Long-term course of epilepsy in a large cohort of intellectually disabled patients.

This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps. RESULTS: Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005). CONCLUSIONS: Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.     

Amplitude envelope correlation detects coupling among incoherent brain signals

Cognitive processing involves gamma-activation over broad cortical regions. Phase coupling of these activities has rarely been reported for areas far apart. Other forms of coupling are generally not detected by conventional measures. Here, we use amplitude envelope correlation (AEC), which can detect signal coupling without phase coherence, even among different frequencies. We apply it to subdural recordings from humans performing a visual delayed match-to-sample task and systematically compare it with spectral amplitude and coherence. The different measures often show divergent results. In particular, AEC reveals y-coupling completely missed by coherence. We argue that coherence and AEC are adapted to different cortical mechanisms of short- and long-range interactions, respectively.     

Bilateral mesial temporal lobe epilepsy: comparison of scalp EEG and hippocampal MRI-T2 relaxometry

OBJECTIVE: Bilateral hippocampal abnormality is frequent in mesial temporal lobe sclerosis and might affect outcome in epilepsy surgery. The objective of this study was to compare the lateralization of interictal and ictal scalp EEG with MRI T2 relaxometry. MATERIAL AND METHODS: Forty-nine consecutive patients with intractable mesial temporal lobe epilepsy (MTLE) were studied with scalp EEG/video monitoring and MRI T2 relaxometry. RESULTS: Bilateral prolongation of hippocampal T2 time was significantly associated with following bitemporal scalp EEG changes: (i) in ictal EEG left and right temporal EEG seizure onsets in different seizures, or, after regionalized EEG onset, evolution of an independent ictal EEG over the contralateral temporal lobe (left and right temporal asynchronous frequencies or lateralization switch; P = 0.002); (ii) in interictal EEG both left and right temporal interictal slowing (P = 0.007). Bitemporal T2 changes were not, however, associated with bitemporal interictal epileptiform discharges (IED). Lateralization of bilateral asymmetric or unilateral abnormal T2 findings were associated with initial regionalization of the ictal EEG in all but one patient (P < 0.005), with lateralization of IED in all patients (P < 0.005), and with scalp EEG slowing in 28 (82,4%) of 34 patients (P = 0.007). CONCLUSION: Our data suggest that EEG seizure propagation is more closely related to hippocampal T2 abnormalities than IED. Interictal and ictal scalp EEG, including the recognition of ictal propagation patterns, and MRI T2 relaxometry can help to identify patients with bitemporal damage in MTLE. Further studies are needed to estimate the impact of bilateral EEG and MRI abnormal findings on the surgical outcome.     

Functional organization of the brain with malformations of cortical development

We examined the localization of cerebral functions in 28 patients with focal epilepsy and malformations of cortical development (MCDs). Polymicrogyria occurred in nine, hemimegalencephaly in four, heterotopia in eight, and focal cortical dysplasia (FCD) in nine cases. We used simple (sensomotor, visual) or complex (language, memory) functional magnetic resonance imaging (fMRI) paradigms. Two thirds of MCDs were activated by simple fMRI paradigms, whereas they less frequently showed activity during complex cognitive fMRI paradigms. During simple paradigms, all disturbances of cortical organization (polymicrogyria, schizencephaly, and mild-type FCD) showed activity, whereas other MCDs (disturbances of earlier steps of cortical development: hemimegalencephaly, Taylor-type FCD, and heterotopia) showed activity in only 44% (p < 0.01). The association between the pathophysiology and morphology of MCDs confirms the recently proposed classification system. Both focal neurological signs (p < 0.05) and focal electroencephalogram slowing (p < 0.05) independently correlated with MCD inactivity, confirming that fMRI showed neuronal functions of MCDs. Conclusively, fMRI visualizes the MCD functions and their relationship to the eloquent cortex, providing useful information before epilepsy surgery. Surgery of cortical organization disturbances should be cautiously performed because these malformations may participate to some degree in brain functions.     

Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy

ObjectiveThe goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI).MethodsA fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided.ResultsA fearful face paradigm led to significant amygdalar activation in all but one patient (p < 0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipislateral amygdalar fMRI-responses.ConclusionUnilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.     

Are ictal vocalisations related to the lateralisation of frontal lobe epilepsy?

The purpose was to analyse whether non-speech vocalisations in seizures originating in the frontal lobe do have lateralising value. Patients were included who had undergone presurgical evaluation with ictal video-EEG monitoring at the Epilepsy Centre, had had resective epilepsy surgery involving the frontal lobe, and who had remained seizure free>1 year postoperatively. Twenty seven patients aged 1-42 years (mean 18) met the inclusion criteria. Age at epilepsy onset ranged from 1 month to 41 years (mean 7.1 years). All selected patients had a unilateral MRI detected lesion within the frontal lobe. Fifteen patients had right sided, 12 patients had left sided epileptogenic zones. Seizures recorded during EEG-video monitoring were re-evaluated to identify the occurrence of ictal vocalisations. Pure ictal vocalisations were distinguished from ictal sound productions due to motor or vegetative seizure activity (for example, cloni or respiratory sounds). Pure ictal vocalisation occurred in 11 patients of whom nine had a left frontal epileptogenic zone (p<0.01). It is concluded that ictal vocalisation could be an additional lateralising sign in frontal lobe epilepsy. The results suggest that not only speech, but vocalisation at a subverbal level also shows a left hemispheric dominance in humans.     

Body weight and the reward system: the volume of the right amygdala may be associated with body mass index in young overweight men

We aimed to investigate the relationship between BMI (body mass index) and the volumes of the structures of the reward system (hippocampus, amygdala, accumbens, caudatum, putamen, and orbitofrontal cortex). The right and left structures were examined separately. Their volumes were assessed using a 3-T MRI scanner and Freesurfer software. Ninety-two healthy subjects were involved (mean BMI: 22.3?±?3.4 kg/m(2), mean age: 23.2?±?2.7). We found that the volume of the right amygdala positively correlated with the BMI in men but not in women. Moreover, we could demonstrate this association only in the overweight male sub-population. We suggest that an association between body weight and the morphological variability of the reward system can be demonstrated by MRI. This may be further evidence for a different body-weight regulation in the two sexes. The potential relationship between the volume of the right amygdala and the BMI in heavier individuals requires further studies with larger samples.