Shigetoshi Takaya

Prefrontal hypofunction in patients with intractable mesial temporal lobe epilepsy

We compared the cognitive functions and interictal cerebral glucose metabolism of 11 patients with mesial temporal lobe epilepsy (MTLE) with frequent seizures to those of 10 patients with MTLE with rare seizures; the groups were matched for age, sex, education, IQ, and focus side. The frequent-seizure group had more set-shifting impairment that correlated with glucose hypometabolism in the prefrontal cortices. Our results suggest that frequent seizures in MTLE are associated with hypofunction of the prefrontal cortex.

Improved cerebral function in mesial temporal lobe epilepsy after subtemporal amygdalohippocampectomy

The functional changes that occur throughout the human brain after the selective removal of an epileptogenic lesion remain unclear. Subtemporal selective amygdalohippocampectomy (SAH) has been advocated as a minimally invasive surgical procedure for patients with medically intractable mesial temporal lobe epilepsy (MTLE). We evaluated the effects of subtemporal SAH on cerebral glucose metabolism and memory function in 15 patients with medically intractable MTLE with hippocampal sclerosis using [(18)F]-fluorodeoxyglucose PET (FDG-PET) and the Wechsler Memory Scale-Revised. The patients were evaluated before and 1-5 years (mean 2.6 years) after surgery. In patients with MTLE of the language-dominant hemisphere, the basal temporal language area was preserved by this surgical approach. Voxel-wise comparison of FDG-PET images was conducted using SPM5 to identify the brain regions showing postoperative changes in glucose metabolism (height threshold, P = 0.01 corrected for multiple comparisons; extent threshold, 100 voxels). During spatial normalization of the postoperative FDG-PET images, we used cost-function masking to minimize any inappropriate image distortion as a result of the abnormal signal within the surgically resected region. Postoperative glucose metabolism increased in extratemporal areas ipsilateral to the affected side, such as the dorsolateral prefrontal cortex, and the dorsomedial and ventromedial frontal cortices. Glucose metabolism also increased in the bilateral inferior parietal lobules and in the remaining temporal lobe regions remote from the resected mesial temporal region, such as the superior temporal gyrus and the temporal pole. By contrast, postoperative glucose metabolism decreased only in the mesial temporal area adjacent to the resected region. Postoperative verbal memory, delayed recall and attention/concentration scores were significantly better than preoperative scores regardless of the resected side. This study suggests that the selective removal of the epileptogenic region in MTLE using a subtemporal approach improved cerebral glucose metabolism in the areas receiving projections from the affected mesial temporal lobe. Cognitive improvement might result from a combination of good seizure control and minimizing the regions of the brain with postoperative functional impairment.

Amygdalar enlargement in patients with temporal lobe epilepsy

Objective The purpose of the study was to clarify the significance of amygdalar enlargement (AE) in patients with temporal lobe epilepsy (TLE) detected by MRI. Methods 11 TLE patients (eight men, mean age 45.3 (SD 18.2) years) with AE treated at Kyoto University Hospital were studied. Clinical history, ictal semiology, EEG, fluorodeoxyglucose–positron emission tomography (FDG-PET), interictal single photon emission CT (SPECT) and MRI were investigated. Amygdalar volume measured by 3 T MRI and its laterality index (LI) were compared with the three other groups: normal controls, patients with partial epilepsy of non-TLE and mesial TLE with hippocampal sclerosis (HS). Results Average age of onset was 39.8 years (SD 19.5). Eight had complex partial seizures and three had generalised seizures. Epileptiform discharges were found in the temporal area ipsilateral to the AE by EEG. Interictal FDG–PET/SPECT revealed regional hypometabolism or hypoperfusion in the ipsilateral temporal area. MRI showed AE on the right in five patients, on the left in five and bilateral in one, all without apparent HS. Ten of 11 patients were diagnosed as unilateral TLE ipsilateral to the AE by neurophysiological and neuroimaging methods. Enlarged amygdalae showed iso- to slightly high intensity in FLAIR images without enhancement. Unilateral AE was not seen in the other three groups for amygdalar volume and LI (p<0.05). Discussion AE is most likely a subtype of TLE without ipsilateral HS. This possibility of AE should be considered in TLE patients if there is no apparent HS.

Corticolimbic balance shift of regional glucose metabolism in depressed patients treated with ECT

BACKGROUND Although the clinical efficacy of electroconvulsive therapy (ECT) has been well established in patients with pharmacotherapy-resistant depression, the physiological mechanism and changes in regional cerebral function after ECT are unclear. METHODS We recruited 16 depressed patients who underwent ECT, and 11 healthy controls. The change in cerebral glucose metabolism was evaluated before and after a series of ECT using [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). RESULTS Before ECT, the patient group showed significant hypometabolism in the superior frontal gyrus, and hypermetabolism in the inferior temporal gyri compared with healthy controls, and these abnormalities remained after ECT. Comparisons between pre- and post-ECT metabolic activity revealed decreased regional metabolism in the frontotemporal neocortical areas after ECT, while increased metabolism was found in the right medial temporal structures including amygdala and pons. In addition, a decrease in glucose metabolism in the fronto-temporo-parietal regions correlated with an increase in glucose metabolism in the right medial temporal regions across subjects. LIMITATIONS There was considerable variability in the interval between the last ECT and FDG-PET scan. Depressed subjects were maintained on medication. The subjects included both major depressive disorder and bipolar disorder patients, as well as both ECT responders and non-responders. CONCLUSION Depression refractory to pharmacotherapy might have functional deficits in specific circumscribed frontal and temporal structures. ECT resolves the clinical symptoms without largely affecting these brain metabolic abnormalities. In contrast, ECT shifts the balance of corticolimbic function, which might explain how ECT ameliorates symptoms of depression in patients.

Temporal lobe epilepsy with amygdala enlargement: a morphologic and functional study.

Temporal lobe epilepsy (TLE) with nontumoral amygdala enlargement (AE) has been reported to be a possible subtype of TLE without hippocampal sclerosis (HS). The purpose of this study was to clarify morphologic and functional characteristics of TLE with AE (TLE + AE).

Task-dependent reorganization of functional connectivity networks during visual semantic decision making

Functional MRI is widely used to study task‐related changes in neuronal activity as well as resting‐state functional connectivity. In this study, we explore task‐related changes in functional connectivity networks using fMRI. Dynamic connectivity may represent a new measure of neural network robustness that would impact both clinical and research efforts. However, prior studies of task‐related changes in functional connectivity have shown apparently conflicting results, leading to several competing hypotheses regarding the relationship between task‐related and resting‐state brain networks.

Frontal nonconvulsive status epilepticus manifesting somatic hallucinations

Somatic hallucinations are subjective experience of false, strange sensations of things occurring in or to the body. They can be seen in psychotic disorders, but have not been well described as an ictal psychosis in patients with nonconvulsive status epilepticus (NCSE) of frontal origin. We reported a 69-year-old woman who had NCSE of frontal origin manifesting prolonged somatic hallucinations mimicking a psychiatric disorder and initially treated as such. Ictal EEG revealed the frontal focus and ictal single-photon emission computed tomography (SPECT) showed the activation, not only in the frontal area but also in the parietal area as the projected regions, both of which might be associated with the development of her symptoms. She also had two generalized tonic-chronic seizures out of psychosis. Her psychosis and ictal rhythmic discharges on EEG ceased with valproate and she has since remained free from the symptoms. The current case suggests that long-lasting somatic hallucinations could be an ictal psychosis in frontal NCSE and thus an EEG study is needed for an early diagnosis and treatment.

Clinical value of magnetoencephalographic spike propagation represented by spatiotemporal source analysis: Correlation with surgical outcome

OBJECTIVE To investigate the correlation between spike propagation represented by spatiotemporal source analysis of magnetoencephalographic (MEG) spikes and surgical outcome in patients with temporal lobe epilepsy. METHODS Thirty-seven patients were divided into mesial (n=27) and non-mesial (n=10) groups based on the presurgical evaluation. In each patient, ten ipsilateral spikes were averaged, and spatiotemporal source maps of the averaged spike were obtained by using minimum norm estimate. Regions of interest (ROIs) were created including temporoparietal, inferior frontal, mesial temporal, anterior and posterior part of the lateral temporal cortex. We extracted activation values from the source maps and the threshold was set at half of the maximum activation at the peak latency. The leading and propagated areas of the spike were defined as those ROIs with activation reaching the threshold at the earliest and at the peak latencies, respectively. Surgical outcome was assessed based on Engels classification. Binary variables were created from leading areas (restricted to the anterior and mesial temporal ROIs or not) and from propagation areas (involving the temporoparietal ROI or not), and for surgical outcome (Class I or not). Fishers exact test was used for significance testing. RESULTS In total and mesial group, restricted anterior/mesial temporal leading areas were correlated with Class I (p<0.05). Temporoparietal propagation was correlated with Class II-IV (p<0.05). For the non-mesial group, no significant relation was found. CONCLUSIONS Spike propagation patterns represented by spatiotemporal source analysis of MEG spikes may provide useful information for prognostic implication in presurgical evaluation of epilepsy.

Network specific change in white matter integrity in mesial temporal lobe epilepsy

OBJECTIVES To identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). METHODS We recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. RESULTS Tractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. CONCLUSION The change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation.

Evaluation of focus laterality in temporal lobe epilepsy: a quantitative study comparing double inversion-recovery MR imaging at 3T with FDG-PET.

To quantitatively compare the diagnostic capability of double inversion‐recovery (DIR) with F‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) for detection of seizure focus laterality in temporal lobe epilepsy (TLE).