Surgical treatment of epilepsy in tuberous sclerosis: strategies and results in 18 patients

BACKGROUND: Seizures in patients with tuberous sclerosis complex (TSC) are often intractable to antiepileptic medications and searching investigation may provide evidence that surgical treatment can be considered. OBJECTIVE: To review the results of investigation and surgical therapy, a treatment modality not generally considered in patients with medically refractory seizures and TSC. METHODS: We report 18 patients (9 male) with TSC who underwent surgical treatment of medically refractory epilepsy. Twelve patients had a well-localized epileptogenic lesion and were treated by lesionectomy or focal resection. Resections were: 7 frontal, 4 temporal, 1 frontotemporal, 1 occipital, and 1 frontoparietal. Four patients underwent more than one operation. Six patients had corpus callosotomy (CC). RESULTS: Follow-up ranged from 1 month to 47 years. Outcome of the patients treated by resection was excellent in 7 (5 were seizure-free and 2 had auras only), good in 1, fair in 3, and 1 was lost to follow-up. Best outcome was obtained in patients who had focal seizures and good imaging and EEG correlation, although they might have multiple seizure types, other imaging abnormalities, and multifocal or generalized EEG findings. When there was no such correlation, CC was found to be an option as five patients had at least some improvement and only one showed no change. CONCLUSION: Surgical treatment of patients with TSC and intractable epilepsy is most effective when a single tuber or epileptogenic area can be identified as the source of seizures and resected. This may be possible even when other tubers or diffuse EEG abnormalities are present. In patients with unlocalizable epileptic abnormalities, palliation may be obtained by CC.     

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.     

Continuous source imaging of scalp ictal rhythms in temporal lobe epilepsy

PURPOSE: We wished to determine whether continuous EEG source imaging can predict the location of seizure onset with sublobar accuracy in temporal lobe epilepsy (TLE). METHODS: We retrospectively analyzed the earliest scalp ictal rhythms, recorded with 23- to 27-channel EEG, in 40 patients with intractable TLE. A continuous source analysis technique with multiple fixed dipoles (Focus 1.1) decomposed the EEG into source components representing the activity of major cortical sublobar surfaces. For the temporal lobe, these were basal, anterior tip, anterolateral, and posterolateral cortex. Ictal EEG onset was categorized according to its most prominent and leading source component. All patients underwent intracranial EEG studies before epilepsy surgery, and all had a successful surgical outcome (follow-up >1 year). RESULTS: Most patients with ictal rhythms having a predominant basal source component had hippocampal-onset seizures, whereas those with seizures with prominent lateral source activity had predominantly temporal neocortical seizure origins. Seizures with a prominent anterior temporal tip source component mostly had onset in entorhinal cortex. Seizures in some patients had several equally large and nearly synchronous source components. These seizures, which could be modeled equally well by a single oblique dipole, had onset predominantly in either entorhinal or lateral temporal cortex. CONCLUSIONS: Multiple fixed dipole analysis of scalp EEG can provide information about the origin of temporal lobe seizures that is useful in presurgical planning. In particular, it can reliably distinguish seizures of mesial temporal origin from those of lateral temporal origin.     

Association of combined MRI, interictal EEG, and ictal EEG results with outcome and pathology after temporal lobectomy

PURPOSE: Magnetic resonance imaging, interictal scalp EEG, and ictal scalp EEG each have been shown to localize the primary epileptic region in most patients with mesial-basal temporal lobe epilepsy (MBTLE), but the association of surgical outcome and pathology with each combination of these test results is not known. METHODS: We reviewed the MRI, interictal scalp EEG, and ictal scalp EEG results of 90 consecutive patients with MBTLE. Twelve patients were excluded from the analysis because inconclusive bitemporal intracranial EEG results precluded anterior temporal lobectomy (ATL); none had concordant MRI and interictal scalp EEG results. We compared all combinations of presurgical MRI, interictal EEG, and ictal EEG results to seizure outcome and tissue pathology in the 78 patients who underwent an ATL. RESULTS: Forty-eight (61%) patients had concordant lateralized MRI and interictal EEG temporal lobe abnormalities, with no discordant ictal EEG results; 77% of these patients were seizure-free after ATL. Concordance of MRI and interictal EEG abnormalities correlated with seizure cessation (p < 0.05), compared to all combinations with discordant or nonlateralizing MRI and interictal EEG results. Mesial temporal sclerosis (MTS) was confirmed pathologically in about 80% of both groups (p = 0.5). Outcome in patients with concordant MRI and ictal EEG with nonlateralizing interictal EEG was significantly worse than combinations with concordant MRI and interictal EEG (p < 0.02). CONCLUSIONS: Compared to other combinations of test results, concordance of MRI and interictal EEG is most closely associated with surgical outcome in MBTLE. However, most selected patients have pathologic confirmation of MTS regardless of test results or outcome. This information may be useful for planning the presurgical evaluation of patients with medically intractable MBTLE.     

Surgical treatment of extratemporal epilepsy: clinical, radiologic, and histopathologic findings in 60 patients

PURPOSE AND METHODS: The aim of this study was to analyze clinical, radiologic, and histopathologic findings in 60 consecutive patients with medically intractable extratemporal epilepsy who were operated on between November 1987 and May 1993. RESULTS: Histologically, there were distinct structural abnormalities in 50 (83%) of the surgical specimens. Signal abnormalities on magnetic resonance imaging (MRI) were present in all patients with neoplastic lesions (n = 17) and in 94% of patients with nonneoplastic focal lesions (n = 32). Overall, structural abnormalities were detected by MRI in 47 (96%) of 49 patients with focal lesions. During a mean follow-up of 4 years, 30 (54%) patients remained completely seizure free, 11 (20%) had < or = 2 seizures per year, seven (12%) showed a seizure reduction of > or = 75%, and eight (14%) had < 75% reduction in seizure frequency. The fraction of seizure-free patients was 12 (80%) of 15 in patients with neoplastic lesions, 16 (52%) of 31 in patients with nonneoplastic focal lesions, and two (20%) of 10 for those without histopathologic abnormalities. The differences in seizure outcome between patients with and without focal lesions were statistically significant (p < 0.05), if seizure-free outcome was compared with persistent seizures. CONCLUSIONS: Focal lesions and particularly neoplasms are associated with improved postoperative seizure control compared with patients without histopathologic abnormalities. We advise caution in considering surgery to treat extratemporal epilepsy in patients who have normal MRI scans, because the outcome with the approach described in this study is poor in such cases.     

Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood

A 21-year-old male presented with temporal lobe epilepsy associated with a venous angioma in the ipsilateral frontal lobe, presenting as intractable complex partial seizures. Neuroimaging showed a cerebral venous angioma in the right dorsolateral and opercular frontal lobe, and atrophy of the right hippocampus. As the ictal electroencephalogram (EEG) obtained with subdural electrodes indicated spike discharges initiating from the right mesial temporal lobe, temporal lobectomy was performed. The patient was seizure-free after the operation. Patients with epilepsy who have a cerebral venous angioma require precise analysis of the seizure pattern and an ictal EEG because of cerebral venous angioma may be associated with an another epileptogenic lesion which is surgically treatable.     

"Esthetic" ambulatory phlebectomy per mini-incisions: indications and technique

An 8-year-old girl presented with coexistence of ganglioglioma and cortical dysplasia manifesting as intractable epilepsy. Preoperative computed tomography demonstrated a small calcified lesion in the left frontal lobe which was not diagnosed as ganglioglioma. Magnetic resonance imaging also failed to demonstrate positive evidence of ganglioglioma or cortical dysplasia. A calcified tumor and the surrounding epileptogenic areas were resected under electrocorticography (ECoG) guidance. Histological examination revealed coexistence of ganglioglioma and cortical dysplasia. The patient became seizure-free after surgery. Resection of the ganglioglioma together with the adjacent epileptogenic area under intraoperative ECoG guidance is important to achieve a successful surgical result in patients with ganglioglioma.     

Immunocytochemical investigation on dysplastic human tissue from epileptic patients

In this report we describe three patients with developmental cortical abnormalities (generally referred as cortical dysplasia), revealed by MRI and operated on for intractable epilepsy. Tissue, removed for strictly therapeutic reasons, was defined as the epileptogenic area by electroclinical data and stereo EEG (SEEG) recordings. Tissue samples were processed initially for histology, and selected sections were further processed for immunocytochemical investigation in order to determine whether the region of cortical dysplasia was co-extensive with the epileptogenic area. In two patients with nodular heterotopia, disorganized aggregates of neurons (as revealed by neuronal cytoskeletal markers) were found within the nodules. Both pyramidal and local circuit neurons were present in the nodules, but no reactive gliosis was present. When nodules reached the cortex, the cortical layers were disrupted. In the patient with localized cortical dysplasia, a complete disorganization of the cortical lamination was found, and numerous neurons were also present in the white matter. Disoriented pyramidal neurons weakly labelled with cytoskeletal neuronal markers were also present but no cytomegalic cells were found. One of the patients with nodular heterotopia underwent only partial resection of both the 'epileptogenic area' and of the lesion; this patient still presents with seizures. The other patient with nodular heterotopia is seizure-free after a complete lesionectomy and excision of the epileptogenic area. The third patient, with focal cortical dysplasia, had two surgeries; she became seizure-free only after the excision of the epileptogenic area detected by SEEG recording. The present data suggest that the dysplastic areas identified by MRI should not be considered as the only place of origin of the ictal discharges. From the neuropathological point of view, the focal cortical dysplasia can be considered as a pure form of migrational disorder. However, the presence of large aggregates of neurons interspersed within the white matter, in the subcortical nodular heterotopia, suggests that a defect of neuronal migration could be associated with an exuberant production of neuroblasts and/or a disruption of mechanisms for naturally occurring cell death.     

Temporal and spatial characteristics of intracerebral seizure propagation: predictive value in surgery for temporal lobe epilepsy

We examined the prognostic value of spatial and temporal characteristics of intracerebral propagation of seizures during temporal lobe epilepsy (TLE) surgery. Seven TLE patients resistant to standard anterotemporal lobectomy who had no known causes of resistance [e.g., extratemporal (ET), lesions, multifocal epilepsy] were matched with 7 seizure-free patients and 7 others who were almost seizure-free after operation. Intracerebral ictal propagation pathways were not different in the three groups. Propagation was multidirectional, most frequently to the frontal lobes and sometimes to the contralateral temporal lobe (CTL). ET propagation delays were significantly shorter in resistant patients than in markedly improved patients. The resistant group also had more frequent propagation delays < 1.0 s, but propagation times > 1.0 s were equally likely in all groups. The extent of ET propagation and frequency of focal onsets were not different among the groups. Results suggest that very short propagation times predict reduced efficacy of operation, and that long propagation times are not related to surgical success.     

Incidence of lesions described by magnetic resonance imaging in the clarification of focal epilepsy of frontal and temporal origin

AIM: Today, MRI is an integral part of the presurgical evaluation of patients suffering from partial epilepsy. These patients frequently show focal morphological abnormalities with potential epileptogenic character and surgical resection of these lesions is associated with superior postsurgical outcome as to seizure frequency. Apart from easily detectable defects, such as post-traumatic lesions or cerebral infarction, as wide variety of mainly small abnormalities can be detected using MRI. METHODS: In this study, 484 patients suffering from partial epilepsy of temporal or frontal onset were evaluated for the incidence of different lesions in this population. RESULTS: All lesions found were included without evaluating their potential epileptogenicity, which remains to be proven using other procedures (EEG, SPECT, PET, etc.). Involvement of the hippocampal formation was a major finding in temporal lobe epilepsy, which could be detected as sclerosis (T2w-images), atrophy (T2w-TSE or T1w-IR-images) or both (15%). In addition and in declining frequency various tumors (14%), post-traumatic lesion (-5%), and focal cortical dysplasia or other disturbances of cortical integrity (-4%) were found. These lesions are detectable with best contrast on different sequences. As a consequence it is suggested to acquire sequences in 3 dimensions including a T1w-SE, two (coronal and axial) double-echo-SE sequences and similarly two T1w-IR-sequences. The application of contrast media can be restricted to special questions, derived either from the first imaging results or from the patients history. CONCLUSION: Using qualitative data for interpretation, the sensitivity as to the detection of any focal pathology of a recent-generation MRI in this population was 75%, with 79% for temporal lobe epilepsies and 67% for frontal lobe epilepsies. Quantitative measurements of hippocampal volume or signal seem to be able to increase the sensitivity of the method.     

Epilepsy surgery in the first three years of life

PURPOSE: Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes. METHODS: We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged <3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery. RESULTS: Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had >90% seizure reduction, and 6 had <90% reduction. There was no significant difference in seizure outcome between hemispherectomy/multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment. CONCLUSIONS: We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and lesion are removed.     

Hippocampal sclerosis revisited

Studies dating back more than 150 years reported a relationship between hippocampal sclerosis and epilepsy. Retrospective studies of patients who underwent temporal lobectomy for intractable partial epilepsy found a relationship between a history of early childhood convulsions, hippocampal sclerosis, and the development of temporal lobe epilepsy. Many believe that febrile seizures lead to hippocampal damage and this in turn predisposes the patient to the development of temporal lobe epilepsy. Studies in adult rats have shown that seizures can lead to hippocampal damage and unprovoked recurrent seizures. However, many questions remain as to the relevance of early childhood seizures to hippocampal sclerosis and temporal lobe epilepsy. Human prospective epidemiologic studies have not shown a relationship between early childhood seizures and temporal lobe epilepsy. Recent MRI studies in humans suggest that a preexisting hippocampal lesion may predispose infants to experience febrile seizures, later on hippocampal sclerosis, and possibly temporal lobe epilepsy may occur. Unlike the studies in adult rats, normal immature rats with seizures have not been shown to develop hippocampal damage or unprovoked seizures in adulthood. Furthermore, animal studies reveal that preexisting brain abnormalities can predispose to hippocampal damage following seizures early in life. This paper reviews evidence for and against the view that early childhood convulsions, hippocampal sclerosis, and temporal lobe epilepsy are related, while also exploring clinical and animal studies on how seizures can lead to hippocampal damage, and how this can result in temporal lobe epilepsy. By better understanding the cause and effect relationship between early childhood seizures and hippocampal injury in normal and abnormal brains specific treatments can be developed that target the pathogenesis of epilepsy.     

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus

BACKGROUND AND OBJECTIVE: Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend. METHODS: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. RESULTS: ESES and drop attack seizures appeared between the ages of 2 and 5 years (mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. CONCLUSIONS: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.     

Magnetoencephalography in partial epilepsy: clinical yield and localization accuracy

The goals of this study were to determine (1) the yield of magnetoencephalography (MEG) according to epilepsy type, (2) if MEG spike sources colocalize with focal epileptogenic pathology, and (3) if MEG can identify the epileptogenic zone when scalp ictal electroencephalogram (EEG) or magnetic resonance imaging (MRI) fail to localize it. Twenty-two patients with mesial temporal (10 patients), neocortical temporal (3 patients), and extratemporal lobe epilepsy (9 patients) were studied. A 37-channel biomagnetometer was used for simultaneously recording MEG with EEG. During the typical 2-3-hour MEG recording session, interictal epileptiform activity was observed in 16 of 22 patients. MEG localization yield was greater in patients with neocortical epilepsy (92%) than in those with mesial temporal lobe epilepsy (50%). In 5 of 6 patients with focal epileptogenic pathology, MEG spike sources were colocalized with the lesions. In 11 of 12 patients with nonlocalizing (ambiguous abnormalities or normal) MRI, MEG spike sources were localized in the region of the epileptogenic zone as ultimately defined by all clinical and EEG information (including intracranial EEG). In conclusion, MEG can reliably localize sources of spike discharges in patients with temporal and extratemporal lobe epilepsy. MEG sometimes provides noninvasive localization data that are not otherwise available with MRI or conventional scalp ictal EEG.     

Preoperative EEG in medically intractable epilepsy

The aim of the preoperative neurophysiological investigations is to identify the primary epileptogenic focus and its relation to functional cortical areas. The investigations include interictal and ictal extracranial (scalp) electroencephalography (EEG) and invasive methods (depth, subdural, foramen ovale electrodes and peroperative electrocorticography). If an epileptic focus is located in the anterior part of the temporal lobe by the use of scalp EEG, this is normally regarded as sufficient for an anterior lobectomy. However, because of poor spatial resolution by scalp EEG, it is difficult to separate mesial from lateral foci, identify the exact extent of posterior temporal or extra-temporal foci, identify the primary focus in patients with bilateral abnormalities and identify cases with minor scalp EEG-changes. As invasive EEG shows higher spatial resolution and gives an opportunity to evaluate functional areas, invasive EEG has significant advantages in these patients. Use of invasive EEG bears a slightly increased risk and discomfort to the patient, but is necessary in the presurgical evaluation of some patients suffering from medically intractable epilepsy.     

Long-term follow-up after temporal lobe resection for lesions associated with chronic seizures

A follow-up study was conducted on 60 patients who had standard en bloc anterior temporal lobe resection, including mesiotemporal structures, as treatment for temporal lobe lesions associated with chronic, medically intractable seizures. Lesions were identified as glial tumors, hamartomas, or vascular malformations. Long-term outcome was assessed in terms of seizure frequency and certain psychosocial sequelae. Seizure onset occurred at an average age of 15 years (median = 13.5 years), and patients experienced seizures for an average of 13 years prior to surgery. The mean time of follow-up was 8.4 years postsurgery (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure-free rate of 80%. Late seizure recurrence was documented for three patients; two had been seizure-free for 10 years and one for 15 years after surgery, before re-onset of seizures in the absence of tumor recurrence. A prolonged history of seizures prior to surgery was associated with a poorer seizure outcome (p = 0.06), suggesting that secondary epileptogenesis at sites distant to the lesion may develop with years of uncontrolled seizures. There was a low tumor recurrence rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67% working or engaged in educational studies, and improvement noted in 59% of cases for one or more of the psychosocial factors investigated. This study confirms that anterior temporal lobe resection for temporal lesions associated with chronic seizures is a successful treatment with a high seizure-free rate following surgery and good psychosocial outcome.     

Bilateral neuropathologic changes in a child with hemimegalencephaly

Evaluation of a 7-month-old girl with developmental delay and intractable seizures revealed hemispheric asymmetry and an enlarged right cerebral hemisphere. Because of a history of seizures refractory to medical therapy, she was admitted for right hemispherectomy, but died of complications of surgery. Postmortem brain examination revealed asymmetric enlargement of the right cerebral hemisphere but no gross abnormalities in the left hemisphere. Microscopic examination demonstrated bilateral neuropathologic changes consistent with severe cortical dysplasia in the right cerebral hemisphere and mild cortical dysplasia in the left. Although white matter abnormalities in the unaffected hemisphere have been reported in hemimegalencephaly, bilateral cortical abnormalities, not reported previously in patients with hemimegalencephaly, may account for the varied clinical outcome with medical therapy or after hemispherectomy.     

A case of intractable temporal lobe epilepsy: discrepancy between epileptogenic area and structural lesion demonstrated by subdural recording

We reported a 25-year-old man with intractable right temporal lobe epilepsy in whom subdural recording successfully delineated the epileptogenic area in the right anterior mesial to basal temporal region in spite of the presence of a postoperative lesion in the right posterior temporal region. The patient underwent right posterior temporal resection due to ependymoma at the age of 8 years. Since age 19, he had suffered from medically intractable psychomotor seizures. Ictal scalp-recorded EEG suggested an epileptogenic area at the right temporal area, but it could not specifically demarcate the site because of bone deficits from the previous surgery. Ictal SPECT showed a hyperactive area in the right anterior temporal area, which was inconsistent with the MRI finding. In case of partial epilepsy associated with structural lesion like in the present case, if results of various non-invasive studies are discrepant as to the epileptogenic area, invasive studies using, for example, subdural EEG monitoring is necessary to determine the responsible area.     

Ictal cerebral blood flow in seizures originating in the posterolateral cortex

In selecting patients for epilepsy surgery, it is important to distinguish mesial temporal seizures from seizures originating in the posterolateral cortex. We studied ictal cerebral perfusion in five patients with complex partial seizures with clear posterior EEG ictal onsets and clinical seizures semiology suggesting seizure origin in the posterolateral cortex. METHODS: Ictal SPECT was performed during video EEG monitoring using 99mTc-HMPAO as a cerebral perfusion tracer and a rotating gamma camera to acquire images. RESULTS: Three patterns of ictal hyperperfusion were seen: pattern A = temporoparieto-occipital junction extending into the lateral temporal cortex, involving the mesial temporal cortex and basal ganglia to a lesser degree and a small area of hyperperfusion in the contralateral parietal cortex (two patients); pattern B = pattern A but with no hyperperfusion of the mesial temporal cortex (one patient); and pattern C = localized hyperperfusion in the area of the temporoparieto-occipital junction (two patients). CONCLUSION: Our results suggest distinct patterns of ictal perfusion in seizures with posterolateral ictal EEG onsets. Ictal SPECT may be useful in distinguishing such seizures.     

Microdysgenesis in mesial temporal lobe epilepsy: a clinicopathological study

The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre-existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty-four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed.