James W. Hugg

Relative utility of 1H spectroscopic imaging and hippocampal volumetry in the lateralization of mesial temporal lobe epilepsy

Objectives: To determine the relative utility of 1H MRSI and hippocampal volumetry for the lateralization of mesial temporal lobe epilepsy (MTLE) in patients with intractable epilepsy. Background: MTLE is the most common partial-onset seizure disorder in patients undergoing temporal lobe epilepsy surgery. MR volumetry and spectroscopy are reliable preoperative imaging techniques for the lateralization of MTLE. Methods: We analyzed the 1H MRSI and hippocampal formation volumes preoperatively in 30 consecutive patients who had undergone temporal lobectomy. Results: Volumetry correctly lateralized the side of surgery in 93% of patients and1 H MRSI did so in 97% of patients. Incorrect lateralization occurred by volumetry in two patients and by 1H MRSI in one patient. Concordance between all MRI modalities was 73%. Pearsons analysis revealed no correlation between the degree of hippocampal volume loss and the creatine-to-N-acetylated-compounds ratio. Conclusions: Volumetry and 1H MRSI correctly lateralized most patients with MTLE and complement each other in final lateralization. The lack of correlation between the severity of volume loss and the degree of metabolic disturbance suggests that the techniques examine distinct pathophysiologic processes in MTLE.

Topiramate increases cerebral GABA in healthy humans

Topiramate (TOP) is a novel anticonvulsant drug with multiple mechanisms of action used in the treatment of epilepsy. Measurements of cerebral GABA were obtained in six controls using 1H MRS at baseline and at 3 and 6 hours following the administration of 3 mg/kg of TOP. Brain GABA concentrations rose by 72% at 3 hours and by 64% at 6 hours compared with baseline (p < 0.004). This study demonstrates that TOP significantly increases human cerebral GABA concentrations in healthy individuals.

Association of combined MRI, interictal EEG, and ictal EEG results with outcome and pathology after temporal lobectomy

Summary: Purpose: Magnetic resonance imaging, interictal scalp EEG, and ictal scalp EEG each have been shown to localize the primaly epileptic region in most patients with mesial‐basal temporal lobe epilepsy (MBTLE), but the association of surgical outcome and pathology with each combination of these test results is not known.

Proton spectroscopic imaging at 4.1 tesla in patients with malformations of cortical development and epilepsy

We used proton magnetic resonance spectroscopic imaging (MRSI) at 4.1 tesla in patients with malformations of cortical development (MCDs) and epilepsy. We compared the spectroscopic results with normative data using 2 SDs (95% confidence) above normal values for detection of significant abnormalities for creatine-N-acetylated compounds (Cr/NA) ratio and choline-N-acetylated compounds (Cho/NA). The results were correlated with clinical, EEG, and histologic findings. Patients with focal cortical dysplasia showed significant metabolic abnormalities in correspondence with the structural lesions, whereas patients with heterotopia and polymicrogyria demonstrated no subcortical MRSI abnormalities. Significant correlations were found between the metabolic abnormalities and the frequency of seizures but not with the degree of interictal EEG discharges. Quantitative neuronal and glial cell counts revealed no statistically significant correlation between cell loss and the abnormal metabolic ratios in those who underwent surgery. These preliminary findings suggest that MRSI-based metabolic abnormalities in patients with MCDs are variable and are likely to be associated with complex cellular mechanisms involving the regulation of NA, total Cr content, and Cho.

Hippocampal 1H-MRSI correlates with severity of depression symptoms in temporal lobe epilepsy

Objective: To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. Methods: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated 1H magnetic resonance spectroscopic imaging (1H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. Results: The extent of hippocampal 1H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value < 0.001), but other clinical factors did not. Conclusion: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability.

Diffusion mapping applied to mesial temporal lobe epilepsy Preliminary observations

Objective: To evaluate whether diffusion mapping could lateralize intractable seizures in mesial temporal lobe epilepsy (MTLE) patients. Background: Animal seizure models show acute postictal depression of the apparent diffusion coefficient of water (ADCw), interictal normalization, then chronic elevation. Methods: The hippocampal plane was imaged with five diffusion weightings along each axis. Three orthogonal ADCw maps were averaged to produce an isotropic ADCw map. Results: In all eight MTLE patients, ADCw was elevated by a mean of 10 ± 3% (p < 0.01, paired t-test) interictally in the ipsilateral hippocampus, where side of seizure focus was determined electrographically with corroboration by volumetric MRI studies. Measured ADCw values in phantoms and five normal brains agree with published values. Conclusions: Brain tissue with interictally increased ADCw may represent an epileptogenic region with neuronal loss, gliosis, and expanded extracellular space (hippocampal sclerosis). Thus, diffusion mapping may confirm seizure lateralization.

Quantitative MRI in temporal lobe epilepsy : Evidence for fornix atrophy

Objective: To investigate whether the fornix and mamillary bodies, being part of the limbic system, are abnormal in patients with mesial temporal lobe epilepsy (MTLE). Background: The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. This system is implicated in complex functions, including memory and emotion, and in diseases such as MTLE. Methods: The authors performed volumetric measurements of hippocampus, amygdala, fornix, and mamillary bodies in 50 patients with MTLE and compared the results with normal controls and patients with extratemporal lobe epilepsy. Results: Control (n = 17) measurements of the amygdala, hippocampus, and fornix revealed larger volumes of the right hemisphere structures (p < 0.001). Normalized fornix volumes revealed atrophy in 86% of studies concordant with hippocampal atrophy in all cases but one. Similarly, the mean hippocampal and fornix volumes for the group discriminated the epileptogenic temporal lobe (p < 0.001). Limbic volumes were normal in all patients with extratemporal lobe epilepsy. Conclusions: Quantitative MRI findings support the concept that MTLE is not a process limited to the hippocampus but also involves other interrelated limbic system structures, in particular, the fornix.

Acute elevation and recovery of intracellular [Mg2+] following human focal cerebral ischemia

We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 ± 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 ± 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 ± 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr + Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 ± 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 ± 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 ± 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 ± 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury.

Predictive value of 1H MRSI for outcome in temporal lobectomy

Objective: To investigate the predictive value of 1H MRSI for outcome in patients with mesial temporal lobe epilepsy (MTLE). Background: 1H MRSI has been shown to be highly sensitive in the lateralization of temporal lob epilepsy. Methods: The authors analyzed the relationship between the 1H MRSI findings and surgical outcome in 40 consecutive patients who underwent temporal lobe surgery for MTLE. Outcome at a mean of 24 months (range 18 to 40 months) was classified as seizure free or not seizure free. Results: At follow-up, 78% of patients were seizure free. Correlations showed no predictive value for the creatine/N-acetylated compound (Cr/NA) ratio of the operated temporal lobe and outcome. However, a relationship was found between surgical failure and the Cr/NA ratio of the nonoperated temporal lobe and with a Cr/NA ratio in the nonoperated lobe above 1.21 in patients with bilateral abnormalities (p < 0.01). Conclusions: Preoperative elevations in the Cr/NA ratio in the nonoperated temporal lobe or the presence of higher metabolic ratios contralateral to the proposed surgery are associated with surgical failure. The predictive value of 1H MRSI absolute metabolite concentrations for outcome in MTLE requires further investigation.

Volumetric MRI of the limbic system : anatomic determinants

Abstract The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system.