Epileptiform EEG Research Articles

Anticonvulsant effect of BmK IT2, a sodium channel‐specific neurotoxin, in rat models of epilepsy

The sodium channel is a primary target for treating central nervous system disorders such as epilepsy. In this study the anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, was evaluated in different animal models of epilepsy. Experiments were performed on freely moving rats made epileptic by administration of either pentylenetetrazole (PTZ) or pilocarpine. BmK IT2 (0.05-0.5 microg in 2 microl) was microinjected into the CA1 area and its effects on PTZ-induced widespread, seizure-like behaviour and cortex epileptiform EEG, as well as on pilocarpine-induced seizure-like behaviour and c-Fos expression were studied. Intrahippocampal application of BmK IT2 dose-dependently inhibited PTZ-induced seizure-like behaviour, and reduced the numbers and duration of the high amplitude and frequency discharges (HAFDs) of the epileptiform EEG component induced by PTZ. Similarly, in the pilocarpine-induced status epilepticus (SE) model, BmK IT2 significantly prolonged the latency to onset of the SE, reduced the severity of SE and suppressed hippocampal c-Fos expression during SE. BmK IT2 showed anticonvulsant activity as it inhibited the widespread seizures induced by PTZ and pilocarpine-induced SE in rats. This activity might be due to the modulation of sodium channels in the hippocampus. Hence, BmK IT2 could be used as a novel tool to explore the molecular and pathological mechanisms of epilepsy with regard to the involvement of sodium channels.

A review of electroencephlagrams done at the Kenyatta National Hospital, Nairobi

Electroencephalogram based studies done elsewhere suggest that epileptiform activity originates predominantly from the left cortical hemisphere. There is evidence that partial epilepsies (focal spike and wave epileptiform discharges on tracings) connotes focal; secondary structural cortical dysfunction. Studies seeking similar findings have not been done locally. To review electroencephalograms (EEGs) done at Kenyatta National Hospital (KNH); looking for various types of epileptiform discharges and their cerebral cortex of origin. Retrospective observational study. Kenyatta National Hospital, Nairobi, Kenya--from January 1986 to June 2004. A total 10431 EEG records were reviewed. Ninety Eight percent of referrals for EEG evaluation was for clinical differential diagnosis of epilepsy. Abnormal EEGs comprised 32.2% of the study population. Epileptiform abnormalities (i.e. focal spike and wave, generalized spike and wave and 3Hz spike and wave) discharges accounted for 75.2% of all abnormal EEG waveform discharges. Of the epileptiform abnormalities, focal spike and wave discharges comprised 71%. Focal spike and wave discharge implies a possible secondary aetiology of epilepsy. The left cerebral hemisphere was the origin of 49.8% of focal spike and wave epileptiform EEG discharges. Multifocal loci in cerebral cortices (i.e. frontal, temporal and parietal) were the foci of origin of abnormal EEG waveforms in 69.9% of recordings. Focal spike and wave epileptiform discharges, with attendant likely secondary aetiology of epilepsy is predominantly evident in this study. It contrasts findings from western literature. The left cerebral hemisphere is more epileptogenic as is noted in other studies.

Autosomal dominant nocturnal frontal lobe epilepsy and mild memory impairment associated with CHRNB2 mutation I312M in the neuronal nicotinic acetylcholine receptor

Certain paroxysmal nocturnal behaviors have been established as features of nocturnal frontal lobe epilepsy (NFLE). Despite insight into its genetics, the majority of patients with NFLE are not linked to a known mutation and clinical diagnosis remains a challenge. We describe a family presenting with stereotyped nocturnal arousals from non-rapid eye movement sleep, bilateral hand posturing, and pelvic thrusting in the mother, but subtle motor activity in the daughter, and minimal or no epileptiform EEG discharges. Despite normal IQ, there were moderate and severe verbal memory deficits in the mother and daughter, respectively. Genetic testing revealed the CHRNB2 mutation I312M in transmembrane region 3 (M3) of the neuronal nicotinic acetylcholine receptor. Phenotypic similarities in unrelated families suggest the determining role of this mutation in NFLE, whereas different inter- and intrafamilial cognitive profiles point to other factors. The absence of clear motor features of NFLE in the daughter emphasizes the shortcomings of current clinical criteria and the potential for genetic testing to further guide clinical diagnostic criteria.

An Investigation of Sleep Characteristics, EEG Abnormalities and Epilepsy in Developmentally Regressed and Non-regressed Children with Autism

This study investigated sleep of children with autism and developmental regression and the possible relationship with epilepsy and epileptiform abnormalities. Participants were 104 children with autism (70 non-regressed, 34 regressed) and 162 typically developing children (TD). Results suggested that the regressed group had higher incidence of circadian rhythm disorders than non-regressed children. The regressed group showed higher Children's Sleep Habits Questionnaire Bedtime Resistance, Sleep Onset Delay, Sleep Duration and Night-Wakings scores. Epilepsy and frequent epileptiform EEG abnormalities were more frequent in regressed children. Past sleep disorders and a history of developmental regression were significantly associated with sleep disorders. This study is an initial step in better understanding sleep problems in regressed children with autism, further studies are necessary to better investigate these aspects.

Seizure activity in the rat hippocampus, perirhinal and prefrontal cortex associated with transient global cerebral ischemia

Epileptiform EEG activity associated with ischemia can contribute to early damage of hippocampal neurons, and seizure activity may also lead to dysfunction in extrahippocampal regions. In this study, seizure activity associated with the four-vessel occlusion model of cerebral ischemia was monitored using chronically implanted electrodes in the CA1/subicular region, the perirhinal cortex, and the prefrontal cortex of the rat. Background EEG amplitude was reduced in all recording sites during occlusion, but spiking and bursting activity was also observed. Seizure activity occurred in most animals during the first several hours of reperfusion, but was not observed on subsequent days. Epileptiform spikes and bursts were often synchronous between two or three recording sites, and spikes in the CA1 region also often occurred just prior to spikes in other sites. These results demonstrate that the four-vessel occlusion model can lead to patterns of seizure activity in the hippocampus, prefrontal and perirhinal cortices.

Electroencephalographic Cerebral Dysrhythmic Abnormalities in the Trinity of Nonepileptic General Population, Neuropsychiatric, and Neurobehavioral Disorders

Electroencephalographic Cerebral Dysrhythmic Abnormalities in the Trinity of Nonepileptic General Population, Neuropsychiatric, and Neurobehavioral Disorders

Electroencephalographic Cerebral Dysrhythmic Abnormalities in the Trinity of Nonepileptic General Population, Neuropsychiatric, and Neurobehavioral Disorders

Subclinical electroencephalographic epileptiform discharges in neurobehavioral disorders are not uncommon. The clinical significance and behavioral, diagnostic, and therapeutic implications of this EEG cerebral dysrhythmia have not been fully examined. Currently the only connotation for distinctive epileptiform electroencephalographic patterns is epileptic seizures. Given the prevailing dogma of not treating EEGs, these potential aberrations are either disregarded as irrelevant or are misattributed to indicate epilepsy. This article reappraises the literature on paroxysmal EEG dysrhythmia in normative studies of the "healthy" nonepileptic general populations, neuropsychiatry, and in neurobehavioral disorders. These EEG aberrations may be reflective of underlying morpho-functional brain abnormalities that underpin various neurobehavioral disturbances.

An evidence‐based approach to the first seizure

Evidence-based care (EBC) is an explicit approach to applying the best evidence to the care of individual patients. We outline the basic principles of EBC and apply them to various clinical questions pertaining to a patient presenting with a first seizure, providing a summary of the best available evidence for each question. Depending on the question at hand, the evidence derives from retrospective, prospective, and randomized controlled studies in children and adults. There is solid evidence that early seizure recurrence is reduced by early initiation of AEDs. A meta-analysis of six randomized trials revealed an average absolute risk reduction of 34% (95% CI 15-52) with AED therapy. However, the prognosis for the development of epilepsy is not altered by early intervention. EEG epileptiform abnormalities, family history of epilepsy, imaging lesions, and remote symptomatic seizures increase the risk of recurrence, and impact the risk-benefit ratio of treatment after a single event. In the end, clinicians must evaluate patients with a first unprovoked seizure on a case-by-case basis to determine the appropriateness of treatment with a given AED.

A novel data reduction method: Distance based data reduction and its application to classification of epileptiform EEG signals

Objective Data reduction methods are a crucial step affecting both performance and computation time of classification systems in pattern recognition applications such as medical decision making systems, intelligent control, and data clustering. The aim of this study is both to increase the classification accuracy and decrease the computation time of classifier system on the classification of epileptiform EEG signals. Methods In this study, we have proposed a novel data reduction method based on distances between groups data double in all dataset and applied this method to the classification of epileptiform EEG signals. The feature extraction methods including autoregressive (AR), discrete Fourier transform (DFT), and discrete wavelet transform (DWT), distance based data reduction, and C4.5 decision tree classifier have been combined to classify the epileptiform EEG signals. As feature extraction part AR, DFT, and DWT methods have been used to determine the features about EEG signals including epileptic seizure patients and eyes open volunteers. As data pre-processing part, distance based data reduction that is proposed firstly by us has been used to reduce data determined by spectral analysis methods (AR, DFT, and DWT). As final part called classification, C4.5 decision tree classifier has been used to classify reduced epileptiform EEG signals. Results To validate and test the proposed data reduction, the classification accuracy, sensitivity, and specifity analysis, computation time, 10-fold cross-validation, and 95% confidence intervals have been used in this study. Six different combined methods have been used to classify the epileptiform EEG signal. These methods are (i) combining DFT and C4.5 decision tree classifier (DCT), (ii) combining DFT, distance based data reduction, and C4.5 DCT, (iii) combining AR and C4.5 DCT, (iv) combining AR, distance based data reduction, and C4.5 DCT, (v) combining DWT and C4.5 DCT, and (vi) combining DWT, distance based data reduction, and C4.5 DCT. The classification accuracies and computation times obtained by these methods are 99.02% – 79 s, 99.12% – 47 s, 99.32% – 65 s, 98.94% – 45 s, 92.00% – 52.06 s, and 89.50% – 29.9 s. Conclusions These results have shown that the proposed distance based data reduction method has produced very promising results with respect to both classification accuracy and computation time for classifying the epileptiform EEG signals. Also, proposed hybrid systems can be used to detect the epileptic seizure.

Epilepsia, epileptiform abnormalities, non-right-handedness, hypotonia and severe decreased IQ are associated with language impairment in autism.

The aim of this study was to categorize speech problems in autistic children in a manner allowing recognition of associated risk factors. We were specifically interested in the role of epilepsy and epileptiform activity in EEG in autistic patients since these dynamic processes can influence each other. We combined subtypes of autism with degrees of their functionality and we selected three speech endpoints: i) delayed development of speech, ii) complete mutism and iii) regression of speech. We retrospectively examined 205 autistic children (boys 145/70.7%, mean age 10 years). Median IQ was 55 (15;104) and median Childhood Autism Rating Scale (CARS) ranged within 38 (32;48). Univariate and multivariate logistic regression helped to define clinical and diagnostic factors that were significantly associated with speech endpoints. Epileptic seizures, epileptiform EEG abnormalities, non-right-handedness, hypotonia and severe decreased IQ score were found to be the most important mutually independent factors contributing to the increased risk of speech-related problems in patients with ASD.

The autism‐epilepsy connection

The high prevalence of epilepsy in children with autism supports a neurobiologic etiology for autism. It remains unclear whether seizures and epileptiform activity on the EEG are causative or comorbid. It is also uncertain if focal epileptiform EEG abnormalities may be associated with stable cognitive impairment. Even less clear is whether these EEG abnormalities can result in the combination of language and social dysfunction seen in autistic spectrum disorders.

Simultaneous glutamate and EEG activity measurements during seizures in rat hippocampal region with the use of an electrochemical biosensor

Excessive release of l-glutamic acid (glu) has been associated with seizures and epilepsy. Some microdialysis studies have demonstrated an increase in glu levels during seizures both in human and in different animal models of experimental epilepsy. With these techniques it is difficult to monitor the glu concentrations with sufficient time resolution to clearly associate them with EEG activity. To solve this, we have built an electrochemical biosensor based on H 2O 2 production. A glu biosensor was inserted in the hippocampus of rats with an attached isolated tungsten wire to simultaneously record epileptiform EEG activity. 4-Aminopyridine (10 nmol) was administered into the entorhinal cortex to induce seizures. EEG activity and glu concentrations were measured in real time in awake rats through the use of a swivel to capture and digitize analogical signals. When the first epileptiform burst appeared, it was accompanied by a single and significant increase in glu that could play an essential role in the initiation of the seizure. Subsequent and lesser glu increases also were observed; however they were not directly correlated with further bursts it could be relevant to maintenance of seizures. Sustained increase in glu concentration associated with a flat EEG recording was present when rats died.

Beneficial effects of antiepileptic medication on absence seizures and cognitive functioning in children

In this prospective clinical study, the effects on cognitive functioning of absence seizures, epileptiform EEG discharges, and their abolishment by antiepileptic medication were evaluated in patients newly diagnosed with childhood absence epilepsy or juvenile absence epilepsy. Eleven children in the study group and ten age- and gender-matched controls with mild asthma underwent combined video/EEG and neurocognitive assessment (IQ, fine-motor fluency, attention, visual and spatial memory). The neuropsychological assessment was repeated after the introduction of antiepileptic medication. Ten children with absence epilepsy became clinically seizure free. The study group improved in attention, fine-motor fluency, and visual memory. The controls improved only in fine-motor and attention skills. Duration of generalized 3-Hz spike–wave discharges and clinical absence seizures was negatively correlated with performance on the visual memory task. Cessation of seizures induced by antiepileptic medication may support neurocognitive functioning in children.

Cortical Substrates of Scalp EEG Epileptiform Discharges

Scalp EEG is an essential component of epilepsy presurgical evaluation during the lateralization and localization of epileptogenic focus. Scalp EEG epileptiform discharges may either guide direct surgical intervention or provide necessary information to further localize the epileptic focus with intracranial EEG recording. Despite the importance and widespread use of scalp EEG epileptiform discharges, the cortical EEG substrates underlying these spikes and seizure discharges are mostly speculative. Misconceptions are therefore prevalent regarding the necessary cortical area, synchrony, and amplitude required to generate those that are recordable at the scalp. Using contemporary EEG recording techniques such as simultaneous scalp and intracranial EEG recording, the authors' recent studies have shown that the cortical area of epileptiform discharges required for the scalp recording is considerably larger than commonly thought. A cortical area of 10 to 20 cm is often required to generate a scalp recognizable interictal spike or ictal rhythm. Sufficient cortical source area and synchrony are mandatory factors for the corresponding scalp EEG epileptiform recording. The amplitude is primarily dependent on source area and synchrony; therefore it is a less important factor. The authors review the previous literatures in conjunction with their recent investigations on this topic.

Corpora amylacea in mesial temporal lobe epilepsy: Clinico-pathological correlations

To investigate the electro-clinical significance of premature accumulation of corpora amylacea (CoA) in the resected hippocampus of patients with medically refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). We compared the clinical and EEG characteristics, and post-operative seizure outcome of 373 (mean age 29.4 years, range 7-55 years) surgically treated MTLE-HS patients with (MTLE-HS-CoA(+), n=129 [34.5%]) and without (MTLE-HS-CoA(-), n=244 [65.5%]) CoA. Age at surgery was significantly higher and duration of epilepsy before surgery was significantly longer for MTLE-HS-CoA(+) patients compared to MTLE-HS-CoA(-) patients. Although the distribution of interictal epileptiform EEG abnormalities did not differ, type 1 ictal EEG pattern was more frequent in MTLE-HS-CoA(+) patients. Among the 21 patients with major interictal psychosis detected prior to epilepsy surgery, 19 (90.5%) belonged to MTLE-HS-CoA(+) group. Schizophrenia-like psychosis was most prevalent. The post-operative seizure-free outcome was comparable, but significantly more MTLE-HS-CoA(-) patients were free of antiepileptic drugs. Overall, our observations support the hypothesis that the pathological process in MTLE-HS is progressive. MTLE-HS-CoA(+) patients are predisposed to increased psychiatric morbidity. In vivo detection of hippocampal CoA accumulation in the future will help us to understand the neurobiological significance of this phenomenon.

Autism and epilepsy: A retrospective follow-up study

So-called “idiopathic” autism, which exhibited no major complications before diagnosis is well-known as one of the risk factors for epilepsy. This retrospective follow-up study aimed to clarify the characteristics of epilepsy in the autism; onset of seizure, seizure types, EEG findings and epilepsy outcome and the differences as a group between the autism with epilepsy and those without epilepsy. One hundred thirty individuals with autistic disorder or atypical autism diagnosed in childhood were followed up over 10 years and were evaluated almost every year up to 18–35 years of age. Their medical records related to perinatal conditions, IQ, social maturity scores and several factors of epilepsy were reviewed in October 2005. Thirty-three of the follow-up group (25%) exhibited epileptic seizures. The onset of epilepsy was distributed from 8 to 26 years of age. Two types of seizure were observed; partial seizure with secondarily generalized seizure and generalized seizure. Twenty of the epileptics (61%) showed the partial seizure. Although 18% of the non-epileptic group exhibited epileptic discharges on EEG, 68% of the epileptic group revealed epileptiform EEG findings before the onset of epilepsy. No differences were observed concerning the sex ratio, autistic disorder/atypical autism and past history of febrile seizures between the epileptic and non-epileptic groups. Lower IQ, lower social maturity score and higher frequency of prescribed psychotropics were observed in the epileptic group compared to the non-epileptics. Idiopathic autism was confirmed as the high risk factor for epilepsy. Epileptiform EEG findings predict subsequent onset of epileptic seizures in adolescence. Epilepsy is one of negative factors on cognitive, adaptive and behavioral/emotional outcomes for individuals with autism.

Pyridoxal phosphate dependency, a newly recognized treatable catastrophic epileptic encephalopathy

Few conditions are as riveting to physicians as devastating encephalopathies that are treatable. In this issue of the Journal, Georg F. Hoffmann and colleagues describe the clinical syndrome of pyridoxal-phosphate dependent seizures with its inherent, and compelling, responsiveness to specific therapy. This story begins over fifty years ago, when Hunt and colleagues reported the successful treatment of infantile seizures with pyridoxine (vitamin B6) (Hunt et al 1954). Hence, pyridoxine-dependent seizures became the prototype of the severe but eminently treatable conditions that no clinician wants to miss. The cardinal diagnostic feature is the presence of refractory seizures, classically during the neonatorum, which cease only when pharmacological doses of pyridoxine are administered. While the condition is rare, with an estimated birth incidence between 1:400 000 and 1:750 000, the importance of early recognition is emphasized by an improved prognosis with early treatment (Baxter 2003). Patients will present with multiple seizure types in the neonatal period or even prenatally, with fetal seizures perceived by mothers as fluttering or hammering sensations beginning at 5 months_ gestation or later. Patients have an associated newborn encephalopathy which may include jitteriness, hypothermia, dystonia, and a prodrome of restlessness, irritability and emesis preceding seizures. The classic diagnostic procedure is intravenous administration of 100 mg of pyridoxine during EEG monitoring, aiming for resolution of a generalized or multifocal spike, or burstsuppression, pattern and cessation of clinical seizures. In an infant with pyridoxine dependency, the seizures and epileptiform EEG abnormalities will typically subside within 2–6 minutes after injection. However, some patients with pyridoxine dependency require up to 500 mg before clinical and electrographic responses are demonstrated. After receiving this initial treatment with pyridoxine, some neonates with pyridoxine dependency may become sleepy and hypotonic for a period of 24 hours. An alternative approach to diagnosis is to treat the patient with daily enteral doses of pyridoxine, 15 mg/kg. In pyridoxine-dependent patients, clinical seizures will resolve within a week of the initiation of this therapy. After a patient is clinically diagnosed by either the acute parenteral administration of pyridoxine or the daily enteral treatment with the vitamin, continued daily supplementation with pharmacological doses of pyridoxine is necessary, as the seizures tend to recur after a median delay of 9 days. Therefore, lifelong maintenance therapy is necessary (Gospe 2002). The classic neonatal phenotype may represent the tip of the iceberg. There are several atypical phenotypes J Inherit Metab Dis (2008) 30:2–4 DOI 10.1007/s10545-008-9974-1

Absence of Seizures Despite High Prevalence of Epileptiform EEG Abnormalities in Children with Autism Monitored in a Tertiary Care Center

Absence of Seizures Despite High Prevalence of Epileptiform EEG Abnormalities in Children with Autism Monitored in a Tertiary Care Center

Discontinuing the Ketogenic Diet in Seizure‐Free Children: Recurrence and Risk Factors

About 10% of children become seizure-free after initiation of the ketogenic diet, and typically stop the diet after 2 yr. A retrospective chart review was performed of all children who became seizure-free on the ketogenic diet at our institution since 1993 and then discontinued the diet. Of 557 children started on the diet since 1993, 66 (12%) discontinued the diet after a median of 2.1 yr due to seizure freedom; 92% were also medication-free. Thirteen (20%) had recurrence of their seizures at a median of 2.4 yr (range: 0-5.5 yr) after the diet was stopped. Seven (58%) became seizure-free a second time, four with anticonvulsant therapy. Four patients (6%) continue to have daily seizures despite both medication and dietary therapies. The presence of recent EEG epileptiform activity, abnormal MRI, lower initial seizure frequency, and tuberous sclerosis complex all significantly increased the likelihood of recurrence.

Lateralizing Value of the Auditory Aura in Partial Seizures

To describe the semiological features of auditory aura and to assess their possible lateralizing value in partial epilepsy. Out of a series of 8,000 patients with epilepsy, we investigated 121 cases with partial seizures in whom auditory features were the first ictal symptom. According to the dominant type of aura, patients were divided into four subgroups-1A (67 cases), 1B (22 cases), 2A (14 cases), and 2B (18 cases)-corresponding to the presence of simple or complex hallucinations and positive or negative illusions, respectively. The side of the epileptic zone (EZ) was defined based on available data: surgical/presurgical study or presence of a neuroradiological lesion, corresponding interictal epileptiform EEG and ictal semiology (level 1); a left EZ was also hypothesized in right-handed patients with ictal aphasia plus a left neuroradiological lesion or a left interictal EEG focus (level 2). Forty-five patients (37%) described the aura as unilateral. The side of epileptogenic zone (EZ) was definable in 36 patients (level 1: 24; level 2: 12). Overall, a unilateral auditory aura was contralateral to the EZ in half of the cases (8/16), but always contralateral in patients studied for presurgical evaluation (4/4). Simple hallucinations lateralized seizure onset on the right side in nine cases, on the left in 12. Among 1B patients (either musical and verbal contents), the EZ was on the left side in all cases (5/5). Positive illusions were associated with right foci in two cases, and left foci in two. Negative illusions always lateralized seizure onset to the dominant hemisphere (6/6). Auditory aura is a rare symptom in partial epilepsy. The perception of the auditory sensation referred to one ear is not a unique lateralizing sign for the contralateral temporal neocortex. Complex hallucinations with verbal content and negative illusion may lateralize seizure onset in the dominant hemisphere. The role of laterality for musical hallucinations remains unclear as it depends on individual musical ability and hemispheric dominance for music.