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OBJECTIVES: To develop a multiparametric machine-learning (ML) framework using high-resolution 3 dimensional (3D) magnetic resonance (MR) fingerprinting (MRF) data for quantitative characterization of focal cortical dysplasia (FCD). MATERIALS: We included 119 subjects, 33 patients with focal epilepsy and histopathologically confirmed FCD, 60 age- and gender-matched healthy controls (HCs), and 26 disease controls (DCs). Subjects underwent whole-brain 3 Tesla MRF acquisition, the reconstruction of which generated T1 and T2 relaxometry maps. A 3D region of interest was manually created for each lesion, and z-score normalization using HC data was performed. We conducted 2D classification with ensemble models using MRF T1 and T2 mean and standard deviation from gray matter and white matter for FCD versus controls. Subtype classification additionally incorporated entropy and uniformity of MRF metrics, as well as morphometric features from the morphometric analysis program (MAP). We translated 2D results to individual probabilities using the percentage of slices above an adaptive threshold. These probabilities and clinical variables were input into a support vector machine for individual-level classification. Fivefold cross-validation was performed and performance metrics were reported using receiver-operating-characteristic-curve analyses. RESULTS: FCD versus HC classification yielded mean sensitivity, specificity, and accuracy of 0.945, 0.980, and 0.962, respectively; FCD versus DC classification achieved 0.918, 0.965, and 0.939. In comparison, visual review of the clinical magnetic resonance imaging (MRI) detected 48% (16/33) of the lesions by official radiology report. In the subgroup where both clinical MRI and MAP were negative, the MRF-ML models correctly distinguished FCD patients from HCs and DCs in 98.3% of cross-validation trials for the magnetic resonance imaging negative group and MAP negative group. Type II versus non-type-II classification exhibited mean sensitivity, specificity, and accuracy of 0.835, 0.823, and 0.83, respectively; type IIa versus IIb classification showed 0.85, 0.9, and 0.87. In comparison, the transmantle sign was present in 58% (7/12) of the IIb cases. INTERPRETATION: The MRF-ML framework presented in this study demonstrated strong efficacy in noninvasively classifying FCD from normal cortex and distinguishing FCD subtypes. ANN NEUROL 2024.
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Single-photon emission computed tomography (SPECT) during seizures and magnetoencephalography (MEG) during the interictal state are noninvasive modalities employed in the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy (DRFE). The present study aims to investigate whether there exists a preferentially high MEG functional connectivity (FC) among those regions of the brain that exhibit hyperperfusion or hypoperfusion during seizures. We studied MEG and SPECT data in 30 consecutive DRFE patients who had resective epilepsy surgery. We parcellated each ictal perfusion map into 200 regions of interest (ROIs) and generated ROI time series using source modeling of MEG data. FC between ROIs was quantified using coherence and phase-locking value. We defined a generalized linear model to relate the connectivity of each ROI, ictal perfusion z score, and distance between ROIs. We compared the coefficients relating perfusion z score to FC of each ROI and estimated the connectivity within and between resected and unresected ROIs. We found that perfusion z scores were strongly correlated with the FC of hyper-, and separately, hypoperfused ROIs across patients. High interictal connectivity was observed between hyperperfused brain regions inside and outside the resected area. High connectivity was also observed between regions of ictal hypoperfusion. Importantly, the ictally hypoperfused regions had a low interictal connectivity to regions that became hyperperfused during seizures. We conclude that brain regions exhibiting hyperperfusion during seizures highlight a preferentially connected interictal network, whereas regions of ictal hypoperfusion highlight a separate, discrete and interconnected, interictal network.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Humanos , Magnetoencefalografia/métodos , Eletroencefalografia/métodos , Convulsões/diagnóstico por imagem , Convulsões/cirurgia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/cirurgia , Encéfalo/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Perfusão , Tomografia Computadorizada de Emissão de Fóton Único , Imageamento por Ressonância MagnéticaRESUMO
Perfusion patterns observed in Subtraction Ictal SPECT Co-registered to MRI (SISCOM) assist in focus localization and surgical planning for patients with medically intractable focal epilepsy. While the localizing value of SISCOM has been widely investigated, its relationship to the underlying electrophysiology has not been extensively studied and is therefore not well understood. In the present study, we set to investigate this relationship in a cohort of 70 consecutive patients who underwent ictal and interictal SPECT studies and subsequent stereo-electroencephalography (SEEG) monitoring for localization of the epileptogenic focus and surgical intervention. Seizures recorded during SEEG evaluation (SEEG seizures) were matched to semiologically-similar seizures during the preoperative ictal SPECT evaluation (SPECT seizures) by comparing the semiological changes in the course of each seizure. The spectral changes of the ictal SEEG with respect to interictal ones over 7 traditional frequency bands (0.1 to 150Hz) were analyzed at each SEEG site. Neurovascular (SEEG/SPECT) relations were assessed by comparing the estimated spectral power density changes of the SEEG at each site with the perfusion changes (SISCOM z-scores) estimated from the acquired SISCOM map at that site. Across patients, a significant correlation (p<0.05) was observed between spectral changes during the SEEG seizure and SISCOM perfusion z-scores. Brain sites with high perfusion z-score exhibited higher increased SEEG power in theta to ripple frequency bands with concurrent suppression in delta and theta frequency bands compared to regions with lower perfusion z-score. The dynamics of the correlation of SISCOM perfusion and SEEG spectral power from ictal onset to seizure end and immediate postictal period were also derived. Forty-six (46) of the 70 patients underwent resective epilepsy surgery. SISCOM z-score and power increase in beta to ripple frequency bands were significantly higher in resected than non-resected sites in the patients who were seizure-free following surgery. This study provides for the first time concrete evidence that both hyper-perfusion and hypo-perfusion patterns observed in SISCOM maps have strong electrophysiological underpinnings, and that integration of the information from SISCOM and SEEG can shed light on the location and dynamics of the underlying epileptic brain networks, and thus advance our anatomo-electro-clinical understanding and approaches to targeted diagnostic and therapeutic interventions.
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Circulação Cerebrovascular/fisiologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletrocorticografia/métodos , Rede Nervosa/fisiopatologia , Acoplamento Neurovascular/fisiologia , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adolescente , Adulto , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Criança , Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/metabolismo , Rede Nervosa/cirurgia , Estudos Retrospectivos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Técnicas Estereotáxicas , Adulto JovemRESUMO
OBJECTIVE: Ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) offers increased signal-to-noise and contrast-to-noise ratios, which may improve visualization of cortical malformations. We aim to assess the clinical value of in vivo structural 7T MRI and its post-processing for the noninvasive identification of epileptic brain lesions in patients with pharmacoresistant epilepsy and nonlesional 3T MRI who are undergoing presurgical evaluation. METHODS: Sixty-seven patients were included who had nonlesional 3T MRI by official radiology report. Epilepsy protocols were used for the 3T and 7T acquisitions. Post-processing of the 7T T1-weighted magnetization-prepared two rapid acquisition gradient echoes sequence was performed using the morphometric analysis program (MAP) with comparison to a normal database consisting of 50 healthy controls. Review of 7T was performed by an experienced board-certified neuroradiologist and at the multimodal patient management conference. The clinical significance of 7T findings was assessed based on intracranial electroencephalography (ICEEG) ictal onset, surgery, postoperative seizure outcomes, and histopathology. RESULTS: Unaided visual review of 7T detected previously unappreciated subtle lesions in 22% (15/67). When aided by 7T MAP, the total yield increased to 43% (29/67). The location of the 7T-identified lesion was identical to or contained within the ICEEG ictal onset in 13 of 16 (81%). Complete resection of the 7T-identified lesion was associated with seizure freedom (P = .03). Histopathology of the 7T-identified lesions encountered mainly focal cortical dysplasia (FCD). 7T MAP yielded 25% more lesions (6/24) than 3T MAP, and showed improved conspicuity in 46% (11/24). SIGNIFICANCE: Our data suggest a major benefit of 7T with post-processing for detecting subtle FCD lesions for patients with pharmacoresistant epilepsy and nonlesional 3T MRI.
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Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Imageamento por Ressonância Magnética/normas , Cuidados Pré-Operatórios/normas , Adolescente , Adulto , Criança , Estudos de Coortes , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/métodos , Eletroencefalografia/normas , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulator (RNS) system. METHODS: We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3 months before MTL resection. RESULTS: We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1 year of follow-up (N = 21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. SIGNIFICANCE: Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.
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Lobectomia Temporal Anterior/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Lobo Temporal/cirurgia , Adulto , Idoso , Epilepsia Resistente a Medicamentos/fisiopatologia , Terapia por Estimulação Elétrica , Eletrocorticografia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Neuroestimuladores Implantáveis , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Procedimentos Neurocirúrgicos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video-electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery. METHODS: We included 123 consecutive patients who had SCSs and CSs during scalp-VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1-year follow-up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome. RESULTS: Sixty-nine patients (56.1%) had seizure-free outcome at 1-year follow-up. In 68 patients (55.3%), the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure-free outcome at 1-year (P = .020) and 2-year follow-up (P = .040). In the temporal lobe epilepsy (TLE) seizure-free group, SCS localization was completely contained within the resection in 44.4% and CS localization was completely contained within the resection in 41.7%; in the extratemporal lobe epilepsy (ETLE) seizure-free group, SCS localization was completely contained within the resection in 54.5% and CS localization was completely contained within the resection in 57.6%. SIGNIFICANCE: Complete concordance between CS and SCS localization is a positive prognostic factor for 1-year and 2-year postoperative seizure-free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.
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Eletroencefalografia/métodos , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/fisiopatologia , Cuidados Pré-Operatórios/métodos , Couro Cabeludo , Gravação em Vídeo/métodos , Adolescente , Adulto , Estudos de Coortes , Eletroencefalografia/instrumentação , Seguimentos , Humanos , Masculino , Cuidados Pré-Operatórios/instrumentação , Estudos Retrospectivos , Couro Cabeludo/fisiologia , Adulto JovemRESUMO
OBJECTIVE: Detection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD. METHODS: We retrospectively included a consecutive cohort of surgical patients who had a negative preoperative MRI by radiology report. MAP was performed on T1-weighted volumetric sequence and QPET was performed on PET/computed tomographic data, both with comparison to scanner-specific normal databases. Concordance between MAP and QPET was assessed at a lobar level, and the significance of concordant QPET-MAP+ abnormalities was confirmed by postresective seizure outcome and histopathology. QPET thresholds of standard deviations (SDs) of -1, -2, -3, and -4 were evaluated to identify the optimal threshold for QPET-MAP analysis. RESULTS: A total of 104 patients were included. When QPET thresholds of SD = -1, -2, and -3 were used, complete resection of the QPET-MAP+ region was significantly associated with seizure-free outcome when compared with the partial resection group (P = 0.023, P < 0.001, P = 0.006) or the no resection group (P = 0.002, P < 0.001, P = 0.001). The SD threshold of -2 showed the best combination of positive rate (55%), sensitivity (0.68), specificity (0.88), positive predictive value (0.88), and negative predictive value (0.69). Surgical pathology of the resected QPET-MAP+ areas revealed mainly FCD type I. Multiple QPET-MAP+ regions were present in 12% of the patients at SD = -2. SIGNIFICANCE: Our study demonstrates a practical and effective approach to combine quantitative analyses of functional (QPET) and structural (MAP) imaging data to improve identification of subtle epileptic abnormalities. This approach can be readily adopted by epilepsy centers to improve postresective seizure outcomes for patients without apparent lesions on MRI.
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Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Adulto JovemRESUMO
Subtraction ictal and interictal single photon emission computed tomography can demonstrate complex ictal perfusion patterns. Regions with ictal hyperperfusion are suggested to reflect seizure onset and propagation pathways. The significance of ictal hypoperfusion is not well understood. The aim of this study was to verify whether ictal perfusion changes, both hyper- and hypoperfusion, correspond to electrically connected brain networks. A total of 36 subtraction ictal and interictal perfusion studies were analysed in 31 consecutive medically refractory focal epilepsy patients, evaluated by stereo-electroencephalography that demonstrated a single focal onset. Cortico-cortical evoked potential studies were performed after repetitive electrical stimulation of the ictal onset zone. Evoked responses at electrode contacts outside the stimulation site were used as a measure of connectivity. The evoked responses at these electrodes were compared to ictal perfusion values noted at these locations. In 67% of studies, evoked responses were significantly larger in hyperperfused compared to baseline-perfused areas. The majority of hyperperfused contacts also had significantly increased evoked responses relative to pre-stimulus electroencephalogram. In contrast, baseline-perfused and hypoperfused contacts mainly demonstrated non-significant evoked responses. Finally, positive significant correlations (P < 0.05) were found between perfusion scores and evoked responses in 61% of studies. When the stimulated ictal onset area was hyperperfused, 82% of studies demonstrated positive significant correlations. Following stimulation of hyperperfused areas outside seizure onset, positive significant correlations between perfusion changes and evoked responses could be seen, suggesting bidirectional connectivity. We conclude that strong connectivity was demonstrated between the ictal onset zone and hyperperfused regions, while connectivity was weaker in the direction of baseline-perfused or hypoperfused areas. In trying to understand a patient's epilepsy, one should consider the contribution of all hyperperfused regions, as these are likely not random, but represent an electrically connected epileptic network.
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Córtex Cerebral/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Potenciais Evocados/fisiologia , Adolescente , Adulto , Idoso , Córtex Cerebral/fisiologia , Criança , Estimulação Elétrica , Eletroencefalografia , Feminino , Neuroimagem Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
OBJECTIVE: Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. METHODS: Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABAA ) antagonist used to provoke generalized seizures as a "second hit." RESULTS: LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. SIGNIFICANCE: Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology.
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Acetamidas/farmacologia , Anticonvulsivantes/farmacologia , Malformações do Desenvolvimento Cortical/fisiopatologia , Convulsões/fisiopatologia , Animais , Eletroencefalografia , Feminino , Antagonistas GABAérgicos/toxicidade , Lacosamida , Levetiracetam , Malformações do Desenvolvimento Cortical/etiologia , Pentilenotetrazol/toxicidade , Piracetam/análogos & derivados , Piracetam/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Exposição à Radiação/efeitos adversos , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamenteRESUMO
OBJECTIVE: In the presurgical workup of magnetic resonance imaging (MRI)-negative (MRI(-) or "nonlesional") pharmacoresistant focal epilepsy (PFE) patients, discovering a previously undetected lesion can drastically change the evaluation and likely improve surgical outcome. Our study utilizes a voxel-based MRI postprocessing technique, implemented in a morphometric analysis program (MAP), to facilitate detection of subtle abnormalities in a consecutive cohort of MRI(-) surgical candidates. METHODS: Included in this retrospective study was a consecutive cohort of 150 MRI(-) surgical patients. MAP was performed on T1-weighted MRI, with comparison to a scanner-specific normal database. Review and analysis of MAP were performed blinded to patients' clinical information. The pertinence of MAP(+) areas was confirmed by surgical outcome and pathology. RESULTS: MAP showed a 43% positive rate, sensitivity of 0.9, and specificity of 0.67. Overall, patients with the MAP(+) region completely resected had the best seizure outcomes, followed by the MAP(-) patients, and patients who had no/partial resection of the MAP(+) region had the worst outcome (p < 0.001). Subgroup analysis revealed that visually identified subtle findings are more likely correct if also MAP(+) . False-positive rate in 52 normal controls was 2%. Surgical pathology of the resected MAP(+) areas contained mainly non-balloon-cell focal cortical dysplasia (FCD). Multiple MAP(+) regions were present in 7% of patients. INTERPRETATION: MAP can be a practical and valuable tool to: (1) guide the search for subtle MRI abnormalities and (2) confirm visually identified questionable abnormalities in patients with PFE due to suspected FCD. A MAP(+) region, when concordant with the patient's electroclinical presentation, should provide a legitimate target for surgical exploration.
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Epilepsias Parciais/patologia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVE: MRI-negative (MRI-) pharmacoresistant focal epilepsy (PFE) patients are most challenging for epilepsy surgical management. This study utilizes a voxel-based MRI postprocessing technique, implemented using a morphometric analysis program (MAP), aiming to facilitate detection of subtle focal cortical dysplasia (FCD) in MRI- patients. Furthermore, the study examines the concordance between MAP-identified regions and localization from magnetic source imaging (MSI). METHODS: Included in this retrospective study were 25 MRI- surgical patients. MAP was performed on T1-weighted MRI, with comparison to a normal database. The pertinence of MAP+ areas was confirmed by MSI, surgical outcome and pathology. Analyses of MAP and MSI were performed blindly from patients' clinical information and independently from each other. RESULTS: The detection rate of subtle changes by MAP was 48% (12/25). Once MAP+ areas were resected, patients were more likely to be seizure-free (p=0.02). There were no false positives in the 25 age-matched normal controls. Seven patients had a concordant MSI correlate. Patients in whom a concordant area was identified by both MAP and MSI had a significantly higher chance of achieving a seizure-free outcome following complete resection of this area (p=0.008). In the 9 resected MAP+ areas, pathology revealed FCD type IA in 7 and type IIB in 2. INTERPRETATION: MAP shows promise in identifying subtle FCD abnormalities and increasing the diagnostic yield of conventional MRI visual analysis in presurgical evaluation of PFE. Concordant MRI postprocessing and MSI analyses may lead to the noninvasive identification of a structurally and electrically abnormal subtle lesion that can be surgically targeted.
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Epilepsia/diagnóstico , Epilepsia/cirurgia , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Monitorização Intraoperatória/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Método Simples-Cego , Adulto JovemRESUMO
AIM: To identify factors that influence diurnal and sleep/wake seizure timing in children undergoing tapered drug withdrawal in an epilepsy monitoring unit. METHODS: Medical charts of patients that underwent video-EEG were reviewed. Seizures were evaluated based on their occurrence in three-hour time intervals (bins) and between wakefulness and sleep. Patients were classified according to EEG localisation and age: infants (≤3 years), children (3-12 years), and adolescents (>12-21 years). Analysis utilising generalised estimating equations with a negative binomial distribution was performed. RESULTS: A total of 390 patients (188 girls; mean age: 9.2 years; SD: 6.0) had 1,754 seizures. Generalised seizures (109 patients; 490 seizures) occurred more during wakefulness (p<0.001) and during the day (p<0.001). Modelling revealed a greater occurrence of seizures at night with increasing age (p=0.046). Temporal lobe seizures (62 patients; 271 seizures) occurred overall more frequently during wakefulness (p=0.03). Frontal lobe seizures (41 patients; 184 seizures) occurred more frequently during wakefulness in infants (p<0.05) and more frequently during sleep in adolescents (p<0.0001). Adolescents with frontal lobe seizures were 3.6 times more likely to have seizures during sleep compared to other children (95% CI: 1.8-7.2). CONCLUSION: These findings are suggestive of changes in circadian rhythmicity that may alter seizure susceptibility in different age groups. The results may assist in prediction of periods of greatest seizure propensity.
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Lobo Frontal/fisiopatologia , Convulsões/fisiopatologia , Sono/fisiologia , Vigília/fisiologia , Adolescente , Fatores Etários , Criança , Ritmo Circadiano/fisiologia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Objective.For medically-refractory epilepsy patients, stereoelectroencephalography (sEEG) is a surgical method using intracranial electrode recordings to identify brain networks participating in early seizure organization and propagation (i.e. the epileptogenic zone, EZ). If identified, surgical EZ treatment via resection, ablation or neuromodulation can lead to seizure-freedom. To date, quantification of sEEG data, including its visualization and interpretation, remains a clinical and computational challenge. Given elusiveness of physical laws or governing equations modelling complex brain dynamics, data science offers unique insight into identifying unknown patterns within high-dimensional sEEG data. We apply here an unsupervised data-driven algorithm, dynamic mode decomposition (DMD), to sEEG recordings from five focal epilepsy patients (three with temporal lobe, and two with cingulate epilepsy), who underwent subsequent resective or ablative surgery and became seizure free.Approach.DMD obtains a linear approximation of nonlinear data dynamics, generating coherent structures ('modes') defining important signal features, used to extract frequencies, growth rates and spatial structures. DMD was adapted to produce dynamic modal maps (DMMs) across frequency sub-bands, capturing onset and evolution of epileptiform dynamics in sEEG data. Additionally, we developed a static estimate of EZ-localized electrode contacts, termed the higher-frequency mode-based norm index (MNI). DMM and MNI maps for representative patient seizures were validated against clinical sEEG results and seizure-free outcomes following surgery.Main results.DMD was most informative at higher frequencies, i.e. gamma (including high-gamma) and beta range, successfully identifying EZ contacts. Combined interpretation of DMM/MNI plots best identified spatiotemporal evolution of mode-specific network changes, with strong concordance to sEEG results and outcomes across all five patients. The method identified network attenuation in other contacts not implicated in the EZ.Significance.This is the first application of DMD to sEEG data analysis, supporting integration of neuroengineering, mathematical and machine learning methods into traditional workflows for sEEG review and epilepsy surgical decision-making.
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Eletrocorticografia , Humanos , Masculino , Feminino , Adulto , Eletrocorticografia/métodos , Eletroencefalografia/métodos , Algoritmos , Eletrodos Implantados , Rede Nervosa/fisiopatologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Epilepsia/diagnóstico , Técnicas Estereotáxicas , Adulto JovemRESUMO
OBJECTIVE: Ictal Single Photon Emission Computed Tomography (SPECT) and stereo-electroencephalography (SEEG) are diagnostic techniques used for the management of patients with drug-resistant focal epilepsies. While hyperperfusion patterns in ictal SPECT studies reveal seizure onset and propagation pathways, the role of ictal hypoperfusion remains poorly understood. The goal of this study was to systematically characterize the spatio-temporal information flow dynamics between differently perfused brain regions using stereo-EEG recordings. METHODS: We identified seizure-free patients after resective epilepsy surgery who had prior ictal SPECT and SEEG investigations. We estimated directional connectivity between the epileptogenic-zone (EZ), non-resected areas of hyperperfusion, hypoperfusion, and baseline perfusion during the interictal, preictal, ictal, and postictal periods. RESULTS: Compared to the background, we noted significant information flow (1) during the preictal period from the EZ to the baseline and hyperperfused regions, (2) during the ictal onset from the EZ to all three regions, and (3) during the period of seizure evolution from the area of hypoperfusion to all three regions. CONCLUSIONS: Hypoperfused brain regions were found to indirectly interact with the EZ during the ictal period. SIGNIFICANCE: Our unique study, combining intracranial electrophysiology and perfusion imaging, presents compelling evidence of dynamic changes in directional connectivity between brain regions during the transition from interictal to ictal states.
Assuntos
Eletroencefalografia , Convulsões , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Masculino , Feminino , Adulto , Convulsões/fisiopatologia , Convulsões/diagnóstico por imagem , Eletroencefalografia/métodos , Adolescente , Adulto Jovem , Eletrocorticografia/métodos , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Criança , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgiaRESUMO
Responsive neurostimulation is a closed-loop neuromodulation therapy for drug resistant focal epilepsy. Responsive neurostimulation electrodes are placed near ictal onset zones so as to enable detection of epileptiform activity and deliver electrical stimulation. There is no standard approach for determining the optimal placement of responsive neurostimulation electrodes. Clinicians make this determination based on presurgical tests, such as MRI, EEG, magnetoencephalography, ictal single-photon emission computed tomography and intracranial EEG. Currently functional connectivity measures are not being used in determining the placement of responsive neurostimulation electrodes. Cortico-cortical evoked potentials are a measure of effective functional connectivity. Cortico-cortical evoked potentials are generated by direct single-pulse electrical stimulation and can be used to investigate cortico-cortical connections in vivo. We hypothesized that the presence of high amplitude cortico-cortical evoked potentials, recorded during intracranial EEG monitoring, near the eventual responsive neurostimulation contact sites is predictive of better outcomes from its therapy. We retrospectively reviewed 12 patients in whom cortico-cortical evoked potentials were obtained during stereoelectroencephalography evaluation and subsequently underwent responsive neurostimulation therapy. We studied the relationship between cortico-cortical evoked potentials, the eventual responsive neurostimulation electrode locations and seizure reduction. Directional connectivity indicated by cortico-cortical evoked potentials can categorize stereoelectroencephalography electrodes as either receiver nodes/in-degree (an area of greater inward connectivity) or projection nodes/out-degree (greater outward connectivity). The follow-up period for seizure reduction ranged from 1.3-4.8 years (median 2.7) after responsive neurostimulation therapy started. Stereoelectroencephalography electrodes closest to the eventual responsive neurostimulation contact site tended to show larger in-degree cortico-cortical evoked potentials, especially for the early latency cortico-cortical evoked potentials period (10-60â ms period) in six out of 12 patients. Stereoelectroencephalography electrodes closest to the responsive neurostimulation contacts (≤5â mm) also had greater significant out-degree in the early cortico-cortical evoked potentials latency period than those further away (≥10â mm) (P < 0.05). Additionally, significant correlation was noted between in-degree cortico-cortical evoked potentials and greater seizure reduction with responsive neurostimulation therapy at its most effective period (P < 0.05). These findings suggest that functional connectivity determined by cortico-cortical evoked potentials may provide additional information that could help guide the optimal placement of responsive neurostimulation electrodes.
RESUMO
Patients with magnetic-resonance-imaging (MRI)-negative (or 'nonlesional') pharmacoresistant focal epilepsy are the most challenging group undergoing presurgical evaluation. Few large-scale studies have systematically reviewed the pathological substrates underlying MRI-negative epilepsies. In the current study, histopathological specimens were retrospectively reviewed from MRI-negative epilepsy patients (n=95, mean age=30 years, 50% female subjects). Focal cortical dysplasia cases were classified according to the International League Against Epilepsy (ILAE) and Palmini et al classifications. The most common pathologies found in this MRI-negative cohort included: focal cortical dysplasia (n=43, 45%), gliosis (n=21, 22%), hamartia+gliosis (n=12, 13%), and hippocampal sclerosis (n=9, 9%). The majority of focal cortical dysplasia were ILAE type I (n=37) or Palmini type I (n=39). Seven patients had no identifiable pathological abnormalities. The existence of positive pathology was not significantly associated with age or temporal/extratemporal resection. Follow-up data post surgery was available in 90 patients; 63 (70%) and 57 (63%) attained seizure freedom at 6 and 12 months, respectively. The finding of positive pathology was significantly associated with seizure-free outcome at 6 months (P=0.035), but not at 12 months. In subgroup analysis, the focal cortical dysplasia group was not significantly correlated with seizure-free outcome, as compared with the negative-pathology groups at either 6 or 12 months. Of note, the finding of hippocampal sclerosis had a significant positive correlation with seizure-free outcome when compared with the negative-pathology group (P=0.009 and 0.004 for 6- and 12-month outcome, respectively). Absence of a significant histopathology in the resected surgical specimen did not preclude seizure freedom. In conclusion, our study highlights the heterogeneity of epileptic pathologies in MRI-negative epilepsies, with focal cortical dysplasia being the most common finding. The existence of positive pathology in surgical specimen may be a good indication for short-term good seizure outcome. There is a small subset of cases in which no pathological abnormalities are identified.
Assuntos
Encefalopatias/patologia , Encéfalo/patologia , Epilepsia/patologia , Adolescente , Adulto , Encefalopatias/complicações , Criança , Pré-Escolar , Epilepsia/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: Subtraction ictal single photon emission computed tomography (SPECT) co-registered to magnetic resonance imaging (MRI) (SISCOM) is a useful modality to identify epileptogenic focus. Using this technique, several studies have generally considered the area of highest ictal hyperperfusion, as outlined by thresholding the difference images with a standard z score of 2, to be highly concordant to the epileptogenic focus. In clinical practice, several factors influence ictal hyperperfusion and using different SISCOM thresholds can be helpful. We aimed to systematically evaluate the localizing value of various z scores (1, 1.5, 2, and 2.5) in a seizure-free cohort following resective epilepsy surgery, and to examine the localizing information of perfusion patterns observed at each z score. METHODS: Twenty-six patients were identified as having ictal-interictal SPECT images, preoperative and postoperative MRI studies, and having remained seizure free for at least 6 months after temporal or extratemporal surgical resection. SISCOM analysis was performed using preoperative MRI studies, and then blindly reviewed for localization of hyperperfused regions. With the added information from postoperative, coregistered MRI, perfusion patterns were determined. KEY FINDINGS: Using pair-wise comparisons, we found that the optimal z score for SPECT-SISCOM localization of the epileptogenic zone was 1.5, not the commonly used z score of 2. The z score of 1.5 was 84.8% sensitive and 93.8% specific. The z score of 1.5 had a moderate interrater agreement (0.70). When an hourglass configuration hyperperfusion pattern was present, a trend toward correctly localizing the seizure onset region was suggested (100% of the 11 observed occurrences). Nonetheless this trend was not statistically significant, possibly reflecting the small number of occurrences in our study. SIGNIFICANCE: SISCOM is a useful modality in evaluating patients for epilepsy surgery. This study shows that the z score of 1.5 represents a highly sensitive and specific SISCOM threshold that should be examined in conjunction with the traditionally used z score of 2 to enhance the chances of correct localization. Further prospective investigations are needed to confirm this finding in large patient series.
Assuntos
Processamento Eletrônico de Dados , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Tomografia Computadorizada de Emissão de Fóton Único , Adolescente , Adulto , Idoso , Algoritmos , Mapeamento Encefálico , Criança , Pré-Escolar , Cisteína/análogos & derivados , Eletroencefalografia , Feminino , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
PURPOSE: Fast ripples are reported to be highly localizing to the epileptogenic or seizure-onset zone (SOZ) but may not be readily found in neocortical epilepsy, whereas ripples are insufficiently localizing. Herein we classified interictal neocortical ripples by associated characteristics to identify a subtype that may help to localize the SOZ in neocortical epilepsy. We hypothesize that ripples associated with an interictal epileptiform discharge (IED) are more pathologic, since the IED is not a normal physiologic event. METHODS: We studied 35 patients with epilepsy with neocortical epilepsy who underwent invasive electroencephalography (EEG) evaluation by stereotactic EEG (SEEG) or subdural grid electrodes. Interictal fast ripples and ripples were visually marked during slow-wave sleep lasting 10-30 min. Neocortical ripples were classified as type I when superimposed on epileptiform discharges such as paroxysmal fast, spike, or sharp wave, and as type II when independent of epileptiform discharges. KEY FINDINGS: In 21 patients with a defined SOZ, neocortical fast ripples were detected in the SOZ of only four patients. Type I ripples were detected in 14 cases almost exclusively in the SOZ or primary propagation area (PP) and marked the SOZ with higher specificity than interictal spikes. In contrast, type II ripples were not correlated with the SOZ. In 14 patients with two or more presumed SOZs or nonlocalizable onset pattern, type I but not type II ripples also occurred in the SOZs. We found the areas with only type II ripples outside of the SOZ (type II-O ripples) in SEEG that localized to the primary motor cortex and primary visual cortex. SIGNIFICANCE: Neocortical fast ripples and type I ripples are specific markers of the SOZ, whereas type II ripples are not. Type I ripples are found more readily than fast ripples in human neocortical epilepsy. Type II-O ripples may represent spontaneous physiologic ripples in the human neocortex.
Assuntos
Eletroencefalografia/métodos , Eletroencefalografia/estatística & dados numéricos , Epilepsia/patologia , Neocórtex/patologia , Convulsões/patologia , Interpretação Estatística de Dados , Eletrodos Implantados , Epilepsia/cirurgia , Humanos , Neocórtex/cirurgia , Procedimentos Neurocirúrgicos , Convulsões/fisiopatologia , Convulsões/cirurgia , Sono/fisiologiaRESUMO
PURPOSE: The orbitofrontal (OF) region is one of the least explored regions of the cerebral cortex. There are few studies on patients with electrophysiologically and surgically confirmed OF epilepsy and a negative magnetic resonance imaging (MRI) study. We aimed to examine the neuroimaging characteristics of MRI-negative OF epilepsy with the focus on a voxel-based morphometric MRI postprocessing technique. METHODS: We included six patients with OF epilepsy, who met the following criteria: surgical resection of the OF lobe with/without adjacent cortex, seizure-free for ≥12 months, invasive video-electroencephalography (EEG) monitoring showing ictal onset from the OF area, and preoperative MRI regarded as negative. Patients were investigated in terms of their image postprocessing and functional neuroimaging characteristics, electroclinical characteristics obtained from noninvasive and invasive evaluations, and surgical pathology. MRI postprocessing on T1 -weighted high-resolution scans was implemented with a morphometric analysis program (MAP) in MATLAB. KEY FINDINGS: Single MAP+ abnormalities were found in four patients; three were in the OF region and one in the ipsilateral mesial frontal area. These abnormalities were included in the resection. One patient had bilateral MAP+ abnormalities in the OF region, with the ipsilateral one completely removed. The MAP+ foci were concordant with invasive electrophysiologic data in the majority of MAP+ patients (four of five). The localization value of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and ictal single-photon emission computed tomography (SPECT) is low in this cohort. Surgical pathology included focal cortical dysplasia, remote infarct, Rosenthal fiber formation and gliosis. SIGNIFICANCE: Our study highlights the importance of MRI postprocessing in the process of presurgical evaluation of patients with suspected orbitofrontal epilepsy and "normal" MRI. Using MAP, we were able to positively identify subtle focal abnormalities in the majority of the patients. MAP results need to be interpreted in the context of their electroclinical findings and can provide valuable targets in the process of planning invasive evaluation.
Assuntos
Epilepsia do Lobo Frontal/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Adolescente , Adulto , Proteínas de Bactérias , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Eletroencefalografia , Epilepsia do Lobo Frontal/fisiopatologia , Exotoxinas , Feminino , Neuroimagem Funcional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons , Adulto JovemRESUMO
PURPOSE: To investigate the utility of magnetic source imaging (MSI) and ictal single photon emission computed tomography (SPECT), each compared with intracranial electroencephalography (EEG) (ICEEG), to localize the epileptogenic zone (EZ) and predict epilepsy surgery outcome in patients with nonlesional neocortical focal epilepsy. METHODS: Studied were 14 consecutive patients with nonlesional neocortical epilepsy who underwent presurgical evaluation including ICEEG, positive MSI, and localizing subtraction Ictal SPECT coregistered to MRI (SISCOM) analysis. Follow-up after epilepsy surgery was ≥ 24 months. ICEEG, MSI, and SPECT results were classified using a sublobar classification. KEY FINDINGS: Of 14 patients, 6 (42.9%) became seizure-free after surgery. Sublobar ICEEG focus was completely resected in 11 patients; 5 (45.5%) of them became seizure- free. Concordance of ICEEG and MSI and complete focus resection was found in 5 (35.7%) patients; 80% of them became seizure-free. Sublobar ICEEG-MSI concordance and complete focus resection significantly increased the chance of seizure freedom after epilepsy surgery (p = 0.038). In contrast, of the 6 patients (42.9%) with concordant ICEEG and SISCOM and complete focus resection, only 66.7% became seizure-free (p = 0.138). Assuming concordant results, the additive value to ICEEG alone for localizing the EZ is higher with ICEEG-MSI (odds ratio 14) compared to ICEEG-SISCOM (odds ratio 6). SIGNIFICANCE: This study shows that combination of MSI and/or SISCOM with ICEEG is useful in the presurgical evaluation of patients with nonlesional neocortical epilepsy. Concordant test results of either MSI or SISCOM with ICEEG provide useful additive information for that provided by ICEEG alone to localize the EZ in this most challenging group of patients. When sublobar concordance with ICEEG is observed, MSI is more advantageous compared to SISCOM in predicting seizure-free epilepsy surgery outcome.