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PubMed1999

Functional MRI and the Wada test provide complementary information for predicting post-operative seizure control.

Prediction of post-surgical seizure relief and potential cognitive deficits secondary to anterior temporal lobectomy (ATL) are important to pre-surgical planning. Although the intracarotid amobarbital test (IAT) is predictive of post-ATL seizure outcome, development of non-invasive and more precise means for determining post-ATL seizure relief are needed. We previously reported on a technique utilizing functional MRI (fMRI) to evaluate the relative functional adequacy of mesial temporal lobe structures in preparation for ATL. In the present study, we report follow-up outcome data on eight temporal lobe epilepsy (TLE) patients 1-year post-ATL who were evaluated pre-surgically using IAT and fMRI. Functional memory lateralization using fMRI predicted post-ATL seizure outcome as effectively as the IAT. In general, asymmetry of functional mTL activation favouring the non-epileptic hemisphere was associated with seizure-free status at 1-year follow-up. Moreover, when combined, fMRI and IAT provided complementary data that resulted in improved prediction of post-operative seizure control compared with either procedure alone.

Adolescent↗
PubMed2000

Inter-ictal and post-ictal psychoses in frontal lobe epilepsy: a retrospective comparison with psychoses in temporal lobe epilepsy.

There have been few studies of the psychopathology of patients with frontal lobe epilepsy (FLE). The majority of studies of both inter-ictal and post-ictal psychoses have strongly suggested the influence of temporal lobe disturbance on psychoses. Patients with organic brain damage or schizophrenia, however, sometimes show frontal lobe dysfunction. The purpose of this study was to better understand the effect, if any, of frontal lobe disturbance and seizure on psychopathology. Patients were divided into four groups based on epilepsy type and preceding seizures; 8 with FLE/inter-ictal psychosis, 3 with FLE/post-ictal psychosis, 29 with temporal lobe epilepsy (TLE)/inter-ictal psychosis, and 8 with TLE/post-ictal psychosis. Psychopathologic symptoms were retrospectively reviewed based on case notes, using a modified brief psychiatric rating scale (BPRS). Psychomotor excitement, hostility, suspiciousness, and hallucinatory behaviour were prominent features in all four groups. Six orthogonal factors were derived by factor analysis from the original data based on the 18 BPRS items. FLE patients with inter-ictal psychosis showed marked hebephrenic characteristics (i.e. emotional withdrawal and blunted effect). Our findings suggest that patients with FLE can exhibit various psychiatric symptoms. However, their psychotic symptoms, hebephrenic symptoms in particular, may often be overlooked.

Adult↗
PubMed1997

The Groucho/transducin-like enhancer of split transcriptional repressors interact with the genetically defined amino-terminal silencing domain of histone H3.

Groucho is a transcriptional repressor implicated in Notch signaling and involved in neural development and segmentation in Drosophila. We are investigating the molecular mechanisms underlying the functions of Groucho and its mammalian homologs, the transducin-like Enhancer of split (TLE) proteins. We report that Groucho/TLEs are associated with chromatin in live cells and that they co-purify with isolated histones. Affinity chromatography and far Western blotting studies show further that native Groucho/TLE proteins interact specifically with histone H3 and not with other core histones. This interaction is mediated by the H3 amino-terminal domain previously shown by genetic analysis in yeast to be essential for the role of H3 in transcriptional silencing. We also demonstrate that Groucho/TLEs form oligomeric structures in vivo. These combined findings suggest that transcription complexes containing Groucho/TLEs may associate with chromatin through interactions with the amino terminus of histone H3 and that these interactions may be propagated along the chromosome due to the ability of Groucho/TLEs to participate in higher order structures.

Animals↗
PubMed2002

Characterization of a novel mammalian Groucho isoform and its role in transcriptional regulation.

The Wnt/beta-catenin/Tcf pathway serves important functions in embryonic development and is constitutively activated in human colorectal cancer. The nuclear output of Wnt signaling is mediated by a complex between DNA-binding proteins of the TCF family and the transcriptional coactivator beta-catenin. Groucho proteins act to repress transcriptional activation by beta-catenin-Tcf complexes, probably by interacting directly with Tcf transcription factors. We have identified several splice forms of the mouse Groucho Grg1 gene expressed in the developing intestine. Prominent among these is a novel and abundant isoform, Grg1-S, which we characterize in this report. Grg1-S has highest homology with the TLE family of large Groucho proteins but features only the amino-terminal Q and glycine- and proline-rich domains typical of the Groucho/AES subfamily. Grg1-S is expressed in development and in several adult mouse tissues. Expression in the adult small intestine is highest at the base of the crypts of Lieberkuhn. Grg1-S acts to antagonize beta-catenin activity in Xenopus axis duplication and luciferase reporter assays in mammalian cells. Taken together, these findings suggest that Grg1-S may operate in conjunction with beta-catenin and Tcf factors to regulate vertebrate gut epithelial cell differentiation.

Alternative Splicing↗
PubMed1998

Ecological validity of list-learning tests and self-reported memory in healthy individuals and those with temporal lobe epilepsy.

We evaluated in patients with temporal lobe epilepsy (TLE) and healthy volunteers whether list-learning tests of episodic verbal/figural memory and subjective self-reports reliably indicate "Memory in Reality" (MIR). MIR was assessed by the incidental memory of the neuropsychological test event one week after testing. Subjective Memory was assessed by a questionnaire (SMQ). Patients achieved poorer results than controls in all measures of memory. Correlation and multiple regression analysis indicates that list-learning is highly predictive regarding performance in MIR. MIR predominantly relied on verbal memory in patients and on visual/figural memory in controls. Subjective memory differentiated patients and controls but it correlated to MIR only in subjects with unimpaired memory. In conclusion, the data indicate a high ecological validity of list-learning paradigms and they seriously question the diagnostic value of self-reported memory. They also indicate that incidentally acquired knowledge might be differentially represented in patients with a memory disorder and healthy persons.

Adult↗
PubMed2002

Familial association of neuropsychological traits in patients with generalized and partial seizure disorders.

To investigate familial effects of neuropsychological deficits associated with seizure disorders, we studied 65 families, in which 1 member had epilepsy. The disorders included childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and temporal lobe epilepsy (TLE). Age-appropriate tests were administered to assess sustained attention, encoding and verbal memory, executive and focused attention and attentional flexibility/impulsivity. CAE probands attained lower scores than other probands in visual sustained attention and the ability to focus on and execute a visual-motor task. Scores of the unaffected relatives tended to fall between those of the probands and the controls. JME relatives had lower scores than other relatives in tests of visual and auditory sustained attention and attentional flexibility, and showed greater variability in response time. Behavioral information of this type may aid in the specification and differentiation of genetic linkages in affected families.

Adolescent↗
PubMed2002

Lateralized changes in autonomic arousal during emotional processing in patients with unilateral temporal lobe seizure onset.

The valence model of emotion, which posits cerebral lateralization for positive and negative emotional processing, was investigated in patients with unilateral mesial temporal lobe epilepsy (TLE) and controls by measuring skin conductance levels (SCLs) and heart rate (HR) while positive and negative emotional photographs were viewed. Left TLEs exhibited selective SCL hyperarousal when viewing negative emotional slides relative to controls and right TLEs. In contrast, right TLEs showed no significant differences compared with the other groups. Results are consistent with left hemispheric specialization for positive emotional expression. Dysfunction of left mesial temporal lobe structures may result in autonomic hyperarousal and a release of the unrestrained negative emotional tendencies of the right hemisphere.

Adolescent↗
PubMed2005

Liver immunobiology.

Tle liver has a number of important functions in innate and adaptive immunity. Contributions to the innate (nonspecific) immune system include production of acute phase proteins, nonspecific phagocytosis of particles, nonspecific pinocytosis of molecules, and nonspecific cell killing. Hepatic involvement in innate immunity contributes to the systemic response to local inflammation, clearance of particles and soluble molecules from the circulation, and killing of invading cells such as neoplastic cells. Liver involvement in the adaptive (specific) immune system includes deletion of activated T cells, induction of tolerance to ingested and self-antigens, extrathymic proliferation of T cells, and deletion of many of the signaling and effector molecules. Hepatic involvement in adaptive immunity allows clearance of activated T cells and signaling molecules following inflammatory reactions, and promotes immunologic tolerance toward potentially antigenic proteins that are absorbed from the intestinal tract. The liver is a major site of extrathymic T cell development, which assumes increasing significance with aging in mammals. Perturbations in hepatic structure or function can result in significant ramifications in both the innate and adaptive immune systems.

Acute-Phase Proteins↗
PubMed2002

Abnormalities of grey and white matter [11C]flumazenil binding in temporal lobe epilepsy with normal MRI.

In 20% of potential surgical candidates with refractory epilepsy, current optimal MRI does not identify the cause. GABA is the principal inhibitory neurotransmitter in the brain, and GABA(A) receptors are expressed by most neurones. [(11)C]Flumazenil (FMZ) PET images the majority of GABA(A) receptor subtypes. We investigated abnormalities of FMZ binding in grey and white matter in 18 patients with refractory temporal lobe epilepsy (TLE) and normal quantitative MRI. Parametric images of FMZ volume of distribution (FMZ-V(d)) were calculated. Twenty-one healthy controls were scanned for comparison. Statistical parametric mapping (SPM99) was used to localize significant changes in FMZ-V(d) in individual patients and between groups, specifically including the entire white matter in all subjects through explicit masking. Sixteen of 18 patients showed single or multiple abnormalities of FMZ-V(d). Six had hippocampal decreases of FMZ-V(d). Eleven patients showed increased FMZ-V(d) in the temporal lobe white matter (TLWM). Outside the mesial temporal structures, seven showed multiple areas of increase or decrease and only one a single area of decrease. In seven of the 16 patients with abnormalities, findings were concordant with EEG and clinical data, enabling further presurgical evaluation. Group findings were: (i) decreased FMZ-V(d) in the ipsilateral (Z = 3.01) and contralateral (Z = 2.56) hippocampus; (ii) increased FMZ-V(d) in the ipsilateral (Z = 3.71) and contralateral TLWM (two clusters, Z = 3.11 and 2.79); and (iii) increased FMZ-V(d) in the ipsilateral frontal lobe white matter between the superior and medial frontal gyrus (Z = 3.80) with similar changes contralaterally (Z = 4.87). No changes were found in the thalamus and basal ganglia. Region-of-interest analyses indicated an average increase in FMZ binding of 16% in the TLWM ipsilateral to the epileptic focus. PET findings were corroborated by invasive EEG or pathology in five cases. FMZ-PET, analysed by SPM with explicit masking, was sensitive in patients with normal MRI, and hippocampal abnormalities were detected in a third of these patients. Furthermore, increases in FMZ binding in TLWM, indicating microdysgenesis, were detected in the majority of these patients and may represent the structural basis of their epilepsy.

Adolescent↗
PubMed2003

SPECT perfusion changes during complex partial seizures in patients with hippocampal sclerosis.

Cerebral perfusion changes reliably reflect changes in neuronal activity. Our aim was to obtain new insights into the pathophysiology of complex partial seizures (CPS) in patients with hippocampal sclerosis (HS) using interictal and ictal single photon emission computed tomography (SPECT). We studied 24 patients with refractory temporal lobe epilepsy (TLE) associated with HS. All had an interictal and ictal SPECT with early injection during a CPS. Images were normalized and co-registered. Using statistical parametric mapping (SPM99), brain regions with significant ictal perfusion changes were determined. To assess possible interrelationships between these regions, Pearson correlation coefficients were calculated. The temporal lobe ipsilateral to the seizure focus, the border of the ipsilateral middle frontal and precentral gyrus, both occipital lobes and two small regions in the contralateral postcentral gyrus showed ictal hyperperfusion. The frontal lobes, contralateral posterior cerebellum and ipsilateral precuneus showed hypoperfusion. Further exploratory analysis suggested an association between ipsilateral temporal lobe hyperperfusion and ipsilateral frontal lobe hypoperfusion, and an inverse association between seizure duration and hyperperfusion in the ipsilateral anterior cerebellum and contralateral postcentral gyrus. We conclude that there is a network of perfusion changes during CPS in patients with HS. Studying a particular seizure type in patients with HS with peri-ictal SPECT performed during a defined time window will allow further analysis of the cerebral network activities, and excitatory, inhibitory and gating mechanisms during seizures associated with HS.

Adult↗
PubMed2005

Correlations between granule cell physiology and bioenergetics in human temporal lobe epilepsy.

Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormalities including decreased phosphocreatine (PCr) normalized to ATP. The physiological consequences of these metabolic alterations have not been established. We hypothesized that impaired bioenergetics would correlate with alterations in physiological functions under conditions that strongly activate neural metabolism. We correlated several physiological variables obtained from epileptic human dentate granule cells studied in slices with hippocampal PCr/ATP measured using in vivo magnetic resonance spectroscopy. The physiological variables included: the ability to fire multiple action potentials in response to single stimuli, the inhibitory postsynaptic potential (IPSP) conductance and the responses to a 10 Hz, 10 s stimulus train. We noted a significant negative correlation between the ability to fire multiple spikes in response to single synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong correlation between PCr/ATP and the recovery of the membrane potential following a stimulus train (P < 0.01), with low PCr/ATP being associated with prolonged recovery times. These data suggest that the bioenergetic impairment seen in this tissue is associated with specific changes in excitatory and inhibitory neuronal responses to synchronized synaptic inputs.

Adenosine Triphosphate↗
PubMed2005

The temporopolar cortex plays a pivotal role in temporal lobe seizures.

We investigated the role of the temporal pole (TP) in 48 consecutive patients with drug-refractory temporal lobe epilepsy (TLE). Chronic depth recordings of TP cortex activity were used in association with video recording of ictal symptoms during 48 spontaneous seizures. In 23 cases (48%, group 1) the TP was involved at the onset of the seizure, before or concurrently with the hippocampus. In the remaining 25 patients (52%, group 2) the TP was involved 16.4 +/- 13.8 s after the hippocampus. A past history of febrile seizures was found in both groups, with no statistical difference. Ictal symptoms did not differentiate TP seizures from seizures originating in the hippocampus but the first clinical sign occurred sooner in group 1 compared with group 2 (respectively 10.56 +/- 9 and 25.7 +/- 19 s, respectively, P = 0.005). Loss of awareness also occurred sooner in the case of TP seizures compared with mesiotemporal lobe (MTL) seizures (22.9 +/- 22.6 versus 42.2 +/- 18.6 s, P = 0.0002). MRI data analysis showed that hippocampal sclerosis was present in both groups of patients, although it was more frequent in patients with MTL onset. Anterior temporal white matter changes were found ipsilateral to the epileptogenic area and tended to be more frequent in patients with TP seizures. All the patients underwent tailored anterior temporal lobectomy that included the TP, the hippocampus, the parahippocampal gyrus and the anterior part of the lateral temporal cortex. A better postoperative outcome was achieved in group 1 compared with group 2 (Engel class 1, 95 and 72% respectively, P = 0.04). We conclude that the frequent TP involvement at the onset of seizures could be a supplementary explanation for some failures of selective amygdalohippocampectomy, which should be addressed preferentially to well-selected patients. Moreover, the involvement of the TP cortex at the onset of the seizures is a good predicting factor for postoperative seizure outcome.

Adolescent↗
PubMed1993

Forecasts of active life expectancy: policy and fiscal implications.

Age-related changes in functional status can be summarized by active life expectancy (ALE) measures. ALE is useful in assessing efforts to improve function and in determining a population's service needs. ALE disaggregates total life expectancy (TLE) into components representing degree and type of impairment. We illustrate the calculation of two ALE measures and their relations to health inputs and service use. First, scores are calculated from 27 measures of function for persons 65 and over, as reported in the National Long Term Care Survey (NLTCS). The scores are then used to calculate the two ALE measures. Results are compared to ALE calculated from the 1982, 1984, and 1989 NLTCS.

Activities of Daily Living↗
PubMed1993

Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease.

A wide spectrum of birth defects are caused by deletions of the DiGeorge syndrome critical region (DGCR) at human chromosome 22q11. Over one hundred such deletions have now been examined and a minimally deleted region of 300kb defined. Within these sequences we have identified a gene expressed during human and murine embryogenesis. The gene, named TUPLE1, and its murine homologue, encodes a protein containing repeated motifs similar to the WD40 domains found in the beta-transducin/enhancer of split (TLE) family. The TUPLE1 product has several features typical of transcriptional control proteins and in particular has homology with the yeast Tup1 transcriptional regulator. We propose that haploinsufficiency for TUPLE1 is at least partly responsible for DiGeorge syndrome and related abnormalities.

Abnormalities, Multiple↗
PubMed1994

Reduced N-acetylaspartate concentration in temporal lobe epilepsy by quantitative 1H MRS in vivo.

We used proton magnetic resonance spectroscopy (1H MRS) to determine concentrations of N-acetylaspartate (NAA), creatine and choline in vivo (63 MHz) and in vitro (400 MHz) in seven patients undergoing surgical treatment of intractable temporal lobe epilepsy (TLE). Nine healthy volunteers were used as controls for in vivo MRS. NAA concentrations in vivo on the ipsilateral and contralateral sides were 6.5 +/- 1.3 (s.d.) and 7.9 (+/- 2.1) mmol l-1, respectively and 8.6 (+/- 0.8) mmol l-1 in the volunteers. NAA concentration in vitro was 3.2 (+/- 0.9) mumol g-1 wet weight (ww) and the corresponding concentration from the macroscopically intact brain tissue was 4.7 (+/- 1.0) mumol g-1 ww. Thus, in vivo quantitative 1H MRS identified the size of seizure focus in patients with temporal lobe epilepsy.

Adolescent↗
PubMed1998

Limbic ERPs predict verbal memory after left-sided hippocampectomy.

Surgical removal of the dominant medial temporal lobe regions runs a considerable risk of verbal memory deficits which may be compensated for postoperatively by corresponding regions in the non-dominant medial temporal lobe. We examined this possibility by recording event-related potentials (ERPs) to words from the medial temporal lobes of patients with left-sided temporal lobe epilepsy (TLE) undergoing presurgical evaluation. N400 amplitudes in the right anterior medial temporal lobe predicted the postoperative verbal recall performance of individual patients with surprising accuracy, indicating that intracranial recordings can be used to quantify the functional capacities of the right hemisphere that can compensate for the verbal memory deficits after loss of medial temporal lobe structures in the left hemisphere.

Adolescent↗
PubMed1998

Localization of mesial temporal lobe seizures with sphenoidal electrodes.

Few studies have compared sphenoidal electrodes with scalp electrodes to determine their localizing value in temporal lobe seizures. We reviewed 76 ictal recordings with the standard International 10-20 System and T1/2 and sphenoidal electrodes from 31 patients whose subsequent intracranial EEG studies precisely localized seizures in one temporal lobe. Ictal EEGs were reviewed in a blinded fashion in both longitudinal bipolar and referential montages. Of the 23 seizures in 11 patients with mesial temporal lobe epilepsy (MTLE), all seven seizures in 3 patients were localized exclusively to one sphenoidal electrode, before involvement of T1/2 and temporal scalp electrodes. The remaining 16 seizures from 8 MTLE patients and all 53 seizures in the 20 patients with neocortical temporal lobe epilepsy (NTLE) had simultaneous involvement of sphenoidal, T1/2, and temporal scalp electrodes at seizure onset when analyzed with referential montages. Sphenoidal electrodes may provide valuable localization data for presurgical evaluation of patients with possible TLE. In particular, seizure rhythms confined to the sphenoidal electrode at ictal onset, without involvement of scalp electrodes, occurred only in patients with MTLE (p < 0.04). Further studies comparing these electrodes with other types of surface electrodes are needed.

Brain Mapping↗
PubMed2001

Effects of sevoflurane and isoflurane on electrocorticographic activities in patients with temporal lobe epilepsy.

To compare the neuroexcitatory effects of sevoflurane and isoflurane, we recorded electrocorticograms (ECoG) during wakefulness and during sevoflurane and isoflurane anesthesia in six patients with temporal lobe epilepsy (TLE). These patients had subdural grid electrodes chronically implanted in the temporal region. During sevoflurane anesthesia at 1.5 minimum alveolar concentration (MAC) of the combination with 67% nitrous oxide (N2O), a marked increase in interictal paroxysmal activities was observed in four patients. Two patients had a slight increase in paroxysmal activities. Activated areas were widely distributed, not being confined to the ictal onset zone of spontaneous seizures. However, isoflurane anesthesia at 1.5 MAC of the combination with 67% N2O was associated with less increased paroxysmal activity. While the neuroexcitatory properties of sevoflurane proved greater than those of isoflurane, the widespread irritative response to sevoflurane administration was not helpful in localizing the epileptogenic area.

Adolescent↗