RESUMEN
OBJECTIVE: This study investigates the prevalence of pathogenic variants in the mechanistic target of rapamycin (mTOR) pathway in surgical specimens of malformations of cortical development (MCDs) and cases with negative histology. The study also aims to evaluate the predictive value of genotype-histotype findings on the surgical outcome. METHODS: The study included patients with drug-resistant focal epilepsy who underwent epilepsy surgery. Cases were selected based on histopathological diagnosis, focusing on MCDs and negative findings. We included brain tissues both as formalin-fixed, paraffin-embedded (FFPE) or fresh frozen (FF) samples. Single-molecule molecular inversion probes (smMIPs) analysis was conducted, targeting the MTOR gene in FFPE samples and 10 genes within the mTOR pathway in FF samples. Correlations between genotype-histotype and surgical outcome were examined. RESULTS: We included 78 patients for whom we obtained 28 FFPE samples and 50 FF tissues. Seventeen pathogenic variants (22 %) were identified and validated, with 13 being somatic within the MTOR gene and 4 germlines (2 DEPDC5, 1 TSC1, 1 TSC2). Pathogenic variants in mTOR pathway genes were exclusively found in FCDII and TSC cases, with a significant association between FCD type IIb and MTOR genotype (P = 0.003). Patients carrying mutations had a slightly better surgical outcome than the overall cohort, however it results not significant. The FCDII diagnosed cases more frequently had normal neuropsychological test, a higher incidence of auras, fewer multiple seizure types, lower occurrence of seizures with awareness impairment, less ictal automatisms, fewer Stereo-EEG investigations, and a longer period long-life of seizure freedom before surgery. SIGNIFICANCE: This study confirms that somatic MTOR variants represent the primary genetic alteration detected in brain specimens from FCDII/TSC cases, while germline DEPDC5, TSC1/TSC2 variants are relatively rare. Systematic screening for these mutations in surgically treated patients' brain specimens can aid histopathological diagnoses and serve as a biomarker for positive surgical outcomes. Certain clinical features associated with pathogenic variants in mTOR pathway genes may suggest a genetic etiology in FCDII patients.
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Epilepsia Refractaria , Epilepsias Parciales , Epilepsia , Malformaciones del Desarrollo Cortical de Grupo I , Malformaciones del Desarrollo Cortical , Adulto , Humanos , Epilepsia Refractaria/genética , Epilepsia Refractaria/cirugía , Serina-Treonina Quinasas TOR , Epilepsias Parciales/genética , Epilepsias Parciales/diagnóstico , Convulsiones , Células Germinativas/patología , Malformaciones del Desarrollo Cortical/patologíaRESUMEN
Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.
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Epilepsia , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Mapeo Encefálico , Electroencefalografía , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , Humanos , Proyectos PilotoRESUMEN
Epilepsy surgery is recommended in selected patients with Tuberous Sclerosis Complex (TSC). However, reports on predictive factors of seizure outcome are variable. Here we report on seizure and cognitive outcome of 35 TSC patients who received surgery for refractory epilepsy in 7 Italian centers over a period of 22 years (1997-2019). The rate of seizure-free individuals at last follow-up (mean 7.5 years, range 1-21 years) was 51%. Patients with longer follow-up (≥10 years) had a lower rate of Engel I outcome (11.1%) than those who received surgery in the last 10 years (65.4%, p = 0.003). Factors associated with Engel II, III, IV outcome in our cohort included: high number of cortical tubers (≥5); presence of subependymal nodules (SENs); seizure onset before age 1 year; and multifocal interictal epileptic discharges (IEDs) on electroencephalogram (EEG). A subset of patients evaluated with Vineland Adaptive Behaviour Scales (VABS) showed developmental gains, in line with their developmental trajectories, but no improvement in standard scores after surgery was noted. Our study demonstrates that the rates of successful seizure outcome of epilepsy surgery in TSC have improved in the last 10 years. More than half of the patients achieved seizure freedom, and a high proportion of affected individuals experienced a reduction in seizure burden and in antiseizure medications. A comprehensive assessment after surgery should be performed in TSC patients to evaluate the overall neurodevelopmental outcome, as measures that are based only on seizure control do not adequately identify the benefits of surgery on global functioning in these patients.
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Epilepsia , Esclerosis Tuberosa , Electroencefalografía , Epilepsia/etiología , Epilepsia/cirugía , Humanos , Lactante , Estudios Retrospectivos , Convulsiones/epidemiología , Convulsiones/etiología , Convulsiones/cirugía , Resultado del Tratamiento , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/cirugíaRESUMEN
Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.
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Encéfalo/fisiología , Epilepsia Refractaria/fisiopatología , Electrocoagulación/métodos , Terapia por Radiofrecuencia/métodos , Sueño/fisiología , Vigilia/fisiología , Encéfalo/diagnóstico por imagen , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Electroencefalografía/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Técnicas EstereotáxicasRESUMEN
OBJECTIVE: We investigated views towards the Internet in a sample of Italian healthcare specialists involved in epilepsy field, to identify factors associated with the attitude of being influenced by information found on the Internet. METHODS: This study was a self-administered survey conducted in a group of members of the Italian Chapter of the International League Against Epilepsy (ILAE) in January 2018. RESULTS: 184 questionnaires were analyzed. 97.8 % of responders reported to seek online information on epilepsy. The Internet was most frequently searched to obtain new information (69.9 %) or to confirm a diagnostic or therapeutic decision (37.3 %). The influence of consulting the Internet on clinical practice was associated with registration to social network(s) (OR: 2.94; 95 %CI: 1.28-6.76; p = 0.011), higher frequency of Internet use (OR: 3.66; 95 %CI: 1.56-9.21; p = 0.006) and higher confidence in reliability of online information (OR: 2.61; 95 %CI: 1.09-6.26; p = 0.031). No association was found with age, sex, years in epilepsy practice or easiness to find online information. CONCLUSION: Internet is frequently used among healthcare professionals involved in the epilepsy to obtain information about this disease. The attitude of being influenced by the Internet for diagnostic and/or therapeutic decisions in epilepsy is independent on age and years of experience in epilepsy, and probably reflects an individual approach towards the Web.
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Epilepsia , Uso de Internet , Médicos/estadística & datos numéricos , Encuestas y Cuestionarios , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND AND PURPOSE: Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight correlations between neuropathology and ultra-high-field imaging. MATERIALS AND METHODS: Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality. RESULTS: We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (n = 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (n = 1/4) and in all those with focal cortical dysplasia IIb (n = 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (n = 4/5), while its incomplete removal yielded unsatisfactory results (n = 1/5). CONCLUSIONS: The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures.
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Imagen por Resonancia Magnética/métodos , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Neuroimagen/métodos , Adolescente , Adulto , Epilepsia Refractaria/etiología , Epilepsia Refractaria/cirugía , Femenino , Humanos , Masculino , Malformaciones del Desarrollo Cortical/complicaciones , Persona de Mediana EdadRESUMEN
Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.
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Electroencefalografía , Epilepsias Parciales/fisiopatología , Sueño REM/fisiología , Encéfalo/patología , Encéfalo/fisiopatología , Epilepsias Parciales/patología , Epilepsia/patología , Epilepsia/fisiopatología , Femenino , Hipocampo/patología , Hipocampo/fisiopatología , Humanos , Masculino , Malformaciones del Desarrollo Cortical de Grupo I/patología , Malformaciones del Desarrollo Cortical de Grupo I/fisiopatología , Convulsiones/fisiopatologíaRESUMEN
Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, headaches, intracerebral hemorrhages, and focal neurological deficits; they can also be clinically silent and occur as a sporadic or an autosomal dominant condition. Three genes have been identified as causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3, mapping, respectively, on chromosomes 7q, 7p, and 3q. Here, we report an Italian family affected by CCM due to a MGC4607 gene mutation, on exon 4. All the affected subjects suffered from seizures, and some of them underwent surgery for removal of a cavernous angioma. Brain MRI showed multiple lesions consistent with CCMs in all patients. Spinal and cutaneous cavernous angiomas were present too. This report underlines the need for a careful interdisciplinarity among neurologists, neuroradiologists, neurosurgeons, geneticists, ophthalmologists, and dermatologists for a total evaluation of the different manifestations of familial CCM. This points out that only referral centers are organized to offer a multidisciplinary management of this disease.
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Proteínas Portadoras/genética , Neoplasias del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Mutación , Neoplasias Cutáneas/genética , Adolescente , Adulto , Anciano , Neoplasias del Sistema Nervioso Central/diagnóstico , Niño , Exones , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico , Humanos , Masculino , Linaje , Neoplasias Cutáneas/diagnósticoRESUMEN
PURPOSE: StereoElectroEncephaloGraphy (SEEG) is done to identify the epileptogenic zone of the brain using several multi-lead electrodes whose positions in the brain are pre-operatively defined. Intracranial hemorrhages due to disruption of blood vessels can cause major complications of this procedure ([Formula: see text]1%). In order to increase the intervention safety, we developed and tested planning tools to assist neurosurgeons in choosing the best trajectory configuration. METHODS: An automated planning method was developed that maximizes the distance of the electrode from the vessels and avoids the sulci as entry points. The angle of the guiding screws is optimized to reduce positioning error. The planner was quantitatively and qualitatively compared with manually computed trajectories on 26 electrodes planned for three patients undergoing SEEG by four neurosurgeons. Quantitative comparison was performed computing for each trajectory using (a) the Euclidean distance from the closest vessel and (b) the incidence angle. RESULTS: Quantitative evaluation shows that automatic planned trajectories are safer in terms of distance from the closest vessel with respect to manually planned trajectories. Qualitative evaluation performed by four neurosurgeons showed that the automatically computed trajectories would have been preferred to manually computed ones in 30% of the cases and were judged good or acceptable in about 86% of the cases. A significant reduction in time required for planning was observed with the automated system (approximately 1/10). CONCLUSION: The automatic SEEG electrode planner satisfied the essential clinical requirements, by providing safe trajectories in an efficient timeframe.
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Electrodos Implantados , Electroencefalografía/métodos , Epilepsia/cirugía , Adulto , Femenino , Lóbulo Frontal/cirugía , Humanos , Hemorragias Intracraneales/prevención & control , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Técnicas Estereotáxicas , Lóbulo Temporal/cirugíaRESUMEN
Cerebral cavernous malformations (CCMs) are a diffuse cerebrovascular disease affecting approximately 0.5% of the population. A CCM is characterized by abnormally enlarged and leaky capillaries arranged in mulberry-like structures with no clear flow pattern. The lesion might predispose to seizures, focal neurological deficits or fatal intracerebral hemorrhage. However, a CCM can also remain neurologically silent. It might either occur sporadically or as an inherited disorder with incomplete penetrance and variable expressivity. Due to advances in imaging techniques, the incidence of CCM diagnoses are increasing, and the patient must be managed on a multidisciplinary basis: genetic counselling, treatment if needed, and follow-up. Advances have been made using radiological and pathological correlates of CCM lesions adding to the accumulated knowledge of this disease, although management of these patients is very variable among centers. This review is aimed at providing an update in genetic and molecular insights of this condition. Included are implications for genetic counselling, and possible approaches to prevention and treatment that derive from the understanding of pathogenetic mechanisms.
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Encéfalo , Sistema Nervioso Central/patología , Hemangioma Cavernoso del Sistema Nervioso Central , Proteínas Asociadas a Microtúbulos , Proteínas Proto-Oncogénicas , Encéfalo/metabolismo , Encéfalo/patología , Sistema Nervioso Central/metabolismo , Hemorragia Cerebral/genética , Hemorragia Cerebral/patología , Asesoramiento Genético , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/fisiopatología , Hemangioma Cavernoso del Sistema Nervioso Central/terapia , Humanos , Proteína KRIT1 , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Terapia Molecular Dirigida , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Convulsiones/genética , Convulsiones/patologíaRESUMEN
BACKGROUND: Sleep-related complex motor seizures have long been considered pathognomonic features of Nocturnal Frontal Lobe Epilepsy (NFLE). In recent years, these manifestations have also been reported to have a temporal or insular origin. METHOD: We describe 40 drug-resistant epileptic patients with complex motor seizures during sleep, submitted to presurgical stereo-EEG (SEEG) evaluation and seizure-free after surgical resection of the epileptogenic zone. RESULTS: In a significant proportion (30%) of these patients, seizures arose from extra-frontal regions, including mainly the temporal lobe and the insular cortex, but also the parietal and occipital lobes. In patients with extra-frontal epilepsy, when complex motor behaviors appeared, SEEG revealed that the ictal discharge involved the cingulate and the frontal regions. Finally, at histology, Taylor's focal cortical dysplasia (TFCD) was the most common finding (90% of patients), independent of the site of seizure onset. CONCLUSION: As previously reported by other studies, this histologic substrate may be a major determinant of sleep-related seizures in drug-resistant epileptic patients.
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Epilepsia/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Adolescente , Encéfalo/patología , Encéfalo/fisiopatología , Encéfalo/cirugía , Niño , Preescolar , Electroencefalografía , Epilepsia/complicaciones , Epilepsia/patología , Epilepsia/cirugía , Femenino , Humanos , Lactante , Masculino , Polisomnografía , Sueño/fisiología , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/patología , Trastornos del Sueño-Vigilia/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
In the Italian oenological industry, the regular practice used to naturally increase the colour of red wines consists in blending them with a wine very rich in anthocyanins, namely Rossissimo. In the Asian market, on the other hand, anthocyanins extracted by black rice are frequently used as correctors for wine colour. This practice does not produce negative effects on health; however, in many countries, it is considered as a food adulteration. The present study is therefore aimed to discriminate wines containing anthocyanins originated from black rice and grapevine by using reliable spectroscopic techniques requiring minimum sample preparation. Two series of samples have been prepared from five original wines, that were added with different amounts of Rossissimo or of black rice anthocyanins solution, until the desired Colour Index was reached. The samples have been analysed by FT-NIR and (1)H NMR spectroscopies and the resulting spectra matrices were subjected to multivariate classification. Initially, PLS-DA was used as classification method, then also variable selection/classification methods were applied, i.e. iPLS-DA and WILMA-D. The classification with variable selection of NIR spectra permitted to classify the test set samples with an efficiency of about 70%. Probably these not excellent performances are due to the matrix effect, together with the lack of sensitivity of NIR with respect to minor compounds. On the contrary, very satisfactory results were obtained on NMR spectra in the aromatic region between 6.5 and 9.5 ppm. The classification method based on wavelet-based variables selection, permitted to reach an efficiency in validation greater than 95%. Finally, 2D correlation analysis was applied to FT-NIR and (1)H NMR matrices, in order to recognise the spectral zones bringing the same chemical information.
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Antocianinas/análisis , Espectroscopía de Resonancia Magnética/métodos , Espectroscopía Infrarroja Corta/métodos , Vino/análisis , Análisis de Fourier , Hidrógeno/química , Análisis de los Mínimos Cuadrados , Oryza/química , Análisis de Componente Principal , Vitis/químicaRESUMEN
OBJECTIVE: The primary goal was to identify risk factors for post-surgical depression in subjects operated on for drug-resistant epilepsy. Secondary goals were to confirm the high rate of depression in subjects suffering from epilepsy (prior to surgery) and to look for first post-surgical depressive episode. METHODS: Case series study of 150 subjects surgically treated for partial epilepsy (side of surgery: 72 right, 78 left; site of surgery: 97 Unilobar Temporal, 17 Unilobar Frontal, 14 Posterior, 22 Multilobar). All subjects routinely had three psychiatric evaluations: before surgery (baseline) and at 6 and 12 months after surgery. Psychiatric diagnoses were made according to DSM-IV-TR criteria. Bivariate (Fisher exact test and Kruskal-Wallis rank sum test) and multivariate (logistic regression model fitting) analyses were performed. RESULTS: Thirty-three (22%) subjects had post-surgical depressive episodes, 31 of them in the first 6 months. Fourteen out of 33 experienced depression for the first time. Post-surgical depressive episodes are not associated with gender, outcome on seizures, side/site of surgical resection, histological diagnosis, psychiatric diagnoses other than depression. Depressive episodes before surgery and older age at surgery time are risk factors for post-surgical depression (p= 0.0001 and 0.01, respectively, at logistic regression analysis). No protective factors were identified. CONCLUSIONS: Our data show that lifetime depressive episodes and older age at surgery time are risk factors for postsurgery depression. Moreover, a prospective study could be useful in order to assess whether depression is really a consequence of surgery.
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Trastorno Depresivo/diagnóstico , Epilepsias Parciales/cirugía , Complicaciones Posoperatorias/diagnóstico , Adulto , Factores de Edad , Estudios Transversales , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/psicología , Recurrencia , Factores de RiesgoRESUMEN
BACKGROUND: Gap junctions are specialized channels composed of several connexins, membrane proteins that mediate electrical and metabolic coupling between cells. Previous data have suggested that changes in the expression of Cx43, the main astrocytic Cx isoform, may be involved in seizure activity in human epileptic tissue. However, Cx43 has never been examined in focal cortical dysplasia (FCD) and in other human refractory epilepsies. METHODS: We analyzed Cx43 protein localization and Cx43 mRNA levels in surgical specimens of cortex from a cohort of patients with intractable epilepsy vs control nonepileptic tissue. Samples had neuropathologically defined diagnosis of cryptogenic epilepsy or epilepsy secondary to FCD. RESULTS: Cx43 immunoreactivity, which labeled punctate elements, did not reveal distinctive features in cryptogenic epilepsy and FCD type IA and IIA. A peculiar pattern of immunolabeling was instead observed in FCD type IIB, in which large aggregates of Cx43-immunopositive puncta were clustered around subsets of balloon cells and astrocytes. Further characterization revealed that these balloon cells do not express markers of precursor cells, such as CD34. Quantitative real-time reverse transcriptase PCR showed elevated levels of Cx43 transcript in a subgroup (25%) of cryptogenic epilepsy specimens compared to control and FCD ones. CONCLUSIONS: Our study points out that a rearrangement of Cx43-positive elements is part of abnormal tissue organization in FCD type IIB, and that cryptogenic epilepsies include forms with increased Cx43 mRNA expression. The data implicate functional consequences of altered Cx43 expression, and therefore of altered gap junctional coupling, in abnormal network properties of subtypes of human refractory epilepsies.
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Corteza Cerebral/metabolismo , Conexina 43/metabolismo , Epilepsia/patología , Adolescente , Adulto , Niño , Estudios de Cohortes , Conexina 43/genética , Femenino , Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/metabolismo , ARN Mensajero/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: The purpose of the study was to investigate the abnormalities of cortical lamination observed in temporal lobe specimens obtained during surgery for intractable temporal lobe epilepsy (TLE) with hippocampal sclerosis. Specifically, we aimed to 1) correlate high-field ex vivo MRI with histopathologic analysis and 2) evaluate the effect of tissue fixation on image contrast. METHODS: A cohort of 13 specimens was considered. T2-weighted imaging and relaxometry were performed during and after fixation using a 7-T experimental scanner. After imaging, the specimens were studied with histopathologic (Black Gold myelin fiber staining) and immunohistochemical (NeuN neuronal staining) methods in order to explore the correspondence between MRI and histopathologic features. RESULTS: The principal findings of this study are that 1) superior MRI contrast is obtained among the cortical layers using completely fixed specimens as opposed to recently excised tissue, 2) the intensity of the T2-weighted MRI signal is lowest (hypointensity) at the site of highest fiber concentration and cellular density, and highest (hyperintensity) when the density of fibers and cells is lowest, and 3) the MRI signal is altered in presence of abnormal cortical lamination (focal cortical dysplasia type IA). CONCLUSIONS: High resolution ex vivo MRI enables the study of intracortical organization in normal and pathologic areas. Comparisons between MRI, NeuN, and Black Gold indicate that the differences apparent in T2-weighted images are mainly related to fiber concentration, although neuronal density might also play a role.
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Epilepsia del Lóbulo Temporal/patología , Imagen por Resonancia Magnética/métodos , Lóbulo Temporal/patología , Adulto , Niño , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Temporal/anatomía & histología , Lóbulo Temporal/fisiopatologíaRESUMEN
The aim of this report is not to make a differential diagnosis between epileptic nocturnal seizures and non-epileptic sleep-related movement disorders, or parasomnias. On the contrary, our goal is to emphasize the commonly shared semiological features of some epileptic seizures and parasomnias. Such similar features might be explained by the activation of the same neuronal networks (so-called 'central pattern generators' or CPG). These produce the stereotypical rhythmic motor sequences - in other words, behaviours - that are adaptive and species-specific (such as eating/alimentary, attractive/aversive, locomotor and nesting habits). CPG are located at the subcortical level (mainly in the brain stem and spinal cord) and, in humans, are under the control of the phylogenetically more recent neomammalian neocortical structures, according to a simplified Jacksonian model. Based on video-polygraphic recordings of sleep-related epileptic seizures and non-epileptic events (parasomnias), we have documented how a transient "neomammalian brain" dysfunction - whether epileptic or not - can 'release' (disinhibition?) the CPG responsible for involuntary motor behaviours. Thus, in both epileptic seizures and parasomnias, we can observe: (a) oroalimentary automatisms, bruxism and biting; (b) ambulatory behaviours, ranging from the classical bimanual-bipedal activity of 'frontal' hypermotor seizures, epileptic and non-epileptic wanderings, and somnambulism to periodic leg movements (PLM), alternating leg muscle activation (ALMA) and restless legs syndrome (RLS); and (c) various sleep-related events such as ictal fear, sleep terrors, nightmares and violent behaviour.
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Conducta/fisiología , Epilepsia del Lóbulo Frontal/psicología , Instinto , Parasomnias/psicología , Convulsiones/psicología , Copulación/fisiología , Emociones/fisiología , Epilepsia del Lóbulo Frontal/fisiopatología , Humanos , Actividad Motora/fisiología , Boca , Trastornos del Movimiento/etiología , Trastornos del Movimiento/psicología , Parasomnias/fisiopatología , Convulsiones/fisiopatologíaRESUMEN
OBJECTIVE: To define distinctive features of nodular heterotopia in specimens derived from drug-resistant patients with epilepsy by evaluating mRNA expression of three different layer-specific markers: Rorbeta, Er81, and Nurr1. METHODS: We analyzed the expression profile of these genes, recognized as markers mainly expressed in layer IV for Rorbeta, in layer V for Er81, and in layer VI for Nurr1, in surgical samples from 14 epileptic patients, using in situ hybridization. Six patients had subcortical nodular heterotopia and 8 patients were controls. The intrinsic organization of nodular formations and of the overlaying neocortex was assessed. RESULTS: In all patients, the 3 selected genes showed high cortical laminar specificity. In subcortical nodular heterotopia, the different gene expression profiles revealed a rudimentary laminar organization of the nodules. In the overlaying cortex, fewer cells expressed the 3 genes in the appropriate specific layer as compared to controls. CONCLUSIONS: These data provide new insights into possible ontogenetic mechanisms of nodular heterotopia formation and show the potential role of layer-specific markers to elucidate the neuropathology of malformations of cortical development.
Asunto(s)
Corteza Cerebral/anomalías , Corteza Cerebral/patología , Heterotopia Nodular Periventricular/genética , Heterotopia Nodular Periventricular/patología , Adolescente , Adulto , Corteza Cerebral/fisiología , Niño , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Femenino , Perfilación de la Expresión Génica/métodos , Marcadores Genéticos/genética , Humanos , Masculino , Malformaciones del Desarrollo Cortical/genética , Malformaciones del Desarrollo Cortical/patología , Miembro 2 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Receptores Citoplasmáticos y Nucleares/biosíntesis , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Adulto JovenRESUMEN
Of the cases with nocturnal frontal lobe epilepsy (NFLE) approximately 30% are refractory to antiepileptic medication, with several patients suffering from the effects of both ongoing seizures and disrupted sleep. From a consecutive series of 522 patients operated on for drug-resistant focal epilepsy, 21 cases (4%), whose frontal lobe seizures occurred almost exclusively (>90%) during sleep, were selected. All patients underwent a comprehensive pre-surgical evaluation, which included history, interictal EEG, scalp video-EEG monitoring, high-resolution MRI and, when indicated, invasive recording by stereo-EEG (SEEG). There were 11 males and 10 females, whose mean age at seizure onset was 6.2 years, mean age at surgery was 24.7 years and seizure frequency ranged from <20/month to >300/month. Nine patients reported excessive daytime sleepiness (EDS). Prevalent ictal clinical signs were represented by asymmetric posturing (6 cases), hyperkinetic automatisms (10 cases), combined tonic posturing and hyperkinetic automatisms (4 cases) and mimetic automatisms (1 case). All patients reported some kind of subjective manifestations. Interictal and ictal EEG provided lateralizing or localizing information in most patients. MRI was unrevealing in 10 cases and it showed a focal anatomical abnormality in one frontal lobe in 11 cases. Eighteen patients underwent a SEEG evaluation to better define the epileptogenic zone (EZ). All patients received a microsurgical resection in one frontal lobe, tailored according to pre-surgical evaluations. Two patients were operated on twice owing to poor results after the first resection. Histology demonstrated a Taylor-type focal cortical dysplasia (FCD) in 16 patients and an architectural FCD in 4. In one case no histological change was found. After a post-operative follow-up of at least 12 months (mean 42.5 months) all the 16 patients with a Taylor's FCD were in Engel's Class Ia and the other 5 patients were in Engel's Classes II or III. After 6 months post-surgery EDS had disappeared in the 9 patients who presented this complaint pre-operatively. It is concluded that patients with drug-resistant, disabling sleep-related seizures of frontal lobe origin should be considered for resective surgery, which may provide excellent results both on seizures and on epilepsy-related sleep disturbances. An accurate pre-surgical evaluation, which often requires invasive EEG recording, is mandatory to define the EZ. Further investigation is needed to explain the possible causal relationships between FCD, particularly Taylor-type, and sleep-related seizures, as observed in this cohort of NFLE patients.
Asunto(s)
Epilepsia del Lóbulo Frontal/cirugía , Sueño , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Mapeo Encefálico/métodos , Niño , Ritmo Circadiano , Resistencia a Medicamentos , Electroencefalografía/métodos , Epilepsia del Lóbulo Frontal/tratamiento farmacológico , Epilepsia del Lóbulo Frontal/patología , Epilepsia del Lóbulo Frontal/fisiopatología , Femenino , Estudios de Seguimiento , Lóbulo Frontal/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Microcirugia/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Grabación en VideoRESUMEN
The clinical features of nocturnal frontal lobe epilepsy (NFLE) consist of a spectrum of paroxysmal motor manifestations ranging from minor motor events (MMEs) to paroxysmal arousals (PAs) and major seizures. During MMEs and PAs scalp EEG generally does not show definite ictal abnormalities. We describe the clinical and electrophysiological features of three patients affected by drug-resistant NFLE studied with intracerebral electrodes during a presurgical evaluation. The stereo-EEG (SEEG) investigation revealed that MMEs can be fragments of the major seizure and occur during a brief epileptic discharge or on the following arousal. PAs, in the same subject, do not show a definite stereotypy despite the morphological and topographic similarity of the epileptic discharges, thus indicating that other variables may influence the clinical features of PAs.
Asunto(s)
Encéfalo/fisiopatología , Epilepsia del Lóbulo Frontal/diagnóstico , Parasomnias/diagnóstico , Adulto , Electroencefalografía , Electrofisiología , Epilepsia del Lóbulo Frontal/complicaciones , Epilepsia del Lóbulo Frontal/fisiopatología , Femenino , Humanos , Masculino , Parasomnias/complicaciones , Parasomnias/fisiopatologíaRESUMEN
Hyperkinetic seizures are considered a typical manifestation of nocturnal frontal lobe epilepsy (NFLE). Patients with temporal lobe epilepsy with mainly sleep-related seizures have been described; however they commonly lack hyperkinetic activity and seizure frequency is low. We retrospectively analysed our population of 442 consecutive patients surgically treated between January 1996 and January 2004. Among these there were 25 patients with sleep-related hyperkinetic epileptic seizures, with a frontal lobe onset in 18 cases and a temporal lobe onset in 7. Patients with sleep-related hyperkinetic seizures with temporal lobe origin had anamnestic and clinical features strikingly similar to those with a frontal onset, with agitated movements, high seizure frequency and no history of febrile convulsions. We confirm our previous findings that this kind of epileptic manifestation is not only peculiar to frontal lobe epilepsy.