RESUMEN
BACKGROUND: Centralized management of queues helps to reduce the surgical waiting time in the publicly funded healthcare system, but this is not a reality in the Brazilian Unified Healthcare System (BUHS). We describe the implementation of the "Patients with Surgical Indication" (PSI) in a Brazilian public tertiary hospital, the impact on waiting time, and its use in rationing oncological surgeries during the COVID-19 Pandemic. METHODS: Retrospective observational study of elective surgical requests (2016-2022) in a Brazilian general, public, tertiary university hospital. We recovered information regarding the inflows (indications), outflows and their reasons, the number of patients, and waiting time in queue. RESULTS: We enrolled 82,844 indications in the PSI (2016-2022). The waiting time (median and interquartile range) in days decreased from 98(48;168) in 2016 to 14(3;152) in 2022 (p < 0.01). The same occurred with the backlog that ranged from 6,884 in 2016 to 844 in 2022 (p < 001). During the Pandemic, there was a reduction in the number of non-oncological surgeries per month (95% confidence interval) of -10.9(-18.0;-3.8) during Phase I (January 2019-March 2020), maintenance in Phase II (April 2020-August 2021) 0.1(-10.0;10.4) and increment in Phase III (September 2021-December 2022) of 23.0(15.3;30.8). In the oncological conditions, these numbers were 0.6(-2.1;3.3) for Phase I, an increase of 3.2(0.7;5.6) in Phase II and 3.9(1,4;6,4) in Phase III. CONCLUSION: Implementing a centralized list of surgical indications and developing queue management principles proved feasible, with effective rationing. It unprecedentedly demonstrated the decrease in the median waiting time in Brazil.
Asunto(s)
Pandemias , Listas de Espera , Humanos , Brasil/epidemiología , Procedimientos Quirúrgicos Electivos , Hospitales Públicos , Estudios RetrospectivosRESUMEN
OBJECTIVE: People with epilepsy are at an increased risk of experiencing executive dysfunction, particularly those with frontal lobe epilepsy (FLE). The literature has also demonstrated alterations in executive functioning (EF) in patients with temporal lobe epilepsy (TLE). However, few studies have examined the neuropsychological profile of posterior cortex epilepsy (PCE), and little attention has been given to cognitive impairments in the pediatric population with PCE. This study aims to investigate EF performance in children with drug-resistant PCE compared to patients with FLE and TLE. METHODS: We analyzed neuropsychological data from 217 patients aged 6-18 years who underwent preoperative evaluation for epilepsy surgery. The EF of patients with PCE was compared to patients with FLE and TLE. RESULTS: There was no significant difference in Full-Scale Intelligence Quotient (FSIQ) means between groups. However, we found a significant effect of brain region on the Coding task, in which patients with PCE and FLE performed worse than those with TLE (p = 0.034). We also observed performance differences between groups on the Stroop test (p = 0.005), with patients with PCE and FLE performing worse than the TLE group. SIGNIFICANCE: These findings suggest that children with PCE have alterations in their EF that are similar to the deficits found in FLE compared to patients with TLE. This emphasizes the importance of understanding the neuroanatomy of executive functions and the model of neural networks extending beyond the prefrontal cortex.
Asunto(s)
Epilepsia del Lóbulo Frontal , Epilepsia del Lóbulo Temporal , Humanos , Niño , Función Ejecutiva , Pruebas Neuropsicológicas , Encéfalo , Lóbulo FrontalRESUMEN
Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and is frequently drug-resistant (DR) to antiseizure medication (ASM), corresponding to approximately one-third of the cases. When left inadequately treated, it can worsen the quality of life, cognitive deficits, and risk of death. The standard treatment for drug-resistant TLE is the surgical removal of the structures involved, with good long-term outcome rates of 60-70 % and a low rate of adverse effects. The goal of successful treatment is sustained seizure freedom. In our study, we evaluated sustained long-term (up to 23 years) surgical outcomes in 621 patients with DR-TLE associated with hippocampal sclerosis, who underwent a temporal lobectomy. We analyzed the main predictive factors that influence the surgical outcome related to seizure control, through a longitudinal and retrospective study, using a multivariable regression model. We found that 73.6% of the patients were free from disabling seizures (Engel Class I), maintained over time in 65% of patients followed up to 23 years after surgery. We found that four independent variables predicted seizure outcomes. The presence of dysmnesic and olfactory aura predicted a less favorable outcome. The history of febrile seizure and the surgical technique predicted a good outcome. Regarding the type of surgical technique, the standard anteromesial temporal lobectomy (ATL) led to significantly better outcomes (78.6% Engel Class I) when compared to the selective amygdalohippocampectomy via subtemporal approach (67.2% Engel Class I; p = 0.002), suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial temporal structures. The multivariable regression model with the above-mentioned predictor variables revealed an ExpB = 3.627 (N = 621, p < 0.001), indicating that the model was able to distinguish between patients with a seizure-free. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.
RESUMEN
BACKGROUND: Cognitive functioning in epileptic syndromes has been widely explored in patients with temporal lobe epilepsy (TLE), but few studies have investigated the neuropsychological profile in posterior cortex epilepsy (PCE). In this study, we investigated the presurgical intellectual profile of children and adolescents with drug-resistant PCE. METHODS: Children and adolescents diagnosed with PCE (nâ¯=â¯25) participated in this study. The data were obtained from medical records, with assessments carried out between the years 2003 and 2019. To compare the intellectual profile, we also included patients diagnosed with frontal (nâ¯=â¯26) and temporal lobe epilepsy (nâ¯=â¯40). The Wechsler Intelligence Scales were used for the assessment of general intelligence. RESULTS: There was an effect of the brain region on the Working Memory Index (pâ¯<â¯0.01), in which patients with TLE had significantly higher scores than groups with FLE (pâ¯<â¯0.01) and PCE (pâ¯<â¯0.05). We also demonstrated that patients with PCE tended to perform worse in the Processing Speed Index than patients with TLE (pâ¯=â¯0.055). The Full-Scale Intelligence Quotient, Verbal Comprehension, and Perceptual Reasoning indexes did not differ among the brain regions. CONCLUSIONS: Children and adolescents with PCE demonstrated significant impairment in working memory and processing speed. The pattern of cognitive dysfunction in PCE was similar to that observed in FLE, which expands the evidence of the involvement of frontoparietal networks on cognitive proficiency.
Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Adolescente , Niño , Cognición , Epilepsia del Lóbulo Temporal/complicaciones , Humanos , Inteligencia , Pruebas NeuropsicológicasRESUMEN
MicroRNAs have been progressively investigated as post-transcriptional regulators playing important roles in epilepsy pathophysiology. Here we investigate three promising microRNAs (miR-27a-3p, miR-328-3p and miR-654-3p) previously described in the literature as possible peripheral biomarkers for epilepsy diagnose and surgical prognosis. Serum samples from 28 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) were analyzed, 14 with good surgical prognosis (Engel I) and 14 with unfavorable surgical prognosis (Engel III-IV). Serum samples from 11 healthy volunteers were the control group. The microRNAs expression analysis was performed using real-time PCR. The present results did not endorse the role of miR-27a-3p as a peripheral biomarker for epilepsy diagnosis or surgical prognosis. MiR-328-3p, however, presented significant area under the curve (AUC) values when comparing controls to Engel I (90.3%), controls to Engel III-IV (96.8%) and controls to Engel I + Engel III-IV (i.e., epilepsy patients, AUC = 93.5%). Additionally, miR-654-3p displayed AUC = 74.7% when comparing controls to Engel I patients (p = 0.004), and AUC = 73.6% (p = 0.04) in the attempt to discriminate unfavorable from favorable surgical prognosis. In conclusion, the ANOVA and ROC analyzes with the respective AUC, specificity and sensitivity values allows us to conclude that miR-328-3p is the most important peripheral biomarker for the diagnosis of MTLE-HS. In terms of predicting the surgical prognosis of MTLE-HS patients, miR-654-3p proved to be the only microRNA evaluated to present statistical power to differentiate, as a peripheral biomarker, Engel I from Engel III-IV patients.
Asunto(s)
MicroARN Circulante/sangre , Epilepsia del Lóbulo Temporal/metabolismo , Epilepsia del Lóbulo Temporal/cirugía , Hipocampo/metabolismo , Hipocampo/patología , Adulto , Biomarcadores/sangre , MicroARN Circulante/genética , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/genética , Femenino , Estudios de Seguimiento , Expresión Génica , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Valor Predictivo de las Pruebas , Esclerosis , Resultado del TratamientoRESUMEN
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.
Asunto(s)
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
Mesial temporal lobe epilepsy with hippocampal sclerosis is the most frequent form of focal epilepsy in adults, and it is often refractory to drug treatment. Regardless of the efforts on developing new antiepileptic drugs for refractory cases, studies suggest a need for better understanding the molecular bases of epilepsy. The microRNAs have been progressively investigated as potential targets for both epilepsy mechanisms elucidation and treatment. Therefore, the goal of this study was to evaluate the differential expression of miR-219, miR-181b, and miR-195, previously described as regulators of the excitatory neurotransmitter receptors NMDA-R1 and AMPA-GluR2 and inhibitory neurotransmitter GABAA (α2, ß3, and γ2 subunits) in the amygdala and hippocampus of patients with mesial temporal lobe epilepsy. Based on genes and miRNAs' quantitative Polymerase Chain Reaction (qPCR) from 18 patients with epilepsy, our results showed an inverse relationship between miR-219 and NMDA-NR1 expression in both the amygdala and hippocampus in comparison to their expression in controls. NR1 and GluR2 were upregulated in the amygdala of epileptic patients. Low miR-195 expression was observed in the amygdala of patients with epilepsy. Our findings indicate that miR-219 has a possible regulatory role in excitatory neurotransmission in patients with epilepsy, contributing to the new avenue of miRNA biology in drug-resistant epilepsy, reserving huge potential for future applications and clinical interventions in conjunction with existing therapies.
Asunto(s)
Epilepsia del Lóbulo Temporal/metabolismo , MicroARNs/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Amígdala del Cerebelo/metabolismo , Epilepsia del Lóbulo Temporal/genética , Regulación de la Expresión Génica/genética , Hipocampo/metabolismo , Humanos , Regulación hacia ArribaRESUMEN
The aim of this study was to analyze the expression profiles of the microRNAs (miRNAs) miR-145, miR-181c, miR-199a and miR-1183 in the hippocampus and blood of patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate whether these can be used as diagnosis and prognosis biomarkers for epilepsy. Hippocampus and blood samples were collected from 20 patients with MTLE-HS, ten of whom had a favorable surgical outcome (Engel I) and ten with an unfavorable surgical outcome (Engel III-IV). Hippocampus samples from autopsied individuals with no neurological or psychiatric medical history (necropsy samples) and blood samples from healthy individuals were used as controls. Real-time quantitative PCR (RQ-PCR) was used to analyze miRNA expression. The results showed that the expressions of these miRNAs differed quantitatively in the hippocampus and blood of patients with MTLE-HS in comparison to the respective control. This difference was most pronounced for miR-145, which was hypo-expressed in the hippocampus and hyper-expressed in the blood of MTLE-HS patients. MiRNAs miR-145, miR-181c, miR-199a and miR-1183 were hyper-expressed in the blood of patients with MTLE-HS. No statistical differences in the levels of these miRNAs in the blood or hippocampus were found between Engel I patients and Engel III-IV patients. These results suggest that the analyzed microRNAs are potential circulating biomarkers for epilepsy diagnosis.
Asunto(s)
Epilepsia del Lóbulo Temporal/diagnóstico , Hipocampo/metabolismo , MicroARNs/genética , Adulto , Biomarcadores/sangre , Biomarcadores/metabolismo , Epilepsia del Lóbulo Temporal/sangre , Epilepsia del Lóbulo Temporal/genética , Epilepsia del Lóbulo Temporal/metabolismo , Femenino , Humanos , Masculino , MicroARNs/sangre , MicroARNs/metabolismo , Persona de Mediana EdadRESUMEN
OBJECTIVES: Approximately one-third of candidates for epilepsy surgery have no visible abnormalities on conventional magnetic resonance imaging. This is extremely discouraging, as these patients have a less favorable prognosis. We aimed to evaluate the utility of quantitative magnetic resonance imaging in patients with drug-resistant neocortical focal epilepsy and negative imaging. METHODS: A prospective study including 46 patients evaluated through individualized postprocessing of five quantitative measures: cortical thickness, white and gray matter junction signal, relaxation rate, magnetization transfer ratio, and mean diffusivity. Scalp video-electroencephalography was used to suggest the epileptogenic zone. A volumetric fluid-attenuated inversion recovery sequence was performed to aid visual inspection. A critical assessment of follow-up was also conducted throughout the study. RESULTS: In the subgroup classified as having an epileptogenic zone, individualized postprocessing detected abnormalities within the region of electroclinical origin in 9.7% to 31.0% of patients. Abnormalities outside the epileptogenic zone were more frequent, up to 51.7%. In five patients initially included with negative imaging, an epileptogenic structural abnormality was identified when a new visual magnetic resonance imaging inspection was guided by information gleaned from postprocessing. In three patients, epileptogenic lesions were detected after visual evaluation with volumetric fluid-attenuated sequence guided by video electroencephalography. CONCLUSION: Although quantitative magnetic resonance imaging analyses may suggest hidden structural lesions, caution is warranted because of the apparent low specificity of these findings for the epileptogenic zone. Conversely, these methods can be used to prevent visible lesions from being ignored, even in referral centers. In parallel, we need to highlight the positive contribution of the volumetric fluid-attenuated sequence.
Asunto(s)
Epilepsia Refractaria/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Mapeo Encefálico , Diagnóstico por Computador/métodos , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVES: Approximately one-third of candidates for epilepsy surgery have no visible abnormalities on conventional magnetic resonance imaging. This is extremely discouraging, as these patients have a less favorable prognosis. We aimed to evaluate the utility of quantitative magnetic resonance imaging in patients with drug-resistant neocortical focal epilepsy and negative imaging. METHODS: A prospective study including 46 patients evaluated through individualized postprocessing of five quantitative measures: cortical thickness, white and gray matter junction signal, relaxation rate, magnetization transfer ratio, and mean diffusivity. Scalp video-electroencephalography was used to suggest the epileptogenic zone. A volumetric fluid-attenuated inversion recovery sequence was performed to aid visual inspection. A critical assessment of follow-up was also conducted throughout the study. RESULTS: In the subgroup classified as having an epileptogenic zone, individualized postprocessing detected abnormalities within the region of electroclinical origin in 9.7% to 31.0% of patients. Abnormalities outside the epileptogenic zone were more frequent, up to 51.7%. In five patients initially included with negative imaging, an epileptogenic structural abnormality was identified when a new visual magnetic resonance imaging inspection was guided by information gleaned from postprocessing. In three patients, epileptogenic lesions were detected after visual evaluation with volumetric fluid-attenuated sequence guided by video electroencephalography. CONCLUSION: Although quantitative magnetic resonance imaging analyses may suggest hidden structural lesions, caution is warranted because of the apparent low specificity of these findings for the epileptogenic zone. Conversely, these methods can be used to prevent visible lesions from being ignored, even in referral centers. In parallel, we need to highlight the positive contribution of the volumetric fluid-attenuated sequence.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Imagen por Resonancia Magnética/métodos , Epilepsia Refractaria/diagnóstico por imagen , Mapeo Encefálico , Estudios Prospectivos , Diagnóstico por Computador/métodos , Electroencefalografía/métodos , Imagen MultimodalRESUMEN
Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is one of the most common types of focal epilepsies. This is an epileptic syndrome commonly associated with treatment-resistant seizures, being also the most prevalent form of drug-resistant epilepsy which is treated surgically in most epilepsy surgery centers. Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system, and one of the most common etiological agents of focal epilepsy, affecting millions of patients worldwide. Recently, researchers reported a curious association between MTLE-HS with NCC, but this association remains poorly understood. Some argue that calcified NCC lesions in MTLE-HS patients is only a coincidental finding, since both disorders are prevalent worldwide. However, others suppose there might exist a pathogenic relationship between both disorders and some even suspect that NCC, by acting as an initial precipitating injury (IPI), might cause hippocampal damage and, eventually, MTLE-HS. In this review, we discuss the various reports that examine this association, and suggest possible explanations for why calcified NCC lesions are also observed in patients with MTLE-HS. We also propose mechanisms by which NCC could lead to MTLE-HS. Finally, we discuss the implications of NCC for the treatment of pharmacologically-resistant focal epilepsies in patients with calcified NCC or in patients with MTLE-HS and calcified NCC lesions. We believe that investigations in the relationship between NCC and MTLE-HS might offer further insights into how NCC may trigger epilepsy, and into how MTLE-HS originates. Moreover, observations in patients with drug-resistant epilepsy with both NCC and hippocampal sclerosis may not only aid in the understanding and treatment of patients with MTLE-HS, but also of patients with other forms of dual pathologies aside from NCC. This article is part of a Special Issue titled Neurocysticercosis and Epilepsy.
Asunto(s)
Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/complicaciones , Neurocisticercosis/complicaciones , Adulto , Epilepsia Refractaria/complicaciones , Epilepsia/complicaciones , Femenino , Hipocampo/patología , Humanos , Masculino , Convulsiones/complicaciones , Convulsiones/cirugíaRESUMEN
OBJECTIVE: Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. METHODS: We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. RESULTS: Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. SIGNIFICANCE: Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.
Asunto(s)
Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/psicología , Hipocampo/patología , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/psicología , Memoria Episódica , Adolescente , Adulto , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Humanos , Masculino , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Esclerosis/complicaciones , Esclerosis/patología , Esclerosis/psicología , Adulto JovenRESUMEN
OBJECTIVE: Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE. METHODS: Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated microglia (human leukocyte antigen-D-related [HLA-DR]), polarized AQP4, and CSPG. RESULTS: Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus. SIGNIFICANCE: Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE.
Asunto(s)
Acuaporina 4/metabolismo , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Epilepsia del Lóbulo Temporal/patología , Gliosis/etiología , Hipocampo/metabolismo , Hipocampo/patología , Adulto , Estudios de Casos y Controles , Imagen de Difusión Tensora , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/patología , Antígenos HLA/metabolismo , Hipocampo/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Neuroglía/metabolismo , Neuronas/metabolismo , Fosfopiruvato Hidratasa/metabolismo , Esclerosis/diagnóstico por imagen , Estadística como Asunto , Factores de TiempoRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0044709.].
RESUMEN
BACKGROUND: Decision-making abilities have rarely been examined in patients with temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). We aimed to investigate the ability to delay gratification, a decision-making subdomain, in patients with intractable TLE-HS and to verify the association of delay gratification performance and cool executive function tests. METHODS: We evaluated 27 patients with TLE-HS (mean age: 35.46 [±13.31] years; 7 males) and their cognitive performance was compared with that of 27 age- and gender-matched healthy controls (mean age: 35.33 [±12.05] years; 7 males), without epilepsy and psychiatric disorders. Patients were assessed using the delay discounting task (DDT) and tests of attention, shifting, inhibitory control, and concept formation. Results were correlated with clinical epilepsy variables such as age of onset, epilepsy duration, AED use, history of status epilepticus, febrile seizures, and the presence of generalized seizures. Statistical analysis was performed using one-way ANCOVA with years of education as a confounding factor. RESULTS: Patients and controls demonstrated similar performance on DDT, showing similar discount rate (p=0.935) and probability rate (p=0.585). Delay gratification was not related to cool executive function tests (Digit Span, Stroop Color Test, Trail Making Test, Wisconsin Card Sorting Test, and Connors' CPT). History of status epilepticus, presence of generalized seizures and higher seizure frequency, age at onset, and epilepsy duration had a significant impact on DDT. CONCLUSION: Patients with intractable TLE-HS showed unimpaired delay gratification abilities, being able to accept a higher delay and a lower amount of chance for receiving a higher reward in the future. Clinical variables related to the epilepsy severity impacted the performance on delay gratification. Impairment on cool aspects of executive function was unrelated to this decision-making domain.
Asunto(s)
Toma de Decisiones , Descuento por Demora , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/psicología , Hipocampo/patología , Adolescente , Adulto , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Esclerosis/patología , Adulto JovenRESUMEN
PURPOSE: To evaluate the efficacy of surgery with neuronavigation compared to conventional neurosurgical treatment of epilepsy in terms of safety and seizure outcomes and to assess the quality of the evidence base of neuronavigation in this clinical context. METHOD: Systematic review using the electronic databases of Cochrane, CRD, PubMed, Embase, SciELO and LILACS in Portuguese, English and Spanish. The [MeSH] terms included "epilepsy" and "neuronavigation". ELIGIBILITY CRITERIA: Studies assessing surgery with neuronavigation for the surgical treatment of epilepsy or brain injuries associated with epileptic seizures. RESULTS: We identified 28 original articles. All articles yielded scientific evidence of low quality. Outcome data presented in the articles identified was heterogeneous and did not amount to compelling evidence that epilepsy surgery with neuronavigation produces higher rates of seizure control, a reduced need for reoperations, or lower rates of complications or postoperative neurological deficits. CONCLUSION: We were unable to find any publications providing convincing evidence that neuronavigation improves outcomes of epilepsy surgery. Whilst this does not mean that neuronavigation cannot improve neurosurgical outcomes in this clinical setting, well-designed research studies evaluating the role of neuronavigation are urgently needed.
Asunto(s)
Epilepsia/cirugía , Neuronavegación , Convulsiones/cirugía , Ensayos Clínicos Controlados como Asunto , Epilepsia/fisiopatología , Humanos , Literatura de Revisión como Asunto , Convulsiones/fisiopatologíaRESUMEN
OBJECTIVE: Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. METHODS: Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. RESULTS: Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. SIGNIFICANCE: Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.
Asunto(s)
Sulfatos de Condroitina/metabolismo , Epilepsia del Lóbulo Temporal/patología , Hipocampo/metabolismo , Hipocampo/patología , Neuroglía/metabolismo , Neuronas/patología , Estudios de Casos y Controles , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Imagen por Resonancia Magnética , Masculino , Neuronas/metabolismo , Fosfopiruvato Hidratasa/metabolismo , Análisis de RegresiónRESUMEN
OBJECTIVE: Characterize the social profile and the need of information from patients with refractory epilepsy. METHOD: A semi-structured questionnaire was applied to 103 patients to investigate sociodemographic aspects, pharmacotherapy and any doubts about epilepsy. RESULTS: Patients were highly dependent on having a free and accessible supply of antiepileptic drugs. Sixty-eight percent of the population was unemployed, and 26% confirmed receiving social security benefits due to epilepsy. Twenty-nine percent of the population reached high school. Eighty-five percent of the patients had at least one doubt about epilepsy; treatment and epilepsy aspects in general were the main topics. CONCLUSION: As observed in developed countries, patients with refractory epilepsy from a developing country also have high rates of unemployment and low educational levels. The results raise a concern about the need of information about epilepsy by patients and their families, urging the necessity to invest in strategies to solve this deficiency in knowledge.
Asunto(s)
Epilepsia/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Centros de Atención Terciaria/estadística & datos numéricos , Adulto , Anticonvulsivantes/uso terapéutico , Brasil/epidemiología , Epilepsia/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Seguridad Social , Factores Socioeconómicos , Encuestas y Cuestionarios , Desempleo/estadística & datos numéricosRESUMEN
Interictal epileptiform discharges (IEDs) can produce haemodynamic responses that can be detected by electroencephalography-functional magnetic resonance imaging (EEG-fMRI) using different analysis methods such as the general linear model (GLM) of IEDs or independent component analysis (ICA). The IEDs can also be mapped by electrical source imaging (ESI) which has been demonstrated to be useful in presurgical evaluation in a high proportion of cases with focal IEDs. ICA advantageously does not require IEDs or a model of haemodynamic responses but its use in EEG-fMRI of epilepsy has been limited by its ability to separate and select epileptic components. Here, we evaluated the performance of a classifier that aims to filter all non-BOLD responses and we compared the spatial and temporal features of the selected independent components (ICs). The components selected by the classifier were compared to those components selected by a strong spatial correlation with ESI maps of IED sources. Both sets of ICs were subsequently compared to a temporal model derived from the convolution of the IEDs (derived from the simultaneously acquired EEG) with a standard haemodynamic response. Selected ICs were compared to the patients' clinical information in 13 patients with focal epilepsy. We found that the misclassified ICs clearly related to IED in 16/25 cases. We also found that the classifier failed predominantly due to the increased spectral range of fMRIs temporal responses to IEDs. In conclusion, we show that ICA can be an efficient approach to separate responses related to epilepsy but that contemporary classifiers need to be retrained for epilepsy data. Our findings indicate that, for ICA to contribute to the analysis of data without IEDs to improve its sensitivity, classification strategies based on data features other than IC time course frequency is required.
Asunto(s)
Mapeo Encefálico , Encéfalo/irrigación sanguínea , Epilepsias Parciales/patología , Imagen por Resonancia Magnética , Análisis de Componente Principal , Encéfalo/fisiopatología , Electroencefalografía , Epilepsias Parciales/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Oxígeno/sangre , Procesamiento de Señales Asistido por ComputadorRESUMEN
Objective Characterize the social profile and the need of information from patients with refractory epilepsy. Method A semi-structured questionnaire was applied to 103 patients to investigate sociodemographic aspects, pharmacotherapy and any doubts about epilepsy. Results Patients were highly dependent on having a free and accessible supply of antiepileptic drugs. Sixty-eight percent of the population was unemployed, and 26% confirmed receiving social security benefits due to epilepsy. Twenty-nine percent of the population reached high school. Eighty-five percent of the patients had at least one doubt about epilepsy; treatment and epilepsy aspects in general were the main topics. Conclusion : As observed in developed countries, patients with refractory epilepsy from a developing country also have high rates of unemployment and low educational levels. The results raise a concern about the need of information about epilepsy by patients and their families, urging the necessity to invest in strategies to solve this deficiency in knowledge. .
Objetivo : Caracterizar o perfil social e a necessidade de informações por parte de pacientes com epilepsia refratária. Método Um questionário semi-estruturado foi aplicado a 103 pacientes para investigar aspectos sociodemográficos, farmacoterapia e quaisquer dúvidas sobre epilepsia. Resultados Os pacientes mostraram-se altamente dependentes de um fornecimento gratuito e acessível de drogas antiepilépticas. Sessenta e oito por cento da população estava desempregada, e 26% confirmaram receber algum benefício social devido à epilepsia. Vinte e nove por cento da população alcançou ensino médio. Oitenta e cinco por cento dos pacientes tinha ao menos uma dúvida sobre epilepsia; tratamento e aspectos gerais da epilepsia foram os principais temas. Conclusão Tal qual observado em países desenvolvidos, pacientes com epilepsia refratária em países em desenvolvimento também apresentam altas taxas de desemprego e baixos níveis educacionais. Os resultados são preocupantes no que diz respeito à necessidade de informações sobre epilepsia por parte dos pacientes e seus familiares, apontando a necessidade de se investir em estratégias que solucionem esta deficiência de conhecimento. .