Asymmetric Gray Matter Volume Changes Associated with Epilepsy Duration and Seizure Frequency in Temporal-Lobe-Epilepsy Patients with Favorable Surgical Outcome

BACKGROUND AND PURPOSE: This study aimed to estimate the changes in gray matter volume (GMV) and their hemispheric difference in patients with mesial temporal lobe epilepsy (MTLE) using a voxel-based morphometry (VBM) methodology, and to determine whether GMV changes are correlated with clinical features. METHODS: VBM analysis of brain MRI using statistical parametric mapping 8 (SPM8) was performed for 30 left MTLE (LMTLE) and 30 right MTLE (RMTLE) patients and 30 age- and sex-matched healthy controls. We also analyzed the correlations between GMV changes and clinical features of MTLE patients. RESULTS: In SPM8-based analyses, MTLE patients showed significant GMV reductions in the hippocampus ipsilateral to the epileptic focus, bilateral thalamus, and contralateral putamen in LMTLE patients. The GMV reductions were more extensive in the ipsilateral hippocampus, thalamus, caudate, putamen, uncus, insula, inferior temporal gyrus, middle occipital gyrus, cerebellum, and paracentral lobule in RMTLE patients. These patients also exhibited notable reductions of GMV in the contralateral hippocampus, thalamus, caudate, putamen, and inferior frontal gyrus. We observed that GMV reduction was positively correlated with several clinical features (epilepsy duration and seizure frequency in RMTLE, and history of febrile seizure in LMTLE) and negatively correlated with seizure onset age in both the RMTLE and LMTLE groups. CONCLUSIONS: Our study revealed GMV decreases in the hippocampus and extrahippocampal regions. Furthermore, the GMV reduction was more extensive in the RMTLE group than in the LMTLE group, since it included the contralateral hemisphere in the former. This difference in the GMV reduction patterns between LMTLE and RMTLE may be related to a longer epilepsy duration and higher seizure frequency in the latter.

The Effect of Topiramate and Lamotrigine on Cerebral Glucose Metabolism in Idiopathic Generalized Epilepsy Patients / 대한간질학회지

BACKGROUND: To investigate the effects of topiramate (TPM) or lamotrigine (LTG) on cerebral glucose metabolism, we performed 18F-fluorodeoxy glucose positron emission tomography (FDG-PET) before and after medication in patients with drug naive idiopathic generalized epilepsy. METHODS: Thiry-three patients with newly diagnosed as idiopathic generalized epilepsy (IGE) or IGE without antiepileptic drugs after diagnosis were included. Pre- and post-antiepileptic drug FDG-PET were performed (before and after TPM or LTG administration) in 33 subjects treated with TPM or LTG who had been seizure free for at least 8 weeks. Sixteen of patients received TPM (M/F=8/8, aged 29.2+/-12.3 years) and 17 LTG (M/F=8/9, 26.8+/-9.3 years). For statistical paramateric (SPM) analysis, all PET images were spatially normalized to the standard PET template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- and post-medication FDG-PET images. RESULTS: SPM analysis of post- and pre-medication FDG-PETs showed TPM reduced glucose metabolism markedly in the thalamus, corpus callosum, and white matters, whereas LTG decreased glucose metabolism in cortico-striato-entorhinal areas with a false discovery rate corrected p<0.05. No brain region showed post-medication hypermetabolism in either group. CONCLUSION: Our study demonstrates that both TPM and LTG affect the cerebral glucose metabolism in drug naive idiopathic generalized epilepsy patients.

Dipole Source Localization and Low Resolution Electromagnetic Tomography(LORETA) of Interictal Spikes in Mesial and Lateral Temporal Lobe Epilepsy / 대한간질학회지

PURPOSE: To investigate the usefulness of dipole source localization (DSL) and low resolution electromagnetic tomography (LORETA) in localizing epileptic focus, we performed DSL and LORETA of interictal spikes in patients with mesial and lateral temporal lobe epilepsy (TLE). METHOD: We analyzed representative interictal spikes in 17 patients with TLE (9:mesial TLE; 8:lateral TLE). We used ASA3 (Advanced Neuro Technology, Netherlands) for DSL, voltage topography (VT) and LORETA of interictal spikes. RESULT: Most interictal spikes for analysis have their maximum amplitudes at electrode F7, 8 or T7, 8 except one patient with lateral TLE (P7). In mesial TLE, VT showed a maximum negative electrical field in ipsilateral fronto-temporal region. DSL showed dipole sources in ipsilateral anterior mesial temporal lobe (33.3%, 3/9), temporal pole (44.5%, 4/9), orbitofrontal (11.1%, 1/9) and anterior inferior frontal (11.1%, 1/9) regions. LORETA showed maximum current density in ipsilateral fronto-temporal or anterior-mid temporal areas with lateral temporal maximum. In lateral TLE, dipole sources were in ipsilateral temporal pole (62.5%, 5/8), thalamus (12.5%, 1/8) and in posterosuperior temporal area (2/8, 25%). VT of spikes at F7 or F8 showed similar results as those of mesial TLE while that of spikes at T7, T8 and P7 had a tendency of electrical fields more extending to the mid- and posterior temporal regions. LORETA showed more diffuse current distribution in whole temporal lobe (anterior to posterior) with lateral temporal maximum. CONCLUSION: The patterns of DSL and LORETA were somewhat helpful to differentiate mesial from lateral TLE. LORETA usually showed more diffuse activity beyond the epileptic focus.

The Statistical Parametric Mapping Analysis between Pre- and Post-Operative FDG-PET Images in Patients with Mesial Temporal Lobe Epilepsy / 대한간질학회지

BACKGROUND: To investigate postoperative changes in the cerebral glucose metabolism of patients with mesial temporal lobe epilepsy (MTLE), statistical parametric mapping (SPM) analysis was performed on pre- and post-operative 18F-fluorodeoxy glucose positron emission tomographic (FDG-PET) images. METHODS: We included 28 patients with MTLE who had under-gone surgery and had been seizure free postoperatively (16 had left MTLE and 12 right MTLE). All patients showed hippocampal sclerosis by pathology or brain MRI. FDG-PET images of the 12 right TLE patients were reversed to lateralize the epileptogenic zone to the left side in all patients. RESULTS: Application of the paired t-test in SPM to pre- and postoperative FDG-PETs showed that the postoperative glucose metabolism decreased in the caudate nucleus, pulvinar of thalamus, fusiform gyrus, lingual gyrus, and in the posterior region of the insular cortex in the hemisphere ipsilateral to resection, whereas postoperative glucose metabolism increased in the anterior region of the insular cortex, temporal stem white matter, midbrain, inferior precentral gyrus, anterior cingulate gyrus, and supramarginal gyrus in the hemisphere ipsilateral to resection. No significant postsurgical changes of cerebral glucose metabolism occurred in the contralateral hemisphere. Subtraction between pre- and postoperative FDG-PET images in individual patients produced similar findings to the SPM results. CONCLUSION: This study suggests that brain regions showing a postoperative increase in glucose metabolism appear to represent the propagation pathways of ictal and interictal epileptic discharges in MTLE while a postoperative decrease in glucose metabolism may be related to a permanent loss of afferents from resected anterior-mesial temporal structures.

Effect of Topiramate on Cerebral Glucose Metabolism / 대한간질학회지

PURPOSE: To investigate the effects of topiramate on cerebral glucose metabolism, we performed 18F-fluorodeoxy glucose positron emission tomography (FDG-PET) in patients with new-onset epilepsy. METHODS: Thirteen patients with new-onset epilepsy or without medication after epilepsy diagnosis were included. Pre- and post-drug FDG-PET were performed (before and after topiramate administration) in all subjects (M/F=9/4, 28.2+/-11.4 years). For SPM analysis, paired pre- and linearly transformed post-drug FDG-PETs were spatially normalized into a standard PET template, provided in SPM-99, using a 12-parameter affine and a non-linear transformation. Spatially normalized images were then smoothed by convolution using an isotopic Gaussian kernel with a 14 mm full width at half maximum. The paired t-test was used to compare pre- and post-drug PET images. RESULTS: Mean dose of topiramate at the time of post-drug FDG-PET scanning was 163+/-71 mg. Mean duration of topiramate administration was 169+/-54 days. Responses to topiramate medication were seizure free in 7, reduced seizures in 3, and no changes in 3 patients. Reported adverse events were headache in 2 patients. SPM analysis between post-drug and pre-drug FDG-PET images showed post-drug hypometabolism in the white matters of both parietal and right temporal lobes, and corpus callosum, both thalami, right cingulate gyrus, left midbrain, both superior frontal gyri, left middle frontal gyrus, right inferior- and left superior parietal lobules, and left inferior temporal gyrus (corrected p<0.05). No brain region showed post-drug hypermetabolism. CONCLUSION: Topiramate reduced glucose metabolism more in the corpus callosum, thalamus and white matters, and less in the cerebral cortex.

Abnormal Cerebral Glucose Metabolism in Patients with Narcolepsy

BACKGROUND: The purpose of this study was to investigate the differences of cerebral glucose metabolism between narcoleptic patients and normal controls. METHODS: We enrolled 24 patients with narcolepsy who underwent night polysomnography and multiple sleep latency tests to confirm the narcolepsy. 18F-fluorodeoxy glucose positron emission tomography scan was performed in all narcoleptic patients and 24 normal age-sex matched controls. To compare the cerebral glucose metabolism between the two groups, statistical parametric mapping (SPM99) was used. RESULTS: Patients with narcolepsy showed significant decreases of cerebral glucose metabolism in the bilateral rectal and subcallosal gyri, right superior frontal gyrus, right medial frontal gyrus, bilateral precuneus, right inferior parietal lobule, and left supramarginal gyrus of the parietal lobe at the uncorrected P<0.001. The bilateral posterior hypothalami and mediodorsal thalamic nuclei showed glucose hypometabolism at the level of corrected P<0.05 with small volume correction. CONCLUSIONS: This study showed cerebral glucose hypometabolism of hypothalamus-thalamus-orbitofrontal pathways in narcoleptic brains. The distribution of abnormal glucose metabolism is concordant to the cerebral pathways of the hypocretin system.

Ictal Hyperperfusion of Brain Structures Related to Ictal Dystonic Posturing in Temporal Lobe Seizures

BACKGROUND: Although dystonic posturing (DP) during temporal lobe seizures is known to be related to basal ganglia activation, the mechanism of the dystonic posturing has not been investigated in greater details . METHODS: Thirty-two patients with mesial temporal lobe epilepsy (TLE) underwent ictal and interictal SPECTs. They were classified into two groups: 1) DP with ictal dystonia during ictal SPECT (N=15) and 2) Non-DP without dystonia (N=17). Ictal-interictal SPECT subtraction was performed as follows: co-registration, intensity normalization, subtraction, thresholding and then an overlay to SPGR MRI. The presence and intensity of ictal hyperperfusion were determined in frontal lobe, basal ganglia, temporal lobe and insular cortex. RESULTS: The incidences of ictal hyperperfusion in DP vs. Non-DP were caudate nucleus [80.0%(12/15 patients) vs. 0% (0/17), p=0.001], putamen [93.3% (14/15) vs. 48.2% (8/17), p=0.005], globus pallidus [53.3% (8/15) vs. 23.5% (4/17), p=0.082], thalamus [80.0% (12/15) vs. 41.2% (7/17), p=0.026], insular cortex [46.7% (7/15) vs.23.5% (4/17), p=0.051], orbitofrontal [46.7% (6/15) vs. 35.3% (7/17), p=0.053], medial frontal [6.7% (1/15) vs. 18.7% (2/17), p=0.621], dorsolateral frontal [13.3% (2/15) vs. 18.7%(2/17), p=0.737] in the hemisphere of epileptic side. In patients who showed ictal hyperperfusion in striatum and thalamus, the average intensity of hyperperfusion in DP vs. Non-DP was caudate nucleus 1.67 vs. 0.0, putamen 2.20 vs. 1.05, globus pallidus 1.2 vs. 0.65, thalamus 2.00 vs. 0.88 in the epileptic hemisphere. CONCLUSIONS: Caudate nucleus as well as putamen appeared to be important for producing ictal dystonia during TLE seizures. The greater intensity of ictal hyperperfusion in putamen, caudate nucleus and thalamus seems to be related to ictal dystonia.

Ictal Hyperperfusion of Brain Structures Related to Ictal Dystonic Posturing in Temporal Lobe Seizures

BACKGROUND: Although dystonic posturing (DP) during temporal lobe seizures is known to be related to basal ganglia activation, the mechanism of the dystonic posturing has not been investigated in greater details . METHODS: Thirty-two patients with mesial temporal lobe epilepsy (TLE) underwent ictal and interictal SPECTs. They were classified into two groups: 1) DP with ictal dystonia during ictal SPECT (N=15) and 2) Non-DP without dystonia (N=17). Ictal-interictal SPECT subtraction was performed as follows: co-registration, intensity normalization, subtraction, thresholding and then an overlay to SPGR MRI. The presence and intensity of ictal hyperperfusion were determined in frontal lobe, basal ganglia, temporal lobe and insular cortex. RESULTS: The incidences of ictal hyperperfusion in DP vs. Non-DP were caudate nucleus [80.0%(12/15 patients) vs. 0% (0/17), p=0.001], putamen [93.3% (14/15) vs. 48.2% (8/17), p=0.005], globus pallidus [53.3% (8/15) vs. 23.5% (4/17), p=0.082], thalamus [80.0% (12/15) vs. 41.2% (7/17), p=0.026], insular cortex [46.7% (7/15) vs.23.5% (4/17), p=0.051], orbitofrontal [46.7% (6/15) vs. 35.3% (7/17), p=0.053], medial frontal [6.7% (1/15) vs. 18.7% (2/17), p=0.621], dorsolateral frontal [13.3% (2/15) vs. 18.7%(2/17), p=0.737] in the hemisphere of epileptic side. In patients who showed ictal hyperperfusion in striatum and thalamus, the average intensity of hyperperfusion in DP vs. Non-DP was caudate nucleus 1.67 vs. 0.0, putamen 2.20 vs. 1.05, globus pallidus 1.2 vs. 0.65, thalamus 2.00 vs. 0.88 in the epileptic hemisphere. CONCLUSIONS: Caudate nucleus as well as putamen appeared to be important for producing ictal dystonia during TLE seizures. The greater intensity of ictal hyperperfusion in putamen, caudate nucleus and thalamus seems to be related to ictal dystonia.

Regional Cerebral Blood Flow Patterns in Unilateral Mesial Temporal Lobe Epilepsy: Statistical Parametric Mapping of Ictal and Interictal SPECT / 대한간질학회지

PURPOSE: To investigate the regional cerebral blood flow of patients with mesial temporal lobe epilepsy (mTLE), we performed the statistical parametric mapping (SPM) analysis in patients with mTLE. METHODS: Nineteen normal subjects and 38 with mTLE (22 left, 16 right) underwent brain SPECT. For SPM analysis, all SPECT images were spatially normalized and then smoothed. The left and right mTLE groups were statistically compared with normal subjects, and the paired t-test was performed between ictal and interictal SPECTs. The positive and negative contrasts displayed the regions of hypo- or hyper-perfusion, respectively. The significance level was set to false discovery rate corrected p<0.05. RESULTS: In the interictal state, the ipsilateral hippocampus, both thalami, pericentral gyri, left insula, and both medial frontal lobes showed hypoperfusion, whereas both posterior lateral temporal areas showed hyperperfusion. In the ictal state, the rCBF of ipsilateral temporal lobe to the epileptic focus and both prefrontal white matters increased, while both medial frontal lobes showed hypoperfusion. In the right mTLE, the left hippocampus and insula showed hypoperfusion during the interictal state. In the paired t-test, ipsilateral temporal lobe, hippocampus, thalamus, putamen, insula, and both precentral gyri showed hyperperfusion. CONCLUSIONS: Surprisingly, the hypoperfusion and hyperperfusion patterns of patients with mTLE were similar both in the interictal and ictal states. These findings indicate that the occurrence and propagation of epileptic discharges happen not only in the ictal state but also during the interictal period. The hypoperfusion patterns suggest that the cortico-thalamo-hippocampal-insula circuit was impaired during the interictal state while temporal and prefrontal regions showed hypofunction during the ictal period.

Normal Values of the Regional Cerebral Blood Flow (rCBF) in Rat Using Digital Autoradiographic Method

To get the normal values of regional cerebral blood flow (rCBF) in rat brain in our laboratory, we used the digital autoradiographic method with C-14 iodoantipyrine (IAP) in 8 Wistar rats. The rats were anesthetized with 1.5% halothane during the experimental procedure. Right femoral artery and vein were cannulated for blood pressure monitoring. Arterial sampling - and injection of radiotracer. Fifty uCi of C-14 IAP was constantly injected over 30 seconds using infusion pump and 10 to 15 arterial samples were obtained with micropipettes At the end of 30 seconds the brain was removed and freezed in liquid nitrogen. Coronal sections of the brain were exposed to film and the images were analyzed by computer-based digital analyzer system. Values of the regional cerebral blood flow in ml/l00g brain/min were as follows. Frontal cortex, 110.7 +/- 31.0; parietal cortex, 120.9 +/- 31.0; temporal cortex, 123.4 +/- 30.5; occipital cortex, 111.2 +/- 31.; cingulate cortex, 112.8 +/- 32.4; pyriform cortex, 1043 +/- 33.8; entorhinal cortex, 114.5 +/- 40.9; corpus callosum, 55.2 +/- 17.2; caudatoputamen 105.3 +/- 39.8, thalamus, 114.6 +/- 35.0; Cal region of hippocanpus, 79.4 +/- 33.3; CA2. 80.2 +/- 34.9; CA3, 83.4 +/- 37.2; dentate gyrus, 80.0 +/- 37.1. These normal values of rCBF in rat brain may be used as a standard index for future experimental researches on therapy and pathophysiology of cerebral ischemia using autoradiographic measurement of rCBF.

A Clinical Study on 16 Cases of Myotonic Dystrophy

Myotonic dystrophy is a familial multisystem disorder transmitted by autosomal dominant pattern, which is the commonest of adult-onset muscular dystrophies. We analyzed clinically 16 patients of myotonic dystrophy who had admitted at Seoul National University Hospital during past 8.5 years (from Jan. 1977 to July 1985). Sex ratio is 7:1 (male; 14, female;2) and the average age is 29.6 (17-49). Chief complaints, at admission, are relaxation difficulty (88%), extremity weakness (69%), speech disturbance (63%), frontal baldness (38%), and impotence(31%), etc. in that order of frequency. Physical examination showed myotonia and typical myopathic appearnace in all cases. EMG and muscle biopsy revealed typical features of myotonic dystrophy. Associated other abnormalities are EKG abnormality (81%), eye involvement (68.7%), abnormal skull X-ray (46.7%), DM (18.8%), increased serum gonadotropin level (90%), abnormal semen composition (80%), decreased pulmonary function (100%) and mild brain atrophy, etc. Diphenylhydantoin was given and physiotherapy with genetic counselling was performed. Seven of sixteen patients showed slight decrement of myotonia.