청소년기 근간대성 간질환자의 뇌 형태 및 혈류 분석

Abstract

This thesis addresses a comprehensive analysis of juvenile myoclonic epilepsy (JME) patients's brain to investigate abnormal structure and regional cerebral blood flow (rCBF). MRI Volumetry, voxel based morphometry (VBM), and cortical thickness analysis were employed to detect structural abnormality, and Statistical Parametric Mapping (SPM) method was employed to detect rCBF abnormality. Study Ⅰ: To investigate the structural brain abnormalities in JME patients. The volumes of cerebrum, hippocampus and frontal lobe, and the area of corpus callosum's subdivisions were semi-automatically measured and optimized VBM was performed in 19 JME patients and 19 age/sex matched normal controls. The rostrum and rostral body of corpus callosum and left hippocampus were significantly smaller than those of normal controls, whereas the volume of JME's left frontal lobe was significantly larger than that of controls. The area of rostral body had a significant positive correlation with the age of seizure onset (r = 0.56, p = 0.012), and the volume of right frontal lobe had a significant negative correlation with the duration of disease (r = -0.051, p = 0.025). In VBM, the gray matter concentration of prefrontal lobe (bilateral gyri rectus, anterior orbital gyri, left anterior middle frontal gyrus, right anterior superior frontal gyrus) was decreased in JME group (corrected p < 0.05). The JME patients showed complex structural abnormalities in corpus callosum, frontal lobe and hippocampus, and decreased gray matter concentration of prefrontal region, which suggest abnormal neural network in JME brain. Study Ⅱ. Previous studies on gray matter concentration changes in patients with juvenile myoclonic epilepsy (JME) are not consistent. To investigate the cortical abnormality in JME, a measurement of cortical thickness was performed in 19 JME patients and 18 normal controls. Results showed that the cortical thickness of superior/middle/medial frontal gyri, and superior/middle/inferior temporal gyri decreased patients. The cortical thicknesses of precentral gyrus and medial orbital gyrus of right hemisphere were negatively correlated with disease duration, while cortical thickness of superior frontal gyrus was positively correlated with number of myoclonic jerks per year. These findings suggest that JME brains have cortical gray matter atrophy in frontal and temporal lobes but hypertrophy of some superior frontal region may be related to frequent myoclonic jerks. Study Ⅲ. The role of thalamus and brainstem in generalized epilepsy has been suggested in previous studies. The aim of the present study was to assess rCBF abnormality in JME patients. ^(99m)Tc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed in 19 drug naive JME patients and 25 normal controls with the similar age and gender distribution. Differences of rCBF between a JME group and a normal control group were examined by the statistical parametric mapping of brain SPECT images using independent t test. The regression analyses in SPM were also performed between rCBF and the age of seizure onset or the disease duration in JME group. Compared to normal controls, the JME group showed a significant rCBF reduction in bilateral thalami, red nucleus, midbrain, pons, left hippocampus, and in the cerebelli (FDR corrected p<0.01) whereas rCBF increase in the left superior frontal gyrus (uncorrected p<0.001 but FDR corrected p>0.05). Disease duration was negatively correlated with rCBF in bilateral frontal cortices, caudate nuclei, brainstem and cerebellar tonsils. Our results suggest that abnormal neural networks in the thalamus, hippocampus, brainstem and cerebellum are associated with JME.