How to establish causality in epilepsy surgery

Abstract

Focality in electro-clinical or neuroimaging data often motivates epileptologists to consider epilepsy surgery in patients with medically-uncontrolled seizures, while not all focal findings are causally associated with the generation of epileptic seizures. With the help of Hill's criteria, we have discussed how to establish causality in the context of the presurgical evaluation of epilepsy. The strengths of EEG include the ability to determine the temporal relationship between cerebral activities and clinical events; thus, scalp video-EEG is necessary in the evaluation of the majority of surgical candidates. The presence of associated ictal discharges can confirm the epileptic nature of a particular spell and whether an observed neuroimaging abnormality is causally associated with the epileptic seizure. Conversely, one should be aware that scalp EEG has a limited spatial resolution and sometimes exhibits propagated epileptiform discharges more predominantly than in situ discharges generated at the seizure-onset zone. Intraoperative or extraoperative electrocorticography (ECoG) is utilized when noninvasive presurgical evaluation, including anatomical and functional neuroimaging, fails to determine the margin between the presumed epileptogenic zone and eloquent cortex. Retrospective as well as prospective studies have reported that complete resection of the seizure-onset zone on ECoG was associated with a better seizure outcome, but not all patients became seizure-free following such resective surgery. Some retrospective studies suggested that resection of sites showing high-frequency oscillations (HFOs) at >80 Hz on interictal or ictal ECoG was associated with a better seizure outcome. Others reported that functionally-important areas may generate HFOs of a physiological nature during rest as well as sensorimotor and cognitive tasks. Resection of sites showing task-related augmentation of HFOs has been reported to indeed result in functional loss following surgery. Thus, some but not all sites showing interictal HFOs are causally associated with seizure generation. Furthermore, evidence suggests that some task-related HFOs can be transiently suppressed by the prior occurrence of interictal spikes. The significance of interictal HFOs should be assessed by taking into account the eloquent cortex, seizure-onset zone, and cortical lesions. Video-EEG and ECoG generally provide useful but still limited information to establish causality in presurgical evaluation. A comprehensive assessment of data derived from multiple modalities is ultimately required for successful management.

Cytochrome c oxidase deficit is associated with the seizure onset zone in young patients with focal cortical dysplasia Type II

“…Surgical resection of dysplastic cortex is recognized as an important therapeutic intervention for FCD, and may be curative for many patients with intractable epilepsy (Lüders et al 2006;Otsubo et al 2005). The seizure onset zone (SOZ), which is defined as the region of cortex associated with the initiation of ictal discharges, is usually determined by electroencephalography (EEG) or intracranial electrocorticography (ICEEG) (Asano et al 2013;Lüders et al 2006). Extraoperative ICEEG, which is regularly used by the current investigators, provides increased probability of capturing the onset of ictal events and improved ability to localize eloquent cortex (Fujiwara et al 2012).…”

“…FCD tissues are highly and intrinsically epileptogenic (Otsubo et al 2005). The epileptogenic zone has been defined as the minimum amount of cortical tissue which will most likely lead to seizure-freedom following surgical resection (Asano et al 2013;Lüders et al 2006). Surgical resection of dysplastic cortex is recognized as an important therapeutic intervention for FCD, and may be curative for many patients with intractable epilepsy (Lüders et al 2006;Otsubo et al 2005).…”

Occurrence of bilaterally independent epileptic spasms after a corpus callosotomy in West syndrome

“…An observation of the changes in ictal semiology after callosotomy may be considered 'experimental evidence' [5] that could be useful toward deducing a causal relationship between the presence of the inter-hemispheric connection and the generalization of ESs. This case may be exceptional because, to our knowledge, bilaterally independent ESs are not known to occur after callosotomy.…”

Contribution of research on ‘Epilepsy & Behavior’ to the refinement of functional brain atlas in four dimensions

“…Consideration of the temporal order of cortical activations is one of the criteria to judge the causal significance of a given region activated during a task [47]. Intracranial ECoG recording provides a unique opportunity to directly sample neural signals from deeply located regions such as medial and inferior surfaces of cerebral cortex in case subdural electrodes happen to be placed on such regions.…”

“…Conversely, scalp EEG and magnetoencephalography recordings may not reliably detect such signals generated by regions distant from censors [10,48–50], and suffer from a larger degree of artifacts difficult to eliminate [51,52]. Investigation of high-gamma ECoG activity combined with stimulation mapping can further clarify the causal significance of event-related high gamma activity during a task [42,47,53]. …”