Reinterpretation of magnetic resonance imaging findings with magnetoencephalography can improve the accuracy of detecting epileptogenic cortical lesions.

OBJECTIVE: This study examined whether the application of magnetoencephalography (MEG) to interpret magnetic resonance imaging (MRI) findings can aid the diagnosis of intractable epilepsy caused by organic brain lesions. METHODS: This study included 51 patients with epilepsy who had MEG clusters but whose initial MRI findings were interpreted as being negative for organic lesions. Three board-certified radiologists reinterpreted the MRI findings, utilizing the MEG findings as a guide. The degree to which the reinterpretation of the imaging results identified an organic lesion was rated on a 5-point scale. RESULTS: Reinterpretation of the MRI data with MEG guidance helped detect an abnormality by at least one radiologist in 18 of the 51 patients (35.2%) with symptomatic localization-related epilepsy. A surgery was performed in 7 of the 51 patients, and histopathological analysis results identified focal cortical dysplasia in 5 patients (Ia: 1, IIa: 2, unknown: 2), hippocampal sclerosis in 1 patient, and dysplastic neurons/gliosis in 1 patient. CONCLUSIONS: The results of this study highlight the potential diagnostic applications of MEG to detect organic epileptogenic lesions, particularly when radiological visualization is difficult with MRI alone.

A novel transmembrane protein defines the endoplasmic reticulum stress-induced cell death pathway.

Mitochondrial membrane potential (ΔΨm) maintenance is physiologically critical in cells; its loss causes apoptotic signalling and cell death. Accumulating DNA mutations and unfolded proteins in stressed cells activate signalling pathways for cell death induction. Cancer cells often fail to die even in the presence of some death signalling proteins. Here, we report a short hairpin RNA (shRNA) with an artificial sequence, denoted Psi1 shRNA, which leads to ΔΨm loss in HCT116 cells. The Psi1 shRNA target gene was shown to encode transmembrane protein 117 (TMEM117). TMEM117 knockdown led to ΔΨm loss, increased reactive oxygen species levels, up-regulation of an endoplasmic reticulum (ER) stress sensor C/EBP homologous protein and active caspase-3 expression, and cell growth impairment, altering homeostasis towards cell death. TMEM117 levels were down-regulated in response to the ER stressor thapsigargin and decreased when cells showed ΔΨm loss. These results suggested that TMEM117 RNAi allowed apoptotic cell death. Therefore, TMEM117 probably mediates the signalling of ΔΨm loss in ER stress-mediated mitochondria-mediated cell death.

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.