Assessing the coupling between local neural activity and global connectivity fluctuations: Application to human intracranial electroencephalography during a cognitive task

Cognitive-relevant information is processed by different brain areas that cooperate to eventually produce a response. The relationship between local activity and global brain states during such processes, however, remains for the most part unexplored. To address this question, we designed a simple face-recognition task performed in patients with drug-resistant epilepsy and monitored with intracranial electroencephalography (EEG). Based on our observations, we developed a novel analytical framework (named “local–global” framework) to statistically correlate the brain activity in every recorded gray-matter region with the widespread connectivity fluctuations as proxy to identify concurrent local activations and global brain phenomena that may plausibly reflect a common functional network during cognition. The application of the local–global framework to the data from three subjects showed that similar connectivity fluctuations found across patients were mainly coupled to the local activity of brain areas involved in face information processing. In particular, our findings provide preliminary evidence that the reported global measures might be a novel signature of functional brain activity reorganization when a stimulus is processed in a task context regardless of the specific recorded areasPeer ReviewedPostprint (published version

Clinical role of subtraction ictal SPECT coregistered to MR Imaging and 18F-FDG PET in pediatric epilepsy

A precise assessment of the drug-resistant epileptic pediatric population for surgical candidacy is often challenging, and to date there are no evidence-based guidelines for presurgical identification of the epileptogenic zone. To evaluate the usefulness of radionuclide imaging techniques for presurgical evaluation of epileptic pediatric patients, we compared the results of video-electroencephalography (EEG), brain MR imaging, interictal SPECT, ictal SPECT, subtraction ictal SPECT coregistered to MR imaging (SISCOM), and interictal PET with (18)F-FDG. METHODS: Fifty-four children with drug-resistant epilepsy who had undergone video-EEG monitoring, brain MR imaging, interictal and ictal brain perfusion SPECT, SISCOM, and (18)F-FDG PET were included in this study. All abnormal findings revealed by these neuroimaging techniques were compared with the presumed location of the epileptogenic zone (PEZ) as determined by video-EEG and clinical data. The proportion of localizing studies for each technique was statistically compared. In the 18 patients who underwent resective brain surgery, neuroimaging results were compared with histopathology results and surgical outcome. RESULTS: SISCOM and (18)F-FDG PET concordance with the PEZ was significantly higher than MR imaging (P < 0.05). MR imaging showed localizing results in 21 of 54 cases (39%), SISCOM in 36 of 54 cases (67%), and (18)F-FDG PET in 31 of 54 cases (57%). If we consider SISCOM and (18)F-FDG PET results together, nuclear medicine imaging techniques showed coinciding video-EEG results in 76% of patients (41/54). In those cases in which MR imaging failed to identify any epileptogenic lesion (61% [33/54]), SISCOM or (18)F-FDG PET findings matched PEZ in 67% (22/33) of cases. CONCLUSION: SISCOM and (18)F-FDG PET provide complementary presurgical information that matched video-EEG results and clinical data in three fourths of our sample. SISCOM was particularly useful in those cases in which MR imaging findings were abnormal but no epileptogenic lesion was identified. Radionuclide imaging techniques are both useful and reliable, extending the possibility of surgical treatment to patients who may have been discouraged without a nuclear medicine approach

Spanish version of the Satisfaction with Epilepsy Care questionnaire: Adaptation and psychometric properties

OBJECTIVE: The objective of this study was to perform a cross-cultural adaption and psychometric evaluation of the Spanish version of the Satisfaction with Epilepsy Care (SEC) questionnaire and analyze patient satisfaction with epilepsy care. METHODS: Transcultural adaptation and validation of the SEC were carried out using translation and back-translation with pilot testing and an expert panel. The SEC-E (Spanish) was analyzed in 213 patients with epilepsy to examine construct and criterion validity and internal consistency. RESULTS: The SEC-E achieved conceptual, semantic, and content equivalence with the original version. For content validity, one question was eliminated from the original questionnaire as it has little relevance in our cultural setting. Positive correlations for criterion validity were obtained using the gold standard measure (Satisfaction in Hospitalized Patients scale). Construct validity replicated the three dimensions of the original questionnaire. The scale showed adequate reliability through internal consistency (Cronbach's α of 0.94) and temporal stability on retest (n = 85). Patients scored (0 to 100) 77.5 [standard deviation (SD): 19.9] for satisfaction with communication, 76.9 (SD: 17) for organization, and 67.2 (SD: 22.1) for information. SIGNIFICANCE: The SEC-E is a valid and reliable tool for the assessment of educational interventions aiming to improve the quality of care in patients with epilepsy in Spanish clinical practice. The results showed a good level of patient satisfaction with epilepsy care

Epileptogenic zone localization with (18)FDG PET using a new dynamic parametric analysis

Introduction: [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is part of the regular preoperative work-up in medically refractory epilepsy. As a complement to visual evaluation of PET, statistical parametric maps can help in the detection of the epileptogenic zone (EZ). However, software packages currently available are time-consuming and little intuitive for physicians. We develop a user-friendly software (referred as PET-analysis) for EZ localization in PET studies that allows dynamic real-time statistical parametric analysis. To evaluate its performance, the outcome of PET-analysis was compared with the results obtained by visual assessment and Statistical Parametric Mapping (SPM). Methods: Thirty patients with medically refractory epilepsy who underwent presurgical 18F-FDG PET with good post-operative outcomes were included. The 18F-FDG PET studies were evaluated by visual assessment, with SPM8 and PET-analysis. In SPM, parametric T-maps were thresholded at corrected p < 0.05 and cluster size k = 50 and at uncorrected p < 0.001 and k = 100 (the most used parameters in the literature). Since PET-analysis rapidly processes different threshold combinations, T-maps were thresholded with multiple p-value and different clusters sizes. The presurgical EZ identified by visual assessment, SPM and PET-analysis was compared to the confirmed EZ according to post-surgical follow-up. Results: PET-analysis obtained 66.7% (20/30) of correctly localizing studies, comparable to the 70.0% (21/30) achieved by visual assessment and significantly higher (p < 0.05) than that obtained with the SPM threshold p < 0.001/k = 100, of 36.7% (11/30). Only one study was positive, albeit non-localizing, with the SPM threshold corrected p < 0.05/k = 50. Concordance was substantial for PET-analysis (κ = 0.643) and visual interpretation (κ = 0.622), being fair for SPM (κ = 0.242). Conclusion: Compared to SPM with the fixed standard parameters, PET-analysis may be superior in EZ localization with its easy and rapid processing of different threshold combinations. The results of this initial proof-of-concept study validate the clinical use of PET-analysis as a robust objective complementary tool to visual assessment for EZ localization

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients

Identificación de las estructuras corticales implicadas en la generación de la actividad epiléptica crítica e intercrítica en pacientes con epilepsia fármacorresistente: un estudio de resonancia magnética funcional con EEG simultáneo.

[spa]A pesar del extenso conocimiento de la epilepsia de que disponemos hoy día, todavía permanece como materia de estudio la localización exacta de los generadores corticales de la actividad epiléptica crítica e intercrítica; así como, de las vías y estructuras cerebrales implicadas en la propagación de las crisis epilépticas. Estos conceptos resultan de vital importancia para poder profundizar en la fisiopatología de la epilepsia, y son esenciales a la hora de la planificación de la cirugía funcional de la epilepsia. Esta tesis consta de tres estudios dónde se desarrolla un nuevo método de análisis de las imágenes de RMf-EEG que permite secuenciar en el tiempo los cambios de señal BOLD relacionados con la actividad ictal e interictal, y, de esta manera, poder indagar en el correlato hemodinámico y metabólico de esta actividad con una resolución temporal y espacial más alta que con los métodos de análisis tradicionales. El hecho de poder acceder a la secuencia de activación de las diferentes estructuras cerebrales implicadas en la generación y propagación de la actividad crítica e intercrítica nos podría proporciona información precisa sobre la localización de los sustratos corticales implicados en su génesis, así como, sobre los fenómenos dinámicos que acontecen durante su evolución y desarrollo.[eng]Purpose: The aim of this thesis was to apply sequential analysis of electroencephalography–functional magnetic resonance imaging (EEG-fMRI) data to study the cortical substrates related to the generation of the ictal and interictal epileptiform activity (IEA) in patients with pharmacoresistant epilepsy. Methods: We analyzed fMRI data from 5 patients who underwent seizures during scanning and 21 children and adolescents, and young adults patients who showed frequent bursts or runs of spikes on EEG. Results: After the sequential analysis, at least one significant blood oxygen level–dependent (BOLD) response spatially consistent with the presumed epileptogenic zone was found. Significance: The EEG-fMRI data sequential analysis could noninvasively identify cortical areas involved in the ictal and IEA generation

Validation of an automatic dose injection system for Ictal SPECT in epilepsy

The purpose of our study was to evaluate the performance and clinical usefulness of an automated injector system (AIS) that administers an automated injection for ictal SPECT after calculating the volume of tracer to be injected over time. Methods: To test the AIS, repeated injections were performed at different times after tracer preparation. The clinical study consisted of 56 patients with drug-resistant, complex partial seizures. Tracer for ictal SPECT was injected using automated injection in 27 patients and manual injection (MI) in the remaining 29. Injection time (TI) was measured in seconds from seizure onset to the end of volume injection. The SISCOM (Subtraction Ictal Spect Co-registered to MRI) procedure was used to locate the epileptogenic seizure focus with SPECT. The definition of seizure focus was made by consensus of the epilepsy unit using conventional diagnostic methods. Results: During the experimental phase, there were no system failures, and the error in injected doses when using automated injection was lower than with MI. During the clinical phase, TI using manual injection was 41 s with a range of 14-103 s, compared with an AIS average of 33 s with a range of 19-63 s (P , 0.05). Ictal SPECT and SISCOM successfully localized the seizure focus in 21 of the 27 patients (78%) by AIS and in 19 of the 29 patients (65%) by MI (P 5 0.14). Furthermore, nursing staff found the AIS method more convenient than the MI method. Conclusion: An AIS can improve the quality of work of the nursing staff in the neurology ward and allow a finer adjustment of the injection dose. Early results using an AIS would indicate a reduction in injection time and improved SPECT accuracy