Focal Spikes Research Articles

EEG and clinical predictors of medically intractable childhood epilepsy

Objectives: To identify electroencephalographic and clinical factors associated with both seizure control and medical intractability in children with epilepsy. Methods: We retrospectively reviewed EEGs and medical records from children with well-controlled epilepsy or medically intractable epilepsy. Subjects: Features of the initial EEG and clinical findings were compared in 39 children with well controlled seizures and 144 with intractable epilepsy using both univariate and multivariate analyses. Results: Strong univariate associates were noted between intractability and several EEG factors: abnormal EEG background including diffuse slowing, asymmetry, abnormal amplitude, a high frequency of spikes or sharp waves, and focal spike and wave activity. With multiple logistic regression, independent predictors of intractability were diffuse slowing and focal spike and wave activity. Strong univariate associates of clinical factors with intractability included: an early age of onset, simple partial, tonic, and myoclonic seizures, a history of status epilepticus, a symptomatic etiology of the seizures, and abnormal magnetic resonance imaging of the head. Multivariate analysis detected 4 independent clinical features associated with intractable epilepsy: symptomatic etiology, tonic seizures, simple partial seizures, and an early age of onset. Conclusions: There are a number of EEG and clinical features that can be identified early in the course of childhood epilepsy that are predictive of outcome. These findings will need to be verified in a prospective study.

Early‐Onset Benign Childhood Occipital Seizure Susceptibility Syndrome: A Syndrome to Recognize

Early-onset benign childhood occipital seizures (EBOS) described by Panayiotopoulos constitute the commoner after the rolandic phenotype of a childhood seizure susceptibility syndrome. EBOS are the clinical representative of occipital spikes. Their cardinal features are infrequent (often single) partial seizures manifested with deviation of the eyes and vomiting, frequently evolving to hemi- or generalized convulsions. Ictal behavioral changes, irritability, pallor, and rarely cyanosis, and eyes wide open are frequent. Retching, coughing, aphemia, oropharyngolaryngeal movements, and incontinence may occur. Consciousness is usually impaired or lost, either from the onset or the course of the fits, but in a few children, it may be preserved. Duration varies from a few minutes to hours (partial status epilepticus). Seizures are usually nocturnal, but semiology is similar in nocturnal or diurnal fits. Onset is between 1 and 12 years with a peak at 5 years. One third of children have a single seizure, the median total number of fits is two to three, and the prognosis is invariably excellent, with remission usually occurring within 1 year from onset. A few children may later develop rolandic or other benign partial seizures. The likelihood to have seizures after age 12 years is exceptional and rarer than that of febrile convulsions. EEG shows occipital paroxysms demonstrating fixation-off sensitivity, but random occipital spikes, occipital spikes in sleep EEG alone, or normal EEG may occur. Centrotemporal and other spike foci may appear in the same or more frequently in subsequent EEGs. The EEG does not reflect clinical course and severity.

Hippocampal damage and the onset of epilepsy

To the Editor: In their interesting study, Kalviainen et al. investigated the hippocampus of 64 patients with temporal lobe epilepsy (TLE) by MRI.1 They divided the subjects into three groups: chronic drug-resistant patients (CDRPs) with large number of seizures, well-controlled patients (WCPs) with rare seizures, and newly diagnosed patients (NDPs). The authors found that CDRPs had significantly smaller hippocampus with longer T2 relaxation time on the side of spike focus than healthy controls. Neither NDPs nor WCPs showed significant hippocampal atrophy compared with control subjects. The authors’ interpretation is that recurrent seizures may cause hippocampal damage. In our opinion, this conclusion is unconfirmed because the results may have been caused by other factors. The authors did not consider many studies that found age dependency of development of hippocampal damage in epilepsy. Re-evaluating the data of Kalviainen et al.,1 we found significant differences regarding mean age and age at onset of epilepsy. WCPs were 10 years older on average than CDRPs. This difference is statistically significant (see table 1) and was not mentioned in the original article. Because median duration of epilepsy was practically equal, we suppose that in WCPs …

Convulsions bénignes du nourrisson. Étude collaboratrice française

Benign infantile non febrile seizures are not well known, leading us to study their clinical and EEG characteristics.Between 1981 and 1994, we assembled 34 patients with the following inclusion criteria: non febrile seizures between 1 month and 2 years of age, normal personal history, no abnormality on clinical, biological and radiological investigations, normal developmental outcome with at least 1 year follow-up.These 34 patients were recognized as 14 familial cases (identical seizures affecting parents) and 11 non familial cases. The other nine cases had different or undefined epilepsy in the family. The clinical and EEG characteristics were the same: at the mean age of 6 months, brief partial seizures (often secondarily or apparently generalized) occurring in a cluster of two to 12 episodes a day for a mean duration of 2.5 days, with ictal EEG showing focal discharge, often slow waves or focal spikes on post-ictal tracing and normal interictal EEG.The clinical and EEG characteristics are important in order to recognize this type of infantile convulsions (familial or not familial), which have a good prognosis and need no aggressive treatment.

Serial electroencephalographic findings in patients with MELAS

To clarify the electroencephalographic characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), the medical records and electroencephalograms of six patients with MELAS and two of their relatives with MELA (mitochondrial myopathy, encephalopathy, and lactic acidosis, without strokelike episodes) were retrospectively reviewed. All have a point mutation in the mitochondrial DNA at nucleotide position 3243. The electroencephalograms (n = 79) were divided into four groups according to the time relation to the strokelike episode: (1) before the first strokelike episode, (2) within 5 days after the strokelike episode (acute stage), (3) between 6 days and 1 month after the strokelike episode (subacute stage), and (4) more than 1 month after the strokelike episode (chronic stage). In the acute stage, 10 of the 11 electroencephalograms (9 strokelike episodes in four patients) revealed focal high-voltage delta waves with polyspikes (FHDPS), which were recognized as ictal electroencephalogram. Ictal events during FHDPS included focal clonic or myoclonic seizure and migrainous headache. In the subacute and chronic stages, focal spikes or sharp waves and 14- and 6-Hz positive bursts were frequently recorded. The authors’ results suggest that FHDPSs present a reliable and accurate indicator of a strokelike episode in patients with MELAS.

Detecting the onset of epileptic seizures.

Seizure is a phenomenon occurring in a large percentage of the population in every country of the world. It represents a distinctive indicator of an abnormality in the central nervous system. The main indicators in the EEG that predict a seizure are the presence of focal or multifocal receptive spikes or sharp waves (or both) and focal mono-rhythmic discharges. In this article we discuss the hardware and software that we developed for a system for automatic detection of these EEG signal characteristics at the beginning of an epileptic seizure. The patient is warned by the sounding of a special alarm. Such early detection helps to alert the patient to an impeding epileptic seizure and so allows him/her to take appropriate action to mitigate its effects.

Increased focal interictal discharges during specific cognitive tasks

We present a patient with pharmacoresistant right temporal lobe epilepsy who showed a significant increase in focal interictal spikes in response to specific visuospatial tasks. Temporal splking was particularly increased during immediate recall of visuospatial material, but not during verbal memory tasks. This reflexive phenomenon, situated in between cognitive alterations as seen in most patients with epilepsy and frank seizures elicited by higher cerebral function as in reflex epilepsy, is discussed in relation to cognition and underlying neural substrates.

Correlation of electroencephalography and the active and inactive forms of neurocysticercosis.

We studied the interictal EEG of 50 epileptic patients (28 males, 22 females) who had parenchymal neurocysticercosis, diagnosed by CAT/MRI of the brain, positive immunological reaction for cysticercosis in cerebral spinal fluid or both. Age ranged from 5 to 61 years old; the mean age of onset was 24.2 +/- 12.2 years. Thirty-six patients had generalized seizures, 13 partial seizures with secondarily generalized seizures, and 1 had complex partial seizures. Twenty-two patients had parenchymal calcifications (inactive form); 21 had parenchymal cysts (active form) and 7 had both. EEG was abnormal in 14 patients (28%): 8 had focal slowing, 3 had focal sharp or spike activity, and 3 had both. The EEG was normal in patients with inactive forms of neurocysticercosis. The EEG was abnormal in 50% of patients with active and mixed forms of neurocystercosis and in 48% of patients with active form only. We conclude that the active forms of neurocysticercosis should be suspected when the EEG is found to be abnormal. In additional, EEG abnormality does not depend on the number of lesions, but rather on location and viability of the cysts, and on host response.

Intraoperative electrocorticography and successful focus resection in a case of Sturge-Weber syndrome

This paper reports a surgically treated case of Sturge-Weber syndrome (SWS) in which the epileptic foci and haemangiomatosis were successfully resected under monitoring of intraoperative electrocorticography. The patient was a 19-month-old female infant who was referred to our hospital because of frequent hemi-tonic-clonic convulsions that were resistant to anticonvulsant therapy. Serial MRI showed progressive atrophy in the left fronto-parieto-temporal lobe, and gyral enhancement by gadolinium corresponded to venous haemangiomatosis of SWS. Three-dimensional reconstruction of the MR images was performed using the Viewing Wand System. Conventional EEG taken before the operation showed slow activity in the left frontal lobe. Intraoperative ECoG revealed spike focus at the posterior temporal cortex to the margin of the haemangiomatosis. Lesionectomy with lobar corticectomy of the total frontal and parietal lobe and part of the temporal lobe was performed. The epileptogenic focus detected by ECoG in the posterior temporal lobe was also resected. In post-excisional ECoG, epileptogenic activities had disappeared. The patient had hemiparesis and hemihypesthesia just after the surgery, but gradually recovered from the paresis and almost has normal motor function except for right-hand clumsiness up to 1 year after Surgery. The present study demonstrated that lobar corticectomy of the haemangiomatosis-affected cortex with resection of the neighbouring epileptogenic focus is a good surgical alternative even if a haemangiomatosis of the SWS affected multilobar corti of the hemisphere.

MRI lesions masked by brain development: a case of infant-onset focal epilepsy

A 3-month-old male presented with right-side–dominant focal seizures. Focal spikes were observed on the left side of an electroencephalogram obtained at the time of onset. The immature development in the left middle temporal lobe was observed by initial magnetic resonance imaging (MRI). The hypoperfusion in the left temporal lobe observed with single-photon computed tomography was consistent with MRI findings. These MRI findings were not observed in a second MRI at 11 months of age. This observation may explain one of the causes of infant-onset focal epilepsy.

Epileptic seizures can be anticipated by non-linear analysis

Epileptic seizures are a principal brain dysfunction with important public health implications, as they affect 0.8% of humans. Many of these patients (20%) are resistant to treatment with drugs. The ability to anticipate the onset of seizures in such cases would permit clinical interventions. The view of chronic focal epilepsy now is that abnormally discharging neurons act as pacemakers to recruit and entrain other normal neurons by loss of inhibition and synchronization into a critical mass. Thus, preictal changes should be detectable during the stages of recruitment. Traditional signal analyses, such as the count of focal spike density, the frequency coherence or spectral analyses are not reliable predictors. Non-linear indicators may undergo consistent changes around seizure onset. Our objective was to follow the transition into seizure by reconstructing intracranial recordings in implanted patients as trajectories in a phase space and then introduce non-linear indicators to characterize them. These indicators take into account the extended spatio-temporal nature of the epileptic recruitment processes and the corresponding physiological events governed by short-term causalities in the time series. We demonstrate that in most cases (17 of 19), seizure onset could be anticipated well in advance (between 2-6 minutes beforehand), and that all subjects seemed to share a similar 'route' towards seizure.

Hemispheric epilepsy.

This report documents clinical and EEG features of 13 patients whose most frequent EEG abnormality was unilateral interictal spike-waves that occurred consistently over the same hemisphere on multiple recordings. These 13 patients were selected from a 25000-patient database encompassing 25 years. The hemisphere involved was the left in 8 (62%) of the 13 patients. Bisynchronous spike-waves also appeared on a majority of recordings in 10 (77%) patients. Focal spikes occurred in a majority of recordings in 7 (54%) patients; these usually predominated in the frontal or frontal temporal regions and were always ipsilateral to hemispheric spike-waves. Their field distribution often merged with regional or hemispheric spike-waves. EEG evidence of ictal origin ipsilateral to hemispheric spike-waves appeared in 7 of 8 patients whose seizures were recorded; ictal potentials never predominated contralaterally. All patients had seizure disorders beginning in childhood or adolescence. Eleven (85%) had more than one type of seizure. Principal ictal types contained no focal phenomena in 10 (77%) patients. Bilateral motor seizures were tonic-clonic (12 patients), myoclonic (3), tonic (3) and atonic (1). Absence-like attacks occurred in 10 patients: only staring, automatisms and loss of awareness occurred in 6, with aurae in 3, and with motor phenomena in 3. Features of some seizures in 9 patients (69%) suggested a focal or unilateral origin or involvement, but these consistently occurred contralaterally to principal spike-waves in only 4 patients. At a median follow-up of 19 years, 11 patients (85 %) continued to have seizures; the 2 seizure-free patients required two anti-epileptic drugs each. History, neurological examination and neuro-imaging failed to disclose an aetiology or structural lesion in any patient. Eleven patients (85%) had normal intelligence. This newly documented syndrome of hemispheric epilepsy therefore comprises four components: (i) diffuse unilateral spike-waves on EEG which consistently appear over the same hemisphere in a given patient; (ii) a persistent, usually intractable seizure disorder with generalized ictal features in all patients and focal in most; (iii) onset of seizures in childhood or adolescence; and (iv) no apparent aetiology or related structural abnormality of the CNS.

Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus.

We explored the relative contributions of cortical and thalamic neuronal networks in the generation of electrical seizures that include spike-wave (SW) and polyspike-wave (PSW) complexes. Seizures were induced by systemic or local cortical injections of bicuculline, a gamma-aminobutyric acid-A (GABAA) antagonist, in cats under barbiturate anesthesia. Field potentials and extracellular neuronal discharges were recorded through arrays of eight tungsten electrodes (0.4 or 1 mm apart) placed over the cortical suprasylvian gyrus and within the thalamus. 1) Systemic injections of bicuculline induced SW/PSW seizures in cortex, whereas spindle sequences continued to be present in the thalamus. 2) Cortical suprasylvian injection of bicuculline induced focal paroxysmal single spikes that developed into full-blown seizures throughout the suprasylvian cortex. The seizures were characterized by highly synchronized SW or PSW complexes at 2-4 Hz, interspersed with runs of fast (10-15 Hz) activity. The intracellular aspects of this complex pattern in different types of neocortical neurons are described in the following paper. Complete decortication abolished the seizure, leaving intact thalamic spindles. Injections of bicuculline in the cortex of athalamic cats resulted in similar components as those occurring with an intact thalamus. 3) Injection of bicuculline in the thalamus decreased the frequency of barbiturate spindles and increased the synchrony of spike bursts fired by thalamocortical and thalamic reticular cells but did not induce seizures. Decortication did not modify the effects of bicuculline injection in the thalamus. Our results indicate that the minimal substrate that is necessary for the production of seizures consisting of SW/PSW complexes and runs of fast activity is the neocortex.

Topographical EEG analysis of rolandic spikes.

We performed topographic EEG investigation with instant voltage mapping in 57 patients with a Rolandic spike focus including 35 patients with benign Rolandic epilepsy. A pronounced maximal negativity of "Rolandic" spikes could be demonstrated over central or mid-temporal electrodes, with a spread to parietal or upper frontal areas with a dipole formation (centrotemporal negativity, frontal positivity) and involvement of midline. There was a moderate correlation between spike amplitude or duration with spread to adjacent areas. No other focal abnormalities such as focal slowing could be revealed by visual or FFT EEG analysis. During light sleep spike activity was pronounced and often associated with generalized spike wave activity. Thus, a functional disturbance rather than a structural lesion can be assumed.

Responses to photic stimulation in patients with occipital spikes

Objective: To determine the effect of intermittent photic stimulation (IPS) and frequency of asymmetric driving responses in patients with occipital spikes. Methods: The amplitude of the driving response at 4 flash frequencies was measured from a referential montage in 60 patients with occipital spikes and in 60 normal EEG records from age-matched patients. Responses were classified as asymmetric if the amplitude at one occipital area was less than 50% of the amplitude at the other. Results: A measurable photic response occurred significantly less frequently in patients with occipital spikes (48%) compared to the control group (70%; Fisher's test P<0.05). The driving response was asymmetric in 7/36 patients (37%) with unilateral spike foci versus none in the control group (Fisher's test, P<0.001). The amplitude was suppressed ipsilateral to the focus in 5 patients, all of whom had an ipsilateral structural lesion or focal slowing. In two cases the amplitude was higher ipsilateral to the focus, neither having slowing or a structural lesion. Conclusions: Patients with occipital spikes have an increased frequency of asymmetric driving response. An attenuated response ipsilateral to the focus seems to be related to an underlying lesion while the presence of an epileptiform focus in some cases with no slowing on EEG and normal imaging studies may lead to an accentuation of this response.

Ictal scalp EEG in unilateral mesial temporal lobe epilepsy.

We wished to determine the predictive significance of unilateral hippocampal atrophy and interictal spikes on localization of ictal scalp EEG changes and assess whether ictal EEG provides information that might change treatment or influence prognosis in patients with such characteristics of epilepsy. We analyzed EEG seizure patterns in 118 seizures in 24 patients with unilateral mesial temporal lobe epilepsy (MTLE) defined by typical clinical seizure semiology, unilateral hippocampal atrophy on magnetic resonance imaging (MRI) and unitemporal spikes on interictal EEG. Two blinded electroencephalographers independently determined morphology, location, and time course of ictal EEG changes. Lateralization was possible in 88.4-92.0% of seizures and always corresponded to the side of the interictal spike focus and of hippocampal atrophy on MRI. Although only 30.4-33.9% of seizures were lateralized at onset, a later significant pattern emerged (12.6-13.3 s after EEG seizure onset) that allowed lateralization in 82.4-91.0% of seizures with nonlateralized onset. Interobserver reliability for lateralization was excellent, with a K-value of 0.85. In most patients, either all (79.2-83.3%) or >50% (8.3-16.7%) of seizures were lateralized. In only a small proportion of patients (4.2-8.3%) were <50% of seizures lateralized. In 1 patient, no seizure could be lateralized by 1 electroencephalographer. The results of ictal EEG recordings did not alter the surgical approach and did not correlate with surgical outcome. We conclude that unilateral hippocampal atrophy on MRI and unitemporal interictal spikes can predict localization of ictal scalp EEG changes with a high degree of reliability and that ictal EEG provides no additional localizing information in this particular patient group.

Liposteroid (Dexamethasone Palmitate) Therapy for West Syndrome: A Comparative Study With ACTH Therapy

Dexamethasone palmitate (liposteroid) was used for the treatment of West syndrome and compared with adrenocorticotropic hormone (ACTH) therapy. A single intravenous injection of liposteroid (0.25 mg/kg) was administered seven times in 3 months (total dosage = 1.75 mg/kg) to five symptomatic patients with West syndrome, aged 4-11 months. ACTH (0.025 mg/kg/day) was administered intramuscularly for 6 weeks according to the conventional therapy in Japan (total dosage = 0.625 mg/kg) to five symptomatic patients with West syndrome, aged 6-10 months. Nodding spasm and hypsarrhythmia on EEG disappeared in all patients in the liposteroid therapy group within four doses; however, partial seizures and focal spikes on EEG reappeared in three patients 2 months after the end of liposteroid therapy. In the ACTH therapy group, nodding spasm and hypsarrhythmia on EEG similarly disappeared during treatment in all patients, but nodding spasm reappeared 2 months after therapy in two patients and partial seizures reappeared in one patient 3 months after therapy. No notable adverse reactions occurred in the liposteroid group, but transient dysfunction of the thyroid and anterior pituitary gland and increased levels of serum cortisol were experienced in the ACTH group. These results suggest that glucocorticoid incorporated in a lipid emulsion is useful for the treatment of West syndrome.

Acute Encephalitis or Encephalopathy Present with Frequent Complex Partial Seizures That Directly Evolve to Partial Epilepsy: A Clinical Study of Five Pediatric Cases

Purpose: Attention has recently been directed to pediatric cases of a peculiar type of postencephalitic or encephalopathic epilepsy proposed by Awaya et al. This type is characterized by an abrupt onset of frequent refractory complex partial seizures followed by the development of partial epilepsy. There is no seizure‐free interval, and the seizure‐type is fundamentally the same as that in the acute phase. Therefore, it is hard to distinguish the encephalitis/encephalopathy‐related seizures from epileptic ones as its sequela. The pathomechanism of this syndrome remains unknown, even though viral infection has been postulated. After studying our cases, we looked for those in this category to elucidate its clinical characteristics. Methods: Five cases (two boys and three girls) with this syndrome were selected for this study from 53 pediatric patients with acute encephalopathy or encephalitis. These patients had been treated at Sendai City Hospital during the years from 1986 to 1996. This is an incidence of 9.4%. Clinical features such as cerebrospinal fluid and EEG findings, neuroimaging, prognosis of epileptic seizures, and mental status were investigated. Results: The age at onset ranged from 4 to 14 years. All cases had no significant previous or family history. In all cases, there was an antecedent infection. Seizure type during the acute phase consisted of complex partial seizures with or without secondarily generalized tonic‐clonic convulsions. All had a high fever during the acute stage. The interictal EEG revealed generalized high‐voltage slow waves, and the ictal EEG showed diffuse spike‐and‐wave discharges developing from temporal or occipital spike foci. Mild cerebrospinal fluid pleocytosis was noted in two cases. The five cases were divided into two groups according to their clinical severity. In the severe group (three cases), the seizures during the acute phase were highly refractory. Pentobarbital (PTB) was administered to two of the three cases. The duration of the acute phase ranged from 1 to 5 months. The computed tomography (CT) and magnetic resonance imaging (MRI) showed diffuse cerebral atrophy. In one case, localized lesions also were detected in the right temporal and both occipital lobes. The lesions coincided with EEG spike foci, which persisted throughout the course. All three had profound mental deterioration and intractable partial epilepsy during the chronic phase. On the other hand, in the mild group (two cases), seizures during the acute phase were suppressed by intravenous midazolam (MDL) or lidocaine. The duration of the acute phase was shorter (12 and 24 days). Neither MRI abnormalities nor mental deterioration was observed. Epileptic seizures after the convalescent phase were rare. Conclusions: Among the three severe cases, one corresponded well to Awaya's description, and the others appeared to be more severe. The mild group apparently showed less severity. After reviewing the literature, previously reported patients were no less severe than Awaya's original cases. Therefore it is noteworthy that the two milder cases might indicate that this syndrome has a wider clinical spectrum than previously suspected. The pathogenesis of the disorder could not be clarified by this study. However, after judging the focal brain lesions detected on the MRI in one case, the focal encephalitic process and localization‐related epilepsy as its sequela might offer a partial explanation for the pathogenesis of this disorder.

Mapping Epileptic Foci with the Dipole Tracing Method: A Comparison with Intraoperative Electrocorticograms

Purpose: To show the high accuracy of the dipole tracing method (DTM; Homma et al.Electroencephalogr Clin Neurophysiol 1994;91: 374–82), we estimated the position of the epileptic foci in two patients with epileptic seizures by using the DTM and compared the results with electrocorticograms (ECoGs) recorded during surgical resection. Case Report: Patient 1 was a 28‐year‐old man. At age 23 years, he began to experience epileptic attacks, which lasted for 1 min 7–8 times a day. During the first stage of the attacks, the patient felt delightful emotions, followed by impairment and finally loss of consciousness. The electroencephalograms (EEGs) showed frequent focal spikes in the right temporal area. Magnetic resonance imaging (MRI) of the head revealed an atrophy of the right hippocampus. Patient 2 was a 24–year‐old man. At age 18 years, the patient began to experience “bad odors” lasting 20–30 s, 2–3 times a day. At age 20 years, he began to experience attacks of unconsciousness lasting ‐1 min, 1–2 times a month. The EEGs showed frequent focal spikes in the right temporal area. An MRI of the head revealed a tumor in the right hippocampal region. Methods: The EEG was recorded from 21 electrodes arranged according to the international 10–20 system. The reference electrode was placed on the left ear lobe. All of the EEGs were recorded by using a data recorder for later analysis. One‐dipole analysis was performed on the spike‐peaks by using an EEG analyzer (CDT1000; Chuo Electronics Co. Ltd., Tokyo, Japan). We used a realistic three‐shell head model for the analysis. Dipole estimations of the same spikes were performed at five different consecutive time points at an interval of 1 ms. The equivalent current dipole (ECD) was computed as a vector on the coordinates of a three‐dimensional model of the head, and the calculated position was marked on a MRI. The EEG recording time was ‐1 h, and representative spikes were chosen by inspection as the subject for the analysis. As a result of the analysis, only ECDs in which the dipolarity was $98% were adopted. In both patients, the ECoGs were recorded from two places, one in the right hippocampus and the other in the right temporal lobe. Results: In patient I, the locations of the two independent foci were analyzed. One was thought to be in the tail of the right hippocampus, and the other, in the right basal temporal cortex. The ECoG recorded spikes in the right hippocampal tail and the right basal temporal cortex. These places matched the positions mapped by the DTM. In patient 2, the locations of the two independent foci were analyzed. One was thought to be in the right hippocampus, and the other, in the right superior temporal gyrus. The ECoG recorded spikes in the right hippocampus and the right superior temporal gyrus. These places matched the positions mapped by the DTM. Conclusions: The results of the DTM in the two patients were in close agreement with those observed by using the ECoGs. Therefore we conclude that the DTM is a highly accurate method for the estimation of foci in patients with epileptic seizures.

Two Patients with Angelman Syndrome Followed Beyond 20 Years of Age

Purpose: Angelman syndrome is now diagnosed appropriately because of the development of the fluorescence in situ hybridization (FISH) method. We encountered two cases of this syndrome, and the follow‐up studies until adulthood produced some interesting clinical findings. Case Reports: Case 1 was a 23‐year‐old man. Albinism, delayed speech development, hyperactivity, avoidance of eye contact, and hypersalivation were noticed. Cerebral palsy ‐was suspected. He could walk independently by age 2 years but could not speak a single word. At age 3 years, epileptic seizures developed and were observed frequently until age 10 years. At that time, his condition was consistent with epilepsia partialis continua because of tremors of the left hand and a continuation of the electroencephalographic (EEG) findings of spikes on the midtemporal and right central regions. The epileptic attacks were controlled with clonazepam (CZP). A constant happy demeanor has been noticed but outbursts of laughter have not been observed. Diffuse high‐amplitude slow‐wave activity with intermittent spike‐wave discharges, which are the characteristic EEG features of Angelman syndrome, disappeared and spike‐wave‐like discharges over the frontal area were observed thereafter. The present clinical features are severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, oculocutaneous albinism, and semiopened large mouth with protruding tongue and salivation. A chromosomal analysis disclosed 46XYde1(15)(qIl.lql2), and the FISH method detected the deletion of the signal SNRNP.Case 2 was a 20‐year‐old man. Intellectual disability and hyperactivity had been noticed since infancy. Cerebral palsy was suspected. He could walk independently by 3 years and 6 months but could not speak a single word. The initial epileptic seizure occurred at age 2 years and 7 months. However, no seizures were observed after age 9 years. He has had a constant happy demeanor but no outbursts of laughter. At the present, he shows severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, hypopigmented skin color, and semiopened large mouth with protruding tongue and salivation. EEG examination during childhood revealed the characteristic EEG activities of Angelman syndrome, diffuse high‐amplitude slow waves with intermittent spikes. However, at the present, only migratory focal spikes are seen. A chromosomal analysis disclosed 46XY del(l5)(qllq13), and the FISH method revealed a deletion of the SNRNP region. Conclusions: We followed up two patients with Angelman syndrome who were diagnosed with the FISH method. Patients with severe intellectual disability and a constant happy demeanor should be studied with the FISH method. Epileptic attacks were well controlled after adolescence, and the characteristic diffuse high‐amplitude slow‐wave activities disappeared thereafter.