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PURPOSE: We assess whether alterations in the convolutional anatomy of the deep perisylvian area (DPSA) might indicate focal epileptogenicity. MATERIALS AND METHODS: The DPSA of each hemisphere was segmented on MRI and a 3D gray-white matter interface (GWMI) geometrical model was constructed. Comparative visual and quantitative assessment of the convolutional anatomy of both the left and right DPSA models was performed. Both the density of thorn-like contours (peak percentage) and coarse interface curvatures was computed using Gaussian curvature and shape index, respectively. The proposed method was applied to a total of 14 subjects; 7 patients with an epileptogenic DPSA and 7 non-epileptic subjects. RESULTS: A high peak percentage correlated well with the epileptogenic DPSA. It distinguished between patients and non-epileptic subjects (P = 0.029) and identified laterality of the epileptic focus in all but one case. A diminished regional curvature also identified epileptogenicity (P = 0.016) and, moreover, its laterality (P = 0.001). CONCLUSION: An increased peak percentage from a global view of the GWMI of the DPSA provides some indication of a propensity toward a focal or regional DPSA epileptogenicity. A diminished convolutional anatomy (i.e., smoothing effect) appears also to coincide with the epileptogenic site in the DPSA and to distinguish laterality.
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Epilepsia , Humanos , Epilepsia/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Corteza Cerebral , Sustancia Gris , Lateralidad Funcional , ElectroencefalografíaRESUMEN
BACKGROUND: A large number of patients have epilepsy that is intractable and adversely affects a child's lifelong experience with addition societal burden that is disabling and expensive. The last two decades have seen a major explosion of new antiseizure medication options. Despite these advances, children with epilepsy continue to have intractable seizures. An option that has been long available but little used is epilepsy surgery to control intractable epilepsy. METHODS: This article is a review of the literature as well as published opinions. RESULTS: Epilepsy surgery in pediatrics is an underused modality to effectively treat children with epilepsy. Adverse effects of medication should be weighed against risks of surgery as well as risks of nonefficacy. CONCLUSIONS: We discuss an approach to selecting the appropriate pediatric patient for consideration, a detailed evaluation including necessary evaluation, and the creation of an algorithm to approach patients with both generalized and focal epilepsy. We then discuss surgical options available including outcome data. New modalities are also addressed including high-frequency ultrasound and co-registration techniques including magnetic resonance imaging-guided laser therapy.
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Epilepsia Refractaria/cirugía , Epilepsias Parciales/cirugía , Epilepsia Generalizada/cirugía , Procedimientos Neuroquirúrgicos , Niño , Congresos como Asunto , Epilepsia Refractaria/diagnóstico , Epilepsias Parciales/diagnóstico , Epilepsia Generalizada/diagnóstico , Humanos , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/normas , Procedimientos Neuroquirúrgicos/tendenciasRESUMEN
The role of fast activity as a potential biomarker in localization of the epileptogenic zone (EZ) remains controversial due to recently reported unsatisfactory performance. We recently identified a "fingerprint" of the EZ as a time-frequency pattern that is defined by a combination of preictal spike(s), fast oscillatory activity, and concurrent suppression of lower frequencies. Here we examine the generalizability of the fingerprint in application to an independent series of patients (11 seizure-free and 13 non-seizure-free after surgery) and show that the fingerprint can also be identified in seizures with lower frequency (such as beta) oscillatory activity. In the seizure-free group, only 5 of 47 identified EZ contacts were outside the resection. In contrast, in the non-seizure-free group, 104 of 142 identified EZ contacts were outside the resection. We integrated the fingerprint prediction with the subject's MR images, thus providing individualized anatomical estimates of the EZ. We show that these fingerprint-based estimates in seizure-free patients are almost always inside the resection. On the other hand, for a large fraction of the nonseizure-free patients the estimated EZ was not well localized and was partially or completely outside the resection, which may explain surgical failure in such cases. We also show that when mapping fast activity alone onto MR images, the EZ was often over-estimated, indicating a reduced discriminative ability for fast activity relative to the full fingerprint for localization of the EZ.
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Ondas Encefálicas/fisiología , Corteza Cerebral/fisiopatología , Electrocorticografía/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Adolescente , Adulto , Biomarcadores , Corteza Cerebral/cirugía , Niño , Epilepsia/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Adulto JovenRESUMEN
OBJECTIVE: Patients with medically refractory localization-related epilepsy (LRE) may be candidates for surgical intervention if the seizure onset zone (SOZ) can be well localized. Stereoelectroencephalography (SEEG) offers an attractive alternative to subdural grid and strip electrode implantation for seizure lateralization and localization; yet there are few series reporting the safety and efficacy of SEEG in pediatric patients. METHODS: The authors review their initial 3-year consecutive experience with SEEG in pediatric patients with LRE. SEEG coverage, SOZ localization, complications, and preliminary seizure outcomes following subsequent surgical treatments are assessed. RESULTS: Twenty-five pediatric patients underwent 30 SEEG implantations, with a total of 342 electrodes placed. Ten had prior resections or ablations. Seven had no MRI abnormalities, and 8 had multiple lesions on MRI. Based on preimplantation hypotheses, 7 investigations were extratemporal (ET), 1 was only temporal-limbic (TL), and 22 were combined ET/TL investigations. Fourteen patients underwent bilateral investigations. On average, patients were monitored for 8 days postimplant (range 3-19 days). Nearly all patients were discharged home on the day following electrode explantation. There were no major complications. Minor complications included 1 electrode deflection into the subdural space, resulting in a minor asymptomatic extraaxial hemorrhage; and 1 in-house and 1 delayed electrode superficial scalp infection, both treated with local wound care and oral antibiotics. SEEG localized the hypothetical SOZ in 23 of 25 patients (92%). To date, 18 patients have undergone definitive surgical intervention. In 2 patients, SEEG localized the SOZ near eloquent cortex and subdural grids were used to further delineate the seizure focus relative to mapped motor function just prior to resection. At last follow-up (average 21 months), 8 of 15 patients with at least 6 months of follow-up (53%) were Engel class I, and an additional 6 patients (40%) were Engel class II or III. Only 1 patient was Engel class IV. CONCLUSIONS: SEEG is a safe and effective technique for invasive SOZ localization in medically refractory LRE in the pediatric population. SEEG permits bilateral and multilobar investigations while avoiding large craniotomies. It is conducive to deep, 3D, and perilesional investigations, particularly in cases of prior resections. Patients who are not found to have focally localizable seizures are spared craniotomies.
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Mapeo Encefálico/métodos , Electroencefalografía/métodos , Epilepsias Parciales/fisiopatología , Procedimientos Quirúrgicos Robotizados/métodos , Técnicas Estereotáxicas , Mapeo Encefálico/instrumentación , Niño , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/cirugía , Electrodos Implantados , Electroencefalografía/instrumentación , Epilepsias Parciales/cirugía , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Robotizados/instrumentación , Técnicas Estereotáxicas/instrumentaciónRESUMEN
OBJECTIVE: Previous findings have been mixed in terms of identifying a distinct pattern of neuropsychological deficits in children with frontal lobe epilepsy (FLE) and in those with temporal lobe epilepsy (TLE). The current study investigated the neuropsychological similarities and differences across these two pediatric medically intractable localization-related epilepsies. METHOD: Thirty-eight children with FLE, 20 children with TLE, and 40 healthy children (HC) participated in this study. A comprehensive battery of standardized tests assessed five neuropsychological domains including intelligence, language, memory, executive function, and motor function. A principal component analysis (PCA) was used to distill our neuropsychological measures into latent components to compare between groups. RESULTS: Principal component analysis extracted 5 latent components: executive function (F1), verbal semantics (F2), motor (F3), nonverbal cognition/impulsivity (F4), and verbal cognition/attention (F5). The group with FLE differed from the HC group on F1, F2, F4, and F5, and had worse performance than the group with TLE on F1; the group with TLE had lower performance relative to the HC group on F2. CONCLUSION: Our findings suggest that, in comparison with neurotypically developing children, children with medically intractable FLE have more widespread neuropsychological impairments than do children with TLE. The differences between the two patient groups were greatest for the factor score most clearly related to executive function. The results provide mixed support for the concept of specificity in neuropsychological dysfunction among different subtypes of localization-related medically intractable childhood epilepsies.
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Cognición , Epilepsia del Lóbulo Frontal/diagnóstico , Epilepsia del Lóbulo Temporal/diagnóstico , Adolescente , Estudios de Casos y Controles , Niño , Epilepsia del Lóbulo Frontal/fisiopatología , Epilepsia del Lóbulo Frontal/psicología , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/psicología , Función Ejecutiva/fisiología , Femenino , Humanos , Masculino , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Dysphoric disorder (DD), characterized by intermittent pleomorphic symptoms, has been believed to be specific to epilepsy. However, our previous study revealed that DD in patients with localization-related epilepsy was associated with a lifetime diagnosis of mood disorders. The present study was conducted to estimate the prevalence of DD in patients with mood disorders, but not epilepsy, and to identify the clinical similarities and differences of DD in patients with either epilepsy or mood disorders. METHODS: Subjects consisted of 104 patients with localization-related epilepsy (group E) and 101 patients with DSM-IV mood disorders, but not with epilepsy (group M). After a diagnostic investigation for DD and the euthymic state, defined as the absence of any mood episodes during the last 12months, we compared the clinical characteristics of DD in patients from groups E and M. RESULTS: Dysphoric disorder was apparently more common in group M (56.4%) than in group E (21.2%). However, 86.0% of patients in group M showed a temporal overlap between DD and the noneuthymic state, while 68.2% of patients in group E did not show this overlap. Moreover, the noneuthymic state was significantly associated with symptoms of DD, indicating that the diagnosis of DD was more likely to be overestimated when the subjects were in a noneuthymic state. The prevalence of DD, temporally independent of the noneuthymic state (pure DD), was estimated at 13.4% and 7.0% in groups E and M, respectively, and pure DD was 1.91 times more common in patients with epilepsy than in those with mood disorders. Diagnosis of pure DD was significantly associated with increased suicidality in group E, but not group M. CONCLUSION: The present results suggest that DD is more familiar to epilepsy than mood disorders, although DD is not specific to epilepsy. Moreover, suicidality is specifically associated with DD in patients with epilepsy.
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Trastorno Depresivo/epidemiología , Epilepsias Parciales/epidemiología , Trastornos del Humor/epidemiología , Adulto , Comorbilidad , Femenino , Humanos , Japón , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Epilepsy is considered to arise from dysfunction in neural networks. Recent advances in neuroimaging and its analysis have made it possible to investigate both functional and structural connectivity in the brain. The aim of this study was to elucidate alterations in the structural connectivity in children with localization-related epilepsy using the mathematical method of graph theoretical analysis. METHODOLOGY: Fifteen children with localization-related epilepsy (8 female subjects; mean age, 8.5±3.5years) as an epilepsy group and 23 children without a history of seizure (12 female subjects; mean age, 8.9±3.7years) as a control group underwent three-dimensional T1-weighted brain magnetic resonance imaging (MRI). Gray matter images segmented and spatially normalized from the MRIs of both groups were analyzed using statistical parametric mapping with the Graph Analysis Toolbox. We compared global networks (global efficiency, clustering coefficient and network strength) and regional networks (betweenness centrality and clustering) between patients and controls. RESULTS: The global efficiency tended to be increased (p=0.081) and the global modularity was significantly increased (p=0.017) in the epilepsy group as compared with the control group. The epilepsy group showed locally decreased betweenness centrality mainly in the bilateral cingulate gyri, right perisylvian area, and bilateral precentral gyri, and locally increased clustering in the bilateral cingulate gyri, right perisylvian area, and medial frontal lobes as compared with the control group. The epilepsy group showed higher network resilience to random attack and targeted attack than the control group. Voxel-based morphometry did not show any difference between the two groups. CONCLUSIONS: We observed globally increased structural connectivity along with excessive network robustness in patients with localization-related epilepsy. Local abnormality of connectivity was observed mainly in the cingulate gyrus, perisylvian area, and precentral gyrus. This alteration in the structural connectivity without any morphometric changes may be related to the underlying epileptogenicity.
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Encéfalo/diagnóstico por imagen , Epilepsias Parciales/diagnóstico por imagen , Adolescente , Niño , Preescolar , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagenRESUMEN
PURPOSE: The peri-ictal autonomic disturbances have been studied as predictors of seizure outcome and as markers of seizure onset. We studied the changes in heart rate (HR), HRV, oxygen saturation and blood pressure (BP) in the peri-ictal period in patients with drug-resistant localization-related epilepsy. METHODOLOGY: Ninety one subjects undergoing video-EEG monitoring, underwent continuous HR, SpO2, BP and Lead II ECG monitoring. The changes during the preictal, ictal and postictal periods were analyzed for 57 seizures in 42 patients with artifact-free recordings and correlated with VEEG ictal onset and MRI characteristics. RESULTS: Ictal tachycardia was noted in 15 (26.3%) seizures, of which, 60% had temporal lobe onset. HR increased by an average of 20.1% from pre-ictal to ictal phases (p=0.04). Ictal bradycardia was noted in one event with right temporal seizure onset. Heart rate variability (HRV) analysis of the preictal, ictal and postictal phases showed an increase in the sympathetic and decrease in parasympathetic activity during the ictus with relatively preserved total power. Ictal oxygen desaturation (84.1%±3.5%) was noticed in 10 (17.5%) seizures. Ictal hypertension was observed in 15 (26.3%); ictal hypotension was noted in 5 (8.7%) seizures. Both the systolic BP and diastolic BPs increased from the pre-ictal to ictal phase (p=0.01). CONCLUSIONS: Peri-ictal dysautonomia can present in variable patterns and can be measured and compared over different modalities such as BP, HR and HRV. Though degree of tachycardia and increase in BP were higher during extratemporal onset of seizures, a fall in variability was noted in seizures of temporal lobe origin. Oxygen desaturation is not an uncommon event during the peri-ictal period in localization related epilepsy.
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Presión Sanguínea , Epilepsia/fisiopatología , Frecuencia Cardíaca , Monitoreo Fisiológico , Oxígeno/metabolismo , Convulsiones/fisiopatología , Presión Sanguínea/fisiología , Bradicardia/diagnóstico , Bradicardia/fisiopatología , Niño , Electrocardiografía , Electroencefalografía , Epilepsia/diagnóstico , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Hipotensión/diagnóstico , Hipotensión/fisiopatología , Masculino , Sistema Nervioso Parasimpático/fisiopatología , Estudios Prospectivos , Convulsiones/diagnóstico , Sistema Nervioso Simpático/fisiopatología , Taquicardia/diagnóstico , Taquicardia/fisiopatología , Grabación en VideoRESUMEN
Although epilepsy is associated with a variety of abnormalities, exactly why some brain regions produce seizures and others do not is not known. We developed a method to identify cellular changes in human epileptic neocortex using transcriptional clustering. A paired analysis of high and low spiking tissues recorded in vivo from 15 patients predicted 11 cell-specific changes together with their 'cellular interactome'. These predictions were validated histologically revealing millimetre-sized 'microlesions' together with a global increase in vascularity and microglia. Microlesions were easily identified in deeper cortical layers using the neuronal marker NeuN, showed a marked reduction in neuronal processes, and were associated with nearby activation of MAPK/CREB signalling, a marker of epileptic activity, in superficial layers. Microlesions constitute a common, undiscovered layer-specific abnormality of neuronal connectivity in human neocortex that may be responsible for many 'non-lesional' forms of epilepsy. The transcriptional clustering approach used here could be applied more broadly to predict cellular differences in other brain and complex tissue disorders.
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Encéfalo/patología , Epilepsia/patología , Transcripción Genética , Adolescente , Adulto , Biomarcadores , Niño , Preescolar , Análisis por Conglomerados , Electroencefalografía , Epilepsia/cirugía , Femenino , Humanos , Lactante , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Neocórtex/patología , Procedimientos Neuroquirúrgicos , ARN/genética , Adulto JovenRESUMEN
BACKGROUND: Generalized paroxysmal fast activity (GPFA) consists of burst of generalized rhythmic discharges; 100-200 µV; 1-9s; 8-26 Hz; with frontal predominance; appearing during NREM sleep. GPFA was originally described as an electrographic feature of Lennox-Gastaut Syndrome (LGS). We analyzed GPFA on scalp video EEG (VEEG) in children to evaluate that GPFA presents in patients with intractable localization-related epilepsy. METHODS: We collected cases with GPFA with intractable localization-related epilepsy who underwent scalp VEEG, MRI, and magnetoencephalography (MEG) prior to intracranial video EEG (IVEEG) and surgical resection. We collected 50 epochs of GPFA per patient during the first night during scalp VEEG. We analyzed amplitude, duration and frequency of GPFA over the bilateral frontal region between surgical resection side with grid placement and non-resection side. RESULTS: We identified 14 (14%) patients with GPFA on scalp VEEG. The mean amplitude ranged from 145 to 589 µV (mean 293 µV). The mean duration ranged from 1.18 to 2.31s (mean 1.6s). The mean frequencies ranged from 9.3 to 14.7 Hz (mean 11.1 Hz). The amplitude (307 ± 156 µV) and duration (1.62 ± 0.8s) of GPFAs in all the patients over the resection side were significantly higher than those (279 ± 141 µV, 1.58 ± 0.8s) of the non-resection side (p<0.001). All nine patients who showed significant duration differences between two hemispheres (p<0.05) had longer duration of GPFA over the resection side. Eight of 12 patients who showed significant amplitude differences between two hemispheres (p<0.05) had higher amplitude of GPFA over the resection side. Four of six patients who showed significant frequency differences between two hemispheres (p<0.05) had higher frequency of GPFA over the resection side. Nine (64%) patients became seizure free after surgical resection including multilobar resections in eight patients. CONCLUSIONS: GPFA can exist in localization-related epilepsy with secondary bilateral synchrony. Although EEG shows GPFA on scalp VEEG, the precise localization of the epileptogenic zone using IVEEG could achieve the successful surgical resection.
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Epilepsias Parciales/fisiopatología , Adolescente , Niño , Preescolar , Electroencefalografía , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Magnetoencefalografía , MasculinoRESUMEN
PURPOSE: We evaluated whether magnetoencephalography (MEG), in addition to surgery, was valuable for the diagnosis and management of epileptic syndromes in patients with neocortical epilepsy (NE). METHODS: We studied MEG in 73 patients (29 females; aged 1-26years; mean 10.3years) for the clinical diagnosis of epilepsy and for preoperative evaluation. MEG data were recorded by 204-channel whole head gradiometers with a 600Hz sampling rate. MEG spike sources were localized on magnetic resonance images (MRI) using a single dipole model to project equivalent current dipoles. RESULTS: MEG localized an epileptic focus with single clustered dipoles in 24 (33%) of 73 NE patients: 16 (25%) of 64 symptomatic localization-related epilepsy (SLRE) patients and eight (89%) of nine idiopathic localization-related epilepsy (ILRE) patients. MEG provided advantageous information in 12 (50%) of 24 patients with clustered dipoles and confirmed the diagnosis in the remaining 12 (50%). Furthermore, the use of MEG resulted in changes to surgical treatments in nine (38%) patients and in medical management in eight (33%). MEG confirmed the diagnosis in eight (16%) of 49 patients with scattered dipoles. MRI identified a single lesion (28 patients, 38%), multiple lesions (5, 7%), and no lesion (40, 55%). MRI provided confirming information in 19 of 28 patients with a single lesion and 18 of them required surgical resections. MRI did not provide any supportive information in 54 (74%) patients with a single (9), multiple (5) and no lesion (40). CONCLUSION: Our study shows that MEG provides fundamental information to aid the choice of diagnostic and therapeutic procedures including changes in medication in addition to surgical treatments for NE.
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Mapeo Encefálico , Ondas Encefálicas/fisiología , Epilepsia/diagnóstico , Magnetoencefalografía , Neocórtex/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Electroencefalografía , Epilepsia/terapia , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
PURPOSE: This study explored the pharmacodynamic and pharmacokinetic effects of combining perampanel (PER) with commonly co-administered AEDs. METHOD: A strong stimulus intensity (three-fold higher than after-discharge threshold) was used to elicit drug-resistant seizures in a rat amygdala kindling model. Vehicle, low-dose PER (0.75 mg/kg), or high-dose PER (1.5mg/kg), in combination with vehicle, levetiracetam (LEV) 50mg/kg, lamotrigine (LAM) 20mg/kg, carbamazepine (CBZ) 20mg/kg, or valproic acid (VPA) 200mg/kg, were administered intraperitoneally to groups of 6-13 rats. Seizure score, electroencephalography (EEG) seizure duration, and motor seizure duration were evaluated, with pharmacodynamic interactions determined by two-way analysis of variance (ANOVA). Motor impairment was evaluated by rotarod test and two-way ANOVA. RESULTS: High-dose PER, but not low-dose PER, LEV, LAM, CBZ, or VPA, reduced EEG seizure duration, motor seizure duration, and seizure score compared with vehicle alone. However, when low-dose PER was administered in combination with LEV, LAM, CBZ, or VPA, seizure severity parameters were reduced compared with the concomitant AEDs alone. These pharmacodynamic interactions were statistically significant in some cases, but the same AED combinations were not associated with statistically significant neurotoxic interactions. Efficacy may have been slightly affected by changes in PER plasma concentrations in the presence of other AEDs:PER plasma concentrations increased with LEV or LAM co-administration, and decreased with CBZ or VPA co-administration. CONCLUSION: Overall, these data support published Phase III data demonstrating the efficacy of PER as adjunctive therapy for the treatment of refractory partial-onset seizures in patients aged ≥ 12 years.
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Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapéutico , Excitación Neurológica/efectos de los fármacos , Piridonas/farmacocinética , Piridonas/uso terapéutico , Análisis de Varianza , Animales , Anticonvulsivantes/sangre , Ondas Encefálicas/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Electroencefalografía , Masculino , Actividad Motora/efectos de los fármacos , Nitrilos , Piridonas/sangre , Ratas , Ratas Wistar , Prueba de Desempeño de Rotación con Aceleración ConstanteRESUMEN
For patients with chronic cryptogenic localisation-related epilepsy (CLRE), conventional MRI does not provide measures to discern between patients with or without cognitive complaints. We investigated, in a preliminary study, whether it is possible to detect cerebral biomarkers of cognitive impairment in patients with CLRE using sensitive quantitative MRI techniques. Neuropsychological assessment and quantitative 3.0 T MRI, comprising T2 relaxometry, diffusion tensor imaging, and spectroscopic imaging, were applied to 35 patients with CLRE and 21 healthy controls. Analysis included the left and right hippocampi, and frontal and temporal lobes. Differences between the groups and correlations with cognitive and clinical characteristics were assessed. Patients with epilepsy scored significantly worse on cognitive tasks compared to healthy controls. Significantly larger CSF fractions in the hippocampi and left temporal lobe, a longer T2 relaxation time in the left hippocampus, and a significantly higher concentration of glutamate/glutamine in the left frontal lobe were observed in patients with epilepsy. Moreover, poor memory performance was significantly correlated with larger CSF fractions in the right hippocampus and left temporal lobe in patients. In the temporal lobe, an association between subtle changes in morphology (indicative of atrophy) and memory performance was found, consistent with previous literature. These results may help to explain the alterations in brain functioning in patients with epilepsy.
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Trastornos del Conocimiento/patología , Epilepsia/patología , Adulto , Cognición , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Imagen de Difusión Tensora , Epilepsia/complicaciones , Epilepsia/psicología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: Birth weight is an important indicator of prenatal environment, and subtle variations of birth weight within the normal range have been associated with differential risk for cognitive and behavioral problems. Therefore, we aimed to determine if there are differences in birth weight between full-term children with uncomplicated new/recent-onset epilepsies and typically developing healthy controls. We further examined the relationships between birth weight and childhood/adolescent cognition, behavior, and academic achievement. METHODS: One hundred eight children with new-onset/recent-onset epilepsy and 70 healthy controls underwent neuropsychological assessment. All participants were born full-term (>37 weeks) without birth complications. Parents were interviewed regarding their child's gestation, birth, and neurodevelopmental history. RESULTS: Birth weight of children with epilepsy was significantly lower than healthy controls (p = 0.023). Whereas birth weight (covaried with age, sex, handedness, and mother's education) was significantly associated with cognition in controls in multiple domains (intelligence, language, aspects of academic achievement), this relationship was absent in children with epilepsy. Birth weight was not associated with clinical epilepsy variables (age of onset, epilepsy syndrome) and was not predictive of a variety of other academic or psychiatric comorbidities of epilepsy. SIGNIFICANCE: Although the origin of lower birth weight in children with epilepsy is unknown, these findings raise the possibility that abnormal prenatal environment may affect childhood-onset epilepsy. Furthermore, the positive relationship between birth weight and cognition evident in healthy controls was disrupted in children with epilepsy. However, birth weight was not related to academic and psychiatric comorbidities of childhood epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
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Peso al Nacer , Cognición , Epilepsia/etiología , Adolescente , Estudios de Casos y Controles , Niño , Escolaridad , Femenino , Humanos , Recién Nacido de Bajo Peso , Masculino , Pruebas Neuropsicológicas , Factores de Riesgo , Escalas de WechslerRESUMEN
OBJECTIVE: Developmental differences in structure and function have been reported along the hippocampal subregions. The aims of this study were to determine if there were volumetric differences in hippocampal head (HH), body (HB), tail (HT), and total hippocampus (TotH)) in children with nonlesional localization-related epilepsy relative to controls, and the relation between hippocampal subregions with episodic memory and clinical parameters. METHODS: Forty-eight children with nonlesional localization-related epilepsy, consisting of 29 left-sided and 19 right-sided epilepsy, and 27 healthy controls were recruited. All patients and controls underwent volumetric T1-weighted imaging, and verbal and nonverbal memory testing. The volume of hippocampal subregions was compared between patients and controls. The associations between left hippocampal subregions with verbal memory; right hippocampal subregions with nonverbal memory; and hippocampal subregions with age, age at seizure onset, and seizure frequency were assessed. RESULTS: Patients with left-sided epilepsy had smaller left HH (p = 0.003) and HB (p = 0.012), right HB (p = 0.021) and HT (p = 0.015), and right TotH (p = 0.020) volumes. Those with right-sided epilepsy had smaller right HT (p = 0.018) volume. There were no statistically significant differences between verbal and nonverbal memory in left-sided and right-sided epilepsy relative to controls (all p > 0.025). In left-sided epilepsy, there was a significant association between left HH volume with verbal memory (ß = 0.492, p = 0.001). There was no significant association between left and right hippocampal subregions with verbal and nonverbal memory, respectively, in right-sided epilepsy and controls (all p > 0.002). In left-sided and right-sided epilepsy, there was no significant association between hippocampal subregions with age, age at seizure onset, and seizure frequency (all p > 0.002). SIGNIFICANCE: We have found hippocampal volume reduction, but did not identify a gradient in the severity of volume reduction along the hippocampal axis in children with localization-related epilepsy. Further study is needed to clarify if there are volumetric changes within the cornu ammonis subfields and dentate gyrus. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
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Epilepsias Parciales/diagnóstico , Epilepsias Parciales/fisiopatología , Hipocampo/patología , Hipocampo/fisiología , Memoria/fisiología , Adolescente , Niño , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Tamaño de los Órganos/fisiología , Grabación en Video/métodosRESUMEN
AIM: To evaluate the long-term efficacy of gabapentin (GBP) and usefulness of measurement of the blood level for the observation of patients that have partial seizures. METHODS: Thirty patients (20 effective cases and 10 ineffective cases) treated with GBP for the localization related epilepsy had their peak blood levels of GBP. The levels were measured seven time points, one, 6, 12, 18, 24, 30, and 36month after the start of medication. The efficacy of GBP was evaluated at one month after the initiation of medication and every year for 3years, based on the R Ratio and the degree of improvement for the paroxysmal strength and length. RESULTS: GBP levels were higher in the effective cases than the levels in the ineffective cases 6months after and 1year after the initiation of medication (p<0.05). The level 6months after the start in the effective cases was 5.429±2.384µg/ml (mean±SD), and 5.837±3.217µg/ml after 1year. The cases that were effective for 1year maintained approximately the same efficacy for 3years after the initiation of medication, but there was no correlation between the level and the R Ratio, paroxysmal strength and length. CONCLUSIONS: No precise definition of the therapeutic range was recognized because of no correlation between GBP level and the improvement of clinical manifestations. We recommend the GBP optimal range that is established the range within 3-8µg/ml (mean; 5µg/ml) as therapeutic target without the side effect.
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Aminas/sangre , Aminas/uso terapéutico , Anticonvulsivantes/sangre , Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/sangre , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Epilepsias Parciales/sangre , Epilepsias Parciales/tratamiento farmacológico , Ácido gamma-Aminobutírico/sangre , Ácido gamma-Aminobutírico/uso terapéutico , Adolescente , Factores de Edad , Aminas/efectos adversos , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Ácidos Ciclohexanocarboxílicos/efectos adversos , Epilepsias Parciales/complicaciones , Femenino , Gabapentina , Humanos , Masculino , Estudios Prospectivos , Convulsiones/sangre , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Ácido gamma-Aminobutírico/efectos adversosRESUMEN
BACKGROUND AND PURPOSE: Temporal lobe epilepsy (TLE) with nontumoral amygdala enlargement (AE) has been reported to be a possible subtype of TLE without hippocampal sclerosis (HS). The purpose of this study was to clarify morphologic and functional characteristics of TLE with AE (TLE + AE). METHODS: We evaluated gray matter volume and cerebral glucose hypometabolism using magnetic resonance imaging (MRI) voxel-based morphometry (VBM) and voxel-based statistical analysis of [(18) F]-fluorodeoxyglucose positron emission tomography (FDG-PET) images in 9 patients with TLE + AE as compared with controls. For VBM analysis, we recruited 30 age- and sex-matched healthy volunteers as controls. For the comparison of FDG-PET analysis, 9 patients with definite mesial TLE with HS (MTLE + HS), and 16 age- and sex-matched healthy controls were recruited. RESULTS: In patients with TLE + AE, a significant increase in gray matter volume was found only in the affected amygdala, and no significant decrease in gray matter volume was detected. In addition, significant glucose hypometabolism was observed in the affected amygdala, whereas significant glucose hypometabolism in the hippocampus, a prominent feature of definite MTLE+HS, was not observed. CONCLUSIONS: TLE + AE is different from MTLE + HS from morphologic and functional points of view, and the enlarged amygdala per se is potentially an epileptic focus in patients with partial epilepsy.
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Amígdala del Cerebelo/patología , Amígdala del Cerebelo/fisiopatología , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/fisiopatología , Glucosa/metabolismo , Sustancia Gris/patología , Sustancia Gris/fisiopatología , Adulto , Anciano , Mapeo Encefálico/métodos , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Humanos , Hipertrofia/etiología , Hipertrofia/patología , Hipertrofia/fisiopatología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
PURPOSE: A subset of patients with epilepsy successfully self-predicted seizures in a paper diary study. We conducted an e-diary study to ensure that prediction precedes seizures, and to characterize the prodromal features and time windows that underlie self-prediction. METHODS: Subjects 18 or older with localization-related epilepsy (LRE) and ≥3 seizures per month maintained an e-diary, reporting a.m./p.m. data daily, including mood, premonitory symptoms, and all seizures. Self-prediction was rated by, "How likely are you to experience a seizure (time frame)?" Five choices ranged from almost certain (>95% chance) to very unlikely. Relative odds of seizure (odds ratio, OR) within time frames was examined using Poisson models with log normal random effects to adjust for multiple observations. KEY FINDINGS: Nineteen subjects reported 244 eligible seizures. OR for prediction choices within 6 h was as high as 9.31 (CI 1.92-45.23) for "almost certain." Prediction was most robust within 6 h of diary entry, and remained significant up to 12 h. For nine best predictors, average sensitivity was 50%. Older age contributed to successful self-prediction, and self-prediction appeared to be driven by mood and premonitory symptoms. In multivariate modeling of seizure occurrence, self-prediction (2.84; CI 1.68-4.81), favorable change in mood (0.82; CI 0.67-0.99), and number of premonitory symptoms (1.11; CI 1.00-1.24) were significant. SIGNIFICANCE: Some persons with epilepsy can self-predict seizures. In these individuals, the odds of a seizure following a positive prediction are high. Predictions were robust, not attributable to recall bias, and were related to self-awareness of mood and premonitory features. The 6-h prediction window is suitable for the development of preemptive therapy.
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Afecto/fisiología , Electroencefalografía , Convulsiones/fisiopatología , Convulsiones/psicología , Adolescente , Adulto , Niño , Autoevaluación Diagnóstica , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Oportunidad Relativa , Convulsiones/diagnóstico , Factores de Tiempo , Adulto JovenRESUMEN
The purpose of this study was to quantify the intelligence of children with epilepsy and to determine the clinical factors associated with intellectual impairment. The medical records of patients diagnosed with childhood-onset epilepsy at a single tertiary medical center in Korea between 2006 and 2011 were retrospectively reviewed. The Korean Education Development Institute-Wechsler Intelligence Scale for Children or Korean Wechsler Intelligence Scale for adults was used to quantify the level of intelligence. Age at seizure onset, etiology, epilepsy duration, number of seizures in the last year, use of antiepileptic drugs, EEG/MRI findings, and epilepsy classification were recorded. The association between clinical factors and the intelligence was determined using logistic regression. Three hundred and twenty-two patients were included in the analysis. One hundred and seventy-six (54.7%) patients had low intelligence (intelligence quotient [IQ]<80) with 18 (5.6%) defined as borderline mental retardation (IQ 70-79), 47 (14.6%) as mild mental retardation (IQ 60-69), and 111 (34.5%) as moderate-to-severe mental retardation (IQ<60). Epilepsy duration, number of seizures in the last year, and epilepsy classification were significantly associated with low intelligence in multivariate logistic regression (p<0.05). However, when analyzed according to etiology, these factors were not associated with low intelligence in children with idiopathic epilepsy. The most important factors associated with low intelligence in childhood-onset epilepsy are the underlying etiology and, in cryptogenic and symptomatic epilepsy, seizure burden. The results of this study underscore the importance of seizure control to alleviate the harmful impact of epilepsy on cognition.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Epilepsia/complicaciones , Inteligencia , Adolescente , Adulto , Edad de Inicio , Niño , Preescolar , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/etiología , Epilepsia/tratamiento farmacológico , Epilepsia/psicología , Femenino , Humanos , Pruebas de Inteligencia , Masculino , Pruebas Neuropsicológicas , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no Paramétricas , Adulto JovenRESUMEN
PURPOSE: With the success that surgical approaches can provide for localization-related epilepsy, accurate seizure localization remains important. Although magnetic resonance (MR) spectroscopy has had success in earlier studies in medial temporal lobe epilepsy, there have been fewer studies evaluating its use in a broader range of localization-related epilepsy. With improvements in signal-to-noise with ultra-high field MR, we report on the use of high resolution 7T MR spectroscopic imaging (MRSI) in 25 surgically treated patients studied over a 3.5-year period. METHODS: Patients were included in this analysis if the region of MRSI study included the surgical resection region. Concordance between region of MRSI abnormalities and of surgical resection was classified into three groups (complete, partial, or no agreement) and outcome was dichotomized by International League Against Epilepsy (ILAE) I-III and IV-VI groups. MRSI was performed with repetition time/echo time 1.5 s/40 msec in two-dimensional (2D) or three-dimensional (3D) encoding for robust detection of singlets N-acetyl aspartate (NAA), creatine (Cr), and choline with abnormalities in NAA/Cr determined with correction for tissue content of gray matter. KEY FINDINGS: The concordance between MRSI-determined abnormality and surgical resection region was significantly related to outcome: Outcome was better if the resected tissue was metabolically abnormal. All 14 patients with complete resection of the region with the most severe metabolic abnormality had good outcome, including five requiring intracranial electroencephalography (EEG) analysis, whereas only 3/11 without complete resection of the most severe metabolic abnormality had good outcome (p < 0.001). SIGNIFICANCE: This is consistent with the seizure-onset zone being characterized by metabolic dysfunction and suggests that high resolution MRSI can help define these regions for the purposes of outcome prediction.