RESUMEN
Rasmussen's encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherotomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Furthermore, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expression of cell-cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest the potential involvement of cell cycle regulators in the progression of RE.
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Encefalitis , Humanos , Encefalitis/genética , Encefalitis/patología , Encefalitis/metabolismo , Masculino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Encéfalo/patología , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corteza Cerebral/patología , Corteza Cerebral/metabolismo , Femenino , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Ciclo Celular/genéticaRESUMEN
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.
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Epilepsia Refractaria , Epilepsias Parciales , Epilepsia Generalizada , Corteza Sensoriomotora , Humanos , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Imagen por Resonancia Magnética/métodos , Proyectos Piloto , Mapeo Encefálico/métodos , Corteza Sensoriomotora/diagnóstico por imagen , Convulsiones , Síncope , Epilepsias Parciales/diagnóstico por imagenRESUMEN
BACKGROUND: Autoantibodies against surface neuronal antigens have been associated with specific neurological presentations including autoimmune encephalitis (AE), with variable association with neoplasia and infections. METHODS: We described the phenotype and environmental associations of patients with neurological syndromes associated with antibodies against neuronal surface antigens who were referred to a tertiary center in the South of Brazil. All patients were tested for neuronal autoantibodies using cell-based assays. Clinical, radiological, and laboratory findings were retrospectively reviewed. RESULTS: We identified 16 patients, 15 had subacute, and one had a progressive disease course. Among patients with subacute onset, 11 (73 %) were N-Methyl-d-Aspartate receptor (NMDAr-IgG)+, 3 (20 %) were Leucine-rich Glioma-Inactivated-1 (LGI1-IgG)+, and 1 (6 %) was positive for Glycine receptor-IgG. The patient with a progressive disease course had antibodies against IgLON5. Most patients had disease onset in spring and summer suggesting environmental factors for the development of AE. Also, we observed a different pattern of brain lesions when NMDAr-IgG encephalitis followed herpes encephalitis and a previously unreported association with Rosai-Dorfman-Destombe disease. All patients with encephalopathy met criteria for possible AE and all proven NMDAr-IgG+ met criteria for NMDAr-IgG encephalitis. However, only one LGI1-IgG+ patient fulfilled clinical criteria for limbic encephalitis. All but one received high-dose intravenous methylprednisolone, 11 also had intravenous human immunoglobulin, and 4 plasma exchange. Furthermore, all patients received second-line immunotherapy. Importantly, most patients improved with immunotherapy, even when initiated later in the disease course. CONCLUSION: We identified seasonal variability associated with neuronal surface antibodies suggesting environmental triggers. Also, we described the coexistence of NMDAr-IgG encephalitis with histiocytosis. In our series, most patients received second-line immunotherapy. We observed neurologic improvement after treatment even in cases of delayed diagnosis. Increasing the recognition and availability of tests and treatments for these conditions is of paramount importance in low- and middle-income countries.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Encefalitis por Herpes Simple , Humanos , Estudios Retrospectivos , Antígenos de Superficie , Autoanticuerpos , Síndrome , Inmunoglobulina G , Moléculas de Adhesión Celular NeuronalRESUMEN
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/ß-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/ß-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.
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Epilepsia Refractaria , Displasia Cortical Focal , Humanos , Niño , Epilepsia Refractaria/genética , Epilepsia Refractaria/cirugía , Vía de Señalización Wnt/genética , beta Catenina , ConvulsionesRESUMEN
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.
RESUMEN
Epilepsy surgery is the treatment of choice for patients with drug-resistant seizures. A timely evaluation for surgical candidacy can be life-saving for patients who are identified as appropriate surgical candidates, and may also enhance the care of nonsurgical candidates through improvement in diagnosis, optimization of therapy, and treatment of comorbidities. Yet, referral for surgical evaluations is often delayed while palliative options are pursued, with significant adverse consequences due to increased morbidity and mortality associated with intractable epilepsy. The Surgical Therapies Commission of the International League Against Epilepsy (ILAE) sought to address these clinical gaps and clarify when to initiate a surgical evaluation. We conducted a Delphi consensus process with 61 epileptologists, epilepsy neurosurgeons, neurologists, neuropsychiatrists, and neuropsychologists with a median of 22 years in practice, from 28 countries in all six ILAE world regions. After three rounds of Delphi surveys, evaluating 51 unique scenarios, we reached the following Expert Consensus Recommendations: (1) Referral for a surgical evaluation should be offered to every patient with drug-resistant epilepsy (up to 70 years of age), as soon as drug resistance is ascertained, regardless of epilepsy duration, sex, socioeconomic status, seizure type, epilepsy type (including epileptic encephalopathies), localization, and comorbidities (including severe psychiatric comorbidity like psychogenic nonepileptic seizures [PNES] or substance abuse) if patients are cooperative with management; (2) A surgical referral should be considered for older patients with drug-resistant epilepsy who have no surgical contraindication, and for patients (adults and children) who are seizure-free on 1-2 antiseizure medications (ASMs) but have a brain lesion in noneloquent cortex; and (3) referral for surgery should not be offered to patients with active substance abuse who are noncooperative with management. We present the Delphi consensus results leading up to these Expert Consensus Recommendations and discuss the data supporting our conclusions. High level evidence will be required to permit creation of clinical practice guidelines.
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Epilepsia Refractaria , Epilepsia , Adulto , Niño , Consenso , Epilepsia Refractaria/psicología , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Epilepsia/cirugía , Humanos , Derivación y Consulta , Convulsiones/diagnósticoRESUMEN
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.
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Epilepsia , Malformaciones del Desarrollo Cortical de Grupo I , Malformaciones del Desarrollo Cortical , Consenso , Epilepsia/diagnóstico , Epilepsia/patología , Humanos , Imagen por Resonancia Magnética , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Malformaciones del Desarrollo Cortical/genética , Malformaciones del Desarrollo Cortical de Grupo I/diagnóstico , Neuroimagen , Estudios RetrospectivosRESUMEN
BACKGROUND: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. OBJECTIVE: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. METHODS: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. RESULTS: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. CONCLUSION: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.
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Epilepsia Refractaria , Epilepsias Parciales , Adulto , Anticonvulsivantes/uso terapéutico , Niño , Método Doble Ciego , Quimioterapia Combinada , Humanos , Levetiracetam/uso terapéutico , Calidad de Vida , Resultado del TratamientoRESUMEN
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.
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Epilepsia , Convulsiones , Adulto , Electroencefalografía , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Reproducibilidad de los Resultados , Convulsiones/diagnósticoRESUMEN
ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.
RESUMO Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.
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Humanos , Niño , Adulto , Epilepsias Parciales , Epilepsia Refractaria , Calidad de Vida , Método Doble Ciego , Resultado del Tratamiento , Quimioterapia Combinada , Levetiracetam/uso terapéutico , Anticonvulsivantes/uso terapéuticoRESUMEN
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.
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Cuerpo Calloso , Epilepsia , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/cirugía , Humanos , Pronóstico , Estudios Prospectivos , Convulsiones , Síncope , Resultado del TratamientoRESUMEN
OBJECTIVE: We aimed to assess frequency of functional seizures or psychogenic nonepileptic seizures (PNES) during the COVID-19 outbreak and to recognize possible factors associated with worsening in this population. METHODS: In this cross-sectional study conducted during the second phase of the pandemic, adult patients with PNES documented by video-EEG and followed up in two tertiary epilepsy centers responded to a structured telephone survey. Data were gathered on demographics, clinical features and frequency of PNES, history of psychiatric comorbidity, access to treatment, as well as on anxiety (GAD-7 items) and depressive symptoms (NDDI-E). RESULTS: Fifty-four patients (78% female; mean age of 31.36â¯years [SDâ¯=â¯10.6]) were contacted and 15 (28%) reported increased frequency of PNES during the pandemic. Higher scores of GAD-7 items (pâ¯<â¯0.001) and NDDI-E (pâ¯<â¯0.001) were associated with PNES worsening. There was strong evidence of a correlation between higher stress levels (pâ¯<â¯0.001) and poor sleep quality (p 0.005) with PNES aggravation. After regression, stress was the strongest predictor of PNES increased frequency. SIGNIFICANCE: Patients with functional neurological disorders are vulnerable during ubiquitously felt stressors. However, the atmosphere of uncertainty did not affect these patients equally. Patients with PNES showing symptoms of anxiety and depression are at higher risk of seizure worsening. Early identification of this subset of patients may prevent this detrimental outcome.
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COVID-19 , Adulto , Estudios Transversales , Brotes de Enfermedades , Electroencefalografía , Femenino , Humanos , Masculino , Trastornos Psicofisiológicos/epidemiología , SARS-CoV-2 , Convulsiones/epidemiologíaRESUMEN
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.
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Epilepsia Refractaria/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Neuropéptidos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Lobectomía Temporal Anterior , Región CA1 Hipocampal/metabolismo , Región CA2 Hipocampal/metabolismo , Región CA3 Hipocampal/metabolismo , Estudios de Casos y Controles , Dendritas/metabolismo , Dendritas/patología , Giro Dentado/metabolismo , Epilepsia Refractaria/patología , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Glutamato Descarboxilasa/metabolismo , Hipocampo/patología , Hipocampo/cirugía , Humanos , Inmunohistoquímica , Masculino , Microscopía Confocal , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , Plasticidad Neuronal , Esclerosis , Proteína 1 de Transporte Vesicular de Glutamato/metabolismoRESUMEN
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.
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Imagen de Difusión Tensora , Convulsiones , Adolescente , Documentación , Femenino , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Síncope , Resultado del TratamientoRESUMEN
Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".
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Epilepsia/clasificación , Guías de Práctica Clínica como Asunto , Sociedades Médicas , HumanosRESUMEN
Focal cortical dysplasia (FCD) is a malformation of cortical development which is strongly associated with drug-refractory epilepsy. Certain studies have demonstrated an increase in mTOR signaling in patients with FCD on the basis of observation of phosphorylated molecules. The aim of the present study was to verify the differences in genes involved in cell proliferation, adhesion, and control of apoptosis during embryonic neurogenesis in iPSCs derived from the Focal Cortical Dysplasia. Fibroblasts were obtained from the skin biopsies of patients with FCD (n = 2) and controls (n = 2). iPSCs were generated by exposing the fibroblasts to viral vectors that contained the Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC genes) responsible for promoving cell reprogramation. The fibroblasts and iPSCs were tested during different phases of neurodifferentiation for migration capacity and expression of the genes involved in the PI3K pathway. Fibroblasts of patients with FCD migrated with greater intensity during the first two time points of analyses. iPSCs did not exhibit any difference in cell migration between the groups. Fibroblasts, brain tissue, and iPSCs of the patients with FCD exhibited a significant reduction in the relative expression values of 4EBP-1. During neurodevelopment, the iPSCs from patients with FCD exhibited a reduction in the expression of cIAP-1, cIAP-2, PI3K, ß-Catenin and 4EBP-1 gene. We suggest that the differences observed in the migration potential of adult cells and in the gene expression related to the fundamental processes involved in normal brain development during the neurodifferentiation process might be associated with cortical alteration in the patients with FCD.
Asunto(s)
Apoptosis/genética , Adhesión Celular/genética , Proliferación Celular/genética , Células Madre Pluripotentes Inducidas/fisiología , Malformaciones del Desarrollo Cortical/genética , Neurogénesis/genética , Adulto , Células Cultivadas , Femenino , Fibroblastos/fisiología , Humanos , Factor 4 Similar a Kruppel , Masculino , Persona de Mediana EdadRESUMEN
This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.