (ADPEAF) or familial lateral temporal lobe epilepsy (FLTLE) reported in the literature. Family report The proband is a 46-year-old female college graduate who had normal development and no history of head trauma, central nervous system infection or febrile seizures. She had four nocturnal generalized tonic-clonic seizures (GTCS), all occurred around 5–6 am, the first one at age 19years. Diphenylhydantoin was prescribed and later replaced by carbamazepine CR. She has been seizure free since adequate compliance with treatment. Her first EEG performed at 19 years showed an excess of slow waves at 2–4Hz over both posterior head regions without epileptic activity. Her second EEG at 22years showed spikes and slow spike waves alternating over both temporal regions, mostly during drowsiness, and increased during hyperventilation. During intermittent photic stimulation, a photomyoclonic response appeared. Her 40-year-old sister had her first GTCS at 12years which was generalized from the onset. All but one of her subsequent attacks occurred during sleep. Before the only seizure that occurred while awake, she felt numbness of her whole body and heard a whooshing sound suggestive of neocortical temporal lobe involvement. The third sister is 52years old; she had her first GTCS at 19years. A year prior to this, she had transient symptoms of a tingling sensation associated with a whooshing noise. She later had other generalized attacks preceded by this aura. A diagnosis of neocortical or lateral temporal lobe epilepsy, possibly ADPEAF or FLTLE, was suggested. Although the proband only had nocturnal GTCS, LGI1 sequencing was performed on the basis of the family history. A c.611delC mutation leading to a frameshift and premature termination of the protein was identified. Discussion Generalized nocturnal and diurnal seizures associated with interictal generalized spike-wave activity occurring in a family with ADPEAF is unusual. They may represent secondarily generalized seizures or primary generalized seizures or both. In addition, photosensitivity in the proband is unusual as well. Among the reported patients with LGI1 mutation, there are several who have had GTCS and interictal generalized spike-wave and/or polyspike-wave discharges [Ottman et al., 2004]. This family further illustrates that patients with ADPEAF or FLTLE may present with generalized seizures and generalized spike and wave epileptic discharges. Intensive monitoring and attention to aura with auditory features should lead to accurate diagnosis of this genetically determined epileptic syndrome. This report points to the importance of detailed family history to help orient the diagnosis by genetic testing.

Targeting Neural Synchrony Deficits is Sufficient to Improve Cognition in a Schizophrenia-Related Neurodevelopmental Model

Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a “discoordination” hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL) rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation–inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that: (1) inter-hippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; (2) the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; (3) ethosuximide not only normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; (4) the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and (5) olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia.

Uppermost synchronized generators of spike–wave activity are localized in limbic cortical areas in late-onset absence status epilepticus

PurposeAbsence status (AS) epilepticus with generalized spike–wave pattern is frequently found in severely ill patients in whom several disease states co-exist. The cortical generators of the ictal EEG pattern and EEG functional connectivity (EEGfC) of this condition are unknown. The present study investigated the localization of the uppermost synchronized generators of spike–wave activity in AS. MethodSeven patients with late-onset AS were investigated by EEG spectral analysis, LORETA (Low Resolution Electromagnetic Tomography) source imaging, and LSC (LORETA Source Correlation) analysis, which estimates cortico-cortical EEGfC among 23 ROIs (regions of interest) in each hemisphere. ResultsAll the patients showed generalized ictal EEG activity. Maximum Z-scored spectral power was found in the 1–6Hz and 12–14Hz frequency bands. LORETA showed that the uppermost synchronized generators of 1–6Hz band activity were localized in frontal and temporal cortical areas that are parts of the limbic system. For the 12–14Hz band, abnormally synchronized generators were found in the antero-medial frontal cortex. Unlike the rather stereotyped spectral and LORETA findings, the individual EEGfC patterns were very dissimilar. ConclusionThe findings are discussed in the context of nonconvulsive seizure types and the role of the underlying cortical areas in late-onset AS. The diversity of the EEGfC patterns remains an enigma. Localizing the cortical generators of the EEG patterns contributes to understanding the neurophysiology of the condition.

Congenital hemiparesis, unilateral polymicrogyria and epilepsy with or without status epilepticus during sleep: a study of 66 patients with long‐term follow‐up

We retrospectively analysed the electroclinical features, treatment, and outcome in patients with unilateral polymicrogyria (PMG), focussing on epileptic syndrome with or without encephalopathy, with status epilepticus during sleep (ESES) or continuous spikes and waves during slow sleep (CSWS) syndrome. From June 1990 to December 2012, 39 males and 27 females, aged 5-26 years, were studied. We did not include patients with bilateral PMG or cases with unilateral PMG associated with other cerebral lesions. The mean follow-up period was 12 years (range: 3-22 years). Mean age at epilepsy onset was 6.5 years. Focal motor seizures occurred in all cases and 25 had secondary generalised seizures. Six patients also had complex focal seizures. Interictal EEG recordings showed focal spikes in all cases. For 43 of 53 patients with epilepsy, aged 2-9.5 years, the electroclinical features changed. An increase in frequency of focal motor seizures was reported in 20 patients, negative myoclonus occurred in 32 patients, atypical absences in 25 patients, and positive myoclonus in 19 patients. All patients had a continuous symmetric or asymmetric pattern of spike-wave activity during slow-wave sleep. For patients presenting with congenital hemiparesis, negative or positive myoclonus, and absences and focal motor seizures with ESES/CSWS, unilateral PMG should be considered. Brain MRI is mandatory to confirm this cortical malformation. The most commonly used treatments were clobazam, ethosuximide, and sulthiame, alone or in combination. For refractory cases, high-dose steroids were administered and surgery was performed in two patients. Outcome was relatively benign.

Absence in childhood absence epilepsy

Clinicians typically breathe a sigh of relief when they make the diagnosis of childhood absence epilepsy. The history is classic-a normal young child with myriad brief periods of staring. The clinic visit is powerful when the phenomena are replicated by having the child hyperventilate. Finally, the EEG is definitive. The ability to demonstrate to a family the abrupt eruption and cessation of spike-wave activity provides a framework for them to understand what is happening to their child. Parents are usually reassured that there are very good therapies, that seizures are typically controlled, and that their child will "outgrow" it. However, data from the multicenter Childhood Absence Epilepsy Study Group are rewriting this narrative.(1-3.)

Non-Convulsive Status Epilepticus Associated With Glutamic Acid Decarboxylase Antibody

Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies (GAD-Ab) often presents with treatment-resistant partial seizures, as well as other central nervous system symptoms. In contrast to several other well-characterized autoantibodies, GAD-Ab has very rarely been associated with status epilepticus. We report a 63-year-old woman initially admitted with somnolence and psychiatric findings. The EEG findings, of generalized and rhythmical slow spike-wave activity over the posterior regions of both hemispheres, together with the clinical deterioration in responsiveness, led to the diagnosis of non-convulsive status epilepticus. Investigation of a broad panel of autoantibodies, revealed only increased serum GAD-Ab levels. Following methylprednisolone and intravenous immunoglobulin treatments, the patient's neurological symptoms improved, EEG findings disappeared and GAD-Ab levels significantly decreased. GAD-Ab should be added to the list of anti-neuronal antibodies associated with non-convulsive status epilepticus. Disappearance of clinical findings and seroreversion after immunotherapy suggest that GAD-Ab might be involved in seizure pathogenesis.