Balloon cells associated with granule cell dispersion in the dentate gyrus in hippocampal sclerosis

Granule cell dispersion (GCD) is a common finding in hippocampal sclerosis in patients with intractable focal epilepsy. It is considered to be an acquired, post-developmental rather than a pre-existing abnormality, involving dispersion of either mature or newborn neurones, but the precise factors regulating it and its relationship to seizures are unknown. We present two cases of GCD with associated CD34-immunopositive balloon cells, a cell phenotype associated with focal cortical dysplasia type IIB, considered to be a developmental cortical lesion promoting epilepsy. This observation opens up the debate regarding the origin of balloon cells and CD34 expression and their temporal relationship to seizures.     

Clinical characteristics of 92 patients with temporal lobe focal cortical dysplasia identified by pathological examination

Focal cortical dysplasia (FCD) is frequently associated with focal epilepsy, and a broad spectrum of histopathology is included in the diagnosis of FCD. In 2011, an International League Against Epilepsy (ILAE) task force proposed an international consensus for a classification system to better characterise specific clinicopathological FCD entities. The clinical characteristics of patients with FCD should be confirmed according to the new ILAE classification. We retrospectively analysed 92 patients who had undergone surgical treatment for temporal lobe epilepsy and received a pathological diagnosis of FCD. The pathological sections were re-examined and diagnosed according to the 2011 ILAE classification. The clinical data from patients with different FCD subtypes were evaluated, including a detailed history regarding spontaneous abortions, trauma, ischaemic injury, encephalitis, and febrile seizures at an early age. The age of epilepsy onset, duration of epilepsy, age at surgery, seizure frequency, history of febrile seizures, and seizure type, particularly whether the seizures were secondarily generalised tonic-clonic seizures, were recorded. Clinical differences were found in the patients with temporal lobe FCD. The associated FCD subtypes have unique clinical characteristics, including a later age of epilepsy onset and a shorter duration of epilepsy, especially in FCD Type IIIc; and a high susceptibility to febrile seizures was observed in FCD Type IIIa.     

Epilepsy in neurofibromatosis type 1

ObjectivesTo describe the characteristics of epilepsy in patients with Neurofibromatosis type 1 (NF1).MethodsAnalysis of a cohort of consecutive NF1 patients seen in our NF1 clinic during a three-year period.ResultsOf the 184 NF1 patients seen during that period, 26 had epilepsy and three had febrile seizures. Of the 26, 17 (65%) had localization-related epilepsy, seven of whom (41%) were drug resistant. Six (23%) had apparently primary generalized epilepsy (0/6 drug resistant), two (8%) Lennox-Gastaut syndrome, and one (4%) West syndrome (all three were drug-resistant). As compared to the patients with no epilepsy, those with epilepsy were more likely to have MRI findings of mesial temporal sclerosis (MTS) (23% vs. 5%, p = 0.0064), and cerebral hemisphere tumors (31% vs. 10%, p = 0.0079), but not of the other MRI findings including neurofibromatosis bright objects, or optic gliomas. Three of the six patients with MTS underwent temporal lobectomy with subsequent control of their seizures with confirmation of MTS on pathology in 3/3 and presence of coexisting focal cortical dysplasia (FCD) in 2/3. We also have observed three additional patients outside the above study with the association of NF1, MTS, and intractable epilepsy.SignificanceEpilepsy is relatively common in NF1, often occurs in patients with brain tumors or with MTS which can coexist with FCD, can be associated with multiple types of epilepsy syndromes, and when localization-related is often drug-resistant. Patients with NF1 and MTS can respond to medial temporal lobectomy and may have coexisting medial temporal lobe cortical dysplasia.     

Tuberous sclerosis complex coexistent with hippocampal sclerosis

Tuberous sclerosis and hippocampal sclerosis are both well-defined entities associated with medically intractable epilepsy. To our knowledge, there has been only one prior case of these two pathologies being co-existent. We report a 7-month-old boy who presented with intractable seizures at 2 months of age. MRI studies showed diffuse volume loss in the brain with bilateral, multiple cortical tubers and subcortical migration abnormalities. Subependymal nodules were noted without subependymal giant cell astrocytoma. Genetic testing revealed TSC2 and PRD gene deletions. Histopathology of the hippocampus showed CA1 sclerosis marked by loss of neurons in the CA1 region. Sections from the temporal, parietal and occipital lobes showed multiple cortical tubers characterized by cortical architectural disorganization, gliosis, calcifications and increased number of large balloon cells. Focal white matter balloon cells and spongiform changes were also present. The patient underwent resection of the right fronto-parietal lobe and a subsequent resection of the right temporal, parietal and occipital lobes. The patient is free of seizures on anti-epileptic medication 69 months after surgery. Although hippocampal sclerosis is well documented to be associated with coexistent focal cortical dysplasia, the specific co-existence of cortical tubers and hippocampal sclerosis appears to be rare.     

Morphometric MRI alterations and postoperative seizure control in refractory temporal lobe epilepsy

Refractory mesial temporal lobe epilepsy (mTLE) is a debilitating condition potentially amenable to resective surgery. However, between 40 and 50% patients continue to experience postoperative seizures. The development of imaging prognostic markers of postoperative seizure outcome is a crucial objective for epilepsy research. In the present study, we performed analyses of preoperative cortical thickness and subcortical surface shape on MRI in 115 of patients with mTLE and radiologically defined hippocampal sclerosis being considered for surgery, and 80 healthy controls. Patients with excellent (International League Against Epilepsy outcome (ILAE) I) and suboptimal (ILAE II–VI) postoperative outcomes had a comparable distribution of preoperative atrophy across the cortex, basal ganglia, and amygdala. Conventional volumetry of whole hippocampal and extrahippocampal subcortical structures, and of global gray and white matter, could not differentiate between patient outcome groups. However, surface shape analysis revealed localized atrophy of the thalamus bilaterally and of the posterior/lateral hippocampus contralateral to intended resection in patients with persistent postoperative seizures relative to those rendered seizure free. Data uncorrected for multiple comparisons also revealed focal atrophy of the ipsilateral hippocampus posterior to the margins of resection in patients with persistent seizures. This data indicates that persistent postoperative seizures after temporal lobe surgery are related to localized preoperative shape alterations of the thalamus bilaterally and the hippocampus contralateral to intended resection. Imaging techniques that have the potential to unlock prognostic markers of postoperative outcome in individual patients should focus assessment on a bihemispheric thalamohippocampal network in prospective patients with refractory mTLE being considered for temporal lobe surgery. Hum Brain Mapp 36:1637–1647, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Epilepsy surgery outcome in coexisting symptomatic refractory focal epilepsy and benign focal epilepsy of childhood

Epilepsy surgery may successfully treat refractory symptomatic focal epilepsy in patients with coexisting benign focal epileptiform discharges. Reported here is the outcome after resective epilepsy surgery in three children with pharmacoresistant lesional focal epilepsy in whom seizures of benign focal epilepsy of childhood had been recorded. Two patients had left temporal epilepsy due to a malformation of cortical development; one of these had dual pathology, with additional ipsilateral hippocampal sclerosis. One child had catastrophic left hemispheric epilepsy due to left hemimegalencephaly. Frequent, habitual seizures of symptomatic epilepsy resolved after surgery (follow-up duration, 32-55 months); however, rare benign focal seizures of childhood have continued. These cases demonstrate that lesional pharmacoresistant focal epilepsy can be successfully treated with resective epilepsy surgery even when coexisting with benign focal epilepsy of childhood. During postoperative follow-up, careful documentation of breakthrough seizures due to benign focal epilepsy of childhood is important, so that these patients are not labeled as surgical failures.     

Assessment and surgical outcomes for mild type I and severe type II cortical dysplasia: A critical review and the UCLA experience

Recent findings on the clinical, electroencephalography (EEG), neuroimaging, and surgical outcomes are reviewed comparing patients with Palmini type I (mild) and type II (severe) cortical dysplasia. Resources include peer-reviewed studies on surgically treated patients and a subanalysis of the 2004 International League Against Epilepsy (ILAE) Survey of Pediatric Epilepsy Surgery. These sources were supplemented with data from University of California, Los Angeles (UCLA). Cortical dysplasia is the most frequent histopathologic substrate in children, and the second most common etiology in adult epilepsy surgery patients. Cortical dysplasia patients present with seizures at an earlier age than other surgically treated etiologies, and 33–50% have nonlocalized scalp EEG and normal magnetic resonance imaging (MRI) scans. 2-(¹⁸F)Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is positive in 75–90% of cases. After complete resection, 80% of patients are seizure free compared with 20% with incomplete resections. Compared with type I, patients with type II cortical dysplasia present at younger ages, have higher seizure frequencies, and are extratemporal. Type I dysplasia is found more often in adult patients in the temporal lobe and is often MRI negative. These findings identify characteristics of patients with mild and severe cortical dysplasia that define surgically treated epilepsy syndromes. The authors discuss future challenges to identifying and treating medically refractory epilepsy patients with cortical dysplasia.     

Surgical treatment of epilepsy associated with cortical dysplasia: 2012 update

Cortical dysplasia is the most common etiology in children and the third most frequent finding in adults undergoing epilepsy neurosurgery. The new International League Against Epilepsy (ILAE) classification grades isolated cortical dysplasia into mild type I (cortical dyslamination), severe type II (dyslamination plus dysmorphic neurons and balloon cells), and dysplasia associated with other epileptogenic lesions (type III). Multilobar type II lesions present at an earlier age and with more severe epilepsy compared with focal type I abnormalities, often in the temporal lobe, and these findings are reflected in types and age of operations for cortical dysplasia. Presurgical evaluation of patients with epilepsy from cortical dysplasia can be challenging. Interictal and ictal scalp electroencephalography (EEG) accurately localizes cortical dysplasia with 50-66% accuracy. Structural magnetic resonance imaging (MRI) is negative in roughly 30% of cases, most often linked with mild type I cases. FDG-PET can be 80-90% accurate, but is not 100% sensitive. Chronic intracranial electrodes are used in about 50% of cases with cortical dysplasia, but often do not capture restricted ictal-onset zones. About 60% of patients with cortical dysplasia are seizure free after epilepsy neurosurgery, with much higher rates of becoming seizure free with complete (80%) compared with incomplete (20%) resections. The most common reason for incomplete resection is the risk of an unacceptable neurologic deficit. Future challenges include better tools in identifying subtle forms of type I cortical dysplasia, and development of adjunctive treatments from basic research for those undergoing incomplete resections.     

Outcomes of resective surgery in children and adolescents with focal lesional epilepsy: The experience of a tertiary epilepsy center

ObjectiveThis study aimed to investigate the efficacy of resective surgery in children with focal lesional epilepsy by evaluating the predictive value of pre- and postsurgical factors in terms of seizure freedom.MethodsThis study included 61 children aged between 2 and 18 years who were admitted to the pediatric video-EEG unit for presurgical workup. Each patient was evaluated with a detailed history, video-EEG, neuroimaging, and postsurgical outcomes according to Engel classification to predict postsurgical seizure freedom. All the possible factors including history, etiology, presurgical evaluation, surgical procedures, and postsurgical results were analyzed for their predictive value for postoperative seizure freedom.ResultsOf the 61 patients, 75% were diagnosed as having temporal lobe epilepsy (TLE), and 25% were diagnosed with extra-TLE. Two years after the surgery, 78.6% were seizure-free, of which 89% had TLE, and 50% had extra-TLE (p < 0.05). Patients were more likely to have a favorable outcome for seizure freedom if they had rare seizure frequency, focal EEG findings, and focal seizures; had a temporal epileptogenic zone; or had TLE and hippocampal sclerosis. On the other hand, patients were more likely to have unfavorable results for seizure freedom if they had younger age of seizure onset, frequent seizures before the surgery, a frontal or multilobar epileptogenic zone, secondarily generalized seizures, extra-TLE with frontal lobe surgery, or focal cortical dysplasia.SignificanceResective surgery is one of the most effective treatment methods in children with intractable epilepsy. A history of young age of seizure onset, frequent seizures before surgery, secondarily generalized seizures, a multilobar epileptogenic zone, frontal lobe surgery, and focal cortical dysplasia (FCD) are the most important predictive factors indicating that a patient would continue having seizures after surgery. On the other hand, focal seizure semiologies, temporal lobe localization, and hippocampal sclerosis indicate that a patient would have better results in terms of seizure freedom.     

Dual pathology in a patient with temporal lobe epilepsy associated with neocortical glial scar after brain abscess and end folium sclerosis/hippocampal sclerosis type 3

End folium sclerosis or hippocampal sclerosis (HS) type 3 is often associated with another coexisting epileptogenic lesion (dual pathology); however, the pathogenesis of HS type 3 remains elusive. A 46‐year‐old man presented with medically intractable focal aware seizures and focal impaired awareness seizures (FIAS) with occasional focal to bilateral tonic–clonic seizures (FBTCS) two years after surgical treatment with extensive cranial reconstruction for a brain abscess in the right temporal lobe associated with intracranial extension of ipsilateral cholesteatoma. Head magnetic resonance imaging (MRI) at age 49 revealed atrophy of the right cerebral hemisphere including the hippocampus and amygdala. The patient's first epilepsy surgery was a lateral temporal lobectomy, in which the mesial temporal structures were preserved because no epileptiform discharge was detected on the intraoperative electrocorticogram. However, FIAS with FBTCS started 15 months after the operation. The second surgery, amygdalohippocampectomy, at age 52, resulted in the patient being seizure‐free again for one year before seizures of the right lateral temporal origin recurred. He underwent a third surgery, resection of the Heschl's and supramarginal gyri, at age 53, but he continued to have drug‐resistant epilepsy over two years after that. Histopathological examination revealed dual pathology consisting of glial scar in the lateral temporal lobe and ipsilateral HS type 3 with an unusually severe lesion in the subiculum. No significant inflammatory change was observed. The clinicopathological features in the present case indicate that HS developed secondarily in the context of neocortical epilepsy due to glial scar, suggesting a role of repetitive abnormal electrical input from neocortical epileptogenic lesions into the hippocampus finally via the perforant pathway in the pathogenesis of HS type 3. Severe hippocampal atrophy on preoperative MRI together with its silent electrocorticogram recording at initial epilepsy surgery may represent clinically pre‐epileptogenic HS in a seizure‐free “silent or latent period” before completion of hippocampal epileptogenesis to the extent that clinical epileptic seizures occur.     

Specific epileptic syndromes are rare even in tertiary epilepsy centers: a patient-oriented approach to epilepsy classification

PURPOSE: To assess the practicability and reliability of a five-dimensional patient-oriented epilepsy classification and to compare it with the International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The dimensions consist of the epileptogenic zone, semiologic seizure type(s), etiology, related medical conditions, and seizure frequency. METHODS: The 185 epilepsy patients (94 adults, 91 children, aged 18 years or younger) were randomly selected from the database of a tertiary epilepsy center and the general neurological department of a metropolitan hospital (28 adults). The charts were reviewed independently by two investigators and classified according to both the ILAE and the patient-oriented classification. Interrater reliability was assessed, and a final consensus among all investigators was established. RESULTS: Only four (4%) adults and 19 (21%) children were diagnosed with a specific epilepsy syndrome of the ILAE classification. All other patients were in unspecific categories. The patient-oriented classification revealed that 64 adults and 56 children had focal epilepsy. In an additional 34 adults and 45 children, the epileptogenic zone could be localized to a certain brain region, and in 14 adults and five children, the epileptogenic zone could be lateralized. Fourteen adults and 21 children had generalized epilepsy. In 16 adults and 14 children, it remained unclear whether the epilepsy was focal or generalized. Generalized simple motor seizures were found in 66 adults and 52 children, representing the most frequent seizure type. Etiology could be determined in 40 adults and 45 children. Hippocampal sclerosis was the most frequent etiology in adults (10%), and cortical dysplasia (9%), in children. Seven adults and 31 children had at least daily seizures. Seventeen adults and 26 children had rare or no seizures at their last documented contact. The most frequent related medical conditions were psychiatric disorders and mental retardation. Interrater agreement was high (kappa values of 0.8 to 0.9) for both the patient-oriented and the ILAE classification. CONCLUSIONS: Specific epilepsy syndromes included in the current ILAE classification are rare even in a tertiary epilepsy center. Most patients are included in unspecific categories that provide only incomplete information. In contrast, all of the patients could be classified by the five-dimensional patient-oriented classification, providing all essential information for the management of the patients with a high degree of interrater reliability.     

Predictors of outcome and pathological considerations in the surgical treatment of intractable epilepsy associated with temporal lobe lesions

OBJECTIVES: To evaluate the influence of clinical, investigative, and pathological factors on seizure remission after temporal lobectomy for medically intractable epilepsy associated with focal lesions other than hippocampal sclerosis. METHODS: From a series of 234 consecutive "en bloc" temporal resections for medically intractable epilepsy performed between 1976 and 1995, neuropathological examination disclosed a focal lesion in 80. The preoperative clinical, neuropsychological, interictal EEG, and neuroimaging characteristics of these patients were assembled in a computerised database. The original neuropathological material was re-examined for lesion classification and completeness of removal. The presence of additional cortical dysplasia and mesial temporal sclerosis was also noted. Survival analysis was performed using Kaplan-Meier curves and actuarial statistics. Logistic regression analysis was used to establish the independent significance of the clinical variables. RESULTS: The probability of achieving a 1 year seizure remission was 71% by 5 years of follow up. Factors predicting a poor outcome on multivariate analysis included the need for special schooling and a long duration of epilepsy. Generalised tonic-clonic seizures, interictal EEG discharges confined to the resected lobe, demonstration of the lesion preoperatively on CT, and complete histological resection of the lesion were not predictive of outcome. Neuropsychological tests correctly predicted outcome in left sided cases but apparently congruent findings in right sided resections were associated with a poor outcome. Pathological reclassification established the dysembryoplastic neuroepithelial tumour as the commonest neoplasm (87%) in this series, with a significantly better seizure outcome than for developmental lesions, such as focal cortical dysplasia. CONCLUSIONS: The findings highlight the importance of dysembryoplastic neuroepithelial tumour in the pathogenesis of medically refractory lesional temporal lobe epilepsy and the prognostic significance of preoperative duration of epilepsy emphasises the need for early recognition and surgical treatment. Cognitive and behavioural dysfunction, however, is associated with a lower seizure remission rate, independent of duration of epilepsy.     

Nodular heterotopia: a neuropathological study of 24 patients undergoing surgery for drug-resistant epilepsy

Purpose:   Despite the availability of detailed electroclinical and imaging data, only a few neuropathological studies of nodular heterotopia have been published. The aim of this study was to describe the neuropathological features of various types of nodular heterotopia obtained from patients undergoing surgery for intractable epilepsy.
Methods: Specimens of heterotopic nodules taken from 24 patients were neuropathologically investigated using routine and immunocytochemical procedures, and the data were compared with magnetic resonance imaging (MRI), electroclinical findings, and surgical outcomes.
Results: The neuropathological data distinguished two groups. Group 1 (14 patients, 78% in Engel class 1) had similar characteristics regardless of the size, number, or location of the nodules, with both projecting and local circuit neurons in the nodules intermingled with glial cells. Thirteen patients had focal cortical dysplasia. The nodules were identified by MRI in all cases. In group 2 (10 patients, 90% in Engel class 1), all of the nodules were within the temporal lobe and associated with hippocampal sclerosis or gangliogliomas. They were very small (undetected by MRI) and mainly formed by projecting neurons with no evidence of glial cells. All of the patients had cortical dysplasia.
Discussion: The distinctive neuropathological features of the nodules in the two groups suggest different etiopathogenetic mechanisms. In group 2, the presence of nodular formations in association with cortical dysplasia and either hippocampal sclerosis or ganglioglioma raises a question concerning so-called dual pathology in the temporal lobe.     

Migrating focal seizures during infancy: a case report and pathologic study

Migrating focal seizures in infancy are an unusual and often overlooked epilepsy syndrome, with onset before age 6 months, in which nearly continuous seizures involve multiple, independent areas of both hemispheres with an arrest of psychomotor development. We describe a patient with migrating focal seizures in infancy whose seizures began at age 45 days. The seizures were refractory to common antiepileptic drugs. At age 6 months, the infant received potassium bromide and became almost seizure-free. The infant developed severe neurologic impairment, with marked axial hypotonia and an absence of visual contact and head control. At age 8 months, the child suddenly died. Pathologic findings included multiple malformations of cortical development, polymicrogyria, and focal cortical dysplasia associated with hippocampal sclerosis.     

The clinical spectrum of focal cortical dysplasia and epilepsy

Focal cortical dysplasia is an important pathologic substrate in patients with epilepsy, but its clinical spectrum has not yet been completely defined. We retrospectively studied 30 epilepsy surgery patients with focal abnormalities of neuronal migration as the only histopathologic finding in resected tissue. Patients comprised two clinical groups. Seventeen patients with extratemporal epilepsy had early (median age, 7.0 years) extratemporal resection or hemispherectomy for severe epilepsy (47% of patients with > 10 partial seizures a day) that began in infancy or early childhood (median age, 1.0 year), usually in the setting of mental retardation or developmental delay (59% of patients), and often with magnetic resonance imaging (MRI) evidence of focal neuronal migration abnormality (44% of patients). In contrast, 13 patients with temporal lobe epilepsy were significantly older at age of seizure onset (median, 8.0 years; p = 0.001) and surgery (median, 22.0 years; p = 0.001), with less severe epilepsy (no patients with an average of > 10 seizures a day; p = 0.004), and without mental retardation or MRI evidence of neuronal migration abnormality (p = 0.001). In both groups, positron emission tomography (PET) was more sensitive than MRI and showed focal hypometabolism in seven patients with normal MRI. Seizure-free outcome tended to be more common after temporal lobectomy (77%) than after extratemporal resection or hemispherectomy (53%). Pathologic abnormalities were more severe in patients with extratemporal epilepsy than in patients with temporal lobe epilepsy. The clinical spectrum of focal cortical dysplasia included not only infants and children with severe extratemporal epilepsy and mental retardation, but also older patients with temporal lobe epilepsy and at least boderline IQ. Preoperative diagnosis may be difficult in cases with less severe pathologic abnormality, but high-resolution MRI and PET can increase the yield.     

Temporal lobe epilepsy due to hippocampal sclerosis in pediatric candidates for epilepsy surgery.

OBJECTIVE: To characterize the clinical, EEG, MRI, and histopathologic features and explore seizure outcome in pediatric candidates for epilepsy surgery who have temporal lobe epilepsy (TLE) caused by hippocampal sclerosis (HS). METHODS: The authors studied 17 children (4 to 12 years of age) and 17 adolescents (13 to 20 years of age) who had anteromesial temporal resection between 1990 and 1998. RESULTS: All patients had seizures characterized by decreased awareness and responsiveness. Automatisms were typically mild to moderate in children and moderate to marked in adolescents. Among adolescents, interictal spikes were almost exclusively unilateral anterior temporal, as opposed to children in whom anterior temporal spikes were associated with mid/posterior temporal, bilateral temporal, extratemporal, or generalized spikes in 60% of cases. MRI showed hippocampal sclerosis on the side of EEG seizure onset in all patients. Fifty-four percent of children and 56% of adolescents had significant asymmetry of total hippocampal volumes, whereas the remaining patients had only focal atrophy of the hippocampal head or body. Subtle MRI abnormalities of ipsilateral temporal neocortex were seen in all children and 60% of adolescents studied with FLAIR images. On histopathology, there was an unexpectedly high frequency of dual pathology with mild to moderate cortical dysplasia as well as HS, seen in 79% of children and adolescents. Seventy-eight percent of patients were free of seizures at follow-up (mean, 2.6 years). A tendency for lower seizure-free outcome was observed in patients with bilateral temporal interictal sharp waves or bilateral HS on MRI. The presence of dual pathology did not portend poor postsurgical outcome. CONCLUSIONS: TLE caused by HS similar to those in adults were seen in children as young as 4 years of age. Focal hippocampal atrophy seen on MRI often was not reflected in total hippocampal volumetry. Children may have an especially high frequency of dual pathology, with mild to moderate cortical dysplasia as well as HS, and MRI usually, but not always, predicts this finding. Postsurgical seizure outcome is similar to that in adult series.     

Coexistent arteriovenous malformation and hippocampal sclerosis

Cavernous angiomas or cavernomas have been occasionally described in patients presenting with medically intractable epilepsy. Reports of cavernomas associated with a second pathology potentially causative of seizures have rarely been documented; most commonly, the second pathology is focal cortical dysplasia or less frequently, hippocampal sclerosis. To our knowledge, cases of arteriovenous malformation arising in this clinical setting and associated with hippocampal sclerosis have not been previously described. We report a 56-year-old woman who initially presented at age 24 years with staring spells. Imaging studies revealed an arteriovenous malformation in the right parietal lobe. At age 51 years, she represented with signs and symptoms related to a hemorrhage from the malformation. The patient underwent Gamma Knife radiosurgery (Elekta AB, Stockholm, Sweden) of the lesion. She subsequently developed seizures, refractory to medical management. MRI studies showed atrophy in the right hippocampus. She underwent resection of the right parietal lobe and hippocampus. Histopathologic examination of the right parietal lesion revealed an arteriovenous malformation marked by focally prominent vascular sclerosis, calcification and adjacent hemosiderin deposition. The hippocampus was marked by prominent neuronal loss and gliosis in the CA1 region, consistent with CA1 sclerosis or hippocampal sclerosis International League Against Epilepsy type 2.     

Degree of hippocampal atrophy is not related to a history of febrile seizures in patients with proved hippocampal sclerosis

OBJECTIVES: To examine the degree of hippocampal atrophy in patients with temporal lobe epilepsy and proved hippocampal sclerosis to determine whether or not patients with febrile seizures have more severe hippocampal atrophy. To determine whether or not there is a relation between age of seizure onset, duration of temporal lobe epilepsy, or seizure frequency, and severity of hippocampal atrophy. METHODS: Hippocampal volumes were measured from volumetrically acquired MR images in 77 consecutive surgical patients with temporal lobe epilepsy (37 febrile seizures (FS)+, 40 FS-) with proved hippocampal sclerosis, and compared with 98 controls. RESULTS: Ipsilateral and contralateral hippocampal volumes were not significantly different between the FS+ and FS- groups. There was no difference in the age of onset of habitual seizures, duration of epilepsy, or age at the time of surgery, between these groups. No clinically significant correlations were found between hippocampal volumes and age of onset of first non-febrile seizure, duration of temporal lobe epilepsy, or complex partial and secondarily generalised seizure frequency, in patients with and without febrile seizures. CONCLUSIONS: Although febrile seizures was associated with hippocampal sclerosis in 48% of patients in this surgical series, the degree of MRI determined hippocampal atrophy was not related to a history of such seizures. The results do not support the view that febrile seizures cause more severe hippocampal sclerosis and are consistent with the hypothesis that hippocampal sclerosis is a pre-existing abnormality.     

Densities of parvalbumin-immunoreactive neurons in non-malformed hippocampal sclerosis-temporal neocortex and in cortical dysplasias

The changes in density of inhibitory parvalbumin-immunoreactive interneurons were quantitatively studied by immunohistochemistry in a series of human neocortical samples comprising the spectrum of malformations of cortical development (MCD) encountered in epilepsy surgery and the non-malformed hippocampal sclerosis-temporal neocortex in patients with refractory temporal lobe epilepsy. The highest relative density of parvalbumin-immunoreactive cells was obtained in the control samples (n = 21). The number of parvalbumin-immunoreactive neurons was significantly decreased in non-malformed hippocampal sclerosis-temporal neocortex (n = 73, 80.5% of control values). In a proportion of the latter samples as well as in two controls we observed patchy regions of absence of parvalbumin staining. The total counts of parvalbumin-immunoreactive cells in all the categories of MCD - "mild MCD" (n = 25), focal cortical dysplasia type I (n = 19) and type II (n = 15) - were decreased representing 72.4%, 55.0% and 12.2% of control values, respectively. Significantly different parvalbumin-immunoreactive cell densities were demonstrated between the focal cortical dysplasia types IIA and IIB. In "mild MCD", we observed a more pronounced decrease of parvalbumin-immunoreactive cells in the infragranular layers. No significant differences were revealed between the temporal and extratemporal examples of analogous MCD types. This study provides evidence for reduction of inhibitory parvalbumin-immunoreactive interneurons in the epileptic neocortex affected by MCD as well as in morphologically unaffected epileptic temporal neocortex, thus representing a possible mechanism for their epileptogenicity.     

Definición clínico-patológica de los subtipos de epilepsia temporal medial con esclerosis del hipocampo

Background and objective

Mesial temporal lobe epilepsy with hippocampal sclerosis is the most common cause of refractory epilepsy, and the most common indication for surgery. Although effective, surgery fails in up to 40% of patients. The objective of our study was to establish a correlation between the different histological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis and the prognosis, seizures control, side effects and anticonvulsivant drug withdrawal in patients with refractory epilepsy.