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PubMed2003

The pathological basis of temporal lobe epilepsy in childhood.

OBJECTIVE: To characterize the pathologic findings of temporal lobe epilepsy (TLE) in children undergoing temporal lobectomy for refractory seizures and to correlate these findings with clinical presentation. METHODS: The authors reviewed the charts of all children who underwent anterior temporal lobectomy for refractory TLE from 1979 through 1999. A new neuropathologic analysis was performed blinded to clinical features and outcome. RESULTS: Twenty-two children met inclusion criteria. Mean age at onset of epilepsy was 3 years, 7 months (range 1 month to 10 years). Mean age at surgery was 10 years, 11 months (range 1 to 18 years). All patients had complex partial seizures, 48% with secondary generalization. Most had daily seizures. Auras were reported in 45% of patients. Post-resection follow-up averaged 5 years, 2 months (range 2 to 19 years). Seizure-free status was achieved in 41% of patients, and 14% had residual auras only. The most frequent neuropathologic abnormalities were cortical dysplasia (CD) of the temporal neocortex (14 of 22) and mesial temporal sclerosis (MTS) (12 of the 15 children with available hippocampal tissue). These two findings coexisted in seven children. MTS was associated with extra-hippocampal pathology in 8 of 12 (67%) of the cases. CONCLUSIONS: MTS occurs frequently in association with CD in this population of children. The high incidence of dual pathology could explain the early age of seizure onset and high seizure frequency rate observed. TLE in childhood may constitute a different entity than in adults, from both the clinical and neuropathologic perspectives.

Adolescent↗

PubMed2006

Perihematomal mitochondrial dysfunction after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Recent measurements in intracerebral hemorrhage (ICH) patients suggest a primary reduction in brain metabolism is responsible for reduced cerebral blood flow and low oxygen extraction surrounding the hematoma. We sought to determine whether reduced mitochondrial respiratory function could account for reduced metabolic demand in ICH patients. METHODS: Brain-tissue samples from 6 patients with acute spontaneous ICH and 6 control patients undergoing brain resection for management of seizure were evaluated. Only tissue removed from the brain adjacent to the hematoma was studied. Specimens were collected in the operating room; mitochondrial studies were begun within 1-hour. Mitochondrial oxygen consumption was measured after the addition of pyruvate, malate, and ADP, followed by oligomycin and carbonylcyanide. RESULTS: The ICH patients ranged in age from 40 to 54 years; 2 were female and half black. Hemorrhages were located in the temporal lobe (3), cerebellum (2) and parietal lobe (1). The average State 3 (active) O2 consumption for mitochondria from ICH patients was approximately 40% lower than that of control patients ( CONTROLS: 129+/-39 versus ICH: 76+/-28 nmol O2/min per mg protein). With increasing time from hemorrhage to testing there was a progressive decline in State 3 respiration. Reduced State 3 respiration was evident even at 6 hours, whereas at 72 hours, there was essentially no O2 consumption. CONCLUSIONS: These data support the hypothesis that mitochondrial dysfunction and not ischemia is responsible for reduced oxygen metabolism in ICH. They point to a new direction for investigation and development of therapeutic interventions for ICH patients.

Adenosine Triphosphate↗

PubMed1994

The role of PET in childhood epilepsy.

Functional brain imaging with positron emission tomography (PET) has led to significant advances in the diagnosis and management of various forms of childhood epilepsy. Interictal PET in temporal lobe epilepsy typically shows decreased glucose utilization (hypometabolism) in one or both temporal lobes. Children with early-onset refractory extratemporal lobe epilepsy who do not manifest structural abnormalities on magnetic resonance imaging often show single or multiple cortical foci of hypometabolism indicating underlying microdysgenesis that corresponds to the area of epileptogenicity. The findings of focal cortical metabolic lesions and metabolic activation of subcortical structures (brain stem and lenticular nuclei) in patients with infantile spasms have allowed many infants with intractable spasms to be treated surgically with cortical resection, and have altered our concepts regarding the pathophysiology of these seizures. New observations in Lennox-Gastaut syndrome, Sturge-Weber syndrome, tuberous sclerosis, hemimegalencephaly, Landau-Kleffner syndrome, and other pediatric epilepsy syndromes have been documented with PET and have improved our understanding of these disorders. Recent PET studies of several neurotransmitter receptors in adult epileptic patients suggest that this approach holds great promise in the study of childhood epilepsy. The current guidelines indicating which patients with epilepsy should be referred for a PET study are outlined.

Blood Glucose↗

PubMed2005

Intraoperative optical spectroscopy identifies infiltrating glioma margins with high sensitivity.

OBJECTIVE: Adult gliomas have indistinct borders. As the ratio of neoplastic cells to normal cells becomes lower, the ability to detect these cells diminishes. We describe a device designed to augment intraoperative identification of both solid tumor and infiltrating tumor margins. METHODS: A novel, intraoperative, optical spectroscopic tool, using both white light reflectance and 337-nm excitation fluorescence spectroscopy, is described. Discrimination algorithms have been developed to segregate neoplastic tissues from normal glial and neuronal elements. The spectroscopy device was used to measure 5 to 10 locations during glioma resection. Beneath the tool, a biopsy sample was obtained and the pathological results were reviewed in a blinded fashion. Samples were classified as solid tumor, infiltrating tumor, or normal gray or white matter. Comparisons were made between the optical spectra and the histopathological results of sampled areas in evaluating the sensitivity and specificity of the tool for tissue discrimination. RESULTS: Spectral data were obtained from 24 patients with glioma and from 11 patients with temporal lobe epilepsy. A sensitivity of 80% and a specificity of 89% in discriminating solid tumor from normal tissues were obtained. In addition, infiltrating tumor margins were distinguished from normal tissues with a sensitivity of 94% and a specificity of 93%. CONCLUSION: We have developed a handheld, optical spectroscopic device that may be used rapidly and in near real time with high sensitivity and reproducibility as an optical tissue discrimination tool in glioma surgery.

Adult↗

PubMed1992

Intractable complex partial seizure: correlation of magnetic resonance imaging with pathology and electroencephalography.

We prospectively analyzed MR studies of 32 patients with intractable complex partial seizures, who later underwent resection of EEG-proven seizure foci. Twenty-seven patients were imaged at 1.5, 4 at 0.35, and 1 at 0.5 Tesla. Correlation was obtained on all patients with EEG and surgical pathology. Of 19 patients with mesial temporal sclerosis (MTS), 13 exhibited an MR abnormality at the site of pathology as determined by EEG and surgery. Abnormalities included increased (8) or decreased (1) signal intensity, distortion of gray-white interface (1) and temporal lobe atrophy (3). Six patients had no abnormalities at the site of the diseased focus. MR was more sensitive in patients with other structural lesions which included tumor, encephalitis, polymicrogyria, cryptic vascular malformation, and tuberous sclerosis. Prior studies indicate some usefulness of MR in intractable seizure patients, but many report relative insensitivity of MR in defining an abnormality (as low as 11%). Our results demonstrate the usefulness of high-resolution thin-section multiplanar MR using cardiac gating or flow compensation techniques in this patient population.

Atrophy↗

PubMed2006

Executive performance on the Wisconsin Card Sorting Test in mesial temporal lobe epilepsy.

Executive dysfunction assessed by the Wisconsin Card Sorting Test has been observed in patients with mesial temporal lobe epilepsy (TLE); however, the mechanism of executive impairment is unclear. We therefore investigated the potential contribution of the hippocampus toward executive dysfunction in 85 mesial TLE patients, and in a control group of 34 patients with neocortical TLE. Standardized regression-based methodology was used for correcting test-retest bias. We found that 56% of mesial TLE patients had impaired sorting performance, with 30% showing severe impairment. A lower full-scale intelligence quotient, older age, longer duration, and preoperative use of topiramate were significantly correlated with poorer preoperative sorting abilities. However, neither these variables nor postoperative discontinuation/reduction of topiramate were related to postoperative changes in sorting abilities. Only preoperative sorting abilities were negatively correlated with postoperative changes in executive performance. That is, patients with better preoperative executive ability showed greater postoperative deterioration in executive function, whereas those with poorer preoperative sorting ability had greater improvement in executive function after mesial temporal resection. There were no differences in card sorting ability between the mesial and neocortical TLE groups. In conclusion, our results suggest that impairment of card sorting performance in the mesial TLE group cannot be explained only by hippocampal dysfunction, but that other processes (possibly epileptic discharges propagated to the extratemporal area) must play a predominant role.

Adult↗

PubMed1998

Selective spatial memory impairment after right unilateral temporal lobectomy.

Deficits in performance of both spatial and visual tasks are common following tissue loss in the right temporal lobe. Since spatial and visual attributes are frequently confounded in experimental tasks, we have studied patients following unilateral temporal lobectomy, in an attempt to determine which aspect mediates the observed deficits. Spatial and visual memory performance was compared in normal controls (n = 16), left temporal (LTL; n = 19) and right temporal (RTL; n = 19) lobectomy patients, by presentation of eight abstract designs in a spatial array for subsequent recall and recognition of the designs (visual memory) and recall of their spatial position (spatial memory). By varying the retention intervals for each group, all three groups were matched on both recall and recognition of the designs at sub-ceiling levels. In contrast, recall of the position of the designs (spatial memory), tested at equivalent delays to those of the visual memory tests, revealed a deficit in the RTL patients compared to both controls and LTL patients (p < 0.05). Magnetic resonance imaging (MRI) was used to quantify the extent of resection of the hippocampus and parahippocampal regions in the two patient groups and showed a significant correlation between hippocampal and parahippocampal removal and spatial memory in the RTL group only. These data support the notion of a disproportionately large involvement of the right hippocampus and adjacent regions in spatial memory.

Adult↗

PubMed1987

Reconstruction of the cranial base following tumour resection.

Twenty-four patients have undergone resection of tumours involving the cranial base by a multidisciplinary team consisting of a neurosurgeon, ENT surgeon and plastic surgeon. The resultant defects of the cranial base have been reconstructed using local fascial flaps, transposition of local muscle flaps and microsurgical transfer of free muscle flaps. Indications for reconstruction have included obliteration of paranasal sinuses, coverage of tenuous dural repairs or dural grafts and separation of the nasopharynx from the dura of the frontal and temporal lobes and posterior fossa to prevent CSF leakage and meningitis.

Adolescent↗

PubMed1997

Surgical treatment of epilepsy from schizencephaly with fused lips.

BACKGROUND: Surgical treatment of schizencephaly with fused lips has been reported in few cases. In all of the previously reported cases, temporal lobectomy was selected as a major surgical treatment, except for one case with cortical resection. We present a case of direct resection of dysplastic walls of the schizencephalic cleft and the surrounding epileptic area. CASE: This 20-year-old college student with medication-resistant epilepsy was surgically treated by subpial cortical resection of the epileptogenic area around a schizencephalic cleft. Magnetic resonance imaging showed an unilateral schizencephalic cleft with fused lips in the right parietal lobe. Pathologic examination demonstrated dysplastic neurons in the epileptogenic cortex. Intraoperative electrocorticography clearly detected epileptiform discharges around the cleft, and the epileptogenic lesion was completely resected. He has been seizure-free for 1 year since the operation and he has no neurologic deficits. CONCLUSION: Subpial resection of the dysplastic cortex surrounding the cleft under the guide of electrocorticography is an effective and minimally invasive procedure for the treatment of schizencephaly.

Adult↗

PubMed1998

Assessment of communication impairment and the effects of resective surgery in solitary, right-sided supratentorial intracranial tumours: a prospective study.

To assess the effects of solitary, right-sided supratentorial intracranial tumours on language and communication function patients were assessed preoperatively using the Western Aphasia Battery (WAB) and Boston Naming Test (BNT). The impact of resective tumour surgery was evaluated prospectively by a comparison of test scores obtained at pre- and postoperative assessments. The WAB scores in 33 patients revealed that 21% were by definition dysphasic (i.e. Aphasia Quotient < 93.8) and 35% obtained an abnormal Language Quotient. Performance was particularly variable on the written picture description and word fluency WAB subtests. Using the BNT 21% of 47 patients were anomic. The tumours were evenly distributed throughout the frontal, temporal and parietal lobes, but none were in the occipital lobe. Reassessment approximately 6 days after excisional tumour surgery showed that mean scores for the BNT, Aphasia Quotient, and the WAB spontaneous speech and comprehension subtests had improved significantly despite a significant reduction in dexamethasone therapy. This study has demonstrated that right-sided intracranial tumours produce subtle, but specific language deficits of a type more usually associated with left-sided brain dysfunction. The pathophysiological basis of these deficits is unclear, but they are not attributable to either limited education or pre-existing dyslexia. Further studies using a discriminating and comprehensive assessment of language in the right hemisphere are required.

Adult↗

PubMed1994

Left temporal neocortex mediation of verbal memory: evidence from functional mapping with cortical stimulation.

We examined the contribution of the temporal neocortex to short-term memory (STM) in 15 patients with left hemisphere language dominance during intraoperative or extraoperative cortical mapping prior to left anterior temporal lobectomy. Recall errors were examined following stimulation during the acquisition, consolidation, and retrieval stages of a verbal STM task. Ten patients showed stimulation-induced recall errors, and five patients showed no significant memory errors. More patients showed errors following stimulation during consolidation than during acquisition or retrieval, possibly because of disrupted transfer of information from the temporal neocortex to the hippocampus. Patients with stimulation-induced recall errors did not differ significantly from patients without memory errors in terms of seizure, demographic, or neuropsychological variables. Patients with resection of sites showing stimulation-induced recall errors had greater postoperative decline in verbal memory than did patients with resection sparing these sites. We suggest that the left temporal neocortex contributes to verbal memory consolidation in patients with chronic epilepsy.

Adult↗

PubMed1995

The syndrome of frontal lobe epilepsy: characteristics and surgical management.

We reviewed the historical features, preoperative diagnostic evaluation, operative procedure, and surgical outcome in 16 patients with refractory frontal lobe epilepsy. Clinical expression of the epilepsy varied widely, particularly with respect to seizure characteristics, although high monthly seizure frequency and absence of a risk factor for epilepsy before age 5 occurred more often than in reported in temporal lobe epilepsy patients. Seizures often caused early bilateral movements, were brief, and lacked oroalimentary automatisms and a prolonged postictal state. Both the interictal and ictal scalp EEGs had relatively poor sensitivity and specificity and often either contained no epileptiform abnormalities or were misleading. MRI usually identified structural lesions when these were present, although it was negative in two patients with tumors. In the absence of an MRI lesion, intracranial EEG usually identified the area to be resected, although it too provided misleading information in one case. Surgical procedures consisted of focal resections with or without anterior corpus callosotomy, or of corpus callosotomy alone. Nearly all patients improved after surgery, with a majority (67%) becoming seizure-free (average follow-up, 46 months). Preoperative seizure frequency correlated with seizure relief after surgery, as did age of seizure onset, whereas presence of tumor did not. We conclude that frontal lobe epilepsy warrants aggressive investigation and that surgical treatment often can be successful.

Adolescent↗

PubMed2003

Inflammatory pseudotumors of the central nervous system: report of 3 cases and a literature review.

Inflammatory pseudotumors (IPs), mostly benign lesions characterized by fibrotic ground tissue and polyclonal mononuclear infiltrate, may affect all organ systems. IPs originating in the central nervous system (IP-CNS) are very rare, and their distinct histopathologic features are poorly characterized. Three otherwise healthy patients (age 8, 15, and 17 years) presented with focal neurologic symptoms (seizures, n = 2; headaches, n = 1), corresponding to a left temporal, left occipital, and left frontal IP, respectively, extending from meningeal structures into brain tissue. After resection, no recurrence was observed in patient 1 during 5 years of follow-up, whereas patient 2 developed a rapidly progressive local recurrence and a second intracerebral lesion despite antiviral, immunosuppressive, antibiotic, and radiation therapy. In patient 3, who also showed local recurrences, sequential histopathologic investigations revealed transformation to a semimalignant fibrohistiocytic tumor. In this patient, anaplastic lymphoma kinase (ALK) expression was also positive, whereas it was negative in patient 1. A detailed literature analysis confirmed that most IP-CNS arise from dural/meningeal structures (n = 34). Intraparenchymatous (n = 7), mixed intraparenchymatous/meningeal (n = 4), and intraventricular lesions (n = 7) or IP extending per continuitatem from intracerebral to extracerebral sites (n = 5) were rare. The recurrence rate was 40% within 2 years in general. It was increased after incomplete resection and in female patients (multivariate Cox regression model, P < 0.02). Although rare, IP-CNS are important differential diagnoses among tumor-like intracranial lesions. Their potential risk of malignant transformation and high risk of recurrence necessitate close follow-up, especially when resection is incomplete. Prospective multicenter trials are needed to optimize classification and treatment of this rare inflammatory lesion.

Adolescent↗

PubMed1999

MR contribution in surgery of epilepsy.

The contribution of MR imaging in patients with drug-resistant epilepsy considered for surgical therapy is discussed. In this review we focus on: (a) focal abnormalities (mesial temporal sclerosis, focal migration disorders, hamartomatous lesions and low-grade tumours, phakomatosis and vascular malformations) associated with therapy-resistant partial epilepsy, requiring resective surgery; (b) abnormalities leading to generalized seizures that require more drastic surgical procedures, such as callosotomy and functional hemispherectomy; and (c) localisation of implanted depth-electrodes.

Blood Flow Velocity↗

PubMed1993

Comparison of scalp electroencephalogram with subdural electrocorticogram recordings and functional mapping in frontal lobe epilepsy.

We compared the findings of scalp electroencephalogram with subdural electrode array (SEA) recordings in 19 patients with refractory frontal lobe epilepsy. Prolonged scalp interictal recordings localized the epileptogenic zone in 12 patients; seven had no interictal sharp waves. The SEAs showed multifocal interictal sharp waves in all patients. Seven patients with localized seizure onset on scalp recording showed extensive ictal onset on the SEA recording. Five patients with lateralized seizure onset to one hemisphere on scalp recording were found to have ictal onset on SEA restricted to a smaller area. Because of the large epileptogenic zone found on SEA recordings, a complete resection was possible in only five (33%) of the 15 patients who had resections. Eight (53%) of the 15 patients benefited from surgery (mean follow-up, 4.6 years). The SEAs also allowed functional localization in most patients. From these data, we suggest that a localizing scalp electroencephalogram in patients with frontal lobe epilepsy may be misleading because SEA recordings show larger epileptogenic zones than anticipated. Furthermore, we postulate that the larger extensive epileptogenic zone may account for the poorer surgical outcome in patients with frontal lobe epilepsy compared with patients with temporal lobe epilepsy.

Adolescent↗

PubMed1996

Temporal lobe epilepsy caused by mesial temporal sclerosis and temporal neocortical lesions. A clinical and electroencephalographic study of 46 pathologically proven cases.

This study aims to determine whether there are important clinico-electrical differences between patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS) and those with TLE secondary to a discrete temporal neocortical lesion (NL). The case histories, interictal EEG, seizure semiology, ictal EEG and postoperative outcome of 46 pathologically proven patients (31 MTS and 15 NL) were compared. A history of febrile convulsions (FC) was more common in MTS patients (58% versus 26%, P < 0.05), as was a history of a significant cerebral event at < 4 years of age (22% versus 0%, P < 0.05). There were no statistically significant differences in the incidence or nature of auras. No statistically significant differences between the groups were found in the interictal-EEG. With ictal semiology dystonic posturing occurred more frequently in MTS patients (mean 52% versus 26%, P < 0.05). Facial grimacing/ twitching occurred earlier in the seizures of NL patients (median 19 s versus 35 s, P < 0.05). There was an increased frequency of fast rhythmic sharp waves (> 4 Hz) in the ictal-EEG of MTS patients (mean 81% versus 60%, P = 0.05). The patients with NL developed bilateral ictal EEG changes more often (mean 55% versus 26%, P < 0.05) and more rapidly (mean 23 s versus 74 s, P < 0.005). The onset of ictal EEG seizure activity was bilateral more often in patients with NL (20% versus 4%, P < 0.005). There were no significant differences between the two groups for any of the video-EEG features, in terms of whether or not the feature occurred at least once in an individual patients. There was a tendency for MTS patients to have a higher seizure-free postsurgical outcome (87% versus 60%, P = 0.057). However, all the NL patients who were not free of seizures had had an incomplete lesion resection. We conclude that there are a number of clinico-electrical differences between patients with mesial TLE (MTLE) and patients with neocortical TLE (NCTLE), but that none of these are sufficient to allow a distinction to be made in an individual patient.

Adolescent↗

PubMed2001

Evidence of peripheral auditory activity modulation by the auditory cortex in humans.

At the auditory periphery, the medial olivocochlear system is assumed to be involved in complex sound processing and may be influenced by feedback from higher auditory nuclei. Indeed, the descending auditory pathway includes fibers coming from the auditory cortex that are anatomically well positioned to influence the superior olivary complex, and thus the medial efferent system. The aim of the present study was to verify the hypothesis of an implied influence of the auditory cortex on the peripheral auditory system. In three rare cases of patients presenting with intractable temporal lobe epilepsy, Heschl's gyrus (i.e. the temporal superior gyrus) was surgically removed in the right hemisphere in two patients and in the left hemisphere in a third patient, in order to minimize epilepsy attacks, as preoperative stereoencephalography had shown the epileptic focus or tumor to be situated in those locations. In all three cases, several weeks after the operation the medial olivocochlear system was clearly less functional on both sides, but especially on the side contralateral to the resection. In healthy controls, no such pattern was obtained. In four other epileptic patients, who were operated unilaterally at the anterior temporal pole, amygdala and hippocampus with the temporal gyrus partially spared, efferent suppression grew stronger in the ear ipsilateral to surgery. These results revealed that, in humans, the primary and secondary auditory cortex play a role in modulating auditory periphery activity through direct or indirect efferent fibers. In accordance with previous findings, this descending influence may improve the auditory afferent message by adapting the hearing function according to cortical analysis of the ascending input.

Adult↗

PubMed1999

Focal ictal direct current shifts in human epilepsy as studied by subdural and scalp recording.

In order to clarify further the characteristics of ictal direct current (DC) shifts in human epilepsy, we investigated them by subdural and scalp recording in six and three patients, respectively, both having mainly neocortical lobe epilepsy (five with frontal lobe epilepsy, two with parietal lobe epilepsy and two with temporal lobe epilepsy). By using subdural electrodes made of platinum, ictal DC shifts were observed in 85% of all the recorded seizures (89 seizures) among the six patients, and they were localized to just one or two electrodes at which the conventional initial ictal EEG change was also observed. They were closely accompanied by the electrodecremental pattern in all patients except for one in whom 1 Hz rhythmic activity was superimposed on clear negative slow shifts. Seizure control after resection of the cortex, including the area showing DC shifts, was favourable irrespective of histological diagnosis. Scalp-recorded ictal slow shifts were observed in 23% of all the recorded seizures (60 seizures) among the three patients. They were, like the subdurally recorded ones, mainly surface-negative in polarity, closely related to the electrodecremental pattern and consistent in their location. It seems that scalp-recorded DC shifts were detected particularly when seizures were clinically intense, while no slow shifts were observed in small seizures. It is concluded that at least subdurally recorded ictal slow shifts are clinically useful before epilepsy surgery to delineate more specifically an epileptogenic area as well as to further confirm the conventional initial ictal EEG change, and that scalp-recorded ictal slow shifts also have high specificity although their low sensitivity is to be taken into account.

Adolescent↗