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Objective: This study was undertaken to analyze the histology underlying increased T2 signal intensity (iT2SI) in anterior temporal lobe white matter (aTLWM) epilepsy due to hippocampal sclerosis (TLE/HS)., Methods: Twenty-three patients were included: 16 with increased T2 signal in the aTLWM and seven with HS only. Magnetic resonance imaging (MRI) findings were consistent across two neuroradiologists (kappa = .89, p < .001). Quantification of neuronal cells, astrocytes, oligodendrocytes, and vacuolization in the white matter of temporal lobe specimens was performed by immunohistochemistry (neuronal nuclear antigen, glial fibrillary acidic protein, oligodendrocyte transcription factor, and basic myelin protein, respectively). Surgical specimens from TLE/HS patients with and without iT2SI in the aTLWM were compared. Samples of aTLWM were divided into three groups, according to MRI features: G1 = samples of iT2SI, G2 = samples with normal T2 signal intensity from patients without white matter imaging abnormalities, and G3 = samples with normal T2 signal intensity adjacent to areas with iT2SI., Results: Patients with increased T2 signal had a significantly younger age at epilepsy onset (p < .035). Histological analysis revealed a higher percentage of vacuolar area in these patients (p < .004) along with a lower number of ectopic neurons (p = .042). No significant differences were found in astrocyte or oligodendrocyte counts among groups., Significance: A higher proportion of vacuoles in regions with iT2SI may be the histopathologic substrate of this signal alteration in the white matter of the temporal lobe in patients with TLE/HS. This method of quantifying vacuoles using digital image analysis proved reliable and cost-effective., (© 2024 International League Against 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., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Objective: Patients with multifocal or generalized epilepsies manifesting with drop attacks have severe refractory seizures and significant cognitive and behavioural abnormalities. It is unclear to what extent these features relate to network abnormalities and how networks in sensorimotor cortex differ from those in patients with refractory focal epilepsies. Thus, in this study we sought to provide preliminary data on connectivity of sensorimotor cortex in patients with epileptic drop attacks, in comparison to patients with focal refractory epilepsies., Methods: Resting-state fMRI (rs-fMRI) data was available for 5 patients with epileptic drop attacks and 15 with refractory focal epilepsies undergoing presurgical evaluation. Functional connectivity was analyzed with a seed-based protocol, with primary seeds placed at the precentral gyrus, the postcentral gyrus and the premotor cortex. For each seed, the subjects' timeseries were extracted and transformed to Z scores. Between-group analysis was then performed using the 3dttest+ + AFNI program., Results: Two clusters of reduced connectivity in the group with drop attacks (DA group) in relation to those with focal epilepsies were found in the between-group analysis: the precentral seed showed reduced connectivity in the surrounding motor area, and the postcentral seed, reduced connectivity with the ipsilateral posterior cingulate gyrus. In the intra-group analyses, sensorimotor and premotor networks were abnormal in the DA group, whereas patients with focal epilepsies had the usual connectivity maps with each seed., Conclusion: This pilot study shows differences in the cerebral connectivity in the sensorimotor cortex of patients with generalized epilepsies and drop attacks which should be further explored to better understand the biological bases of the seizure generation and cognitive changes in these people., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Focal cortical dysplasia (FCD) is a malformation of cortical development that causes medical refractory seizures, and one of the main treatments may be surgical resection of the affected area of the brain. People affected by FCD may present with seizures of variable severity since childhood. Despite many medical treatments available, only surgery can offer cure. The pathophysiology of the disease is not yet understood; however, it is known that several gene alterations may play a role. The WNT/β-catenin pathway is closely related to the control and balance of cell proliferation and differentiation in the central nervous system. The aim of this study was to explore genes related to the WNT/β-catenin pathway in lesional and perilesional brain tissue in patients with FCD type II., Methods: Dysplastic and perilesional tissue from the primary dysplastic lesion of patients with FCD type IIa were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array (super array) containing 84 genes related to the WNT pathway., Results: Our results suggest the existence of molecular alteration in some genes of the WNT pathway in tissue with dysplastic lesions and of perilesional tissue. We call this tissue of normal-appearing adjacent cortex (NAAC). Of all genes analyzed, a large number of genes show similar behavior between injured, perilesional and control tissues. However, some genes have similar characteristics between the perilesional and lesional tissue and are different from the control brain tissue, presenting the perilesional tissue as a molecularly altered material., Conclusion: Our results suggest that the perilesional area after surgical resection of tissue with cortical dysplasia presents molecular changes that may play a role in the recurrence of seizures in these patients. The perilesional tissue should receive expanded attention beyond the somatic mutations described and associated with FCD, such as mTOR, for example, to new signaling pathways that may play a crucial role in seizure recurrence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico-pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinical-imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and "no definite FCD on histopathology" as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Focal cortical dysplasias (FCD) represent highly intrinsically epileptogenic lesions that require complete resection for seizure control. Resection of pure motor strip FCD can be challenging. Effective control of postoperative seizures is crucial and extending the boundaries of resection in an eloquent zone remains controversial., Observations: The authors report a 52-year-old right-handed male with refractory epilepsy. The seizure phenotype was a focal crisis with preserved awareness and a clonic motor onset of right-hemibody. Epilepsy surgery protocol demonstrated a left pure motor strip FCD and a full-awake resective procedure with motor brain mapping was performed. Further resection of surgical boundaries monitoring function along intraoperative motor tasks with no direct electrical stimulation corroborated by intraoperative-neuromonitorization was completed as the final part of the surgery. In the follow-up period of 3-years, the patient has an Engel-IB seizure-control with mild distal lower limb palsy and no gate compromise., Lessons: This report represents one of the few cases with pure motor strip FCD resection. In a scenario similar to this case, the authors consider that this variation can be useful to improve seizure control and the quality of life of these patients by extending the resection of a more extensive epileptogenic zone minimizing functional damage.

Objective: The differential diagnosis between epileptic and psychogenic nonepileptic seizures (PNES) is challenging, yet suspicion of PNES is crucial to rethink treatment strategies and select patients for diagnostic confirmation through video EEG (VEEG). We developed a novel scale to prospectively suspect PNES., Methods: First, we developed a 51-item scale in two steps, based upon literature review and panel expert opinion. A pilot study verified the applicability of the instrument, followed by a prospective evaluation of 158 patients (66.5% women, mean age 33 years) who were diagnosed for prolonged VEEG. Only epileptic seizures were recorded in 103 patients, and the other 55 had either isolated PNES or both types of seizures. Statistical procedures identified 15 items scored between 0 and 3 that best discriminated patients with and without PNES, with a high degree of consistency., Results: Internal consistency reliability of the scale for suspicion of PNES was 0.77 with Cronbach's Alpha Coefficient and 0.95 with Rasch Item Reliability Index, and performance did not differ according to the patient's gender. For a cut-off score of 20 (of 45) points, area under the curve was 0.92 (95% IC: 0.87-0.96), with an accuracy of 87%, sensitivity of 89%, specificity of 85%, positive predictive value of 77%, and negative predictive value of 94% (95% IC) for a diagnosis of PNES., Conclusions: The scale for suspicion of PNES (SS-PNES) has high accuracy to a reliable suspicion of PNES, helping with the interpretation of apparent seizure refractoriness, reframing treatment strategies, and streamlining referral for prolonged VEEG., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: In a previous proof of concept study, selective posterior callosotomy achieved similar degree of control of drop attacks as total callosotomy, while sparing prefrontal interconnectivity. The present study aims to confirm this finding in a larger cohort and to provide anatomical and prognostic data., Methods: Fifty-one patients with refractory drop attacks had selective posterior callosotomy and prospective follow up for a mean of 6.4 years. Twenty-seven patients had post-operative magnetic resonance imaging (MRI) and 18 had tractography (DTI) of remaining callosal fibers. Pre and postoperative falls were quantified and correlated with demographic, clinical and imaging data., Results: Mean monthly frequency of drop attacks had a 95 % reduction, from 297 before to 16 after the procedure. Forty- one patients (80 %) had either complete or greater than 90 % control of the epileptic falls. Age and duration of epilepsy at surgery correlated with outcome (p values, respectively, 0.042 and 0.005). Mean index of callosal section along the posterior-to-anterior axis was 53.5 %. Extending the posterior section anterior to the midbody of the corpus callosum did not correlate with seizure control (p 0.91), providing fibers interconnecting the primary motor (M1) and caudal supplementary motor areas (SMA) were sectioned. Only one patient had a notable surgical complication which resolved in two days., Conclusions: This level III cohort study with objective outcome assessment confirms that selective posterior callosotomy is safe and effective to control epileptic falls. Younger patients with smaller duration of epilepsy have better results. A posterior section contemplating the splenium, isthmus and posterior half of the body (posterior midbody) seems sufficient to achieve complete or almost complete control of drop attacks., (Copyright © 2020. Published by Elsevier B.V.)

This is a surgical technique video of selective posterior callosotomy (SPC), a novel surgical procedure to alleviate refractory epileptic drop attacks.1 Departing from traditional approaches aiming the anterior half or the entire callosum, SPC sections the posterior half of the callosum sparing prefrontal connectivity.1 Drop attacks are generalized epileptic seizures characterized by sudden falls.1 These seizures are often seen in diffuse brain pathology associated with generalized or multifocal epilepsies, whose electroencephalogram (EEG) "fingerprint" is bilaterally synchronous epileptic discharges.1 Sectioning the callosum to control drop attacks follows the rationale that the rapid synchronization of discharges between motor and premotor regions of both hemispheres is the basis.1 The standard approach to callosotomies always contemplated the anterior fibers of the callosum.2 Literature reports that anterior sections lead to unsatisfactory control of drop attacks, and results are improved when extended into a total callosotomy.2,3 This evidence coupled with diffusion tensor imaging (DTI) findings showing that motor and premotor fibers actually cross through posterior half of the callosum led us to hypothesize that selective section of the posterior half of the callosum would section all relevant motor fibers and control drop attacks to a similar extent to total callosotomies, with the advantage of sparing prefrontal interconnectivity3 and no split-brain syndrome. Both our series, one retrospective, followed by a new prospective study have confirmed SPC to be a safe procedure, leading to complete or greater than 90% control of epileptic falls in 85% of patients.1 The video presented here was recorded during a selective posterior callosotomy performed on a 13-yr-old girl who had hundreds of uncontrollable drop attacks per day. Falls were completely controlled with significant gains in psychomotor development and cognition, after 5 yr of follow-up. The patient provided signed consent to the surgical procedure, video acquisition, photo acquisition, and storage at operations, and the publication of this material., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objective: Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively., Methods: Hippocampal sections from drug-resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan-drebrin expression. Double-labeling immunofluorescences were performed to localize drebrin A-positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers., Results: Compared to controls, TLE patients had increased pan-drebrin in all hippocampal subfields and increased drebrin A-immunopositive area in all hippocampal subfields but CA1. Drebrin-positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin-positive spines with VGlut1-positive puncta, but not with GAD65-positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin-immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin-immunopositive area in IML compared with OML., Significance: Our results suggest that changes in drebrin-positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome., (© 2020 International League Against Epilepsy.)

Objective: To investigate demographic, epidemiologic and psychiatric features suggestive of the coexistence epilepsy (ES) and psychogenic nonepileptic seizures (PNES) that may contribute to precocious suspicion of the association., Methods: In this exploratory study, all patients older than 16 years admitted to prolonged video-electroencephalogram monitoring were evaluated about demographic, epileptological and psychiatric features. Detailed psychiatric assessment using M.I.N.I.-plus 5.0, Beck Anxiety Inventory, Beck Depression Inventory and the Childhood Trauma Questionnaire (CTQ) was performed. Data were collected previous to the final diagnosis and patients with ES-only, PNES-only or coexistence of ES/PNES were compared., Results: Of 122 patients admitted to epilepsy monitoring unit, 86 patients were included and 25 (29%) had PNES. Twelve (14%) had PNES-only, 13 (15%) had ES/PNES and the remaining 61 (71%) had only ES. A coexistence of ES and PNES was associated with clinical report of more than one seizure type (p˂0.001), nonspecific white matter hyperintensities on MRI (p < .001) and a past of psychotic disorder (p = .005). In addition, these patients had significantly more emotional abuse and neglect (p < .002 and 0.001, respectively). Somatization (including conversion disorder) was the most common diagnosis in patients with PNES- only (83%) and co-existing of PNES and ES (69.2%), differentiating both from ES-only patients (p < .001)., Conclusion: The high prevalence of this coexistence ES/PNES in this study reinforces a need to properly investigate PNES, especially in patients with confirmed ES who become refractory to medical treatment with antiepileptic drugs. The neuropsychiatric assessment may help to diagnostic suspicion and in the planning of therapeutic interventions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Focal cortical dysplasia (FCD) is caused by numerous alterations, which can be divided into abnormalities of the cortical architecture and cytological variations; however, the exact etiology of FCD remains unknown. The generation of induced pluripotent stem cells (iPSCs) from the cells of patients with neurological diseases, and their subsequent tissue‑specific differentiation, serves as an invaluable source for testing and studying the initial development and subsequent progression of diseases associated with the central nervous system. A total of 2 patients demonstrating seizures refractory to drug treatment, characterized as FCD Type IIb, were enrolled in the present study. Fibroblasts were isolated from residual skin fragments obtained from surgical treatment and from brain samples obtained during surgical resection. iPSCs were generated following exposure of fibroblasts to viral vectors containing POU class 5 homeobox 1 (OCT4), sex determining region Y‑box 2 (SOX2), Kruppel‑like factor 4 and c‑MYC genes, and were characterized by immunohistochemical staining for the pluripotent markers homeobox protein NANOG, SOX2, OCT4, TRA1‑60 and TRA1‑81. The brain samples were tested with antibodies against protein kinase B (AKT), phosphorylated‑AKT, mechanistic target of rapamycin (mTOR) and phosphorylated‑mTOR. Analysis of the AKT/mTOR pathway revealed a statistically significant difference between the cerebral tissues of the two patients, which were of different ages (45 and 12 years old). Clones with the morphological features of embryonic cells were detected on the 13th day and were characterized following three subcultures. The positive staining characteristics of the embryonic cells confirmed the successful generation of iPSCs derived from the patients' fibroblasts. Therefore, the present study presents a method to obtain a useful cellular source that may help to understand embryonic brain development associated with FCD.

Precise anatomical knowledge of the structure of the corpus callosum is important in split-brain research and during neurosurgical procedures sectioning the callosum. According to the classic literature, commissural fibers connecting the motor cortex are situated in the anterior part of the corpus callosum. On the other hand, more recent imaging studies using diffusion tensor imaging indicate a more posterior topography of callosal fibers connecting motor areas. Topographical knowledge is especially critical when performing disconnective callosotomies in epilepsy patients who experience sudden loss of leg motor control, so-called epileptic drop attacks. In the current study, we aim to precisely delineate the topography of the leg motor connections of the corpus callosum. Of 20 hemispheres obtained at autopsy, 16 were dissected according to Klingler's fiber dissection technique to study the course and topography of callosal fibers connecting the most medial part of the precentral gyrus. Fibers originating from the anterior bank of the central sulcus were invariably found to be located in the isthmus of the corpus callosum, and no leg motor fibers were found in the anterior part of the callosum. The current results suggest that the disconnection of the pre-splenial fibers, located in the posterior one-third of the corpus callosum, is paramount in obtaining a good outcome after callosotomy.

Objective: To evaluate a novel approach to control epileptic drop attacks through a selective posterior callosotomy, sparing all prefrontal interconnectivity., Methods: Thirty-six patients with refractory drop attacks had selective posterior callosotomy and prospective follow-up for >4 years. Falls, episodes of aggressive behavior, and IQ were quantified. Autonomy in activities of daily living, axial tonus, and speech generated a functional score ranging from 0 to 13. Subjective effect on patient well-being and caregiver burden was also assessed., Results: Median monthly frequency of drop attacks decreased from 150 to 0.5. Thirty patients (83%) achieved either complete or >90% control of the falls. Need for constant supervision decreased from 90% to 36% of patients. All had estimated IQ below 85. Median functional score increased from 7 to 10 (p = 0.03). No patient had decrease in speech fluency or hemiparesis. Caregivers rated the effect of the procedure as excellent in 40% and as having greatly improved functioning in another 50%. Clinical, EEG, imaging, and cognitive variables did not correlate with outcome., Conclusions: This cohort study with objective outcome assessment suggests that selective posterior callosotomy is safe and effective to control drop attacks, with functional and behavioral gains in patients with intellectual disability. Results are comparable to historical series of total callosotomy and suggest that anterior callosal fibers may be spared., Classification of Evidence: This study provides Class III evidence that selective posterior callosotomy reduces falls in patients with epileptic drop attacks., (© 2016 American Academy of Neurology.)

Subcortical epilepsy has been a controversial issue, partially settled by evidence showing seizure generation in hypothalamic hamartomas and also by reports of seizures caused by cerebellar lesions. We report 4-year-old girl with right hemifacial seizures and autonomic phenomena, in whom MRI showed an irregular mass in the right cerebellar peduncle. Despite several unremarkable video-EEG recordings, seizure origin in the lesion was hypothesized. Complete resection was feasible, histopathology showed a ganglioglioma, and she has been seizure free for 3 years. A fine line separates these developmental tumors from focal cortical dysplasia, and the homogeneous presentation of this entity led us to propose the terminology dysplastic cerebellar epilepsy.

Purpose: Epileptic seizures (ES) have many mimickers, perhaps the most relevant being psychogenic nonepileptic seizures (PNES). The picture is even more challenging when PNES are associated with ES in a given patient. The aim of this research paper was to delineate the demographic, epileptological and psychiatric profile of that specific population., Methods: A systematic review was carried out from 2000 to 2015 for articles in English, French, Italian, Spanish and Portuguese in PUBMED and EMBASE. Cohort or case-control studies reporting prospective or retrospective original data comparing patients with co-existing ES and PNES with those who had PNES only and ES only have been included. In retained studies, the presence of PNES was confirmed by video-electroencephalography (V-EEG). Forty-eight abstracts were identified., Results: Nine studies were retained. Most showed that female gender predominated in both groups with PNES. Patients with co-existing ES and PNES take higher number of antiepileptic drugs (AEDs) than PNES alone. Two studies showed association of concomitant ES and PNES with earlier age of seizure onset. Localizing EEG features and ES type were evaluated in only two studies and their association with either group was inconclusive. Somatoform, conversion or cluster B personality disorders were more frequent in subjects with PNES than with ES., Discussion: Patients with concomitant ES and PNES are highly heterogeneous, challenging differentiation on clinical grounds. A diagnosis of conversion or somatoform, anxiety disorders, and the use of a higher number of AEDs than psychiatric medications may have an association with co-existing ES and PNES. Further studies are warranted to differentiate patients who only have PNES from those with co-existing ES and PNES., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Epilepsia partialis continua is often refractory to antiepileptic medication and its causal relation to peripheral sensory stimuli has only rarely been suggested. We report a man who received surgery for temporal lobe epilepsy 10 years ago, who presented "de novo" epilepsia partialis continua following mild traumatic injury of the left hand. Continuous myoclonus of the left upper limb started the day after injury and persisted unabated for several weeks. Non-invasive evaluation was inconclusive. Acute electrocorticography during surgery under local anaesthesia revealed continuous, rhythmic spiking over the right sensorimotor cortex. Tailored excision of the posterior bank of the motor and adjacent sensory cortex immediately stopped the continuous myoclonus. Histopathology showed abnormal radial lamination and was compatible with focal cortical dysplasia type IA. Epilepsia partialis continua did not recur for seven years. Afferent stimuli from peripheral injury can disinhibit hyperexcitable sensorimotor cortex leading to epilepsia partialis continua. [Published with video sequences online].

Object: The central lobe consists of the pre- and postcentral gyri on the lateral surface and the paracentral lobule on the medial surface and corresponds to the sensorimotor cortex. The objective of the present study was to define the neural features, craniometric relationships, arterial supply, and venous drainage of the central lobe., Methods: Cadaveric hemispheres dissected using microsurgical techniques provided the material for this study., Results: The coronal suture is closer to the precentral gyrus and central sulcus at its lower rather than at its upper end, but they are closest at a point near where the superior temporal line crosses the coronal suture. The arterial supply of the lower two-thirds of the lateral surface of the central lobe was from the central, precentral, and anterior parietal branches that arose predominantly from the superior trunk of the middle cerebral artery. The medial surface and the superior third of the lateral surface were supplied by the posterior interior frontal, paracentral, and superior parietal branches of the pericallosal and callosomarginal arteries. The venous drainage of the superior two-thirds of the lateral surface and the central lobe on the medial surface was predominantly through the superior sagittal sinus, and the inferior third of the lateral surface was predominantly through the superficial sylvian veins to the sphenoparietal sinus or the vein of Labbé to the transverse sinus., Conclusions: The pre- and postcentral gyri and paracentral lobule have a morphological and functional anatomy that differentiates them from the remainder of their respective lobes and are considered by many as a single lobe. An understanding of the anatomical relationships of the central lobe can be useful in preoperative planning and in establishing reliable intraoperative landmarks.

Background: Epilepsia partialis continua (EPC) is a life-threatening condition often caused by focal cortical dysplasia (FCD). Resection of the motor cortex is contemplated in the hope that the trade-off between a severe motor deficit and complete seizure control justifies the procedure., Methods: Report of 3 patients with EPC due to histologically confirmed FCD, who underwent resection of the motor cortex under acute electrocorticography., Results: All had re-emergence of medically intractable EPC in the other side of the body after rolandic resection. Two patients died and the third continues with refractory attacks., Conclusion: In some instances, EPC due to FCD may shift sides and re-emerge in the contralateral, previously asymptomatic, hemibody. A mechanism of disinhibition by surgery of a suppressed contralateral and homologous epileptogenic zone is speculated., (© 2014 American Academy of Neurology.)

Objective: To establish preoperatively the localization of the cortical projection of the inferior choroidal point (ICP) and use it as a reliable landmark when approaching the temporal horn through a middle temporal gyrus access. To review relevant anatomical features regarding selective amigdalohippocampectomy (AH) for treatment of mesial temporal lobe epilepsy (MTLE)., Method: The cortical projection of the inferior choroidal point was used in more than 300 surgeries by one authors as a reliable landmark to reach the temporal horn. In the laboratory, forty cerebral hemispheres were examined., Conclusion: The cortical projection of the ICP is a reliable landmark for reaching the temporal horn.

Cavernous cerebral malformations (CCMs) are a well-defined epilepsy-associated pathology. They represent lesions/conglomerates of abnormally configured vessels leading to seizures either as a result of physiological changes affecting the cerebral cortex immediately surrounding the CCM (an epileptogenic mechanism that is relevant for both temporal and extratemporal lesions), or as a result of promoting epileptogenicity in remote but anatomo-functionally connected brain regions (a mechanism that is particularly relevant for temporal lobe lesions). This review details the pathological findings in CCMs and discusses the mechanisms of epileptogenicity in this context. The bulk of the review will focus on therapeutic strategies. Medical therapy using antiepileptic drugs is recommended as a first-line therapy, but surgical removal of the CCM with the surrounding cortex should be pursued if seizures prove to be drug resistant. Early timing of the resection and complete removal of any associated epileptic pathology are critical for best outcomes. In addition to reviewing the available data from prior series, we present original research from two specialized epilepsy centers targeted at answering particularly pressing clinical questions mainly related to the ideal timing and extent of surgery. Further research is needed to define the best surgical strategies in patients with temporal lobe CCMs and structurally normal hippocampi.

Developmental tumors often lead to refractory partial seizures and constitute a well-defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Hemispherectomy often leads to a loss of contralateral hand function. In some children with congenital hemiparesis, however, paretic hand function remains unchanged. An immediate improvement of hand function has never been reported. A 17-year-old boy with congenital hemiparesis and therapy-refractory seizures due to a large infarction in the territory of the middle cerebral artery underwent epilepsy surgery. Intraoperatively, electrical cortical stimulation of the affected hemisphere demonstrated preserved motor projections from the sensorimotor cortex to the (contralateral) paretic hand. A frontoparietal resection was performed, which included a complete disconnection of all motor projections originating in the sensorimotor cortex of the affected hemisphere. Surprisingly, the paretic hand showed a significant functional improvement immediately after the operation. This observation demonstrates that, in congenital hemiparesis, crossed motor projections from the affected hemisphere are not always beneficial, but can be dysfunctional, interfering with ipsilateral motor control over the paretic hand by the contralesional hemisphere., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: Interest in the association of epilepsy and pseudobulbar palsy was rekindled since the identification through magnetic resonance imaging (MRI) of bilateral perisylvian polymicrogyria (PMG). Seizures are often intractable, but resective epilepsy surgery has not been recommended. However, a similar clinical picture can be encountered in patients with bilateral perisylvian destructive lesions, which fit the description of ulegyria (ULG). We report a series of patients with epilepsy and pseudobulbar palsy due to bilateral perisylvian ULG (BP-ULG), show that hippocampal sclerosis (HS) is often associated and highlight the fact that in this entity, unlike in malformative bilateral perisylvian PMG, seizures may be surgically treated., Methods: The motor, cognitive, epileptologic, and imaging features of 12 patients with perisylvian ULG followed at three institutions are described. For patients with refractory seizures, we detail extracranial and intracranial electrographic recordings, surgical strategies, histopathologic analyses of the resected tissue, and outcome of surgical treatment. Descriptive statistics were used for quantitative and categorical variables. Student's t-test was used to compare means, and a p < 0.05 was considered significant., Key Findings: Pseudobulbar palsy and mental retardation were present in all patients with symmetrical BP-ULG. Five had refractory seizures. There was no relationship between the severity of the pseudobulbar palsy or of the mental retardation and the degree of seizure control with medication. The five patients in whom seizures were refractory to medication had significantly earlier age of onset and longer duration of epilepsy (p < 0.05). Dual pathology with associated unilateral HS was present in four. One patient with dual pathology had a temporolimbic electroclinical picture and had an anterior temporal lobectomy (ATL) based upon noninvasive evaluation. The other four had ictal semiology suggesting involvement of both temporolimbic and perisylvian cortex. Intracranial electroencephalography (EEG) showed concomitant seizure onset in the anterior temporal region and in the ipsilateral ULG in three of the four with dual pathology and in the ulegyric cortex in the one without HS. Resection guided by a combination of semiology, MRI, and extra and intracranial EEG led to complete seizure control in two and almost complete seizure control (Engel class II) in two other patients. The only surgical failure was an isolated ATL in a patient with dual pathology, and concomitant seizure onset in both lesions according to semiology and intracranial EEG., Significance: Our findings suggest that BP-ULG mimics the clinical features of bilateral perisylvian PMG. In patients with refractory seizures, recognition of this entity should lead to consideration of resective surgery despite the bilateral ULG., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Objectives: To evaluate the very long-term clinical outcome of surgery for mesial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE/HS) without atypical features. The impact of surgical technique and postoperative reduction of medication on this outcome was investigated., Design: Prospective longitudinal cohort follow-up study for up to18 years., Setting: Epilepsy surgery centre in a university hospital., Patients: 108 patients who underwent unilateral MTLE/HS., Intervention: Surgery for MTLE/HS., Main Outcome Measure: Engel classification (I). Clinical evaluations were based on systematic interviews in person or by phone. Kaplan-Maier survival curves estimated the probability of remaining seizure free. The impact of medication management in the postoperative outcome was analysed using Cox regression., Results: The probability of remaining completely seizure-free at 12 and 18 years after MTLE/HS surgery was 65% and 62%, respectively. The risk of having any recurrence was 22% during the first 24 months and increased 1.4% per year afterwards. Type of surgical technique (selective amygdalohippocampectomy vs anterior temporal lobectomy) did not impact on outcome. Remaining on antiepileptic drugs and history of generalised clonic seizure diminished the probability of remaining seizure free., Conclusions: MTLE/HS surgery is able to keep patients seizure free for almost up to two decades. Removal of the neocortex besides the mesial portion of the temporal lobe does not lead to better chances of seizure control. These findings are applicable to the typical unilateral MTLE/HS syndrome and cannot be generalised for all types of TLE. Future longitudinal randomised controlled studies are needed to replicate these findings.

Epilepsy surgery is an accepted treatment option in patients with medically refractory focal epilepsy. Despite various advances in recording and localization noninvasive and invasive techniques (including electroencephalography (EEG), magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetoencephalography (MEG), subdural grids, depth electrodes, and so on), the seizure outcome following surgical resection remains suboptimal in a significant number of patients. The availability of long-term outcome data on an increasing number of patients suggests two major temporal patterns of seizure recurrence (early vs. late) that implicate the following two different mechanisms for seizure recurrence: (1) a failure to either define/resect the epileptogenic zone, and (2) the nonstatic nature of epilepsy as a disease through the persistence of proepileptic cortical pathology. We describe the temporal patterns of epilepsy surgery failures and discuss their potential clinical, histopathologic, genetic, and molecular mechanisms. In addition, we review predictors of successful surgical interventions and analyze the natural history of epilepsy following surgical intervention. We hypothesize that the acute/early postoperative failures are due to errors in localizing and/or resecting the epileptic focus, whereas late recurrences are likely due to development/maturation of a new and active epileptic focus (de novo epileptogenesis)., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Rasmussen's encephalitis (RE) is an inflammatory, probably autoimmune disorder manifested by refractory seizures and progressive deterioration of one cerebral hemisphere [1]. Here, we describe the unfortunate history of a girl with a progressive disorder which, upon clinical, neuroimaging, and histopathological evaluation, proved to be bilateral RE associated with type II focal cortical dysplasia. Whether the second pathology is relevant for the extent of the disease is discussed. We demonstrated histopathological evidence of RE and type II FCD in the left hemisphere, which led to EPC on the right hemibody at presentation. In addition, there was unequivocal progressive cortical and subcortical atrophy of the right hemisphere, which accounted for the EPC on the left hemibody. This is highly compatible with RE (+/- FCD) in the right hemisphere as well. Although the association of FCD and RE - as well as the occasional occurrence of bilateral RE - has already been reported [3-5], this is the first such case in which bilateral RE and FCD co-occur.

Unlabelled: The deep knowledge of hippocampal microsurgical anatomy is paramount in epilepsy surgery. One of the most used techniques is those proposed by Niemeyer., Purpose: To describe the hippocampal anatomy in detail and to present a technique in which preoperative anatomical points in MRI are identified to guide the corticotomy., Method: Microsurgical dissections were performed in twenty brain hemispheres and eight cadaveric heads to identify temporal lobe and hippocampus structures. Thirty two patients with drug-resistant temporal lobe epilepsy underwent a selective amygdalohippocampectomy with Niemeyer's technique being measured three preoperative MRI preoperative distances to guide the corticotomy., Results: The hippocampus was divided in head, body and tail and its microsurgical anatomy described in detail. The MRI measurements are presented and discussed., Conclusion: The knowledge of the complex anatomy of the hippocampus can be achieved in a three-dimensional way during microsurgical dissections. The preoperative MRI measurement is a reasonable guide to perform temporal corticotomy in Niemeyer's technique.

Patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE/HS) have a distinct neuropsychological profile, but there is still debate on whether executive dysfunction is part of this profile and also whether temporal lobe surgery can modify this dysfunction., Objective: To study the presence and reversibility of executive dysfunction in patients with unilateral TLE/HS., Methods: Twenty-five patients with refractory seizures due to TLE/HS underwent presurgical evaluation which included the application of the Wiconsin Card Sorting Test (WCST). Nineteen were re-evaluated in follow up, at least 6 months after selective amygdalo-hippocampectomy (SAH). Twenty-two control subjects matched for age and education also performed the WCST., Results: Sixteen of the 25 patients (64%) completed fewer than four categories in the WCST whereas only 4 of the 22 controls (18%) did not complete at least four categories (p<0.005). In addition, the performance of the patients involved significantly more perseverative responses and errors compared to controls. The patient group demonstrated significant post-operative improvement in many measures of the WCST following SAH., Conclusions: These findings support the presence of executive dysfunction in patients with TLE/HS and suggest that such dysfunction can be partially reversed by selective resection of epileptogenic mesial temporal structures.

Object: The aim of this study was to compare seizure and memory outcome in patients with medically refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) treated using an anterior temporal lobectomy (ATL) or a selective amygdalohippocampectomy (SA)., Methods: Surgical outcome data were prospectively collected for 2 to 11 years in 161 consecutive patients with MTLE/ HS. Eighty patients underwent an ATL and 81 an SA. Seizure control achieved with each technique was compared using the Engel classification scheme. Postoperative memory testing was performed in 86 patients (53%). At the last follow up, 72% of the patients who had undergone an ATL (mean follow up 6.7 years) and 71% of those who had undergone an SA (mean follow up 4.5 years) were seizure free (Engle Class IA). Estimated survival in patients in Engel Classes I, IA, and I and II combined did not differ between the two surgical techniques. Preoperatively, 58% of the patients had verbal memory scores one standard deviation (SD) below the normal mean. One third of the patients with preoperative scores in the normal range worsened after surgery, although this outcome was not related to the surgical technique. In contrast, one third of those whose preoperative scores were less than -1 SD experienced improvement after surgery. Nine (18%) of the 50 patients whose left side had been surgically treated improved their verbal memory scores by more than one SD. Seven (78%) of these nine underwent an SA (p = 0.05)., Conclusions: Both ATL and SA can lead to similar favorable seizure control in patients with MTLE/HS. Preliminary data suggest that postoperative verbal memory scores may improve in patients who undergo selective resection of a sclerotic hippocampus in the dominant temporal lobe.

Purpose: Surgical results in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) are often reported in conjunction with other etiologies of TLE., Methods: We prospectively collected surgical outcome data for 2 to 11 years for 134 consecutive patients who specifically had MTLE and unilateral HS, according to magnetic resonance imaging (MRI) and confirmed by histopathology. Sixty-five had postoperative neuropsychological testing. Outcome was analyzed by using Engel's classification (a) through Kaplan-Meier estimated survival curves (as a function of the time to seizure recurrence), (b) as percentage of patients in each outcome class on a yearly basis, and (c) at the last updated follow-up., Results: Kaplan-Meier estimates of complete seizure freedom (Engel's class IA) for years 1, 2, 5, and 10 were 85%, 77%, 74%, and 66%, and of Engel's class I were 89%, 86%, 83%, and 81%. Only nine (6.7%) patients had outcome classes III or IV at any point during follow-up. Of the patients tested, 26% of those operated on the left side and 22% of those operated on the right had postoperative decline of >1 SD in verbal or visual memory, respectively., Conclusions: High rates of seizure freedom can be obtained and remain stable over the years in patients operated on for unilateral MTLE/HS, even in countries with limited resources.

Unlabelled: Hippocampal sclerosis (HS) is the commonest pathology in epileptic patients undergoing temporal lobe epilepsy surgery. Beside, there are an increased density of corpora amylacea (CA) founded in 6 to 63% of those cases., Objective: verify the presence of CA and the clinical correlates of their occurrence in a consecutive series of patients undergoing temporal surgery with diagnosis of HS., Method: We reviewed 72 hippocampus specimens from January 1997 to July 2000. Student's t test for independent, samples, ANOVA and Tukey test were performed for statistical analysis., Results: CA were found in 35 patients (49%), whose mean epilepsy duration (28.7 years) was significantly longer than that group of patients without CA (19.5 years, p=0.001). Besides, when CA were found, duration was also significantly correlated with distribution within hippocampus: 28.7 years with diffuse distribution of CA, 15.4 with exclusively subpial and 17.4 years with distribution subpial plus perivascular (p=0.001)., Conclusion: Our findings corroborate the presence of CA in patients with HS and suggest that a longer duration of epilepsy correlate with a more distribution of CA in hippocampus.

The purpose of this study was to assess the cortical representation of sensorimotor functions in patients undergoing perirolandic epilepsy surgery, focusing on somatotopy, mosaicism, and variability of function in relation to the classic motor homunculus. The authors studied 36 patients in whom intraoperative or extraoperative electrical cortical stimulation to map motor functions was performed. A computer program was devised to register electrode number, stimulation parameters, and response to each stimulus. Electrode position was represented graphically whenever a stimulus was delivered. A total of 43 maps from 36 patients were analyzed. The authors found variations in the organization of M1 (primary motor cortex) in seven patients (19.4%). Four patients (11.1%) presented mosaicism (overlapping of functional areas), two (5.6%) presented variability (inverted disposition of M1 functional areas), and one (2.8%) had both. The results of this study challenge the notion of orderly topographic relationships between the human sensorimotor functions and their representation in the primary motor cortex. These results confirm those of other studies with animals and humans using novel imaging techniques, suggesting that the motor homunculus may not always be considered a definite and absolute representation of M1.

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.

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.

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.

Cortical dysplastic lesions (CDLs) are usually identified by magnetic resonance imaging (MRI). Clinical, electrographic and histologic findings suggest that focal CDLs (FCDLs) are highly epileptogenic, often involve the rolandic cortex, and can present variable degrees of histopathologic abnormalities. An ictal or "ictal-like" bursting pattern of electrographic activity was recorded over dysplastic cortex in 65% of our patients. Resective surgery can eliminate or significantly reduce seizure frequency in many medically intractable patients, depending on lesion location, degree, and extent of histopathologic abnormalities. Best results are achieved when complete or major excision of both the MRI-visible lesion and the cortical areas displaying ictal electrographic activity can be performed. This is more likely when the degree of histopathologic abnormality is mild to moderate or when the lesion is in a temporal lobe. More severe histopathologic abnormalities and central insular or multilobar lesions usually lead to less favorable results: either major excision of the visualized lesion is impractical or the lesion is microscopically more extensive than shown by MRI. Multilobar resection or hemispherectomy for patients with infantile spasms associated with CDLs and for patients with hemimegalencephaly are often associated with dramatic improvement in seizure control. Callosotomy can be performed in selected patients with diffuse CDLs who have intractable drop attacks.