ABSTRACT
OBJECTIVE: To evaluate the interactions of metabolic neuronal-glial changes with the presence and hemispheric-side of hippocampal sclerosis (HS) and its potential role in predicting pharmacoresistance in temporal lobe epilepsy (TLE). METHODS: We included structural magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1 H-MRS) metabolic data for 91 patients with unilateral TLE and 50 healthy controls. We measured the values of total N-acetyl aspartate/total creatine (tNAA/tCr), glutamate/tCr (Glu/tCr), and myo-inositol/tCr (mIns/tCr). To assess the influence of the pharmacoresponse and hemispheric-side of HS on metabolic data, the relationship between clinical and MRI data, and the predictive value of NAA/Cr, we used analysis of variance/covariance and built a logistic regression model. We used bootstrap simulations to evaluate reproducibility. RESULTS: Bilateral tNAA/tCr reduction was associated with pharmacoresistance and with left HS, a decrease of Glu/tCr ipsilateral to the seizure focus was associated with pharmacoresistance, and ipsilateral mIns/tCr increase was related to pharmacoresistance and the presence of left HS. The logistic regression model containing clinical and 1 H-MRS data discriminated pharmacoresistance (area under the curve [AUC] = 0.78). However, the reduction of tNAA/tCr was the main predictor, with the odds 2.48 greater for pharmacoresistance. SIGNIFICANCE: Our study revealed a spectrum of neuronal-glial changes in TLE, which was associated with pharmacoresistance, being more severe in left-sided HS and less severe in MRI-negative TLE. These noninvasive, in vivo biomarkers provide valuable additional information about the interhemispheric differences in metabolic dysfunction, seizure burden, and HS, and may help to predict pharmacoresistance.
Subject(s)
Anticonvulsants/therapeutic use , Drug Resistant Epilepsy/pathology , Epilepsy, Temporal Lobe/drug therapy , Hippocampus/pathology , Neuroglia/pathology , Neurons/pathology , Adult , Biomarkers , Case-Control Studies , Creatine/metabolism , Drug Resistant Epilepsy/drug therapy , Epilepsy, Temporal Lobe/diagnostic imaging , Epilepsy, Temporal Lobe/metabolism , Epilepsy, Temporal Lobe/pathology , Female , Glutamic Acid/metabolism , Hippocampus/diagnostic imaging , Humans , Inositol/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , N-Methylaspartate/metabolism , Neuroimaging , Proton Magnetic Resonance Spectroscopy , Sclerosis , Treatment Outcome , Young AdultABSTRACT
BACKGROUND/PURPOSE: Previous imaging studies in the Machado-Joseph disease (MJD/SCA3) have mostly concentrated on the cerebellum and brainstem. Our goal was to perform a whole brain longitudinal evaluation. METHODS: We included 45 patients and 51 controls, who underwent two brain magnetic resonance imaging and magnetic resonance spectroscopy (mean interval of 12.5 ± 1.5 months). We used voxel-based morphometry (VBM) and the MarsBar analysis toolbox to extract grey matter density (GMD) values from regions of interest. We used a linear regression model and a general linear model to correlate GMD with clinical markers, and paired t-test for the longitudinal evaluation. RESULTS: We observed decreased GMD (P < .01) at frontal, parietal, temporal and occipital lobes, subcortical grey matter, cerebellum, and brainstem. White matter atrophy was restricted to the cerebellum. Age, CAG, and disease duration predicted GMD in different areas, but age and CAG were the most important predictors. The longitudinal analysis failed to demonstrate changes. Changes in regions other than the cerebellum appeared to contribute significantly to the final International Cooperative Ataxia Rating Scale score. CONCLUSION: We confirmed cortical involvement in MJD/SCA3. The most important factors in predicting GMD were age and CAG. The lack of progression of atrophy may indicate floor effect and/or short duration of follow-up.
Subject(s)
Machado-Joseph Disease/genetics , Machado-Joseph Disease/pathology , Magnetic Resonance Imaging/methods , Neocortex/pathology , Neocortex/physiopathology , Adult , Aged , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young AdultABSTRACT
PURPOSE: To compare relative N-acetylaspartate (NAA) measurements in temporal lobe epilepsy (TLE) patients with good response to the first trial of antiepileptic drugs (AEDs) (an important prognostic factor) to TLE patients who failed the first AED monotherapy and required further AED trials with monotherapy or polytherapy. METHODS: We studied 25 consecutive TLE patients who responded to first AED (responders) and 21 who did not (failure-group), as well as 27 controls. Patients were seen regularly in our Epilepsy Service and underwent electroencephalography (EEG) investigation, high-resolution magnetic resonance imaging (MRI), and single-voxel proton MR spectroscopy. Voxels were tailored to the medial temporal region on each side and involved the anterior hippocampus. RESULTS: Analysis of variance (ANOVA) demonstrated significant variation of NAA/creatine (NAA/Cr) values in both hippocampi, ipsilateral and contralateral to the EEG focus (p < 0.001 and p = 0.021) across the groups. Pairwise post hoc comparisons showed reduced NAA/Cr in both hippocampi of failure-group compared to controls (p < 0.001) and compared to responders (p < 0.05), but not between the controls and responders. Individual analyses showed NAA/Cr ratios lower than 2 SDs (standard deviations) below the mean of controls in 9 of 21 patients (42.8%) in the failure-group (6 with unilateral and 3 with bilateral reduction) but in none of the responders. DISCUSSION: These results indicate that patients with TLE who respond well to the first AED have significantly less evidence of neuronal and axonal damage/dysfunction compared to those who are refractory to the first AED trial.
