Thalamohippocampal atrophy in focal epilepsy of unknown cause at the time of diagnosis.

BACKGROUND AND PURPOSE: Patients with chronic focal epilepsy may have atrophy of brain structures important for the generation and maintenance of seizures. However, little research has been conducted in patients with newly diagnosed focal epilepsy (NDfE), despite it being a crucial point in time for understanding the underlying biology of the disorder. We aimed to determine whether patients with NDfE show evidence of volumetric abnormalities of subcortical structures. METHODS: Eighty-two patients with NDfE and 40 healthy controls underwent magnetic resonance imaging scanning using a standard clinical protocol. Volume estimation of the left and right hippocampus, thalamus, caudate nucleus, putamen and cerebral hemisphere was performed for all participants and normalised to whole brain volume. Volumes lower than two standard deviations below the control mean were considered abnormal. Volumes were analysed with respect to patient clinical characteristics, including treatment outcome 12 months after diagnosis. RESULTS: Volume of the left hippocampus (p(FDR-corr)  = 0.04) and left (p(FDR-corr)  = 0.002) and right (p(FDR-corr)  = 0.04) thalamus was significantly smaller in patients relative to controls. Relative to the normal volume limits in controls, 11% patients had left hippocampal atrophy, 17% had left thalamic atrophy and 9% had right thalamic atrophy. We did not find evidence of a relationship between volumes and future seizure control or with other clinical characteristics of epilepsy. CONCLUSIONS: Volumetric abnormalities of structures known to be important for the generation and maintenance of focal seizures are established at the time of epilepsy diagnosis and are not necessarily a result of the chronicity of the disorder.

Neuroradiological findings in patients with "non-lesional" focal epilepsy revealed by research protocol.

AIM: To evaluate whether a dedicated epilepsy research protocol with expert image re-evaluation can increase identification of patients with lesions and to attempt to ascertain the potential reasons why lesions were not identified previously on earlier clinical magnetic resonance imaging (MRI). MATERIALS AND METHODS: Forty-three patients (26 female) with focal refractory epilepsy who had failed at least two trials of anti-epileptic drug treatments were studied. Patients were recruited prospectively into the study if previous clinical MRI was deemed to be "non-lesional" by the clinicians involved in the initial assessment. Three-dimensional (3D) T1-weighted (T1W), T2-weighted (T2W), T2 fluid-attenuated inversion recovery (T2-FLAIR) sequences, and two-dimensional (2D) coronal T1-/T2W FLAIR were assessed by a neuroradiologist, including the previous clinical MRI of individual patients. RESULTS: Twenty-nine or 43 (67%) patients remained MRI-negative after scanning with the epilepsy-dedicated protocol and image reappraisal by expert consultant neuroradiologists; however, 14/43 (33%) patients were found to have potentially epileptogenic brain lesions. The lesion that most frequently escaped the attention of clinicians was hippocampal sclerosis (nine cases, of which two had an additional focal cortical dysplasia, FCD), followed by single FCDs (two cases), and others including gliosis, encephalocoele, and amygdala enlargement (one case each). Eleven of the 14 (79%) previously "non-lesional" patients had electroencephalogram (EEG) imaging-concordant localisation features, rendering them potential candidates for resective surgery. CONCLUSIONS: The primary factors explaining the newly identified lesions were the choice of MRI sequences, imaging parameters, data quality, lesion not reported (human factor), and loss of information through incomplete documentation. It is important for all clinicians to proceed meticulously in the detailed assessment of epilepsy-dedicated in-vivo MRI and discuss difficult patient cases in multidisciplinary team meetings.

Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes.

OBJECTIVE: To investigate the clinical and surgical outcome correlates of preoperative hippocampal subfield volumes in patients with refractory temporal lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence segmentation technique. METHODS: We recruited 106 patients with TLE and hippocampal sclerosis (HS) who underwent conventional T1-weighted and T2 short TI inversion recovery MRI. An automated hippocampal segmentation algorithm was used to identify twelve subfields in each hippocampus. A total of 76 patients underwent amygdalohippocampectomy and postoperative seizure outcome assessment using the standardized ILAE classification. Semiquantitative hippocampal internal architecture (HIA) ratings were correlated with hippocampal subfield volumes. RESULTS: Patients with left TLE had smaller volumes of the contralateral presubiculum and hippocampus-amygdala transition area compared to those with right TLE. Patients with right TLE had reduced contralateral hippocampal tail volumes and improved outcomes. In all patients, there were no significant relationships between hippocampal subfield volumes and clinical variables such as duration and age at onset of epilepsy. There were no significant differences in any hippocampal subfield volumes between patients who were rendered seizure free and those with persistent postoperative seizure symptoms. Ipsilateral but not contralateral HIA ratings were significantly correlated with gross hippocampal and subfield volumes. CONCLUSIONS: Our results suggest that ipsilateral hippocampal subfield volumes are not related to the chronicity/severity of TLE. We did not find any hippocampal subfield volume or HIA rating differences in patients with optimal and unfavorable outcomes. In patients with TLE and HS, sophisticated analysis of hippocampal architecture on MRI may have limited value for prediction of postoperative outcome.

The role of the corpus callosum in seizure spread: MRI lesion mapping in oligodendrogliomas.

BACKGROUND: Some patients with oligodendrogliomas have generalized tonic-clonic seizures (GTCS) while others have only partial seizures (PS). We investigated the relationship between tumour localization and seizure generalization using quantitative lesion mapping on magnetic resonance images. METHODS: Twenty one patients with histologically proven oligodendrogliomas and GTCS (n=11) or PS (n=10) were studied. Data were acquired on a 3 Tesla MRI System. We performed lesion mapping techniques to compare the spatial distribution of oligodendrogliomas between patient groups, and quantitatively determined the extent to which lesions intersected each probabilistic regions-of-interest, including the cerebral lobes, thalamus, striatum, and genu of the corpus callosum. RESULTS: In patients experiencing GTCS, the greatest lesion load was observed in mesial frontal regions, including cortex connected to the genu. In contrast, the greatest lesion load in patients experiencing PS was observed more caudo-laterally in orbitofrontal and temporal lobes, but typically sparing cortex connected to the genu. The number of lesion intersections with genu region of interest was significantly greater in patients experiencing GTCS relative to patients with PS (p=0.03). There were no significant differences between patient groups with respect to lesion intersection with the individual cerebral lobes, thalamus and striatum, or with respect to overall oligodendroglioma size. CONCLUSION: Our data suggest that the genu of the corpus callosum may be a major pathway for seizure generalization in patients with oligodendrogliomas.

Nerve fiber impairment of anterior thalamocortical circuitry in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a syndrome of idiopathic generalized epilepsy (IGE) without structural brain abnormalities detectable by MRI or CT. OBJECTIVE: In the present study, we addressed the question of whether diffusion tensor MRI (DTI) can detect disease-specific white matter (WM) abnormalities in patients with JME. METHODS: We performed whole head DTI at 3 T in 10 patients with JME, 8 age-matched patients with cryptogenic partial epilepsy (CPE), and 67 age-matched healthy volunteers. Nerve fiber integrity was compared between the groups on the basis of optimized voxel-by-voxel statistics of fractional anisotropy (FA) maps obtained by DTI (analysis of covariance, categorical factor "group," covariate "age"). RESULTS: FA was reduced in a WM region associated with the anterior thalamus and prefrontal cortex in patients with JME compared to both control subjects and patients with CPE (p < 0.001). The patients with CPE showed normal values in this particular WM region. The FA reductions in the patients with JME correlated with the frequency of generalized tonic-clonic seizures (Spearman R = 0.54, p = 0.05). No significant correlations were found in the JME sample between FA reduction and the duration of antiepileptic medication. CONCLUSIONS: The results support the hypothesis that juvenile myoclonic epilepsy is associated with abnormalities of the thalamocortical network that can be detected by diffusion tensor MRI.

Degree of hippocampal atrophy is related to side of seizure onset in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy (TLE) is associated with pathologic changes in hippocampal physiology and morphology. Our aim was to quantify volume reduction of the right and left hippocampus in patients with TLE and to investigate whether the degree of hippocampal atrophy is related to the side of seizure onset. METHODS: The volume of the right and left hippocampus was estimated for 50 controls and 101 patients with TLE, by applying the unbiased Cavalieri method on MR images. RESULTS: Pairwise comparisons, within a multivariate analysis of variance and adjusted by using the Bonferroni correction, revealed that both right and left hippocampal volumes were, on average, significantly smaller in patients with right-sided seizure onset (R-patients) relative to those of controls (P < .001 and P = .04, respectively). Furthermore, left hippocampal volume was significantly smaller in patients with left-sided seizure onset (L-patients) compared with controls (P < .001), but the right-sided hippocampal volume was not significantly smaller (P = .71). Moreover, a correlation analysis revealed that the strong linear association between the right and left hippocampal volumes existing in the control population (r = 0.73) is partially lost in patients with TLE (r < or = 0.48), and this loss in correlation appears to be more pronounced in L-patients than in R-patients. CONCLUSION: Our MR imaging results suggest that although the major damage in patients with TLE is located in the hippocampus ipsilateral to the side of seizure onset, R-patients are more likely to have bilateral hippocampal volume reduction. These findings support the hypothesis that cerebral hemispheres may not only differ in their functionality organization but also in their vulnerability to a neurologic insult.

Voxel based morphometry of grey matter abnormalities in patients with medically intractable temporal lobe epilepsy: effects of side of seizure onset and epilepsy duration.

OBJECTIVES: To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine the relation between side, duration, and age of onset of temporal lobe epilepsy, history of childhood febrile convulsions, and grey matter structure. METHODS: Three dimensional magnetic resonance images were obtained from 58 patients with left sided seizure onset (LSSO) and 58 patients with right sided seizure onset (RSSO), defined using EEG and foramen ovale recordings in the course of presurgical evaluation for temporal lobectomy. Fifty eight normal controls formed a comparison group. VBM was used to characterise whole brain grey matter concentration, while the Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal and amygdala volume. Age and sex were used as confounding covariates in analyses. RESULTS: LSSO and RSSO patients showed significant reductions in volume (using stereology) and grey matter concentration (using VBM) of the hippocampus, but not of the amygdala, in the presumed epileptogenic zone when compared with controls, but hippocampal (and amygdala) volume and grey matter concentration were not related to duration or age of onset of epilepsy. LSSO and RSSO patients with a history of childhood febrile convulsions had reduced hippocampal volumes in the presumed epileptogenic zone compared with patients without such a history. Left amygdala volume was also reduced in LSSO patients with a history of childhood convulsions. VBM results indicated bilateral thalamic, prefrontal, and cerebellar GMC reduction in patients, which correlated with duration and age of onset of epilepsy. CONCLUSIONS: Hippocampal sclerosis is not necessarily the consequence of recurrent temporal lobe seizures. A major cause of hippocampal sclerosis appears to be an early aberrant neurological insult, such as childhood febrile seizures. Secondary brain abnormalities exist in regions outside the presumed epileptogenic zone and may result from recurrent seizures.