RESUMEN
High frequency oscillations (HFOs) are recognized as biomarkers for epileptogenic brain tissue. A remaining challenge for epilepsy surgery is the prospective classification of tissue sampled by individual electrode contacts. We analysed long-term invasive recordings of 20 consecutive patients who subsequently underwent epilepsy surgery. HFOs were defined prospectively by a previously validated, automated algorithm in the ripple (80-250 Hz) and the fast ripple (FR, 250-500 Hz) frequency band. Contacts with the highest rate of ripples co-occurring with FR over several five-minute time intervals designated the HFO area. The HFO area was fully included in the resected area in all 13 patients who achieved seizure freedom (specificity 100%) and in 3 patients where seizures reoccurred (negative predictive value 81%). The HFO area was only partially resected in 4 patients suffering from recurrent seizures (positive predictive value 100%, sensitivity 57%). Thus, the resection of the prospectively defined HFO area proved to be highly specific and reproducible in 13/13 patients with seizure freedom, while it may have improved the outcome in 4/7 patients with recurrent seizures. We thus validated the clinical relevance of the HFO area in the individual patient with an automated procedure. This is a prerequisite before HFOs can guide surgical treatment in multicentre studies.
Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Epilepsia Refractaria/diagnóstico , Electroencefalografía/métodos , Convulsiones/diagnóstico , Adulto , Algoritmos , Epilepsia Refractaria/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurocirugia , Estudios Prospectivos , Convulsiones/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
High frequency oscillations (HFOs, 80-500 Hz) in invasive EEG are a biomarker for the epileptic focus. Ripples (80-250 Hz) have also been identified in non-invasive MEG, yet detection is impeded by noise, their low occurrence rates, and the workload of visual analysis. We propose a method that identifies ripples in MEG through noise reduction, beamforming and automatic detection with minimal user effort. We analysed 15 min of presurgical resting-state interictal MEG data of 25 patients with epilepsy. The MEG signal-to-noise was improved by using a cross-validation signal space separation method, and by calculating ~ 2400 beamformer-based virtual sensors in the grey matter. Ripples in these sensors were automatically detected by an algorithm optimized for MEG. A small subset of the identified ripples was visually checked. Ripple locations were compared with MEG spike dipole locations and the resection area if available. Running the automatic detection algorithm resulted in on average 905 ripples per patient, of which on average 148 ripples were visually reviewed. Reviewing took approximately 5 min per patient, and identified ripples in 16 out of 25 patients. In 14 patients the ripple locations showed good or moderate concordance with the MEG spikes. For six out of eight patients who had surgery, the ripple locations showed concordance with the resection area: 4/5 with good outcome and 2/3 with poor outcome. Automatic ripple detection in beamformer-based virtual sensors is a feasible non-invasive tool for the identification of ripples in MEG. Our method requires minimal user effort and is easily applicable in a clinical setting.
Asunto(s)
Algoritmos , Epilepsia/fisiopatología , Magnetoencefalografía/métodos , Procesamiento de Señales Asistido por Computador , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: Fast ripples (FR, 250-500Hz) in the intraoperative corticogram have recently been proposed as specific predictors of surgical outcome in epilepsy patients. However, online FR detection is restricted by their low signal-to-noise ratio. Here we propose the integration of low-noise EEG with unsupervised FR detection. METHODS: Pre- and post-resection ECoG (N=9 patients) was simultaneously recorded by a commercial device (CD) and by a custom-made low-noise amplifier (LNA). FR were analyzed by an automated detector previously validated on visual markings in a different dataset. RESULTS: Across all recordings, in the FR band the background noise was lower in LNA than in CD (p<0.001). FR rates were higher in LNA than CD recordings (0.9±1.4 vs 0.4±0.9, p<0.001). Comparison between FR rates in post-resection ECoG and surgery outcome resulted in positive predictive value PPV=100% in CD and LNA, and negative predictive value NPV=38% in CD and NPV=50% for LNA. Prediction accuracy was 44% for CD and 67% for LNA. CONCLUSIONS: Prediction of seizure outcome was improved by the optimal integration of low-noise EEG and unsupervised FR detection. SIGNIFICANCE: Accurate, automated and fast FR rating is essential for consideration of FR in the intraoperative setting.
Asunto(s)
Electrocorticografía/métodos , Monitorización Neurofisiológica Intraoperatoria/métodos , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Adolescente , Adulto , Anciano , Niño , Preescolar , Electroencefalografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Convulsiones/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: High frequency oscillations (HFOs) and in particular fast ripples (FRs) in the post-resection electrocorticogram (ECoG) have recently been shown to be highly specific predictors of outcome of epilepsy surgery. FR visual marking is time consuming and prone to observer bias. We validate here a fully automatic HFO detector against seizure outcome. METHODS: Pre-resection ECoG dataset (N=14 patients) with visually marked HFOs were used to optimize the detector's parameters in the time-frequency domain. The optimized detector was then applied on a larger post-resection ECoG dataset (N=54) and the output was compared with visual markings and seizure outcome. The analysis was conducted separately for ripples (80-250Hz) and FRs (250-500Hz). RESULTS: Channel-wise comparison showed a high association between automatic detection and visual marking (p<0.001 for both FRs and ripples). Automatically detected FRs were predictive of clinical outcome with positive predictive value PPV=100% and negative predictive value NPV=62%, while for ripples PPV=43% and NPV=100%. CONCLUSIONS: Our automatic and fully unsupervised detection of HFO events matched the expert observer's performance in both event selection and outcome prediction. SIGNIFICANCE: The detector provides a standardized definition of clinically relevant HFOs, which may spread its use in clinical application.
Asunto(s)
Mapeo Encefálico/métodos , Ondas Encefálicas , Electrocorticografía/métodos , Epilepsia/fisiopatología , Epilepsia/cirugía , Monitorización Neurofisiológica Intraoperatoria/métodos , Ondas Encefálicas/fisiología , Electroencefalografía/métodos , Epilepsia/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
OBJECTIVE: The somatosensory evoked potential (SEP) elicited by median nerve stimulation consists of the N20 peak together with the concurrent high frequency oscillation (HFO, > 500 Hz). We describe the conditions for HFO detection in ECoG and scalp EEG in intraoperative recordings. METHODS: During neurosurgical interventions in six patients under propofol anesthesia, the SEP was recorded from subdural electrode strips (15 recordings) and from scalp electrodes (10/15 recordings). We quantified the spatial attenuation of the Signal-to-Noise Ratio (SNR) of N20 and HFO along the contacts of the electrode strip. We then compared the SNR of ECoG and simultaneous scalp EEG in a biophysical framework. RESULTS: HFO detection under propofol anesthesia was demonstrated. Visual inspection of strip cortical recordings revealed phase reversal for N20 in 14/15 recordings and for HFO in 10/15 recordings. N20 had higher maximal SNR (median 33.5 dB) than HFO (median 23 dB). The SNR of N20 attenuated with a larger spatial extent (median 7.2 dB/cm) than the SNR of HFO (median 12.3 dB/cm). We found significant correlations between the maximum SNR (rho = 0.58, p = 0.025) and the spatial attenuation (rho = 0.86, p < 0.001) of N20 and HFO. In 3/10 recordings we found HFO in scalp EEG. Based on the spatial attenuation and SNR in the ECoG, we estimated the scalp EEG amplitude ratio N20/HFO and found significant correlation with recorded values (rho = 0.65, p = 0.049). CONCLUSIONS: We proved possible the intraoperative SEP HFO detection under propofol anesthesia. The spatial attenuation along ECoG contacts represents a good estimator of the area contributing to scalp EEG. The SNR and the spatial attenuation in ECoG recordings provide further insights for the prediction of HFO detectability in scalp EEG. The results obtained in this context may not be limited to SEP HFO, but could be generalized to biological signatures lying in the same SNR and frequency range.
Asunto(s)
Anestésicos Intravenosos/administración & dosificación , Ondas Encefálicas/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiopatología , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Propofol/administración & dosificación , Relación Señal-Ruido , Adulto , Anciano , Estimulación Eléctrica , Electrocorticografía , Electroencefalografía , Femenino , Humanos , Masculino , Nervio Mediano/fisiopatología , Persona de Mediana EdadRESUMEN
OBJECTIVE: We hypothesized that high frequency oscillations (HFOs) with irregular amplitude and frequency more specifically reflect epileptogenicity than HFOs with stable amplitude and frequency. METHODS: We developed a fully automatic algorithm to detect HFOs and classify them based on their morphology, with types defined according to regularity in amplitude and frequency: type 1 with regular amplitude and frequency; type 2 with irregular amplitude, which could result from filtering of sharp spikes; type 3 with irregular frequency; and type 4 with irregular amplitude and frequency. We investigated the association of different HFO types with the seizure onset zone (SOZ), resected area and surgical outcome. RESULTS: HFO rates of all types were significantly higher inside the SOZ than outside. HFO types 1 and 2 were strongly correlated to each other and showed the highest rates among all HFOs. Their occurrence was highly associated with the SOZ, resected area and surgical outcome. The automatic detection emulated visual markings with 93% true positives and 57% false detections. CONCLUSIONS: HFO types 1 and 2 similarly reflect epileptogenicity. SIGNIFICANCE: For clinical application, it may not be necessary to separate real HFOs from "false oscillations" produced by the filter effect of sharp spikes. Also for automatically detected HFOs, surgical outcome is better when locations with higher HFO rates are included in the resection.
Asunto(s)
Electroencefalografía/métodos , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Ondas Encefálicas/fisiología , Bases de Datos Factuales/normas , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVES: High frequency oscillations (HFOs) have been proposed as a new biomarker for epileptogenic tissue. The exact characteristics of clinically relevant HFOs and their detection are still to be defined. METHODS: We propose a new method for HFO detection, which we have applied to six patient iEEGs. In a first stage, events of interest (EoIs) in the iEEG were defined by thresholds of energy and duration. To recognize HFOs among the EoIs, in a second stage the iEEG was Stockwell-transformed into the time-frequency domain, and the instantaneous power spectrum was parameterized. The parameters were optimized for HFO detection in patient 1 and tested in patients 2-5. Channels were ranked by HFO rate and those with rate above half maximum constituted the HFO area. The seizure onset zone (SOZ) served as gold standard. RESULTS: The detector distinguished HFOs from artifacts and other EEG activity such as interictal epileptiform spikes. Computation took few minutes. We found HFOs with relevant power at frequencies also below the 80-500 Hz band, which is conventionally associated with HFOs. The HFO area overlapped with the SOZ with good specificity > 90% for five patients and one patient was re-operated. The performance of the detector was compared to two well-known detectors. CONCLUSIONS: Compared to methods detecting energy changes in filtered signals, our second stage - analysis in the time-frequency domain - discards spurious detections caused by artifacts or sharp epileptic activity and improves the detection of HFOs. The fast computation and reasonable accuracy hold promise for the diagnostic value of the detector.