Long-term follow up of an adult with alternating hemiplegia of childhood and a p.Gly755Ser mutation in the ATP1A3 gene.

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.

The presence of short and sharp MEG spikes implies focal cortical dysplasia.

PURPOSE: 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. METHODS: 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 (p < 0.05). 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. RESULTS: The average spike duration was significantly shorter in the FCD and non-lesion groups than in the non-FCD group (p < 0.05). 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). SIGNIFICANCE: 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.

Advantageous information provided by magnetoencephalography for patients with neocortical epilepsy.

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 1-26years; mean 10.3years) for the clinical diagnosis of epilepsy and for preoperative evaluation. MEG data were recorded by 204-channel whole head gradiometers with a 600Hz 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.

Direct correlation between the facial nerve nucleus and hemifacial seizures associated with a gangliocytoma of the floor of the fourth ventricle: a case report.

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.

The applications of time-frequency analyses to ictal magnetoencephalography in neocortical epilepsy.

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.

MEG time-frequency analyses for pre- and post-surgical evaluation of patients with epileptic rhythmic fast activity.

PURPOSE: To evaluate the effectiveness of surgery for epilepsy, we analyzed rhythmic fast activity by magnetoencephalography (MEG) before and after surgery using time-frequency analysis. To assess reliability, the results obtained by pre-surgical MEG and intraoperative electrocorticography were compared. METHODS: Four children with symptomatic localization-related epilepsy caused by circumscribed cortical lesion were examined in the present study using 204-channel helmet-shaped MEG with a sampling rate of 600Hz. One patient had dysembryoplastic neuroepithelial tumor (DNT) and three patients had focal cortical dysplasia (FCD). Aberrant areas were superimposed, to reconstruct 3D MRI images, and illustrated as moving images. RESULTS: In three patients, short-time Fourier transform (STFT) analyses of MEG showed rhythmic activities just above the lesion with FCD and in the vicinity of DNT. In one patient with FCD in the medial temporal lobe, rhythmic activity appeared in the ipsilateral frontal lobe and temporal lateral aspect. These findings correlate well with the results obtained by intraoperative electrocorticography. After the surgery, three patients were relieved of their seizures, and the area of rhythmic MEG activity disappeared or become smaller. One patient had residual rhythmic MEG activity, and she suffered from seizure relapse. CONCLUSION: Time-frequency analyses using STFT successfully depicted MEG rhythmic fast activity, and would provide valuable information for pre- and post-surgical evaluations to define surgical strategies for patients with epilepsy.

Application of magnetoencephalography in epilepsy patients with widespread spike or slow-wave activity.

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.

Dynamic statistical parametric mapping for analyzing the magnetoencephalographic epileptiform activity in patients with epilepsy.

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.