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

Abstract

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. H ippocampal sclerosis is the most common finding in patients with medically intractable temporal lobe epilepsy.1 However, the relation between the duration of epilepsy and hippocampal sclerosis is not fully understood. Some cross sectional research has found evidence for progressive hippocampal volume loss in patients with temporal lobe epilepsy, [2][3][4][5] suggesting that hippocampal atrophy is a consequence of recurrent temporal lobe seizures. Conversely, others have found no relation between hippocampal volume and duration of epilepsy, 6 7 which suggests that hippocampal abnormalities do not result from repeated seizures. Hippocampal sclerosis has been related to the age of onset of epilepsy and a history of childhood febrile convulsions in some studies.3 7 However, although atrophy of the amygdala, 8 9 entorhinal cortex, 10-12 parahippocampal gyrus, 13 14 lateral temporal lobe, 15 16 and thalamus 17 h...

MR-based in vivo hippocampal volumetrics: 1. Review of methodologies currently employed

“…As early as 1993, Colombo et al 28 introduced an automated method for determining the volume of the amygdala-hippocampal complex. Voxel-based morphometry is an automatic method, which is gaining popularity and has been used to determine hippocampal morphometric changes; 31,[118][119][120][121][122][123][124][125][126][127] however, these do not provide absolute hippocampal volumes.…”

Thalamic atrophy and cognition in unilateral temporal lobe epilepsy

“…These findings are consistent with the hypothesis that different mechanisms contribute to the integrity of the hippocampus and thalamus in unilateral TLE. Hippocampal volume was influenced by both early neurodevelopmental features (e.g., an early neurologic insult) and course features such as duration (Bernasconi et al, 2005;Keller et al, 2002;Seidenberg et al, 2005;Theodore et al, 1999). In contrast, thalamic volume was affected only by course variables (e.g., duration of epilepsy).…”

“…The ipsilateral hippocampus showed the largest volume reduction, but thalamic volume was also significantly reduced compared with controls and was evident on both the ipsilateral (9%) and contralateral side (6%). Thalamic volume reduction in unilateral TLE has been reported, although the findings concerning the presence of ipsilateral or bilateral volume abnormality are mixed (Dlugos et al, 1999;Dreifuss et al, 2001;Keller et al, 2002;Muel- Thalamus and TLE 389 …”

Epileptic baboons have lower numbers of neurons in specific areas of cortex

“…11 and 12), and intrinsic numbers of cells and neurons (13)(14)(15)(16). Chronic seizures have been associated with progressive changes in the region of the epileptic focus and in remote but functionally connected cortical or subcortical structures (3,17). Because areas of the cortex are functionally and structurally different, they may also differ in susceptibility to pathological changes resulting from epilepsy.…”