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.

The localizing value of auras in partial seizures: a prospective and retrospective study.

Doubts concerning the localizing significance of auras in partial seizures have recently been expressed. Prompted by this, we studied this issue by re-examining two groups of patients; the first, studied retrospectively, consisted of patients in whom the site of origin of the seizures was known beyond a reasonable doubt; the second, studied prospectively, comprised patients in whom specific auras were correlated with the localization of interictal epileptiform EEG abnormalities and the final diagnostic impression. The data from the retrospective series were suitable for rigorous statistical analysis. The two groups yielded similar results: the frequency of auras in partial seizures and the localizing significance of those for which large enough numbers could be collected was high. We conclude that the type of aura, when elicited by careful history-taking, provides as useful localizing, but often not lateralizing, information as the EEG and modern high-technology procedures such as CT, MRI, and PET.

Diffuse cortical dysplasia, or the 'double cortex' syndrome: the clinical and epileptic spectrum in 10 patients.

Diffuse neuronal migration disorders associated with epilepsy can now be recognized by modern neuroimaging techniques, particularly high-resolution MRI. We report 10 patients with a recently described MRI picture of continuous or generalized band heterotopia underlying the cortical mantle, giving the appearance of a "double cortex." They have epilepsy, and almost all have mental retardation. The epileptic disorder varies in nature and degree of severity. Patients may present with infantile spasms, a Lennox-Gastaut syndrome, or other forms of secondary generalized or multifocal epilepsy. Response to medical treatment is variable. Callosotomy may lead to considerable reduction of drop attacks, present in 60%. Mental retardation is usually mild or moderate, and only rarely severe. It correlates with the type of epileptic syndrome, and is greater in patients with more disorganized cortex overlying the heterotopia. Recognition of this entity by MRI is important for appropriate diagnosis of the epileptic disorder, planning of therapeutic strategy, and prognosis.

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.

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.

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.

Naltrexone blocks the enhancing effect of novel experiences on performance in memory tests in humans.

Two experiments were carried out in healthy human volunteers in order to investigate the effect of novel experiences on retrieval, and the influence of naltrexone thereupon. Naltrexone (50 mg) and placebo (50 mg of starch) were given orally using a double blind design. In Experiment 1, the subjects were asked, on two consecutive days, to recall well-known facts or events, and to recall the year in which major events took place. On Day 2, some subjects were, and others were not, exposed to a nonsense text prior to testing, which was viewed as a novel experience by the subjects. Exposure to the text was followed by enhanced scores in both memory tests. The effect was blocked by naltrexone, but not by the placebo, given 1 hr prior to the novel experience; the treatments had no effect of their own in subjects unexposed to the nonsense text. In Experiment 2, the memory tests were the recognition of famous faces, and the dates test (see above); and the novel experience was being taken for 5 min to a room where they had never been before. Again, the novel experience was followed by increased scores in both memory tests in the untreated and placebo groups, but not in the naltrexone treated subjects. These results confirm previous findings on memory enhancement by pre-test exposure to novel experiences, and suggest that endogenous opioid, or at least naltrexone-sensitive, mechanisms are involved in the effect.

Pre-training adrenaline recovers the amnestic effect of Met-enkephalin in demedullated rats.

The intracerebroventricular administration of 25 ng of Met-enkephalin causes retrograde amnesia for a shuttle avoidance task in intact rats. In demedullated rats, this effect of Met-enkephalin was lost. Intraperitoneal injection of 1.2 micrograms/kg adrenaline recovered the amnestic effect of Met-enkephalin. These results confirm the idea that the amnestic effect of Met-enkephalin is centrally mediated and that adrenal enkephalins do not seem to be important to the amnestic effect of Met-enkephalin since adrenaline recovers this effect in demedullated rats.

Intracerebroventricular administration of nanogram amounts of beta-endorphin and Met-enkephalin causes retrograde amnesia in rats.

The intracerebroventricular (icv) administration of 5.0 or 25.0 ng of beta-endorphin or Met-enkephalin causes retrograde amnesia for a shuttle avoidance task ion rats. In both cases, the higher dose was more effective than the lower one. The present results confirm previous similar findings obtained using systemic administrations of these compounds, and suggest that the amnestic effect of beta-endorphin and Met-enkephalin is mediated centrally.

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.

Neuronal migration disorders: a contribution of modern neuroimaging to the etiologic diagnosis of epilepsy.

Computed tomography and magnetic resonance imaging enable the identification of neuronal migration disorders during life. Several specific syndromes have been identified and early diagnosis of previously unrecognized entities is now possible. We report 51 patients with imaging. Thirty-two had a single widespread cortical dysplastic lesion. Twenty-eight had focal corticectomies. From a pathological standpoint, these encompassed focal cortical dysplasia (14 cases) and forme fruste of tuberous sclerosis (10 cases). These two groups of patients were indistinguishable from the clinical and radiological standpoint. In only two was the MRI examination normal. In addition, there were 10 with bilateral perisylvian dysplasia, four with diffuse cortical dysplasia or the "double cortex" syndrome, three with hemimegalencephaly, one with megalencephaly, and one with nodular neuronal heterotopia. The electroclinical and imaging findings led to the development of specific surgical strategies for the alleviation of the intractable seizures in each of these radiologically-defined syndromes.

[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.

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.

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.

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.

Pure amnestic seizures in temporal lobe epilepsy. Definition, clinical symptomatology and functional anatomical considerations.

Pure amnestic seizures (PAS) sometimes occur in patients with temporal lobe epilepsy. They never represent the only type of seizures in these patients. Pure amnestic seizures are defined as seizures during which the only clinical manifestation is the patients' inability to retain in memory what occurs during the seizure coupled with the preservation of other cognitive functions and the ability to interact normally with their physical and social environment. It is postulated that PAS result from selective ictal inactivation of mesial temporal (MT) structures without isocortical involvement. This occurs most often in patients with neuropsychological and electroencephalographic (EEG) evidence of bilateral dysfunction of MT structures (six out of eight patients in this study). In the few patients without such evidence as well as in some with bilateral MT dysfunction, PAS may result from seizure discharge limited to the MT structures of both temporal lobes. In the light of current anatomical knowledge, contralateral spread of seizure discharge from the MT structures of one side to those of the other through the dorsal hippocampal commissure is the only likely explanation for this situation. One observation with depth electrode stimulation of MT structures supports this view. In patients with evidence for bilateral MT dysfunction, a unilateral seizure may presumably suffice to induce a PAS, the contralateral MT structures being unable to ensure normal memory function. In most instances PAS can be distinguished from episodes of transient global amnesia on clinical grounds.