Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
MEG Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Brain. 2019 Nov 1;142(11):3514-3529. doi: 10.1093/brain/awz284.
In patients with medically refractory epilepsy, resective surgery is the mainstay of therapy to achieve seizure freedom. However, ∼20-50% of cases have intractable seizures post-surgery due to the imprecise determination of epileptogenic zone. Recent intracranial studies suggest that high frequency oscillations between 80 and 200 Hz could serve as one of the consistent epileptogenicity biomarkers for localization of the epileptogenic zone. However, these high frequency oscillations are not adopted in the clinical setting because of difficult non-invasive detection. Here, we investigated non-invasive detection and localization of high frequency oscillations and its clinical utility in accurate pre-surgical assessment and post-surgical outcome prediction. We prospectively recruited 52 patients with medically refractory epilepsy who underwent standard pre-surgical workup including magnetoencephalography (MEG) followed by resective surgery after determination of the epileptogenic zone. The post-surgical outcome was assessed after 22.14 ± 10.05 months. Interictal epileptic spikes were expertly identified, and interictal epileptic oscillations across the neural activity frequency spectrum from 8 to 200 Hz were localized using adaptive spatial filtering methods. Localization results were compared with epileptogenic zone and resected cortex for congruence assessment and validated against the clinical outcome. The concordance rate of high frequency oscillations sources (80-200 Hz) with the presumed epileptogenic zone and the resected cortex were 75.0% and 78.8%, respectively, which is superior to that of other frequency bands and standard dipole fitting methods. High frequency oscillation sources corresponding with the resected cortex, had the best sensitivity of 78.0%, positive predictive value of 100% and an accuracy of 78.84% to predict the patient's surgical outcome, among all other frequency bands. If high frequency oscillation sources were spatially congruent with resected cortex, patients had an odds ratio of 5.67 and 82.4% probability of achieving a favourable surgical outcome. If high frequency oscillations sources were discordant with the epileptogenic zone or resection area, patient has an odds ratio of 0.18 and only 14.3% probability of achieving good outcome, and mostly tended to have an unfavourable outcome (χ2 = 5.22; P = 0.02; φ = -0.317). In receiver operating characteristic curve analyses, only sources of high-frequency oscillations demonstrated the best sensitivity and specificity profile in determining the patient's surgical outcome with area under the curve of 0.76, whereas other frequency bands indicate a poor predictive performance. Our study is the first non-invasive study to detect high frequency oscillations, address the efficacy of high frequency oscillations over the different neural oscillatory frequencies, localize them and clinically validate them with the post-surgical outcome in patients with medically refractory epilepsy. The evidence presented in the current study supports the fact that HFOs might significantly improve the presurgical assessment, and post-surgical outcome prediction, where it could widely be used in a clinical setting as a non-invasive biomarker.
在药物难治性癫痫患者中,切除术是实现无癫痫发作的主要治疗方法。然而,由于致痫区的确定不精确,约 20-50%的病例术后仍有癫痫发作。最近的颅内研究表明,80-200 Hz 之间的高频振荡可以作为定位致痫区的一致性致痫性生物标志物之一。然而,这些高频振荡并未在临床中采用,因为其难以进行非侵入性检测。在这里,我们研究了高频振荡的非侵入性检测和定位及其在准确术前评估和术后结果预测中的临床应用。我们前瞻性招募了 52 名药物难治性癫痫患者,这些患者接受了标准的术前检查,包括磁共振脑磁图(MEG),然后在确定致痫区后进行切除术。术后 22.14±10.05 个月后评估术后结果。通过自适应空间滤波方法,专家识别出癫痫发作间期棘波,并定位神经活动频谱中 8-200 Hz 的癫痫发作间期振荡。将定位结果与致痫区和切除皮层进行比较,以进行一致性评估,并与临床结果进行验证。高频振荡源(80-200 Hz)与假定致痫区和切除皮层的一致性率分别为 75.0%和 78.8%,优于其他频带和标准偶极子拟合方法。与切除皮层对应的高频振荡源具有 78.0%的最佳灵敏度、100%的阳性预测值和 78.84%的准确性,可预测患者的手术结果,所有其他频带的准确性均优于其他频带。如果高频振荡源与切除皮层空间一致,患者发生有利手术结果的几率为 5.67 倍,概率为 82.4%。如果高频振荡源与致痫区或切除区域不一致,患者发生有利手术结果的几率为 0.18 倍,概率仅为 14.3%,且大多倾向于出现不良结果(χ2=5.22;P=0.02;φ=-0.317)。在受试者工作特征曲线分析中,只有高频振荡源在确定患者手术结果方面表现出最佳的灵敏度和特异性特征,曲线下面积为 0.76,而其他频带则显示出较差的预测性能。我们的研究是首次进行非侵入性检测高频振荡的研究,探讨了高频振荡在不同神经振荡频率下的疗效,对其进行定位,并在药物难治性癫痫患者的术后结果中进行临床验证。目前研究中的证据支持这样一个事实,即高频振荡可能显著改善术前评估和术后结果预测,可广泛应用于临床作为一种非侵入性生物标志物。
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