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[11 C]Flumazenil binding in the medial temporal lobe in patients with temporal lobe epilepsy: correlation with hippocampal MR volumetry, T2 relaxometry, and neuropathology.

OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model. RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.

Adolescent↗

Detection of mesial temporal lobe hypoperfusion in patients with temporal lobe epilepsy by use of arterial spin labeled perfusion MR imaging.

BACKGROUND AND PURPOSE: Interictal hypometabolism has lateralizing value in cases of temporal lobe epilepsy and positive predictive value for seizure-free outcome after surgery to treat epilepsy. Alterations in regional cerebral metabolism can also be inferred from measurements of regional cerebral perfusion. The purpose of this study was to determine the feasibility of detecting cerebral blood flow (CBF) asymmetries in the mesial temporal lobes using continuous arterial spin labeling perfusion MR imaging, which is a noninvasive method for calculating regional CBF. METHODS: Twelve patients with medically refractory temporal lobe epilepsy who underwent preoperative evaluation for temporal lobectomy and 12 normal control participants were studied retrospectively. Absolute and normalized mesial temporal CBF measurements were compared between the patient and control groups. Lateralization based on a perfusion asymmetry index was compared with metabolic ((18)[F]-fluorodeoxyglucose positron emission tomography) and hippocampal volumetric asymmetry indices and with clinical lateralization. RESULTS: Mesial temporal CBF was more asymmetric in patients with temporal lobe epilepsy than in normal control participants, although asymmetric mesial temporal CBF was also found in normal participants, with the left side dominant. Ipsilateral mesial temporal CBF was significantly decreased compared with contralateral mesial temporal CBF in patients with temporal lobe epilepsy. Global CBF measurements were significantly decreased in patients compared with control participants. Asymmetry in mesial temporal blood flow in patients persisted after normalization to global CBF. Lateralization using continuous arterial spin labeling perfusion MR imaging asymmetry index significantly correlated with lateralization based on (18)[F]-fluorodeoxyglucose positron emission tomography hypometabolism, hippocampal volumes, and clinical evaluation. CONCLUSION: Continuous arterial spin labeling perfusion MR imaging can detect interictal asymmetries in mesial temporal lobe perfusion in patients with temporal lobe epilepsy. This technique is readily combined with routine structural assessment and potentially offers an inexpensive and noninvasive means of screening for asymmetries in interictal mesial temporal lobe function.

Adult↗

Prognostic factors in anterior temporal lobe resections for mesial temporal lobe epilepsy: multivariate analysis.

PURPOSE: Even though there have been several studies on the prognostic factors of temporal lobe epilepsy (TLE) after lobectomy, no studies have been performed for homogeneous mesial TLE. Furthermore, most studies on the predictors of outcome of epileptic surgery were based on univariate analyses and did not consider modern epileptic surgery investigation modalities such as brain magnetic resonance imaging (MRI) and positron emission tomography (PET). We attempted to identify the prognostic factors in anterior temporal lobectomy (ATL) for mesial TLE with multivariate analysis. METHODS: Ninety-three patients with mesial TLE (54 men and 39 women, mean age at surgery, 28.3 +/- 8.2 years) were included in the study. The primary outcome variable was the status of patients in the second postoperative year, classified as either seizure free (except aura), or not seizure free. Clinical, electroencephalographic, MRI, PET, Wada test, and pathological data were considered. RESULTS: Seventy-eight (84.0%) patients had remission of seizures. With univariate analysis, age at surgery (p < 0.001), epilepsy duration before surgery (p = 0.04), and ipsilateral hippocampal sclerosis on MRI (p = 0.02) were found to be significant. By using multivariate analysis, age at surgery (p = 0.001) and ipsilateral hippocampal sclerosis on MRI (p = 0.03) were found to be the most significant prognostic factors. CONCLUSIONS: Age at surgery and hippocampal sclerosis are independent prognostic factors for ATL in mesial TLE. These findings suggest that mesial TLE may be a progressive disorder, and surgical outcome is better when early ATL is performed.

Adolescent↗

Temporal lobe volumetric cell densities in temporal lobe epilepsy.

Volumetric cell densities in 13 different subfields of the temporal lobe were calculated to test various hypotheses about mesial and lateral temporal lobe sclerosis in patients with complex partial epilepsy. In patients benefitting (primary group) from anterior temporal lobectomy (ATL), sclerosis was greater (fewer cells) in anterior than in posterior hippocampus. By contrast, the patients lacking full benefit (nonprimary group) from ATL had decreased numbers of neurons equally distributed from anterior to posterior hippocampus, indicating that zones of mesial temporal cell loss are linked to zones of epileptogenicity. These data support a model of focal hippocampal epilepsy originating from zones of cell loss and synaptic reorganization that is epileptic. There were no differences in cell densities in gyrus hippocampi or in lateral temporal gyri when patients with temporal lobe epilepsy and controls were compared. Hippocampal cell densities in mesial temporal lobe were not reduced in psychomotor epileptic patients with extrahippocampal foci consisting of foreign tissue. Variables in seizure histories were not correlated with Ammon's horn cell densities, indicating that most of the sclerosis preceded the seizures, which did virtually no significant further damage to hippocampus with repeated partial or generalized seizures.

Brain Diseases↗

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection.

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.

Adult↗

Microsurgical anatomy of the temporal lobe: part 1: mesial temporal lobe anatomy and its vascular relationships as applied to amygdalohippocampectomy.

OBJECTIVE: We review the anatomy of the mesial temporal lobe region, establishing the relationships among the intraventricular, extraventricular, and surrounding vascular structures and their angiographic characterization. We also demonstrate the clinical application of these anatomic landmarks in an anatomic temporal lobectomy plus amygdalohippocampectomy. METHODS: Fifty-two adult cadaveric hemispheres and 12 adult cadaveric heads were studied, using a magnification ranging from 3x to 40x, after perfusion of the arteries and veins with colored latex. RESULTS: The intraventricular elements are the hippocampus, fimbria, amygdala, and choroidal fissure; the extraventricular elements are the uncus and parahippocampal and dentate gyri. The uncus has an anterior segment, an apex, and a posterior segment that has an inferior and a posteromedial surface; the uncus is related medially to cisternal elements and laterally to intraventricular elements. The anterior segment is related to the proximal sylvian fissure, internal carotid artery, proximal M1 segment of the middle cerebral artery, proximal cisternal anterior choroidal artery, and amygdala. The apex is related to the oculomotor nerve, uncal recess, and amygdala; the posteromedial surface is related to the P2A segment of the posterior cerebral artery inferiorly, to the distal cisternal anterior choroidal artery superiorly, and to the head of the hippocampus and amygdala intraventricularly. The choroidal fissure is located between the thalamus and fimbria; it begins at the inferior choroidal point behind the head of the hippocampus and constitutes the medial wall of the posterior two-thirds of the temporal horn. CONCLUSION: Not only is the knowledge of these relations useful to angiographically characterize the mesial temporal region, but it has also proven to be of extreme value during microsurgeries involving this region.

Adult↗

Bilateral temporal lobe pathology with sparing of medial temporal lobe structures: lesion profile and pattern of memory disorder.

The lesion sustained by the amnesic patient H.M. consisted of bilateral ablation of medial temporal lobe structures with relative sparing of more lateral white matter and neocortical structures. We present the first detailed report of a case where the reverse pattern of lesions predominated, namely bilateral pathology of white matter and neocortical temporal lobe structures, with spared medial temporal lobe structures. This damage, which was particularly severe in anterior loci in the temporal lobes, was sustained as a result of radionecrosis. High-resolution magnetic resonance imaging was carried out to document the distinctive anatomical profile of our patient, and this profile was compared to that reported for the patient H.M. At the anatomical level, there was an almost "mirror image" profile, with contrasting involvement of lateral and medial temporal lobe structures. At the neuropsychological level, our patient was not amnesic but showed patchy impairment on traditional tests of anterograde memory functioning, in the context of notable "semantic" memory loss for knowledge acquired before and after the onset of his illness. Our findings demonstrate that bilateral temporal lobe pathology by itself does not lead to a classical amnesic syndrome, but may result in a significant but more subtle "semantic" memory loss. Our data highlight the distinctive and dissociable contribution of lateral and medial temporal lobe structures to human memory processing, and suggest a major role for anterior-inferior neocortical temporal lobe mechanisms in aspects of knowledge acquisition, storage and retrieval.

Amnesia↗

Temporal lobe injury in temporal bone fractures.

OBJECTIVE: To determine the incidence of intracranial injury, specifically in the temporal lobe, in patients with longitudinal fractures of the temporal bone. DESIGN: Prospective inception cohort. SETTING: University of Maryland Division of Otolaryngology-Head and Neck Surgery and the Maryland Shock Trauma Center, Baltimore. PATIENTS: Twenty-seven consecutive patients with unilateral or bilateral temporal bone fractures. MAIN OUTCOME MEASURES: Evaluation of temporal bone and intracranial trauma using computed tomography (CT) and magnetic resonance imaging (MRI). RESULTS: Of the 27 patients enrolled in the study, 12 had the complete battery of MRI, CT, and physical and audiological examinations. In all 12 patients, MRI demonstrated adjacent middle cranial fossa meningeal enhancement. Results of non-contrast-enhanced CT and MRI demonstrated ipsilateral temporal lobe contusions in 6 of the 13 fractures for an overall incidence of 46%. In addition, MRI demonstrated 4 cerebral contusions not seen in the results of non-contrast-enhanced CT. CONCLUSIONS: While high-resolution CT remains the criterion standard for evaluation of temporal bone fractures, MRI revealed a higher incidence of related temporal lobe injuries. Magnetic resonance imaging data may be valuable in preoperative evaluation of patients who require surgical intervention through a middle cranial fossa approach to document pre-existing injury and potential morbidity before retraction of the middle cranial fossa dura mater and temporal lobe.

Adolescent↗

Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy.

OBJECTIVE: The objective of this study was to assess the volumes of medial temporal lobe structures using high resolution magnetic resonance images from patients with chronic refractory medial temporal lobe epilepsy (MTLE). METHODS: We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1 mm isotropic voxels, and applied a field non-homogeneity correction and a linear stereotaxic transformation into a standard space. The structures of interest are the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar cortex, hippocampus, and amygdala. Structures were identified by visual examination of the coronal, sagittal, and axial planes. The threshold of statistical significance was set to p<0.05. RESULTS: Patients with right and left MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients with right MTLE exhibited a significant asymmetry of all studied structures; the right hemisphere structures had smaller volume than their left side counterparts. We did not observe linear correlations between the volumes of different structures of the medial temporal lobe in patients with MTLE. CONCLUSION: Patients with refractory MTLE have damage in the temporal lobe that extends beyond the hippocampus, and affects the regions with close anatomical and functional connections to the hippocampus.

Adult↗

Self-report of memory function in patients with temporal lobe epilepsy and temporal lobectomy.

Thirty-one surgical candidates with a unilateral temporal lobe seizure focus, 72 temporal lobectomy patients, 63 non-epileptic controls and their relatives, respectively, filled in the Memory Observation Questionnaire. The two patient groups rated their current memory similarly, but significantly worse than controls rated their own memory. Memory status was judged to be improved approximately three years after a temporal lobectomy. The relatives' ratings agreed with those of the patients. Thus patients who underwent surgical resection for relief of temporal lobe epilepsy did not report further subjective deterioration in memory compared to pre-operative cases. Laterality of excision did not affect self-report of general memory function. Nevertheless, a brief Verbal memory subscale yielded the expected material specific pattern after unilateral temporal lobectomy.

Adult↗

Contralateral medial temporal lobe damage in right but not left temporal lobe epilepsy: a (1)H magnetic resonance spectroscopy study.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) of the hippocampus is useful in lateralising the epileptic focus in temporal lobe epilepsy for subsequent surgical resection. Previous studies have reported abnormal contralateral MRS values in up to 50% of the patients. OBJECTIVE: To identify the contributing factors to contralateral damage, as determined by MRS, and its extension in patients with temporal lobe epilepsy. METHODS: Single voxel MRS was carried out in the hippocampus and lateral temporal neocortex of both hemispheres in 13 patients with left temporal lobe epilepsy (LTLE) and 16 patients with right temporal lobe epilepsy (RTLE). All patients had mesial temporal lobe epilepsy with hippocampal sclerosis. Controls were 21 healthy volunteers of comparable age. RESULTS: Consistent with previous studies, the NAA/(Cho+Cr) ratio was abnormally low in the hippocampus ipsilateral to the focus (p < 0.0001), and there were lower values in both patient groups in the ipsilateral temporal neocortex (p < 0.0001). Patients with RTLE had left hippocampal MRS anomalies (p = 0.0018), whereas the right hippocampus seemed to be undamaged in LTLE patients. CONCLUSIONS: Unilateral mesial temporal lobe epilepsy is associated with widespread metabolic abnormalities which involve contralateral mesial and neocortical temporal lobe structures. These abnormalities appear to be more pronounced in patients with RTLE.

Adult↗

Mesiobasal versus lateral temporal lobe epilepsy: metabolic differences in the temporal lobe shown by interictal 18F-FDG positron emission tomography.

Metabolic abnormalities in the temporal lobe (TL) of 25 patients suffering from temporal lobe epilepsy of mesiobasal or lateral TL origin have been investigated using interictal [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). The epileptogenic area was determined by ictal EEG recordings using foramen ovale and scalp electrodes in 20 patients, and by the use of stereo-electroencephalography in one patient. Four patients with structural lesions on their MRIs had noninvasive ictal surface EEG recordings. Sixteen patients had a clear-cut mesiobasal seizure onset, and in five patients the seizures originated from the lateral temporal neocortex. Twenty-four patients underwent selective surgery. Patients with temporal limbic seizures associated with mesial gliosis (n = 15) had the lowest FDG uptake in the entire TL, followed by patients with lateral temporal seizure origin (n = 5). Patients with tumors located in the mesiobasal TL (n = 5) showed, in general, only a slight decrease of glucose metabolism in all TL structures. There was no clear-cut correlation between the degree of hypometabolism and the location of EEG-defined epileptogenic focus. The metabolic pattern, however, differed between the patient groups and allowed a discrimination between patients of mesial temporal and lateral temporal seizure onset.

Adolescent↗

Panic attacks and temporal lobe seizures associated with a right temporal lobe arteriovenous malformation: case report.

A 33-year-old woman developed temporal lobe seizures and was found to have a right frontotemporal arteriovenous malformation. She subsequently developed panic attacks that could be induced by lactate infusion and were successfully treated with imipramine. The possibility that the panic attacks were caused by a structural lesion of the right temporal lobe is discussed.

Adult↗

Access to the posterior medial temporal lobe structures in the surgical treatment of temporal lobe epilepsy.

The authors describe a surgical technique that allows access to the posterior temporal horn of the lateral ventricle with preservation of the most functional lateral temporal cortex. Development of the technique was stimulated by the need to resect posteromedial temporal lobe structures in patients with intractable complex partial epilepsy and well-identified unilateral posterior hippocampal foci. This technique has also been of value in the resection of some lateral ventricular and posteromedial temporal lobe masses. The operation consists of three steps. No more than 4.5 cm of the anterolateral temporal lobe is removed en bloc such that the most anterior aspect of the temporal horn is entered. An incision is carried from the floor of the temporal horn through the inferior longitudinal fasciculus to the middle fossa dura mater and posteriorally into the lateral ventricular atrium. The lateral temporal cortex and white matter are then elevated with a self-retaining retractor. This exposes the posteromedial temporal horn or intraaxial mass for excision or allows en bloc resection of the entire hippocampus and medial temporal lobe structures while preserving the functional association areas of the lateral temporal cortex, including speech and visual spatial function.

Epilepsy, Temporal Lobe↗

Positive and negative network correlations in temporal lobe epilepsy.

Temporal lobe seizures are accompanied by complex behavioral phenomena including loss of consciousness, dystonic movements and neuroendocrine changes. These phenomena may arise from extended neural networks beyond the temporal lobe. To investigate this, we imaged cerebral blood flow (CBF) changes during human temporal lobe seizures with single photon emission computed tomography (SPECT) while performing continuous video/EEG monitoring. We found that temporal lobe seizures associated with loss of consciousness produced CBF increases in the temporal lobe, followed by increases in bilateral midline subcortical structures. These changes were accompanied by marked bilateral CBF decreases in the frontal and parietal association cortex. In contrast, temporal lobe seizures in which consciousness was spared were not accompanied by these widespread CBF changes. The CBF decreases in frontal and parietal association cortex were strongly correlated with increases in midline structures such as the mediodorsal thalamus. These results suggest that impaired consciousness in temporal lobe seizures may result from focal abnormal activity in temporal and subcortical networks linked to widespread impaired function of the association cortex.

Adolescent↗

Quantitative analysis of temporal lobe white matter T2 relaxation time in temporal lobe epilepsy.

The objective of this study was to assess temporal lobe white matter (WM) quantitatively using T2 relaxometry in patients with pharmacologically intractable temporal lobe epilepsy (TLE). T2 relaxometry was performed using a dual-echo sequence with 23 contiguous oblique coronal slices in 56 consecutive TLE patients and in 30 healthy subjects. Averages of six slices were chosen to calculate T2 relaxation time in the temporal lobe WM (WM-T2) and the hippocampus (Hippo-T2). Twenty-seven patients had unilateral hippocampal atrophy (HA), and twenty-nine patients had normal hippocampal volumes (NV) on volumetric MRI. Mean WM-T2 was increased ipsilateral to the seizure focus in TLE patients with HA and those with NV (P < 0.001). Contralateral mean WM-T2 was increased in left and right TLE with HA (P < 0.001) and in right TLE with NV (P = 0.001). There was a positive correlation between WM-T2 and Hippo-T2. Individual analysis showed a prolongation of WM-T2 in about 70% of TLE patients with HA and NV. In half of the patients, WM-T2 increase was bilateral and symmetric. However, in 33% of patients with NV and bilateral symmetric increase in Hippo-T2, WM-T2 provided a correct lateralization of the seizure focus. Regardless of the pattern of T2 abnormalities, that is, bilateral symmetric or ipsilateral, the majority of patients with HA became seizure-free after surgery, while those with NV did not have a favorable outcome. In patients with NV, WM-T2 measurement may provide additional lateralizing information compared to Hippo-T2.

Adolescent↗