Memory changes in patients with hippocampal sclerosis submitted to surgery to treat mesial temporal lobe epilepsy.

PURPOSE: This study was performed with the purpose of analysing the relationship between epileptological and surgical variables and post-operative memory performance, following surgery for refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). METHODS: Logical memory (LM) and visual memory (VM) scores for immediate and late follow-up of 201 patients operated for MTLE/HS were reviewed. Scores were standardized with a control group of 54 healthy individuals matched for age and education. The Reliable Change Index (RCI) was calculated to verify individual memory changes for late LM and VM scores. A multiple linear regression analysis was carried out with the RCI, using LM and VM scores as well as the clinical variables. RESULTS: A total of 112 (56%) patients had right HS. The RCI of the right HS group demonstrated that 6 (7%) patients showed improvement while 5 (6%) patients showed decreased scores in late LM; for late VM, 7 (8%) patients presented improvement, and 2 (3%) patients showed poorer scores. RCI of the left HS group showed that 3 (3%) individuals showed improved scores, while scores of 5 (4%) patients worsened for late LM; for late VM, 3 (3%) patients presented higher scores and 6 (5%) showed lower scores. Left HS and advanced age at onset of the first epileptic seizure were predictors of late LM loss (p<.05). CONCLUSION: Left MTLE/HS and seizure onset at advanced ages were predictive factors for the worsening of late LM. We observed poorer baseline LM function in the left HS group and improvement of LM in some patients who had resection of the right MTL. Patients in the right HS group showed a higher percentage of reliable post-operative improvement for both VM and LM scores.

Canonical decomposition of ictal scalp EEG reliably detects the seizure onset zone.

Long-term electroencephalographic (EEG) recordings are important in the presurgical evaluation of refractory partial epilepsy for the delineation of the irritative and ictal onset zones. In this paper we introduce a new algorithm for an automatic, fast and objective localizing of the ictal onset zone in ictal EEG recordings. We extracted the potential distribution of the ictal activity from EEG using the higher order canonical decomposition method, also referred to as the CP model. The CP model decomposes in a unique way a higher order tensor in a minimal sum of rank-1 'atoms'. We showed that only one atom is related to the seizure activity. Simulation experiments demonstrated that the method correctly extracted the potential distribution of the ictal activity even with low signal-to-noise ratios. In 37 ictal EEGs, the CP method correctly localized the seizure onset zone in 34 (92%) and visual assessment in 21 cases (57%) (p=0.00024). The CP method is a fast method to delineate the ictal onset zone in ictal EEGs and is more sensitive than visual interpretation of the ictal EEGs.

Correlations of interictal FDG-PET metabolism and ictal SPECT perfusion changes in human temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: The pathophysiological role of the extensive interictal cerebral hypometabolism in complex partial seizures (CPS) in refractory mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) is poorly understood. Our aim was to study ictal-interictal SPECT perfusion versus interictal fluorodeoxyglucose (FDG)-PET metabolic patterns. METHODS: Eleven adults with refractory unilateral mTLE-HS, who were rendered seizure free after epilepsy surgery, were included. All had an interictal FDG-PET and an interictal and ictal perfusion SPECT scan. FDG-PET data were reconstructed using an anatomy-based reconstruction algorithm, which corrected for partial volume effects, and analyzed semi-quantitatively after normalization to white matter activity. Using Statistical Parametric Mapping (SPM), we compared interictal metabolism of the patient group with a control group. We correlated metabolic with ictal perfusion changes in the patient group. RESULTS: Global cerebral grey matter glucose metabolism in patients was decreased 10-25% compared with control subjects. Interictal PET hypometabolism and ictal SPECT hypoperfusion were maximal in the ipsilateral frontal lobe. Ictal frontal lobe hypoperfusion was associated with crossed cerebellar diaschisis. The ipsilateral temporal lobe showed maximal ictal hyperperfusion and interictal hypometabolism, which was relatively mild compared with the degree of hypometabolism affecting the frontal lobes. CONCLUSION: Interictal hypometabolism in mTLE-HS was greatest in the ipsilateral frontal lobe and represented a seizure-related dynamic process in view of further ictal decreases. Crossed cerebellar diaschisis suggested that there is a strong ipsilateral frontal lobe inhibition during CPS. We speculate that surround inhibition in the frontal lobe is a dynamic defense mechanism against seizure propagation, and may be responsible for functional deficits observed in mTLE.

Terminology and classification of the cortical dysplasias.

BACKGROUND: There have been difficulties in achieving a uniform terminology in the literature regarding issues of classification with respect to focal cortical dysplasias (FCDs) associated with epilepsy. OBJECTIVE: S: To review and refine the current terminology and classification issues of potential clinical relevance to epileptologists, neuroradiologists, and neuropathologists dealing with FCD. METHODS: A panel discussion of epileptologists, neuropathologists, and neuroradiologists with special expertise in FCD was held. RESULTS: The panel proposed 1) a specific terminology for the different types of abnormal cells encountered in the cerebral cortex of patients with FCD; 2) a reappraisal of the different histopathologic abnormalities usually subsumed under the term "microdysgenesis," and suggested that this terminology be abandoned; and 3) a more detailed yet straightforward classification of the various histopathologic features that usually are included under the heterogeneous term of "focal cortical dysplasia." CONCLUSION: The panel hopes that these proposals will stimulate the debate toward more specific clinical, imaging, histopathologic, and prognostic correlations in patients with FCD associated with epilepsy.

Resection of the lesion in patients with hypothalamic hamartomas and catastrophic epilepsy.

BACKGROUND: Patients with hypothalamic hamartomas (HH) often have severe refractory epilepsy, incapacitating behavioral abnormalities, and cognitive decline. Attempts to control the seizure disorder by resection of apparently epileptogenic mesial temporal or other cortical structures have failed consistently. OBJECTIVE: To report a series of 13 patients in whom the hamartoma itself was resected. METHODS: All patients underwent preoperative evaluation between ages 2 and 33 years and had subtotal or complete resection of the hamartoma. Follow-up ranged from 1 to 5.5 years (mean: 2.8 y). RESULTS: Preoperatively, all patients had variable combinations of gelastic, complex partial, and generalized seizures. Eight had drop attacks. In addition, all had marked behavior abnormalities and cognitive impairment. Postoperatively, two patients are completely seizure-free and 11 are either seizure-free or have achieved a greater than 90% reduction of drop attacks and generalized tonic-clonic seizures. However, minor gelastic, complex partial, and atypical absence seizures have persisted in 11 patients, although at significantly reduced rates. In addition, there has been a dramatic improvement in behavior and cognition. Three patients had an anterior thalamic and one a capsular infarct, which left only minimal long-term deficits. Exact location of the lesion in relation to the interpeduncular fossa and the walls of the third ventricle correlated with extent of excision, seizure control, and complication rate. CONCLUSION: Resection can alleviate both the seizures and the behavioral and cognitive abnormalities of hypothalamic hamartomas, but complications are frequent.

Surgical resection for intractable epilepsy in "double cortex" syndrome yields inadequate results.

PURPOSE: To analyze the results of surgical treatment of intractable epilepsy in patients with subcortical band heterotopia, or double cortex syndrome, a diffuse neuronal migration disorder. METHODS: We studied eight patients (five women) with double cortex syndrome and intractable epilepsy. All had a comprehensive presurgical evaluation including prolonged video-EEG recordings and magnetic resonance imaging (MRI). RESULTS: All patients had partial seizures, with secondary generalization in six of them. Neurologic examination was normal in all. Three were of normal intelligence, and five were mildly retarded. Six patients underwent invasive EEG recordings, three of them with subdural grids and three with stereotactic implanted depth electrodes (SEEG). Although EEG recordings showed multilobar epileptic abnormalities in most patients, regional or focal seizure onset was recorded in all. MRI showed bilateral subcortical band heterotopia, asymmetric in thickness in three. An additional area of cortical thickening in the left frontal lobe was found in one patient. Surgical procedures included multiple subpial transections in two patients, frontal lesionectomy in one, temporal lobectomy with amygdalohippocampectomy in five, and an additional anterior callosotomy in one. Five patients had no significant improvement, two had some improvement, and one was greatly improved. CONCLUSION: Our results do not support focal surgical removal of epileptogenic tissue in patients with double cortex syndrome, even in the presence of a relatively localized epileptogenic area.

Disorders of cortical development.

It is only a decade since the realization (facilitated by magnetic resonance imaging) in early 1990s that disorders of cortical development occupy an important place in the aetiologic categorization of epilepsy. Since then research has demonstrated the intrinsic epileptogenicity of disorders of cortical development, their genetic bases and their functional properties. Some of the key points of this most exciting medical and scientific enterprise are reviewed here, with an emphasis in the advances seen within the past 2 years.

Medical and surgical strategies for epilepsy care in developing countries.

Epilepsy is a major health problem, and there is hope that current international initiatives--epitomized in the "Epilepsy: Out of the Shadows" campaign--will increase the commitment of the general public and health officials to the care of patients. Particularly in developing countries, there is great need for alleviation of the extremely difficult situation of people with epilepsy and their families. Doctors can play their part by adhering to specific medical and surgical strategies aimed at the improvement of epilepsy care in these countries. Included in the former are joining efforts to guarantee a regular distribution of conventional antiepileptic drugs (AEDs), make optimal use of the more easily available AEDs, and improve communication with patients and families at all levels. It is also important to support the creation of local and regional specialized epilepsy centers with the capability to perform presurgical evaluation and epilepsy surgery in many patients with medically refractory seizures. The establishment of such centers in developing countries will face several challenges, including a critical view of technological advances and the need to support well-trained, creative people who can evaluate and operate on patients with relatively limited resources. This article proposes that the success of such an approach depends on the progressive build-up of a "critical mass" of specialized people who are trained locally to select or reject epilepsy patients for surgery using the available resources. A stepwise approach to the increasing levels of complexity involved in the evaluation and surgical treatment is proposed, with the expectation that each center will find its level and adhere to its capability.

Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment.

Two familial X-linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X-linked transmission. On the other hand, the pedigrees of 2 families ruled out X-linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X-linked syndrome of cortical maldevelopment.

[Neuropathology of hard to control epilepsy. Study of 300 consecutive cases]. / Neuropatologia das epilepsias de difícil controle. Estudo de 300 casos consecutivos.

We report histopathological findings in 300 consecutive surgical specimens from epilepsy surgery during 6 years. Our material was mainly from temporal lobe epilepsy (70.33%). In 44% the diagnosis was hippocampal sclerosis. There were tumors in 15% of cases and neuronal migration disorders in 10%. The most common tumors were gangliogliomas (42.22%) and dysembryoplastic neuroepithelial tumors (20%). We review the more frequent diagnosis in epilepsy surgery based on this series and comparing with literature.

Localization of the epileptogenic zone by ictal and interictal SPECT with 99mTc-ethyl cysteinate dimer in patients with medically refractory epilepsy.

PURPOSE: To evaluate the accuracy, feasibility and clinical value of both ictal and interictal 99mTc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients with medically refractory epilepsy. METHODS: The study included 75 consecutive patients, 48 with temporal lobe epilepsy (TLE group), and 27 with extratemporal epilepsy (ExT group). The accuracy of SPECT was analyzed considering the final diagnosis reached by convergence of clinical, electrophysiologic, structural, pathologic and outcome data. RESULTS: Ictal SPECT correctly identified the epileptogenic zone in 21 (91.3%) of 23 patients, whereas interictal SPECTs could correctly identify the epileptogenic zone in only 41 (62.1%) of 66 patients (chi2 = 5.56, df = 1, p < 0.05). Results were similar when the two study groups were analyzed separately. Moreover, ictal studies had significantly higher specificity (91.3 vs. 60.6%) and positive predictive value (91.3 vs. 66.2%) than interictal studies for the whole series of patients. Considering all tools used in the preoperative workup of these patients, ictal SPECT significantly contributed to the final topographic diagnosis in seven of 14 patients from TLE group and in six of nine patients from the ExT group. In these patients, ictal SPECT either obviated the need for invasive EEG or helped to define where to concentrate the efforts of invasive investigation. CONCLUSIONS: These data demonstrate that ictal SPECT can be easily achieved by using 99mTc-ECD and can accurately localize the epileptogenic zone in both temporal and extratemporal epilepsies. Ictal ECD SPECT proved to be significantly more sensitive and specific than interictal ECD SPECT, and clinically useful in the definition of the epileptogenic zone.

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.

Cortical dysplasia: an immunocytochemical study of three patients.

Human cortical dysplastic lesions are frequently associated with severe partial epilepsies. We report an immunocytochemical investigation on cortical tissue from three surgically treated patients, 20, 38, and 14 years old, with intractable epilepsy due to cortical dysplasia. The studies were performed using antibodies recognizing cytoskeletal proteins, calcium-binding proteins, and some subunits of glutamate receptors. The specimens from the three patients displayed common features: (1) focal cytoarchitectural abnormalities with an increased number of giant pyramidal neurons through all cortical layers except layer I; (2) large, round-shaped balloon cells mainly concentrated in the deepest part of the cortex and in the white matter; (3) a decrease of calcium binding protein immunopositive gamma-aminobutyric acid (GABA)ergic neurons; and (4) abnormal baskets of parvalbumin-positive terminals around the excitatory (pyramidal and large, round-shaped) neurons. These data provide evidence that the epileptogenicity in these types of cortical dysplasia is due to an increase in excitatory neurons coupled with a decrease in GABAergic interneurons.

Vigabatrin in refractory childhood epilepsy. The Brazilian Multicenter Study.

Children, 47, with various types of severe drug-resistant epilepsy were entered into a prospective, add-on, open trial with vigabatrin. Patients with West syndrome and idiopathic generalized epilepsies were excluded. Seven children had the drug withdrawn, five because of increase in seizure frequency and two because of adverse effects. Drug efficacy, measured according to seizure type, showed a 100% decrease in seizure frequency in 18.6% of partial seizures and 17.3% of the generalized seizures. There was a higher than 50% decrease in 39.5% of partial and 60.8% of generalized seizures, and less than 50% decrease or increase in seizure frequency in 41.8% and 21.8% of partial and generalized seizures, respectively. Vigabatrin mean dosage during phase 3 was 63.6 mg/kg per day (S.D. = 30.5), ranging from 19.3 to 110.5 mg/kg per day. Parametric statistical analysis (Student's t-test) of seizure frequency between phases 1 and 3 showed a significant decrease in seizure frequency for partial (P = 0.022), and generalized seizures (P < 0.0001). Drug-related adverse effects were observed in 18/47 cases (38.3%), consisting mainly of irritability, hyperactivity, dizziness, somnolence and gastrointestinal symptoms.

Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy.

We examined the significance and frequency of occurrence of rhythmic epileptiform discharges (REDs) on the scalp EEGs of 74 patients with intractable partial epilepsy. We also analyzed the relationship of this abnormality to the continuous epileptiform discharges (CEDs) recorded on ECoG. Both REDs and CEDs had been found to be highly specific and sensitive indicators of focal cortical dysplastic lesions. Thirty-four patients (group I) had focal cortical dysplastic lesions (FCDLs) and 40 (group II) had non-dysplastic structural lesions. REDs were observed in 15 (44%) of the 34 patients of group I and in none of group II. REDs did not occur in isolation, were associated with more intermittent interictal spikes involving other regions, but had a greater (P < 0.05) significance for the localization of the epileptogenic area. A strong relationship was observed between the presence of REDs on scalp EEG and the occurrence of CEDs on ECoG recordings. Twelve (80%) of 15 patients with REDs had CEDs. Focal cortical dysplastic lesions are likely to be present when rhythmic epileptiform discharges are found.

Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results.

Cortical dysplastic lesions (CDyLs) are often associated with severe partial epilepsies. We describe the electrographic counterpart of this high degree of epileptogenicity, manifested by continuous or frequent rhythmic epileptogenic discharges recorded directly from CDyLs during intraoperative electrocorticography (ECoG). These ictal or continuous epileptogenic discharges (I/CEDs) assumed one of the following three patterns: (1) repetitive electrographic seizures, (2) repetitive bursting discharges, or (3) continuous or quasicontinuous rhythmic spiking. One or more of these patterns were present in 23 of 34 patients (67%) with intractable partial epilepsy associated with CDyLs, and in only 1 of 40 patients (2.5%) with intractable partial epilepsy associated with other types of structural lesions. I/CEDs were usually spatially restricted, thus contrasting with the more widespread interictal ECoG epileptic activity, and tended to colocalize with the magnetic resonance imaging-defined lesion. Completeness of excision of cortical tissue displaying I/CEDs correlated positively with surgical outcome in patients with medically intractable seizures; i.e., three-fourths of the patients in whom it was entirely excised had favorable surgical outcome; in contrast, uniformly poor outcome was observed in those patients in whom areas containing I/CEDs remained in situ. We conclude that CDyLs are highly and intrinsically epileptogenic, and that intraoperative ECoG identification of this intrinsically epileptogenic dysplastic cortical tissue is crucial to decide the extent of excision for best seizure control.

Prenatal events and genetic factors in epileptic patients with neuronal migration disorders.

Because disorders of neuronal migration to cerebral cortex in humans are believed to occur in the first half of gestation, prenatal events or genetic factors are suspected to have a pathogenetic role. We evaluated this by comparing the frequency of potentially harmful prenatal events and of genetic factors in a series of 40 patients (38 with epilepsy) with neuronal migration disorders (NMD) and in 40 epileptic controls, using a predetermined standardized questionnaire to minimize interviewer bias. Potentially harmful prenatal events (significant maternal physical trauma, ingestion of medications, exposure to roentgenograms, infections, uterine or metabolic abnormalities) were reported in the pregnancy histories of 58% of patients with NMD but in only 15% of epileptic controls (p = 0.0002). In contrast, peri- and postnatal potentially relevant etiologic factors were reported in the histories of only 22% of patients with NMD but in 50% of the epileptic controls (p = 0.01). Genetic factors (a family history of epilepsy, mental retardation, or congenital malformations of the CNS) were noted in 13 and 20% of the families, respectively. Stillbirths occurred only in the group with NMD, accounting for 3.06% of sibling pregnancies. The findings suggest that prenatal potentially harmful environmental events play a central role in the pathogenesis of NMD in humans.