Hippocampal N-acetylaspartate in neocortical epilepsy and mesial temporal lobe epilepsy

Previous magnetic resonance spectroscopy (MRS) studies have shown that N?acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE). The reason for the contralateral damage is not clear. To test whether the hippocampus is also damaged if the focus is outside the hippocampus, we have measured patients with neocortical epilepsy (NE). Therefore, the goals of this study were to determine if hippocampal NAA is reduced in NE and if hippocampal NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10 NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16 controls. The results show that, in contrast to mTLE, NAA was not reduced in the hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure focus. These results suggest that repeated seizures do not cause secondary damage to the hippocampus. The absence of spectroscopic differences in NE may help to distinguish NE from mTLE.     

Regional neocortical thinning in mesial temporal lobe epilepsy

PURPOSE: To determine the nature and extent of regional cortical thinning in patients with mesial temporal lobe epilepsy (MTLE). METHODS: High-resolution volumetric MRIs were obtained on 21 patients with MTLE and 21 controls. Mean cortical thickness was measured within regions of interest and point-by-point across the neocortex using cortical reconstruction and parcellation software. RESULTS: Bilateral thinning was observed within frontal and lateral temporal regions in MTLE patients relative to controls. The most striking finding was bilateral cortical thinning in the precentral gyrus and immediately adjacent paracentral region and pars opercularis of the inferior frontal gyrus, extending to the orbital region. Within the temporal lobe, bilateral thinning was observed in Heschl's gyrus only. Ipsilateral only thinning was observed in the superior and middle temporal gyri, as well as in the medial orbital cortex. Greater asymmetries in cortical thickness were observed in medial temporal cortex in patients relative to controls. Individual subject analyses revealed that this asymmetry reflected significant ipsilateral thinning of medial temporal cortex in 33% of patients, whereas it reflected ipsilateral thickening in 20% of MTLEs. DISCUSSION: Patients with MTLE show widespread, bilateral pathology in neocortical regions that is not appreciated on standard imaging. Future studies are needed that elucidate the clinical implications of neocortical thinning in MTLE.     

Low-frequency electric cortical stimulation has an inhibitory effect on epileptic focus in mesial temporal lobe epilepsy

PURPOSE: This study was conducted to investigate the effect of low-frequency electric cortical stimulation on epileptic focus in humans. METHODS: We stimulated the epileptic focus in a patient with medically intractable mesial temporal lobe epilepsy (MTLE) by means of subdural electrodes and evaluated the change in the number of interictal epileptiform discharges. We used biphasic electric current of 0.3-ms duration presented at 0.9-Hz frequency for 250 s, comparing stimulus intensity of 7.5, 2, and 0.5 mA. RESULTS: Interictal epileptiform discharges at the ictal focus occurred less frequently after the stimulation with the intensity of 0.5 mA. With the intensity of 7.5 mA and 2.0 mA, however, habitual auras were elicited by the stimulation, and afterdischarges were seen on the cortical EEG. CONCLUSIONS: Low-frequency, low-intensity electric cortical stimulation could produce inhibitory effects on epileptic activity. At the same time, however, a caution for possible induction of EEG seizures is needed, even when applying low-frequency electric stimulation.     

Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy

ObjectiveThe aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG).MethodsAccording to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ–mesial MRI-negative TLE or neocortical SOZ–neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology.ResultsThirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p = 0.031) and more seizures without clear lateralization of ictal activity (p = 0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found.ConclusionsAccording to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach.     

Benign mesial temporal lobe epilepsy

Benign mesial temporal lobe epilepsy (bMTLE), which is defined as at least 24 months of seizure freedom with or without antiepileptic medication, has probably been under-recognized because of a literature bias toward refractory epilepsy cases. Seizure onset in bMTLE tends to be in adolescence or adulthood, and patients frequently have a family history of febrile seizures and epilepsy. Long-term seizure freedom is observed with or without antiepileptic medication. On brain MRI, nearly 40% of patients with long-standing bMTLE show evidence of hippocampal sclerosis, a feature usually associated with refractory temporal lobe epilepsy. Prospective studies are needed to determine the features that allow prediction of a benign course, and to clarify the significance of hippocampal MRI changes.     

Metabolic profiles and correlation with surgical outcomes in mesial versus neocortical temporal lobe epilepsy

Aims

Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using ¹⁸F-FDG-PET.

Methods

A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). ¹⁸F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient.

Results

The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05).

Conclusions

The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.     

Atypical handedness in mesial temporal lobe epilepsy

ObjectiveThe main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population.MethodsHandedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated.ResultsWe found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p = 0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8 years of age [median; min-max 0.5–17] in left-handers versus 15 years of age [median; min-max 3–30] in right-handers (p < 0.001).ConclusionsLeft-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE.     

Superselective anterior temporal resection in mesial temporal lobe epilepsy

We report the case of a patient with pharmacoresistant mesial temporal lobe epilepsy presenting psychomotor seizures with onset at early childhood. MRI showed a blurred internal structure of the right hippocampus and right mammillary body atrophy. Neuropsychological testing revealed deficits in selective attention and visual planning. Non-invasive recording was not sufficient to precisely detect the seizure onset zone. Invasive recording showed seizure onset in the temporo-polar neocortex, with spread to the amygdalum and hippocampus. A superselective resection of the temporal pole and amygdalum was performed with preservation of the hippocampus. Histology revealed the presence of focal cortical dysplasia (Palmini type Ib). Seizure frequency was reduced after surgery, and seizure freedom for two years was achieved with optimisation of the antiepileptic drug regime. Memory functions were preserved, and selective attention and visual planning improved following limited resection. This case suggests that, in selected cases, highly targeted resections with preservation of memory-relevant structures may be the best choice considering both seizure control and unimpaired cognitive functioning.     

Electrical stimulation of the contralateral mesial temporal structure induces an ipsilateral seizure pattern in mesial temporal lobe epilepsy

PURPOSE: We examined the mode of seizure development induced by electrical stimulation in patients with mesial temporal lobe epilepsy. METHODS: Of 25 patients undergoing intracranial EEG evaluation and electrical stimulation ipsilateral to the presumed site of habitual seizure origin, 17 patients had additional stimulation studies on the contralateral temporal lobe. RESULTS: Fourteen of the 25 patients had seizures induced with ipsilateral stimulation, and two of the 17 patients had seizures with contralateral stimulation. Seizures induced by ipsilateral stimulation started in the ipsilateral temporal lobe, whereas those induced by contralateral stimulation originated from the ipsilateral temporal lobe structure and were identical to the habitual seizures. CONCLUSIONS: Electrical stimulation of the temporal lobe structure opposite the site of habitual seizure origin is said to induce a seizure rarely. However, according to our preliminary results, if contralateral stimulation elicits a habitual seizure in the ipsilateral temporal lobe, it might be considered additional confirmatory evidence of seizure lateralization.     

Role of immediate postictal diffusion-weighted MRI in localizing epileptogenic foci of mesial temporal lobe epilepsy and non-lesional neocortical epilepsy.

OBJECTIVE: To determine whether meaningful changes in signal intensity or in the apparent diffusion coefficient of water (ADC) in the ictal onset zone can be detected through immediate postictal and interictal diffusion-weighted magnetic resonance imaging (DWMRI) in patients with localization-related epilepsy. METHOD: In randomly selected 10 medial and lateral temporal lobe epilepsy (TLE) and four extratemporal epilepsy patients, DWMRI was performed immediately after a seizure and during the interictal period. All 14 patients were non-lesional except for hippocampal sclerosis detected on MRI. The mean time interval from seizure onset to postictal DWMRI was 81 min. Regions of interest (ROI) were selected in both the cortex, which was believed to be the ictal onset zone, and the corresponding anatomical region of the contralateral hemisphere in the postictal and interictal DWMRI. The mean ADC measured from all ROIs was compared. Ictal onset zones were determined by ictal electroencephalography (EEG) and seizure semiology. RESULTS: On visual inspection of postictal and interictal DWMRI, signal changes in the ictal onset zone could be identified in only one patient with medial TLE. The mean ADC values from the ictal onset zones were not significantly different from those of the corresponding contralateral regions of the cortices in both postictal and interictal DWMRI. However, the postictal ADC values of the epileptogenic foci of neocortical epilepsy or neocortical temporal portion of TLE without hippocampal sclerosis were decreased compared with interictal ones in whom both interictal and postictal DWMRIs were obtained (P = 0.028). CONCLUSION: Our results demonstrate that water diffusion can change even after a single seizure in non-lesional neocortical epilepsy.     

Molecular neuropathology of human mesial temporal lobe epilepsy.

With the recent progress in surgical treatment modalities, human brain tissue from patients with intractable focal epilepsies will increasingly become available for studies on the molecular pathology, electrophysiological changes and pathogenesis of human focal epilepsies. An inherent problem for studies on human temporal lobe epilepsy (TLE) is the lack of suitable controls. Strategies to alleviate this obstacle include the use of human post mortem samples, hippocampus from experimental animals and, in particular, the comparative analysis of surgical specimens from patients with Ammon's horn sclerosis (AHS) and with focal temporal lesions but anatomically preserved hippocampal structures. In this review we focus on selected aspects of the molecular neuropathology of TLE: (1) the potential impact of persisting calretinin-immunoreactive neurons with Cajal-Retzius cell morphology, (2) astrocytic tenascin-C induction and redistribution as potential regulator of aberrant axonal sprouting and (3) alterations of Ca2+ -mediated hippocampal signalling pathways. The diverse and complex changes described so far in human TLE specimens require a systematic interdisciplinary approach to distinguish primary, epileptogenic alterations and secondary, compensatory mechanisms in the pathogenesis of human temporal lobe epilepsies.