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Significance of simple partial seizures in temporal lobe epilepsy.

We determined how localization of simple partial seizures (SPS) correlated with localization of complex partial seizure (CPS) in scalp/sphenoidal EEG and assessed prognosis after temporal lobe resective surgery in patients with an ictal correlate of SPS in scalp/sphenoidal EEG recordings. EEGs were recorded with the 10-20 system of electrode placement and supplemented with sphenoidal electrodes. Between 1985 and 1992, 183 patients with temporal lobe epilepsy (TLE) reported an aura (SPS) during inpatient monitoring; all were eligible for inclusion in our study. The EEGs during SPS showed ictal changes in 51 patients (28%, 117 SPS). Forty-four patients had unilateral temporal interictal spikes (IIS), and SPS and CPS always arose from the same region. Seven patients had bitemporal interictal spikes; SPS colocalized with CPS in 4 patients (57%), SPS were contralateral to CPS in 2 patients, and 1 patient had bilateral independent CPS but unilateral SPS. SPS accompanied by EEG ictal changes conveyed a favorable prognosis in patients who underwent epilepsy surgery. Scalp/sphenoidal recorded IIS but were less reliable in identifying the location of CPS onset in patients with bitemporal spikes.

Adult↗

Temporal lobe developmental malformations and hippocampal sclerosis: epilepsy surgical outcome.

BACKGROUND: Temporal lobe developmental malformations coexist with mesial temporal sclerosis in the form of dual pathology with a high frequency of bilateral amygdala or hippocampal abnormalities. OBJECTIVE: The aim of this study was to correlate and compare the MRI findings and the surgical outcome in patients with temporal lobe developmental malformations (n = 20) and isolated mesial temporal sclerosis (n = 36). METHODS: MRI-based normalized volumetry of the amygdala and hippocampal formation in patients with unilateral temporal lobe developmental malformations and isolated mesial temporal sclerosis who underwent temporal lobe resections was performed. Seizure outcome was compared between groups at follow-up. RESULTS: The frequency of bilateral hippocampal or amygdala atrophy (p < 0.04) and combined hippocampal-amygdala atrophy (p < 0.02) was higher in patients with temporal lobe developmental malformations. Although no significant difference in postsurgical seizure-free status was found between the temporal lobe developmental malformations and isolated mesial temporal sclerosis groups (70% versus 91%), patients with temporal lobe developmental malformations and bilateral amygdala or hippocampal-amygdala atrophy had a significantly worse outcome (p < 0.02). CONCLUSION: Bilateral hippocampal atrophy is frequent in patients with temporal lobe developmental malformations. However, it is the presence of bilateral amygdala or amygdalo-hippocampal atrophy that is associated with a higher risk of seizure recurrence.

Adolescent↗

Ictal fear in temporal lobe epilepsy: surgical outcome and focal hippocampal changes revealed by proton magnetic resonance spectroscopy imaging.

BACKGROUND: Ictal fear (IF) is most frequently associated with epileptic discharges from mesial temporal areas. OBJECTIVES: To determine whether patients with IF were more likely to become seizure free after anteromesial temporal lobe resection compared with those without IF and whether they show more anteriorly pronounced metabolic changes assessed by means of multivoxel magnetic resonance spectroscopy (MRS) along the hippocampal axis. METHODS: Surgical outcome was assessed in 33 consecutive patients with temporal lobe epilepsy after a mean follow-up of 25 months (range, 12-38 months). Proton multivoxel MRS of the hippocampal formation was applied to detect regional differences along the axis of the hippocampus in patients with and without IF. Magnetic resonance tomography showed typical features of hippocampal sclerosis in all patients. RESULTS: Twelve (36%) of the 33 patients reported fear at the beginning of their habitual seizures. Eleven of these patients were seizure free postoperatively. In contrast, only 11 of 21 patients without IF had a favorable outcome. Results of MRS revealed significantly higher pathologic N-acetylaspartate-choline ratios in the anterior portion of the hippocampal formation in patients with than in those without IF, indicating focal metabolic and/or morphologic changes in the head of the hippocampus. CONCLUSIONS: These results indicate the importance of diagnosing auras with IF to provide a more detailed prognosis of the surgical outcome. In addition, our data emphasize that multivoxel MRS is a valuable tool in the presurgical evaluation, as it may reveal different topographical patterns of hippocampal sclerosis.

Adult↗

[Effects of unilateral temporal lobectomy on verbal dichotic listening test].

Verbal dichotic listening test was conducted before and after anterior temporal lobectomy on 25 patients who underwent the operation because of their medication-resistant epileptic seizures. Their speech dominance by Wada test was all left sided. 1. Preoperatively, patients having the epileptogenic focus in the right temporal lobe (R-TLE) and those having the focus in the left (L-TLE) were, as expected, all right-ear dominant. The mean number of correct responses was fewer in L-TLE than in R-TLE group. 2. Postoperatively, no detrimental effects for recognition of verbal auditory stimuli by the ear contralateral to the focus was observed both in L-TLE and in R-TLE group. 3. Postoperatively, the ear-dominance shifted: to the left in patients with L-TLE, and to the right more conspicuously in patients with R-TLE compared to the preoperative scores. In other words, the recognition ability by the ears ipsilateral to the side of focus, or of resected temporal lobe, was ameliorated. Summarizing, the unilateral anterior temporal lobectomy did not cause "lesion effect" but yielded improvement of verbal auditory recognition by ears ipsilateral to the epileptogenic focus. Diminished epileptic bombardment resulted in by the resection surgery may be a possible explanation.

Adult↗

Interictal temporal delta activity in temporal lobe epilepsy: correlations with pathology and outcome.

PURPOSE: To determine the characteristics and the clinical significance of focal slow activity and its association with focal epileptogenesis in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed the interictal EEGs of 141 patients who had temporal lobe resections for intractable focal seizures and correlated the findings with pathologic changes and outcome. The pathologic changes were categorized into medial temporal sclerosis, tumors, and nonspecific changes. RESULTS: Lateralized slow activity was found in 66% of the patients, and it was mainly temporal, of delta frequency and irregular morphology. None of its characteristics, including quantity and reactivity to eye opening, was substrate specific. It was highly concordant with temporal spiking (60%), without any difference across the three groups, but provided additional information in 19 (15%) patients who had no lateralizing spikes. The effect of sleep also was similar in all three groups and included transition of slow waves into spikes. Lateralized slow activity to the side of the operation was significantly associated with favorable outcome only in the group with nonspecific pathology (p = 0.008), regardless of the presence, laterality, or topography of spikes. CONCLUSIONS: Our findings suggest that in patients with TLE whose brain magnetic resonance imaging (MRI) is either normal or suggestive of medial temporal sclerosis, interictal temporal slow activity has a lateralizing value similar to that of temporal spiking. Its association with a favorable outcome in patients with nonspecific pathology also suggests that candidates with lateralizing temporal delta and normal MRI should not be barred from further preoperative assessment.

Adolescent↗

Positron emission tomography and single photon emission computed tomography in epilepsy care.

Radiopharmaceutical brain imaging is clinically applied in planning resective epilepsy surgery. Cerebral sites of seizure generation-propagation are highly associated with regions of hyperperfusion during seizures, and with glucose hypometabolism interictally. For surgical planning in epilepsy, the functional imaging modalities currently established are ictal single photon emission computed tomography (SPECT) with [(99m)Tc]technetium-hexamethylpropyleneamine oxime (HMPAO) or with [(99m)Tc]technetium-ethylene cysteine dimer (ECD), and interictal positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxyglucose (FDG). Ictal SPECT and interictal FDG PET can be used in presurgical epilepsy evaluations to reliably: (1) determine the side of anterior temporal lobectomy, and in children the area of multilobar resection, without intracranial electroencephalographic recording of seizures; (2) select high-probability sites of intracranial electrode placement for recording ictal onsets; and, (3) determine the prognosis for complete seizure control following anterior temporal lobe resection. Coregistration of a patient's structural (magnetic resonance) and functional images, and statistical comparison of a patient's data with a normal data set, can increase the sensitivity and specificity of these SPECT and PET applications to the presurgical evaluation.

Brain↗

Bcl-2 immunoreactive cells with immature neuronal phenotype exist in the nonepileptic adult human brain.

Bcl-2, a cell death suppressor protein, is expressed during brain development but is largely down-regulated in the adult central nervous system. We previously reported strong expression of bcl-2 in small, "oligodendrocyte-like" cells (OLC) found in glioneuronal hamartias. These hamartias are microscopic cell rests found in temporal lobe resections from patients with intractable epilepsy and are considered a form of cerebral microdysgenesis. However, a causative relationship between these rests and seizures is not clear. We now report the identification, lineage characterization, and postnatal ontogeny of hamartia-like cell rests in temporal lobes of nonepileptic humans. Postmortem temporal lobes from 28 patients without history of neurologic disease (mean age = 53 years; range = 20 to 83 years) were studied. Microscopic cellular aggregates containing immature-appearing, bcl-2-immunoreactive cells (BIC) (identical to OLC) were observed in 23 of 28 (82%) temporal lobes from nonepileptic individuals. BIC were strongly immunoreactive for neuronal-specific class III beta tubulin, neuronal nuclear antigen, and MAP-2, but were consistently negative for neurofilament proteins and Ki67. Such cells were localized to subventricular regions of the caudal amygdala and often extended into the adjacent subcortical white matter and periamygdaloid cortex. BIC became less abundant with advancing age. These findings suggest that hamartia-like rests containing immature postmitotic neurons are normally present in the human brain and that glioneuronal hamartias may not always represent a maldevelopmental lesion associated with epilepsy.

Adult↗

Hippocampal resections impair associative learning and recognition memory in the monkey.

Damage to the hippocampus has been implicated in the permanent loss of memory in patients with medial temporal lobe resections. In two previous studies, it was established that bilateral ablations of the hippocampus in the monkey impaired performance on an associative learning task and on an object discrimination retention task. The two objectives of the present study were to assess the long term effects of hippocampal resections in the monkey and to extend the analysis of the effects of these resections to recognition memory. Therefore, the performance of monkeys with either hippocampal ablations or fornix transections, sustained 5 years earlier, was compared (1) on a concurrent discrimination task--a previously unencountered associative learning task--and (2) on a nonmatching-to-sample recognition task with either delays interposed between the presentation of the sample object and the recognition trial or with lists of either 1-, 3-, 5-, or 10-object samples. Significant impairment on both tasks was found after hippocampal, but not after fornix, damage. Though monkeys in the hippocampal group were impaired on both delays and lists, the impairment was more severe on the lists, with abnormal sensitivity to pro- and retroactive interference as a possible source of difficulty. Thus, in parallel with clinical findings, ablations of the hippocampus in the nonhuman primate produce an enduring disruption of memory.

Animals↗

Surgical treatment for epilepsy: a retrospective Swedish multicenter study.

The characteristics of patients suffering from drug resistant epilepsy, including the results of the preoperative evaluation and epilepsy surgery were retrospectively analyzed in a Swedish multicenter 10-year cohort of children and adults. Altogether 152 patients (65 children and 87 adults) treated during the period 1980-1990 in three epilepsy centers were included and followed-up 2 years after surgery. Median age at onset of seizures was 4 years for the children and 12 years for the adults. A localization related epilepsy was present in 85% of the children and in 95% of the adults. The mean number of seizure types in the children was 1.7 (range 1-4) and in the adults 1.8 (range 1-4). The median monthly seizure frequency was 52 and 15 for children and adults respectively. Resective surgery was performed in 143 cases (94 temporal, 31 extratemporal, 9 multilobar and 9 major resection procedures) and palliative procedures in 16 cases (13 callosotomies and 3 stereotactic amygdalotomies). Postoperative neurological deficits were detected in 9% of the patients after temporal lobe resections and in 15% of the patients after extratemporal and multilobar resection procedures. Two years after resective surgery 53% of the children and 49% of the adults were seizure free. Another 25% of the patients had a more than 50% reduction of seizure frequency. In the postoperative non seizure free group of patients there was a negative correlation between decrease in weighted seizure severity and decrease in seizure frequency. This finding stresses the need for including other parameters than seizure frequency when evaluating the outcome of epilepsy surgery.

Adolescent↗

Loss of memory for auditory-spatial associations following unilateral medial temporal-lobe damage.

The goal of the present experiment was to determine the role of medial temporal-lobe structures in episodic memory of auditory-spatial associations. By using a two-alternative forced choice paradigm in which an association between eight different sounds and their spatial location must be recognized, learning abilities over 10 learning sessions were tested in 19 patients who had undergone a right or a left medial temporal-lobe resection for the relief of intractable seizures as well as in nine normal control participants. The data demonstrated that significant learning took place over the successive sessions for all the participants. In addition, the results showed that patients with left but not right medial temporal-lobe lesion were impaired in this learning task as compared to normal participants, suggesting the predominant implication of left medial temporal-lobe structures in auditory-spatial associative learning. The predominant role of left hemisphere structures in this memory task could be explained by a spatial categorical coding, which was enhanced by the use of eight loud-speakers. This result also suggests that the ability to store an episodic event associated with a rich spatial (or temporal) context depends on the left medial temporal-lobe structures. Thus, this finding provides an interesting parallel with data obtained in the visual modality by documenting for the first time the role of the left medial temporal-lobe in episodic learning of auditory-spatial associations.

Adult↗

Functional MRI predicts memory performance after right mesiotemporal epilepsy surgery.

PURPOSE: Anterior temporal lobe resection (ATR) is a treatment option in drug-resistant epilepsy. An important risk of ATR is loss of memory because mesiotemporal structures contribute substantially to memory function. We investigated whether memory-activated functional MRI (fMRI) can predict postoperative memory loss after anterior temporal lobectomy in right-sided medial temporal lobe epilepsy (MTLE). METHODS: We included 16 patients (10 women) aged 16-54 years. The mean age at epilepsy onset was 12.5 years (range, 1-26 years). The patients' mean Wechsler IQ score was 95.2 (range, 62-125). The activation condition of fMRI consisted of retrieval from long-term memory induced by self-paced performance of an imaginative walk. All but one patient had left-sided speech dominance according to speech-activated fMRI. Outside the scanner, we evaluated the pre- and postoperative visual memory retention by using Rey Visual Design Learning Test. RESULTS: We found a correlation between the preoperative asymmetry index of memory-fMRI and the change between pre- and postsurgical measures of memory retention. Reduced activation of the mesiotemporal region ipsilateral to the epileptogenic region correlated with a favorable memory outcome after right-sided ATR. CONCLUSIONS: In light of the postoperative results, the theoretical implication of our study is that fMRI based on a simple introspective retrieval task measures memory functions. The main clinical implication of our study is that memory-fMRI might replace the invasive Wada test in MTLE by using a simple fMRI paradigm. Predictive power, however, will be studied in larger patient samples. Other studies are required for left-sided MTLE and neocortical epilepsies to assess the clinical usefulness of memory-fMRI.

Adolescent↗

Wada memory performance predicts seizure outcome after epilepsy surgery in children.

PURPOSE: Wada memory asymmetries were examined in children from four comprehensive epilepsy surgery centers who subsequently underwent epilepsy surgery to determine whether Wada memory performance could predict degree of seizure relief in children. METHODS: One hundred fifty-six children (between ages 5 and 16 years) with intractable epilepsy underwent Wada testing before resective epilepsy surgery (93 within the left hemisphere, and 63 within the right hemisphere). Memory stimuli were presented soon after intracarotid amobarbital injection, and recognition memory for the items was assessed after return to neurologic baseline. Eighty-eight children underwent unilateral temporal lobe resection, and 68 had extratemporal lobe resections. One hundred four (67%) children were seizure free (Engel class I), and 52 (33%) were not seizure free (Engel classes II-IV) at follow-up (mean follow-up interval, 2.3 years). RESULTS: Seizure-free children recalled 19.3% more Wada memory items after ipsilateral injection than did non-seizure-free children (p = 0.008). If analysis was restricted to youngsters with temporal lobectomies (TLs), seizure-free children recalled 27.7% more items after ipsilateral injection than did non-seizure-free TL children (p = 0.004). With regard to individual patient prediction, 75% of children who had memory score asymmetries consistent with the seizure focus were seizure free. In contrast, only 56% of children whose memory score asymmetries were inconsistent with the seizure focus were seizure free (p = 0.01). CONCLUSIONS: Results suggest that Wada memory performance asymmetries are related to the degree of seizure relief after epilepsy surgery in children and adolescents.

Adolescent↗

Differential spatial memory impairment after right temporal lobectomy demonstrated using temporal titration.

In this study a temporal titration method to explore the extent to which spatial memory is differentially impaired following right temporal lobectomy was employed. The spatial and non-spatial memory of 19 left and 19 right temporal lobectomy (TL) patients was compared with that of 16 normal controls. The subjects studied an array of 16 toy objects and were subsequently tested for object recall, object recognition and memory for the location of the objects. By systematically varying the retention intervals for each group, it was possible to match all three groups on object recall at sub-ceiling levels. When memory for the position of the objects was assessed at equivalent delays, the right TL group revealed disrupted spatial memory, compared with both left TL and control groups (P < 0.05). MRI was used to quantify the extent of temporal lobe resection in the two groups and a significant correlation between hippocampal removal and both recall of spatial location and object name recall in the right TL group only was shown. These data support the notion of a selective (but not exclusive) spatial memory impairment associated with right temporal lobe damage that is related to the integrity of the hippocampal functioning.

Adult↗

Pathology of temporal lobe epilepsy: An analysis of 100 consecutive surgical specimens from patients with medically refractory epilepsy.

The neuropathological features of temporal lobe epilepsy were studied utilising 100 consecutive surgical specimens from patients with medically refractory complex partial seizures. A wide spectrum of neuropathological changes was recorded in 98 specimens. Fifty-eight specimens showed features of Ammon's horn sclerosis. Diffuse accumulation of corpora amylacea were demonstrated in the resected temporal lobes from 54 patients. Six patients had neoplastic lesions of temporal lobe. One unique case of dysembryoplastic neuroepithelial tumour showed a melanotic component within the tumour. The neuropathological features were regarded as nonspecific in 31% of cases. Our results indicate that a majority of patients with medically intractable epilepsy of temporal lobe origin reveal significant neuropathological features. Careful documentation of the neuropathological features and its correlation with radiological, electrophysiological and pre- and post-surgical clinical features will help in predicting the seizure outcome after temporal lobectomy for medically refractory epilepsy.

Brain Neoplasms↗

Optimizing epilepsy surgery with intraoperative MR imaging.

PURPOSE: The surgical treatment of medically intractable temporal lobe epilepsy includes the resection of temporal lobe structures. Although the reported seizure-free outcomes are highly variable, there is growing evidence that the extent of resection of the mesiotemporal lobe directly correlates with seizure control. METHODS: A moveable, high-field intraoperative magnetic resonance (MR) system was used to monitor and optimize the resection of the amygdala and hippocampus in 14 epilepsy patients. Fourteen patients with intractable seizures of temporal lobe origin underwent standard preoperative investigations including MR imaging, EEG telemetry, single-photon emission computed tomography, and neuropsychologic and sodium amytal testing. Anterior temporal lobectomy was performed on 10 patients, whereas four were treated with selective amygdalohippocampectomy. Intraoperative electrocorticography was applied as required. For all procedures, the objective was to resect the amygdala completely, and hippocampus to the posterior margin of the brainstem. RESULTS: Interdissection intraoperative MR imaging taken when optimal resection was thought to have been achieved revealed residual unresected amygdala or hippocampus in seven of 14 patients. An unexpected acute hematoma was found in one patient. At 17 months' follow-up, 13 (93%) of 14 patients are seizure free or have significantly improved seizure control. CONCLUSIONS: The mobile high-field intraoperative MR system provides high-resolution images without restriction on surgical instruments or techniques. The ability to identify and resect residual mesial temporal lobe targets before craniotomy closure is of potentially tremendous value in optimizing seizure control.

Adult↗

Focal functional deficits in temporal lobe epilepsy on PET scans and the intracarotid amobarbital procedure: comparison of patients with unitemporal epilepsy with those requiring intracranial recordings.

PURPOSE: To analyze the relationship between the intracarotid amobarbital procedure (IAP) and positron emission tomography (PET) and study the lateralizing value of these tests in patients with unitemporal epilepsy and those requiring intracranial recordings. METHODS: We compared 51 patients with unitemporal epilepsy (group1) with 26 patients in whom surface recordings failed to reveal a distinct unitemporal focus, necessitating invasive recordings (group 2). RESULTS: The brain magnetic resonance imaging (MRI) scans for group 1 showed mesial temporal sclerosis in 70.5% of the patients. PET showed unilateral temporal hypometabolism in 88%. In addition, 74.5% of the patients in group 1 had impaired memory on the epileptogenic side on the IAP, and 89.4% of those patients also had ipsilateral temporal hypometabolism on PET scans. All the group 1 patients underwent temporal resections. The pathologic examination showed hippocampal sclerosis in 72% of the patients. Eighty percent of group 1 patients became seizure free, and 16% had rare seizures (follow-up, 2-7 years). MRIs for group 2 showed mesial temporal sclerosis in 31% of the patients; PET scans showed temporal hypometabolism in 39%. The IAP was lateralized in 47.8%. Sixty-nine percent had temporal lobe resections. The pathologic examination showed hippocampal sclerosis in 44% of the patients. Forty-four percent of group 2 patients became seizure free, and 27.7% had rare seizures (follow-up, 2-8 years). CONCLUSIONS: Ninety-six percent of the patients with unitemporal foci had focal functional deficits on the epileptogenic side on 18-fluorodeoxyglucose-(FDG) PET scans, the IAP, or both. The results of the FDG-PET were predictive of impaired memory on the IAP. Memory impairment contralateral to the temporal hypometabolism found on the PET scans was never seen. These patients had an excellent outcome. In contrast, <50% of the patients requiring intracranial recordings had focal functional deficits, suggesting that more a diffuse pathology may account for their less favorable outcome.

Adolescent↗

The impact of temporal lobe surgery on cure and mortality of drug-resistant epilepsy: summary of a workshop.

The Third International Spring Epilepsy Research Conference took place in Georgetown, Cayman Islands from April 26 to May 3, 2003. One workshop discussed the impact of epilepsy surgery on seizure outcome and mortality of antiepileptic drug (AED)-resistant temporal lobe epilepsy. This article summarizes the information presented at this workshop. Although two-thirds of adult patients undergoing epilepsy surgery become seizure-free with continued AED treatment, current clinical experience shows that seizure recurrence occurs in one-third of patients when AEDs are withdrawn under medical supervision. Additional seizure recurrence occurring after AED taper, poor drug compliance and even while patients continue on AEDs after surgery leave only approximately one-third of patients cured after temporal lobe resection. Mostly because so many patients prefer to stay on AEDs although they are free of disabling seizures after surgery, a randomised controlled trial of AED discontinuation is needed to determine if in fact only one-third of patients are cured after surgery. Based on the functional anatomy of temporal lobe surgery two hypotheses are presented why only a minority of patients are cured after surgery. The type and the prognostic significance of seizures after surgery is discussed. Recent studies have suggested that successful temporal lobe surgery may be able to normalize the increased standard mortality ratio (SMR) of drug-resistant temporal lobe epilepsy. However, pre-existing differences in SMR between those cured and those not cured by temporal lobe surgery and other unresolved methodological issues make it difficult at present to fully evaluate the impact of surgery on mortality. Future studies are thus warranted to specifically address the impact of temporal lobe surgery on cure and mortality.

Drug Resistance↗