Reappraisal of abnormal EEG findings in children with ADHD: on the relationship between ADHD and epileptiform discharges.

INTRODUCTION: Attention-deficit hyperactivity disorder is suggested to be closely related to epilepsy. A recent large-scale study revealed that ADHD in children is often accompanied by epilepsy. In Japan, methylphenidate (MPH) as a sustained-action tablet and atomoxetine (ATX) became commercially available as medications for children recently. Since then, the number of prescriptions of both medicines has increased rapidly. Methylphenidate, as a psychostimulant, has been a source of concern because of the perceived lowered threshold for convulsions in children. Based on this background, reappraisal of EEG findings in children with ADHD is important in order to detect indications of potential comorbid epilepsy and to investigate the developmental mechanisms of the neurophysiological manifestations in patients with ADHD. MATERIAL AND METHOD: EEG findings in children newly diagnosed with ADHD and their relationship with clinical findings were investigated. The author evaluated 208 patients with ADHD newly diagnosed between 2008 and 2013. Of these, there were 145 patients for whom EEG findings were obtained along with a clinical follow-up for at least three months. Patients with IQ<70 were excluded in order to obtain a homogenous group of patients with ADHD. The male-to-female ratio was 130:15, and the age range was between 5 years, 9 months and 19 years, 9 months, with mean age of 11 years, 4 months. RESULTS: The results revealed that about half (48.3%) of the children with ADHD had abnormal EEG findings and that 22.1% of them had epileptiform discharges. Patients without comorbidity of autism spectrum disorder (ore homogenous group with ADHD) were especially likely to show abnormal EEG findings (51.0%) including epileptiform discharges (24.5%). Afebrile seizures, that is, epileptic seizures, occurred in a boy three days after commencement of administration with MPH as a sustained-action tablet. In four patients with a past history of epilepsy, neither relapse of EEG abnormality nor epileptic seizures were observed during the follow-up period. CONCLUSION: There was to be a significantly close relationship between ADHD and epileptiform discharges. Therefore, in patients with ADHD, it is important to obtain more precise information about seizures and presence of epilepsy from the personal and family histories, as well as to undertake a thorough EEG examination.

Brain maturation-related spike localization in Panayiotopoulos syndrome: magnetoencephalographic study.

Focal spike activities in Panayiotopoulos syndrome involve all brain regions in electroencephalography, and commonly reveal multiple foci, often through occipital predominance. To investigate correlations between developmental brain maturation and spike origin in Panayiotopoulos syndrome, we evaluated age-related or duration-related magnetoencephalographic spike localization in 25 patients with Panayiotopoulos syndrome. Regarding age at examination, patients with frontal spikes were significantly older than patients with spikes on rolandic, parieto-occipital, or calcarine sulci. Occipital spikes were classified into two subgroups, located at the calcarine sulcus and parieto-occipital sulcus. Both calcarine and parieto-occipital localizations were seen in patients around the same age. Follow-up magnetoencephalography was performed on three patients, and demonstrated shifting localization or disappearance of magnetoencephalographic spikes. These results suggest that the location of spike discharges is not directly related to seizure symptoms, but instead indicates maturation-related cortical hyperexcitability in patients with Panayiotopoulos syndrome.

[An infant with multiple cavernous angiomas presenting with frequent epileptic seizures - detection of epileptic focus by magnetoencephalography].

We report on a six-year-old girl with frequent partial seizures secondary to multiple cavernous angiomas (CAs) since the age of 17 months. MRI showed two CAs in the left parietal and right frontal lobes. Ictal scalp video EEG demonstrated complex partial seizures of left hemispheric origin, indicating that the left parietal CA was the epileptogenic lesion. Ictal SPECT showed extensive hyper-perfusion in the left frontal and parietal lobes, indicating the left hemispheric focus. Magnetoencephalography (MEG) showed clustered equivalent current dipoles of interictal spikes in the left parietal cortex adjacent to the left parietal CA. We performed lesionectomy of the left parietal CA at 19 months old. The patient became seizure-free for four years. Postoperative MEG yielded no residual interictal spikes. Our study suggests that early surgical intervention of CA may prevent from further development of epileptic seizures. MEG can identify both the epileptogenic zone and lesion underlying the multiple CAs in the infants with catastrophic partial seizures.

Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and adult epilepsies: a consensus view.

PURPOSE: To discuss and propose a definition of autonomic status epilepticus (SE), describe its clinical and EEG features, and review what is known about its epidemiology, pathophysiology, differential diagnosis, and management. METHODS: An international consortium of established researchers in the field was identified from their published work, agreed the purpose of the project, searched the literature, and, by use of e-mail communication, agreed the consensus document. RESULTS: Autonomic SE is a condition lasting at least 30 min and characterized by epileptic activity causing altered autonomic function of any type at seizure onset or in which manifestations consistent with altered autonomic function are prominent (quantitatively dominant or clinically important) even if not present at seizure onset. It is best described, and probably most commonly encountered in children, with Panayiotopoulos syndrome. However, it also occurs in children with symptomatic epilepsies and, exceptionally, in adults. Its pathogenesis and most appropriate management are poorly understood. CONCLUSIONS: It is hoped that this document will help clinical recognition of Autonomic SE, reduce misdiagnosis, and promote further interest and studies into what has been a relatively neglected area.

Magnetoencephalographic findings of Panayiotopoulos syndrome with frontal epileptic discharges.

We previously reported the results of a magnetoencephalographic study in patients with Panayiotopoulos syndrome manifesting occipital epileptic discharges, in which the equivalent current dipoles of spike discharges were clustered alongside the major cortical sulci, such as parieto-occipital and calcarine. This report is the result of a magnetoencephalographic study of three patients with Panayiotopoulos syndrome exhibiting equivalent current dipoles clustering in the frontal area. Patient 1, a 13-year-old male, exhibited clustering equivalent current dipoles alongside right inferior frontal sulcus, but the orientations were irregular. Patient 2 is an 11-year-old younger brother of Patient 1, whose magnetoencephalograph revealed equivalent current dipoles clustering alongside right prefrontal sulcus and regular orientations. Patient 3 is a 10-year-old female who had equivalent current dipoles clustering alongside right superior frontal sulcus and extremely regular orientations. The locations of clustering equivalent current dipoles of frontal spike discharges were not restricted to one specific frontal sulcus but were present in various locations over the convexity of the prefrontal area. In conclusion, these findings suggest that it is inappropriate to classify Panayiotopoulos syndrome as occipital epilepsy. In addition, the result of this study, that frontal spike discharges seem to occur in relatively older patients, may suggest a correlation between brain maturation and spike occurrence.

Magnetoencephalography in patients with tuberous sclerosis and localization-related epilepsy.

PURPOSE: To clarify the usefulness of magnetoencephalography (MEG) for diagnosis of the spatial relations between spike foci and suspicious epileptogenic tubers on MRI in patients with tuberous sclerosis (TS) and to compare MEG spike foci with single-photon emission computed tomography (SPECT) findings. METHODS: We analyzed magnetic fields of epileptic spike discharges in 15 patients with TS and localization-related epilepsy (LRE) by using MEG (a whole-head 204-channel magnetometer system). We investigated the spatial relation between the equivalent current dipoles (ECDs) of interictal spike discharges and visible cortical tubers on MRI. We also compared results of MEG and MRI with SPECT findings. RESULTS: MEG detected a cluster of ECDs around one cortical tuber in six of 15 patients and clusters of ECDs around two cortical tubers in five patients. Interictal SPECT was disappointing in detection of epileptic foci in TS. However, MEG spike foci showed spatial consistency with ictal hyperperfusion areas in two patients. Three patients with single ECD clusters underwent surgical treatment: two have been seizure free, and one has obtained seizure reduction of >90%. CONCLUSIONS: ECDs were located around visible tuber nodules. MEG enabled precise localization of the epileptic foci and provided crucial information for surgical treatment in patients with TS and partial epilepsy. TS patients showing a single ECD cluster on MEG may be appropriate candidates for surgical treatment.

Single and multiple clusters of magnetoencephalographic dipoles in neocortical epilepsy: significance in characterizing the epileptogenic zone.

PURPOSE: To characterize the epileptogenic zone in neocortical epilepsy (NE) by using magnetoencephalography (MEG). METHODS: We defined and compared locations of single and multiple clusters of equivalent current dipoles (ECDs) for interictal spikes with MRI findings, ictal-onset zones (IOZs) from subdural electroencephalography (SDEEG), resected areas, and postsurgical outcomes of 20 patients who underwent cortical resection for medically intractable NE. RESULTS: Fourteen patients had single clusters; six had multiple clusters. Overlap of clusters and IOZs defined group A (nine patients), in which a single cluster coincided with the IOZ; group B1 (four patients), in which a single cluster was within or partially overlapped the IOZ; group B2 (five patients), in which multiple-cluster sections overlapped IOZs; group C (two patients; one single; one multiple), in which no overlap was seen. More single clusters (nine of 14) than multiple clusters (none of six) coincided with the IOZ (p = 0.014). More patients with single clusters (10 of 14) than patients with multiple clusters (one of six) had seizure-free outcomes (p = 0.049). Eight of nine patients in group A, versus three of 11 in groups B1, B2, and C, achieved seizure-free outcomes (p = 0.0098). Correlations between MRI findings and postsurgical outcomes were not statistically significant; eight of 13 patients with single lesions, one of four with no lesions, and two of three with multifocal lesions had seizure-free outcomes. CONCLUSIONS: In neocortical epilepsy, MEG ECD clusters correlated with SDEEG IOZs. Single clusters indicated discrete epileptogenic zones that required complete resection for seizure-free outcome. Multiple clusters necessitated that the multiple or extensive epileptogenic zones be completely identified and delineated by SDEEG.

A magnetoencephalographic study of patients with Panayiotopoulos syndrome.

PURPOSE: Panayiotopoulos syndrome (PS) is a newly identified type of benign childhood epilepsy characterized by ictal vomiting and eye deviation. It is usually accompanied by occipital spike discharges; however, its classification as an early-onset benign childhood occipital epilepsy is controversial. To characterize this condition further, we examined the localization of equivalent current dipoles (ECDs) of spike discharges by magnetoencephalography (MEG) in patients with PS. METHODS: We studied 13 patients with a mean age at time of examination of 5 years (range, 3-14 years). MEG was measured by using a whole-head 204-channel neuromagnetometer with simultaneous EEG recordings. The estimated locations of ECDs of each peak of the spike discharges were overlaid on magnetic resonance images of the brain. RESULTS: Eleven (84.6%) patients showed clustered ECDs in the areas alongside the parietooccipital sulcus (eight of 13; 61.5%) and/or the calcarine sulcus (four of 13; 30.8%). Despite Fp-O synchronization of the spike discharges in the scalp EEG of five patients, no frontal locations of ECDs were found. All five (38.5%) boys with sylvian seizures, who also showed clustered ECDs in rolandic areas, had an earlier age at onset and higher seizure frequency than did other patients. ECD orientations were regular in all but one patient, who showed irregular and dispersed ECDs alongside bilateral calcarine sulci. CONCLUSIONS: Our results demonstrate localized cortical hyperexcitability in the areas alongside major cortical sulci in PS and indicate that PS is closely related to benign childhood epilepsy with centrotemporal spikes.

Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy.

While there is an abundance of literature describing the association of chromosome aberrations with epilepsy, only a few refer to the detailed features of epilepsy. It is important to investigate the associations between specific chromosome abnormalities and features of epilepsy to identify genes involved in epilepsy and treat them more effectively. We investigated the correlation between specific chromosome aberrations and epilepsy by sending questionnaires to the members of Kyoto Multi-institutional Study Group of Pediatric Neurology. Seventy-six patients were collected from 10 institutions. Chromosome abnormalities included: Down syndrome (n = 19); Angelman syndrome (n = 8); Prader-Willi syndrome (n = 4); 4p- syndrome (n = 3); 1q- syndrome (n = 2); 5p- syndrome (n = 2); Miller-Dieker syndrome (n = 2); 18q- syndrome; (n = 2); Klinefelter syndrome; (n = 2); and 32 other individual chromosomal aberrations. Overall, the severity of mental retardation correlated with the severity of epilepsy. We could abstract characteristic features of epilepsy in some syndromes. In Angelman and Prader-Willi syndromes, febrile seizures occurred frequently, the onset of epilepsy was in early childhood and seizure phenotype was multiple. Paroxysmal discharge of the occipital region and diffuse high voltage slow wave on electroencephalography were characteristic in Angelman syndrome. In Down syndrome, West syndrome and focal epilepsy were common and the prognosis of epilepsy in West syndrome with Down syndrome was good. In 4p- syndrome, febrile seizures were often seen, and unilateral or generalized clonic or tonic-clonic status epilepticus were characteristic. For the other chromosomal aberrations investigated here, the patient numbers were too small to abstract common features of epilepsy.

[Serial MEG change in a boy with Landau-Kleffner syndrome].

We report a 7-year-old boy with Landau-Kleffner syndrome (LKS), with emphasis on the effect of therapy and serial MEG. The equivalent current dipoles (ECDs) of spike discharges accumulated in the bilateral Heschl gyri, predominantly on the right. Although spike discharges on the scalp EEGs disappeared by treatment with clonazepam and sodium valproate, the auditory agnosia did not improve. Therapeutic trials with conventional antiepileptic drugs were unsuccessful. A high-dose corticosteroid was effective, with disappearance of ECDs, appearance of auditory evoked fields (AEF) in the bilateral Heschl gyri on MEG, and improvement of behavioral problems and amelioration of acquired aphasia. The clinical course of this patient suggests that MEG findings are useful not only in making precise diagnosis of LKS but also in assessing and predicting the effects of treatment.

[A case of bilateral paramedian thalamic infarction in childhood with the sensory disturbance and the sensory loss of taste].

Bilateral paramedian thalamic infarcts are characterized by disturbance of consciousness, followed by persisting dementia, decreased spontaneity, apathy, amnesia and paralysis of eye movement. We report a 15-year-old boy with this syndrome, who exhibited transient coma at the onset. In addition to the typical symptoms, he complained of sensory disturbance in the lower extremities and face and the loss of taste sense. MRI showed symmetric paramedian thalamic infarction. There was no lesion in the midbrain. The etiology of infarct in this boy remained unknown despite extensive laboratory and neuroradiological examination. His sensory disturbance in the extremities and face may be due to extensive involvement of the inferolateral area of the thalamus by infarction of the paramedian thalamic artery. This patient illustrates that bilateral paramedian thalamic infarction can occur in a previously healthy child.