Outcome of surgical treatment in familial mesial temporal lobe epilepsy

PURPOSE: To describe postoperative outcome in patients with familial mesial temporal lobe epilepsy (FMTLE). METHODS: We studied FMTLE patients who underwent surgical treatment for refractory seizures. FMTLE was defined when at least two individuals in a family had a clinical EEG diagnosis of MTLE. Preoperative investigation included magnetic resonance imaging (MRI), interictal/ictal EEGs, and neuropsychological evaluation. We used Engel's classification for postoperative outcome. RESULTS: To date, 20 FMTLE patients have been operated on, with 1.6 to 9.8 years of follow-up (mean, 5.5 years). Hippocampal atrophy (HA) and other signs of mesial temporal sclerosis (MTS) were present in 18 patients (15 unilateral). Seizures were recorded in 19 patients. Seventeen (85%) patients are in class I. Two patients had normal hippocampal volumes (HcV): one (5%) is in class II and the other (5%) in class IV (extratemporal seizures developed after surgery). One (5%) patient had bilateral HA and is in class III. Qualitative histopathology showed MTS with different degrees of severity. CONCLUSIONS: Refractory FMTLE patients have good surgical outcome when unilateral or clearly asymmetric HA is identified. Preoperative investigation should be the same as that in patients with sporadic refractory MTLE.     

Seizure outcome and hippocampal atrophy in familial mesial temporal lobe epilepsy

OBJECTIVE: To describe the clinical, genetic and MR characteristics of patients with familial mesial temporal lobe epilepsy (MTLE). DESIGN/METHODS: The familial occurrence of MTLE was identified by a systematic search of family history of seizures in patients followed in the authors' epilepsy clinic. All probands and, whenever possible, other affected family members underwent EEG and MR investigations. RESULTS: Twenty-two unrelated families with at least two individuals with MTLE were identified by clinical and EEG findings. Ninety-eight individuals with history of seizures were evaluated. Sixty-eight patients fulfilled the diagnostic criteria for MTLE. MRI was performed in 84 patients, and showed hippocampal atrophy with increased T2 signal in 48 (57%). The distribution of hippocampal atrophy according to the seizure outcome groups was 6 of 13 patients (46%) with seizure remission, 16 of 31 (51%) with good seizure control under medication, and all 16 patients with refractory MTLE. Hippocampal atrophy was found also in patients that did not fulfill the criteria for MTLE: 3 of 10 (30%) patients with febrile seizure alone, 6 of 10 (60%) patients with recurrent generalized tonic-clonic seizures, and 1 of 4 (25%) patients with a single partial seizure. CONCLUSION: Familial MTLE is a clinically heterogeneous syndrome. Hippocampal atrophy was observed in 57% of patients, including those with benign course or seizure remission, indicating that the relationship between hippocampal atrophy and severity of epilepsy might be more complex than previously suspected. In addition, these findings indicate the presence of a strong genetic component determining the development of mesial temporal sclerosis in these families.     

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.     

Linkage study of voltage-gated potassium channels in familial mesial temporal lobe epilepsy

Voltage-gated potassium channels (VGKCs) play a critical role in the regulation of neuronal excitability and have been implicated in some types of epilepsies. Recently, autoimmune limbic encephalitis (LE) was associated with antibodies against VGKC. In addition, patients with LE showed partial epilepsy and increased T2 signal abnormalities in limbic structures. We have reported familial mesial temporal lobe epilepsy (FMTLE) associated with hippocampal atrophy (HA) and other signs of mesial temporal sclerosis detected by magnetic resonance imaging (MRI). In order to investigate whether VGKC may be associated to HA present in FMTLE, we perform linkage study in these candidate genes. Seventy-three microsatellites markers were genotyped in different human autosomal chromosome. Two-point LOD scores did not show evidence for linkage with any of the microsatellite markers genotyped (Zmax ranging from 0.11to-9.53 at theta=0.00). In the present study, linkage data showed no evidence that VGKC are involved in the determination of HA in FMTLE.     

Grey and white matter abnormalities in temporal lobe epilepsy with and without mesial temporal sclerosis

Temporal lobe epilepsy with (TLE-mts) and without (TLE-no) mesial temporal sclerosis display different patterns of cortical neuronal loss, suggesting that the distribution of white matter damage may also differ between the sub-groups. The purpose of this study was to examine patterns of white matter damage in TLE-mts and TLE-no and to determine if identified changes are related to neuronal loss at the presumed seizure focus. The 4 T diffusion tensor imaging (DTI) and T1-weighted data were acquired for 22 TLE-mts, 21 TLE-no and 31 healthy controls. Tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) maps and voxel-based morphometry (VBM) was used to identify grey matter (GM) volume atrophy. Correlation analysis was conducted between the FA maps and neuronal loss at the presumed seizure focus. In TLE-mts, reduced FA was identified in the genu, body and splenium of the corpus callosum, bilateral corona radiata, cingulum, external capsule, ipsilateral internal capsule and uncinate fasciculus. In TLE-no, FA decreases were identified in the genu, the body of the corpus callosum and ipsilateral anterior corona radiata. The FA positively correlated with ipsilateral hippocampal volume. Widespread extra-focal GM atrophy was associated with both sub-groups. Despite widespread and extensive GM atrophy displaying different anatomical patterns in both sub-groups, TLE-mts demonstrated more extensive FA abnormalities than TLE-no. The microstructural organization in the corpus callosum was related to hippocampal volume in both patients and healthy subjects demonstrating the association of these distal regions.     

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.     

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.