Search

Alternating hemiplegia of childhood (AHC) is a rare neurological disease mainly caused by mutations in the ATP1A3 gene and showing varied clinical severity according to genotype. Patients with a p.Gly755Ser (p.G755S) mutation, one of minor genotypes for AHC, were recently described as having a mild phenotype, although their long-term outcomes are still unclear due to the lack of long-term follow up. Here, we demonstrate the full clinical course of a 43-year-old female AHC patient with p.G755S mutation. Although her motor dysfunction had been relatively mild into her 30 s, she showed a subsequent severe aggravation of symptoms that left her bedridden, concomitant with a recent recurrence of seizure status. The seizures were refractory to anti-epileptic drugs, but administration of flunarizine improved seizures and the paralysis. Our case suggests that the phenotype of AHC with p.G755S mutation is not necessarily mild, despite such a presentation during the patient’s younger years.

This study focused on the characteristic needle-like epileptic spikes of short duration and steep shape seen on magnetoencephalography (MEG) in patients diagnosed with focal cortical dysplasia (FCD) morphologically. We aimed to validate the analysis of MEG spike morphology as a noninvasive method of identifying the presence and location of FCD.MEG was collected by 204-channel helmet-shaped gradiometers. We analyzed MEG spike sources for 282 patients with symptomatic localization-related epilepsy. MEG showed clustered equivalent current dipoles when superimposed on their three-dimensional-magnetic resonance images (MRI) in 85 patients. Fifty-seven patients were excluded from our study, because they had destructive brain lesions or an insufficient number of spikes for statistical analysis. Twenty-eight patients (18 males, 10 females; aged 1-34 years) were finally matched to our inclusion criteria, and were categorized into three groups: FCD (7 patients), non-FCD (10 patients), and non-lesion (11 patients), based on the MRI findings. We measured the duration, amplitude, and tilt manually for at least 15 spikes per patient, and compared the three groups using a one-way analysis of variance, followed by the Tukey test when statistically significant (p0.05). In 17 patients with visible MRI lesions, we investigated the correlation between the depth of the lesion and the tilt using the Pearson product moment correlation.The average spike duration was significantly shorter in the FCD and non-lesion groups than in the non-FCD group (p0.05). The average amplitude was not significantly different between the three groups. The average spike tilt was significantly steeper in the FCD group than in the non-FCD group (p = 0.0058). There was no significant difference between FCD and non-lesion patients in both duration and tilt. Our additional study revealed a significant negative correlation between the depth of the lesion and the average tilt (p = 0.0009).MEG epileptiform discharges of short duration and steep tilt characterize FCD, especially when located at the superficial neocortical gyrus. We speculate that this particular spike morphology results from the intrinsic epileptogenicity of FCD. Morphological analysis of MEG spikes can evaluate the etiology of epileptogenic lesions and detect a strong, localized epileptogenic focus such as that typically observed in FCD.

Purpose : We evaluated whether magnetoencephalography (MEG), in addition to surgery, was valuable for the diagnosis and management of epileptic syndromes in patients with neocortical epilepsy (NE). Methods : We studied MEG in 73 patients (29 females; aged 1–26 years; mean 10.3 years) for the clinical diagnosis of epilepsy and for preoperative evaluation. MEG data were recorded by 204-channel whole head gradiometers with a 600 Hz sampling rate. MEG spike sources were localized on magnetic resonance images (MRI) using a single dipole model to project equivalent current dipoles. Results : MEG localized an epileptic focus with single clustered dipoles in 24 (33%) of 73 NE patients: 16 (25%) of 64 symptomatic localization-related epilepsy (SLRE) patients and eight (89%) of nine idiopathic localization-related epilepsy (ILRE) patients. MEG provided advantageous information in 12 (50%) of 24 patients with clustered dipoles and confirmed the diagnosis in the remaining 12 (50%). Furthermore, the use of MEG resulted in changes to surgical treatments in nine (38%) patients and in medical management in eight (33%). MEG confirmed the diagnosis in eight (16%) of 49 patients with scattered dipoles. MRI identified a single lesion (28 patients, 38%), multiple lesions (5, 7%), and no lesion (40, 55%). MRI provided confirming information in 19 of 28 patients with a single lesion and 18 of them required surgical resections. MRI did not provide any supportive information in 54 (74%) patients with a single (9), multiple (5) and no lesion (40). Conclusion : Our study shows that MEG provides fundamental information to aid the choice of diagnostic and therapeutic procedures including changes in medication in addition to surgical treatments for NE.

A K-complex (KC) in the electroencephalographs (EEGs) indicates a moderate depth of slow-wave sleep (SWS) in humans and animals. The cortical activities are upregulated during the periods between the KCs (“up state”), and it is proposed that temporarily stored memories during wakeful periods will be consolidated during these periods. Although the underlying mechanism for KCs is proposed to be in the cortex itself, the involvement of the brainstem has not been explored. Here we investigate the excitability changes of the brainstem preceding, during, and after KCs in humans. We simultaneously recorded brainstem auditory evoked potentials (BAEPs) with EEGs, and sequentially analyzed BAEPs around the KCs. The results showed a transient activation of the ventral brainstem preceding the KC and a sustained activation of the dorsal brainstem outlasting the KC. Thus, it is suggested that KCs are triggered by the activation of the brainstem and that the “up state” is maintained by the sustained activation of the brainstem.

Summary Purpose Ictal magenetoencephalographic (MEG) discharges convey significant information about ictal onset and propagation, but there is no established method for analyzing ictal MEG. This study sought to clarify the usefulness of time-frequency analyses using short-time Fourier transform (STFT) for ictal onset and propagation of ictal MEG activity in patients with neocortical epilepsy. Methods Four ictal MEG discharges in two patients with perirolandic epilepsy and one with frontal lobe epilepsy (FLE) were evaluated by time-frequency analyses using STFT. Prominent oscillation bands were collected manually and the magnitudes of those specific bands were superimposed on individual 3D-magnetic resonance images. Results STFT showed specific rhythmic activities from alpha to beta bands at the magnetological onset in all four ictal MEG records. Those activities were located at the vicinity of interictal spike sources, as estimated by the single dipole method (SDM), and two of the four ictal rhythmic activities promptly propagated to ipsilateral or bilateral cerebral cortices. The patients with FLE and perirolandic epilepsy underwent frontal lobectomy and resection of primary motor area, respectively including the origin of high-magnitude areas of a specific band indicated by STFT, and have been seizure free after the surgery. Conclusions STFT for ictal MEG discharges readily demonstrated the ictal onset and propagation. These data were important for decisions on surgical procedure and extent of resection. Ictal MEG analyses using STFT could provide a powerful tool for noninvasive evaluation of ictal onset zone.

Landau-Kleffner syndrome (LKS) is a childhood disorder of unknown etiology characterized by an acquired aphasia and epilepsy. We have performed comprehensive neurofunctional studies on an 8-year-old girl with typical LKS, with the aim of identifying lesions that may be responsible for her condition. 18F-fluoro-D-glucose (FDG) positron emission computed tomography (PET), 11C-Flumazenil (FMZ) PET, 99mTc-hexamethylpropyleneamine oxime single photon emission computed tomography (SPECT) and magnetoencephalography were performed before and after changes to the patient's medication led to a clinical improvement. Interictal SPECT showed hypoperfusion in the left frontal, left temporal, and left occipital lobes. 18F-FDG PET demonstrated a decrease in glucose metabolism medially in both temporal lobes and superiorly in the left temporal lobe. 11C-FMZ PET revealed a deficit in benzodiazepine receptor binding at the tip of the left temporal lobe. Magnetoencephalography demonstrated equivalent current dipoles located superiorly in the left temporal lobe. Our results suggest that the tip of the left temporal lobe plays an important role in the pathogenesis of LKS in our patient.

This study charted the magnetoencephalographic (MEG) findings with clinical course for atypical benign partial epilepsy in childhood (ABPE). We discuss the etiology and epileptogenesis of this condition. Three patients with ABPE (age: 8–10 years old) underwent MEG analysis using a 204ch helmet-shape MEG system. MEG showed unilateral epileptic activities over the frontal and temporal operculum and insular cortex during the worst seizures. The findings changed as the seizures were reduced by localized clustering of equivalent current dipoles (ECDs) at the unilateral temporal and frontal operculum near the primary motor area. We concluded that the localizations and directions of the ECDs in our patients during seizure remission resembled those of benign Rolandic epilepsy (BRE). We suggest a similar pathogenesis for ABPE and BRE.

Summary: Purpose: To examine whether magnetoencephalography (MEG) can be used to determine patterns of brain activity underlying widespread paroxysms of epilepsy patients, thereby extending the applicability of MEG to a larger population of epilepsy patients. Methods: We studied two children with symptomatic localization-related epilepsy. Case 1 had widespread spikes in EEG with an operation scar from a resection of a brain tumor; Case 2 had hemispheric slow-wave activity in EEG with sensory auras. MEG was collected with a 204-channel helmet-shaped sensor array. Dynamic statistical parametric maps (dSPMs) were constructed to estimate the cortical distribution of interictal discharges for these patients. Equivalent current dipoles (ECDs) also were calculated for comparison with the results of dSPM. Results: In case 1 with widespread spikes, dSPM presented the major activity at the vicinity of the operation scar in the left frontal lobe at the peak of the spikes, and some activities were detected in the left temporal lobe just before the peak in some spikes. In case 2 with hemispheric slow waves, the most active area was located in the left parietal lobe, and additional activity was seen at the ipsilateral temporal and frontal lobes in dSPM. The source estimates correlated well with the ictal manifestation and interictal single-photon emission computed tomography (SPECT) findings for this patient. In comparison with the results of ECDs, ECDs could not express a prior activity at the left temporal lobe in case 1 and did not model well the MEG data in case 2. Conclusions: We suggest that by means of dSPM, MEG is useful for presurgical evaluation of patients, not only with localized epileptiform activity, but also with widespread spikes or slow waves, because it requires no selections of channels and no time-point selection. Ke yW ords: MEG—Dynamic statistical parametric mapping—Generalized spike—Slow wave— Epilepsy. The appropriate diagnosis of the epileptic syndrome based on the international classification of the epilepsies and epileptic syndromes is the most important factor in treatment decisions by the epileptologist (1). Currently, the diagnosis depends mainly on symptomatic and electrophysiologic findings. In this process, the analysis of interictal discharges (IIDs) and ictal discharges (IDs) in the EEG has played one of the most valuable parts. Magnetoencephalography (MEG) is complementary to EEG; the magnetic fields seen with MEG are selectively sensitive to tangentially oriented source current and are less influenced by the differences in conductivities in the head than are the electrical scalp potentials.

Our current purpose is to evaluate the applicability of dynamic statistical parametric mapping, a novel method for localizing epileptiform activity recorded with magnetoencephalography in patients with epilepsy. We report four pediatric patients with focal epilepsies. Magnetoencephalographic data were collected with a 306-channel whole-head helmet-shaped sensor array. We calculated equivalent current dipoles and dynamic statistical parametric mapping movies of the interictal epileptiform discharges that were based in the minimum-L2 norm estimate, minimizing the square sum of the dipole element amplitudes. The dynamic statistical parametric mapping analysis of interictal epileptiform discharges can demonstrate the rapid change and propagation of interical epileptiform discharges. According to these findings, specific epileptogenic lesion—focal cortical dysplasia could be found and patients could be operated on successfully. The presurgical analysis of interictal epileptiform discharges using dynamic statistical parametric mapping seems to be promising in patients with a possible underlying focal cortical dysplasia and might help to guide the placement of invasive electrodes. ( J Child Neurol 2005;20:363—369).

The excitability change of the brainstem was investigated before and during the conspicuous epileptic discharge in six patients with generalized convulsive seizures. The discharge consisted of a short duration of recruiting rhythm, which was considered equivalent to the seizure discharge on electroencephalogram. The excitability of the brainstem was measured with the parameters (amplitude and area) of component waves (wave-III and -V) of brainstem auditory evoked potentials. The theoretical background of the analysis is that brainstem auditory evoked potentials are 'far-field' potentials, by which they convey the information on the activity change of the brainstem even during the paroxysmal discharge within the cortex. The excitability of both the ventral (parameters of wave-III) and the dorsal brainstem (parameters of wave-V) exhibited a synchronized change (activation-inactivation). They were enhanced from -2.4+/-0.4 s, reaching the maxima before the onset of the seizure discharge, and decayed corresponding to the emergence of the recruiting rhythm. The results suggest the possibility that the widespread (ventral and dorsal) and synchronized activation of the brainstem triggers the seizure discharge in human generalized epilepsy. During the widespread activation of the brainstem, both the thalamus and the cortex probably undergo a suppressed inhibitory state through the cholinergic activation, precipitating the seizure discharge.

Summary A dysplastic neuronal lesion of the floor of the fourth ventricle (DNFFV) causes hemifacial seizures (HFS) from early infancy. However, it is still controversial whether HFS is generated by the facial nerve nucleus or cerebellar cortex. In this study, we confirm a direct correlation between the rhythmic activities in the DNFFV and HFS using intraoperative electroencephalography (EEG) and electromyography (EMG) monitoring. Our results support the theory that a DNFFV provokes ipsilateral HFS via the facial nerve nucleus.

Simultaneous analysis of brainstem auditory evoked potentials (BAEPs) with reference to electroencephalography (EEG) was designed to examine the brainstem function corresponding to the EEG event. With this method, we investigated the brainstem function pre- and during the paroxysmal discharge in human absence seizures classified as primary generalized epilepsy (PGE). Two types of functional change in the lower brainstem were revealed as parameters of wave-III components (amplitude and area) of BAEPs without significant change in the upper brainstem. One was long-range biphasic fluctuation (acceleration followed by abrupt deceleration with the maximum -6.4+/-3.2 s before the seizure onset), and the other was rhythmic oscillation with 3 Hz. The latter, synchronized with the cortical spike-and-wave complex, imposed on the descending slope of the former. One important point is that both preceded the onset of cortical paroxysmal discharge. The results reappraise the classical hypothesis of "centrencephalic system" on seizure generating mechanism in human PGE. The results prove the primary triggering role of the lower brainstem that is independent of sleep-related synchronizations. The method is applicable to other types of EEG event for the investigation of brainstem involvement.

A dysplastic neuronal lesion of the floor of the fourth ventricle (DNFFV) causes hemifacial seizures (HFS) from early infancy. However, it is still controversial whether HFS is generated by the facial nerve nucleus or cerebellar cortex. In this study, we confirm a direct correlation between the rhythmic activities in the DNFFV and HFS using intraoperative electroencephalography (EEG) and electromyography (EMG) monitoring. Our results support the theory that a DNFFV provokes ipsilateral HFS via the facial nerve nucleus.

A vertex sharp wave followed by spindle (VS-spindle) is one of the hallmarks of human stage 2 sleep. We recorded sleep electroencephalograms (EEG) simultaneously with brainstem auditory evoked potentials (BAEP) from nine healthy male subjects. To investigate the generating mechanism of the VS-spindle, sequentially changing BAEP were analyzed around the VS-spindle. The results revealed the preceding changes of wave-V amplitude to the onset of the VS-spindle. When the generator site of wave-V in the brainstem was considered, the results suggest that the functional changes in the dorsal area of the midbrain-pontine junction participate in the organization of the VS-spindle.

To investigate the effects of evening bright light on the autonomic nervous system, heart rate variability (HRV) during sleep was analyzed in dim light (DL) and bright light (BL) conditions. We recorded polysomnography in nine healthy young women aged 20–21 years. Time series of % delta power was calculated in the 0.49–2.20 Hz band. Heart rate variability was analyzed from a 10-min segment of slow wave sleep. The low- to high-frequency ratio and the low-frequency component decreased significantly in the BL conditions compared with the DL conditions. However, the power of the high-frequency component did not change in the two conditions. These results indicate that evening BL affects the autonomic nervous system during slow wave sleep.

In human subjects, the excitability change of the brainstem was investigated over the course of the spindle oscillation. The investigation was carried out by a sequential analysis of brainstem auditory evoked potentials (BAEPs) with reference to one sequence of spindle oscillation. The method was based on the characteristics of BAEPs, i.e. far-field evoked potential. The brainstem revealed two types of excitability change: one in the lower ventral brainstem (wave-III components), and the other in the upper dorsal brainstem (wave-V components). The excitability in the dorsal brainstem showed an oscillation with one cycle period of about 1.5 s, whereas in the ventral brainstem, the excitability showed a long-range biphasic (decaying-growing) fluctuation. Both excitability changes in the brainstem preceded the spindle oscillation, and the phase was reversed during the emerging period of spindle oscillation. The results suggest a primary triggering mechanism of the brainstem for the spindle oscillation, which is independent of preceding cortical drives (K-complexes) upon the thalamus. The difference of the excitability change between the spindle oscillation and the paroxysmal discharge (spike-and-wave complex) was also discussed.

Sleep EEG of eight healthy males and eight females aged 54–72 years were recorded at their homes. The electroencephalograms were visually scored and analyzed by spectral analysis using the FFT method. There were no significant differences in sleep parameters except for a higher percentage of stage 3 + 4 in females. The spectral power of the delta band EEG was classified into two frequencies: 0.5–2 Hz and 2–4 Hz. The total amount of the delta band spectral power through the night was significantly larger in females. Periodic fluctuation of delta band power was observed in females along with non-rapid eye movement–rapid eye movement cycles.

The inter- and intrahemispheric phase characteristics were investigated on diffuse 3 Hz spike-and-wave complex (D3SW) in eight epileptic patients who were diagnosed with typical absence. The phase of D3SW was analyzed sequentially using cross-power spectral arrays dividing D3SW into two components (spike-and-wave complex, spike component). The phase of spike-and-wave complex preceded most at the midline structure, and delayed symmetrically toward the lateral side of each hemisphere in all cases, while not in all cases when spike component was investigated. In spite of this symmetry, there was sparse correlation in phase change between the homologous hemispheres. There was almost no linear correlation between the phase of spike-and-wave complex and the corresponding spike component. The author concludes that the 'centrencephalic system' hypothesis still plays an important role for the generation of D3SW, and suggest a mechanism other than the cortical recurrent inhibition for the generation of wave component.

Purpose: In the previous studies (1 and 11), we had disclosed 2 types of functional changc in the lower brainstem beforc and during diffuse 3 Hz spike-and-wave complexes (SWC) in human primary generalized epilepsy (PGE): a long-range biphasic fluctuation and rhythmic oscillations imposing on the descending limb of the former. Both were found to precede the onset of 3 H7. SWC. The results agreed with the “centrencephalic system” hypothesis for thc generating mcchanism 01 human PGE. In this study, we furthcr investigated the time coursc of development of rhythmic oscillations during the progrcssion of 3 Hz SWC. Methods: Six paticnts with typical absence scizure (TA) werc selected for this study. Six-channel EEGs (Cz-AI, Cz-A2, T3-C3, C3-Cz, C Z -C and C4-T4; band-pass filter, I .S Hz - I .5 kHz) were recorded together with 1 channel of acoustic trigger signal (SO dB hinaurally applied clicks, 20 times/sec) and stored on a magnetic tape. Thc data were replayed and sampled (sampling frequency, 10 kHz) through a personal computer, then spontaneous 3 Hz SWC was selected for the investigation. From the onset of SWC, 24 spike components were located with a pair of 3 segments (segment, 512-point EEG data triggered by 1 trial of acoustic signal). As the averaging area composed of 3x24 segments was shifted forward by 1 segment, a series of 9 sequential brainstem auditory evoked potentials (BAEPs) were calculated in each shift using Cz-A I and Cz-A2. These sequential averaging procedures were repeated as the averaging area was shifted forward by 2 cycles of SWC until the first pair of segments reached the 17-th SWC. The EEG trends were effectively subtracted by fitting a 7-order polynomial curve before the average. Following these procedures, functional changes of the brainstem were investigated in 9 series composed of 9 sequential tracings of BAEPs from the onset of 3 Hz SWC. The sequence of BAEPs in a series corresponded to I cycle of SWC. Amplitude and area of both wave-I11 and wave-V were measured then tested for the differences within a cycle of SWC by 1-way repeated measures of ANOVA in each series among the patients. One cycle of background EEGs was also averaged by reducing the data points to correlate the results of BAEPs. Results: Wave-111 amplitude exhibited significant oscillatory changes synchronizing with I cycle of SWC: it gradually increased during the wave component, and then abruptly decreased predicting the next spike component. Both wave-V parameters showed no significant changes. The oscillatory changes of wave-I11 amplitude lasted from the onset to the middle stage of 3 Hz SWC development, They temporarily disappeared as the seizure progressed and then reappeared while background EEGs continued to exhibit 3 HZ SWC. Therefore, they were not considered as secondary phenomena generated by the cortical SWC. The phase of the reappearing oscillation was different from that of the preceding oscillations: the phase delayed so as to maintain its excitability during the spike component. Conclusion: The results confirm the previous conclusion that functional oscillations in the lower brainstem act pacemaker for cortical SWC, however they occur only during the early stage of SWC development. The results further suggest that the lower brainstem participates in the cessation of the seizure by changing the oscillatory phase against the cortical SWC.

Objective To evaluate the role of the gamma-aminobutyric acid type A (GABA A ) receptor in Angelman syndrome (AS). Study design We performed [ 11 C]flumazenil positron emission tomography (PET) and examined GABA A receptor expression in 7 patients with AS of various genotypes (5 with the deletion, 1 with an imprinting defect [ID], and 1 with a UBE3A mutation) and 4 normal control healthy volunteers. Results Relative to the control subjects, the [ 11 C]flumazenil binding potentials (BPs) were significantly higher in the cerebral cortex and cerebellum in the 5 patients with the deletion and in the 1 patient with a UBE3A mutation, and were less frequently or barely increased in adult patients with the deletion and in the patient with IDs. Conclusions Total GABA A receptor expression was increased in patients with AS with various genotypes. We suggest that a developmental dysregulation of the GABA A receptor subunits occurs in patients with AS.

We report on a family in which a male infant had the asplenia syndrome, a younger brother had the polysplenia syndrome, and their father had situs inversus totalis. The occurrence of the asplenia and the polysplenia syndromes in a sibship of the present family and in two other previously reported sibships indicates that the two syndromes are causally and pathogenetically related to each other. If it is assumed that the father had an incomplete form of the polysplenia complex, then the condition in this family either is an autosomal dominant trait or is multifactorially determined.

Sixty patients (age-range one month to 14 years) with other types of epilepsy than infantile spasms were treated with clonazepam. Disappearance of seizures and normalization of abnormal EEG with disappearance of seizures were recognized in 77% and 50%, respectively. Seizures disappeared in 71% of the patients with generalized seizures and 89% of partial seizures. Improvement of abnormal EEG was noticed in 76% of diffuse paroxysms and in 67% of focal paroxysms. In excellent cases, mean effective dosages were 0.086 +/- 0.021 mg/kg/day in infants and 0.057 +/- 0.022 mg/kg/day in schoolchildren, this difference was statistically significant (p less than 0.005). The incidence of side effects such as drowsiness and ataxia was only 5%.

We compared the establishment of motor cortex kindling by daily electrical stimulation in adult cats and in 4-week-old kittens. All the adult cats and kittens examined reached a stable state of kindled seizures. There was no significant difference in afterdischarge (AD) thresholds, the course of clinical seizure development, or the number of stimuli required for the establishment of kindling between adult cats and kittens. During the development of the kindling stage, AD frequency increased in both adult cats and kittens, although AD duration did not show a clear change.

A 9-year-old female MELAS patient with myoclonus is reported, with emphasis on the results of electrophysiological studies of the myoclonus. At age 5 years she experienced a stroke-like episode, and a diagnosis of MELAS was made at age 6 years on the basis of muscle biopsy findings. At age 9 years spontaneous and segmental myoclonus, predominantly affecting the upper extremities, developed because of complications. Electrophysiological examination, including of somatosensory-evoked potentials (SEPs) and averaged EMG for long loop reflexes, revealed the so-called “giant SEP” and enhanced long loop reflexes reflecting cortical hyperexcitability. Jerk-locked averaging yielded no myoclonus related spikes, but myoclonus-contingent 4-5 Hz theta bursts appeared. These findings suggest that some types of MELAS may be associated with cortical types of myoclonus.