Thursday, September 20, 2018

Epilepsy surgery near or in eloquent cortex in children

Jayakar P, Jayakar A, Libenson M, Arzimanoglou A, Rydenhag B, Cross JH, Bhatia S, Tassi L, Lachhwani D, Gaillard WD; Pediatric Epilepsy Surgery Task Force; International League Against Epilepsy. Epilepsy surgery near or in eloquent cortex in children-Practice patterns and recommendations for minimizing and reporting deficits. Epilepsia. 2018 Aug;59(8):1484-1491.


We aimed to investigate the current practices guiding surgical resection strategies involving epileptogenic zones (EZs) near or in eloquent cortex (EC) at pediatric epilepsy surgery centers worldwide.

A survey was conducted among 40 respondents from 33 pediatric epilepsy surgery centers worldwide on the weight assigned to diagnostic tests used to define the EZ and EC, how EC is viewed, and how surgeries are planned for foci near or in eloquent cortex.

A descriptive analysis was performed that revealed considerable variation in the use of diagnostic tests and resective strategies toward EZ and EC.

The wide variation in strategies may contribute to undesirable outcomes characterized by poor seizure control with added deficits and underscores the need to establish best practices in pediatric epilepsy surgery. The survey data were used to formulate a set of recommendations to help minimize deficits and to report them consistently.

From the article

In defining the EZ, the seizure aura was weighted heavily by participants, with 73% scoring it as a 4 or 5, whereas the early seizure semiology and postictal findings scored lower (63% and 9%, respectively) (Table 2). The type of magnetic resonance imaging (MRI) lesion played a significant role in the amount of weight given to the MRI. Although focal cortical dysplasia and vascular lesions were weighted heavily along with the MRI findings of hemimegalencephaly and Rasmussen's encephalitis, weights assigned to other types of lesions including polymicrogyria showed considerable variation across centers. With regard to nuclear medicine imaging, 35% of respondents weighted ictal single‐photon emission computed tomography (SPECT) hyperperfusion and positron emission tomography (PET) hypometabolism heavily in favor of extending the resection to EC, with 50% considering subtraction ictal and interictal SPECT co‐registered to MRI (SISCOM) and PET hypermetabolism reliable. This percentage was 75% for magnetoencephalography/electrophysiologic source imaging (MEG/ESI) clusters, a rating that was even higher than for interictal epileptiform discharges recorded on intracranial electroencephalography (EEG)…

The different types of focal background abnormalities seen on intraoperative electrocorticography (ECoG) were weighted variably; continuous epileptiform discharges were regarded as a reliable marker of the EZ by 90% of the respondents. Regarding extraoperative recordings, the ictal‐onset zone on the intracranial EEG was seen as the most reliable marker of the EZ by all respondents, but early seizure propagation and specific patterns such as high‐frequency oscillations and ictal direct current (DC) shifts were variably weighted…

Electrical stimulation mapping (ESM) was regarded as a reliable modality to define eloquent cortex by 90% of the respondents; functional MRI (fMRI) and MEG were also felt to be reliable by 75% of the respondents, whereas transcranial magnetic stimulation (TMS) was lower at 45%. Centers were asked to grade how “critical” they viewed specific functions. Broca's and Wernicke's areas were regarded as highly critical by all respondents.

Verbal memory and the dominant hand motor function were likewise regarded highly critical by more than 90% respondents. The nondominant hand (83%) came in next followed by leg motor at 66% and homonymous visual fields with 63%. Motor face, executive function, nonverbal memory, and calculation were regarded critical by less than 50% of respondents. With regard to plasticity of language cortex, 85% of the respondents considered it to be maximum below age 5 years, whereas 15% considered maximum plasticity to extend to the end of the first decade.

There was a wide range in the threshold of the chance of seizure freedom based on the preoperative assessment that would be required to accept postoperative deficits. Thirty percent of the respondents considered that the possibility of seizure freedom would have to exceed 90% to accept postoperative deficits, whereas the majority accepted a moderate chance (60%‐80%) chance of seizure freedom and 10% of respondents were comfortable accepting deficits at estimated rates of seizure freedom as low as 50%. Eighty‐five percent of respondents adopted a conservative strategy favoring an initial EC‐sparing resection, whereas the remaining generally opted for more aggressive “complete” resections at initial surgery. Involvement of EC by an MRI lesion prompted its resection by nearly 30% of respondents. In patients for whom the MRI lesion was nearby but did not involve EC, 25% would extend the resection to include EC based solely on functional abnormalities; the remaining would opt for lesionectomy alone. In nonlesional cases, 12% of respondents would consider resection of EC based on functional abnormalities.

With respect to dominant mesial temporal resections, in patients with proven unilateral temporal lobe onsets and with preserved verbal memory function, 40% would resect the hippocampus only if there was evidence of sclerosis on MRI scans, 30% would resect it in any case, and 20% would tailor using invasive EEG, whereas only 10% would refrain from pursuing surgery.

Protective strategies such as intraoperative functional mapping including motor mapping under anesthesia were employed by 90% of respondents, and awake surgery required for language mapping was used by 65% when feasible. Fifty percent of respondents also performed subcortical tract mapping; multiple subpial transections were performed by 30%. With regard to specific etiologies, respondents were more inclined to resect EC if the substrate was focal cortical dysplasia vs all other substrates (85% vs 60%)….

Current views of how critical the various functions of EC displayed some variation. Although there was near unanimous agreement that language, dominant hand motor function, and memory were critical, the perceived importance of leg motor, nondominant hand, visual fields, and other functions was much more variable, with a substantial proportion of respondents regarded these as relatively reasonable to sacrifice. Specifically, with regard to mesial temporal resections with preserved memory function, the majority would consider resection only in the presence of mesial temporal sclerosis on MRI. Resection strategies were further compounded by uncertainties surrounding plasticity and impact of deficit on quality of life across different age groups. It was generally agreed that face motor function recovers almost completely following resection. With regard to language cortex, although most respondents accept age of 5 years as the upper limit beyond which plasticity starts to decline, a minority believed that full plasticity extended to the end of the first decade; a presumption that prompts resection strategies carrying risk of incurring long‐term deficits. 

Irrespective of one's biases toward the handling of EC, wider usage of protective strategies such as awake surgery when feasible, tractography and intraoperative navigation tools, and intraoperative functional mapping is justified and strongly recommended. There is also increasing emphasis on ensuring the integrity of white matter tracts via subcortical mapping to maximize preservation of eloquent function36 and deployment of minimally invasive surgical strategies.

The respondents varied considerably in their expectation of the chances of seizure freedom that were considered acceptable thresholds to “justify” a new deficit ranging from 50% to exceeding 90%. This is of considerable concern, as lowering the acceptable threshold for expected seizure freedom increases the chance of a category IV outcome. However, there was virtually unanimous agreement that surgical decisions toward EC resection should be made in conjunction with the family. This is worthy of further dialogue. Although most parents and caregivers are aware of the seizure burden and are rightfully concerned in alleviating it, they are generally less aware of the consequences of new deficits and their potential impact on quality of life. Bias in how this information is presented to the family may thus significantly influence their willingness to accept a new deficit for their child. Better attempts to explicitly explain deficits including video clips of subjects who have undergone EC resection are used by some centers and should be considered as a standard protocol in counseling families faced with this difficult decision.

Whereas seizure freedom following surgery is reported uniformly, reporting of other outcomes including the occurrence of planned deficits is variable. Whereas some studies use specific tools to document deficits, most epilepsy surgical outcome series do not document the type or severity of new deficits incurred. Sometimes deficits are reported under the broader category of complications or unplanned deficits, and it not possible to sort out those that were a part of planned surgical strategy.39 The majority of respondents perform neuropsychological testing postoperatively, yet there is little reporting on cognitive outcomes, neurodevelopment, and the long‐term impact of surgery on quality of life. We recommend the deficit index scale proposed in Table 5 to standardize reporting of both planned and unplanned deficits. Such data reporting is the first step toward measuring impact on quality of life at various ages and the development of more objective decision analysis algorithms balancing the tradeoff between seizure freedom and acceptable deficits.

The survey responses and comments reflect different practice patterns and help to explain the biases that influence surgical strategies toward resection of EC across centers. The survey participants represent a majority of the main epilepsy surgery centers worldwide. The survey results show that among these centers, there is a considerable amount of variability in how the EZ and EC are delineated. Furthermore, there does not appear to be a set of standard circumstances that are agreed upon to justify resection of EC. These results raise grave concern that some of the deviant strategies may contribute to unacceptably high levels of category 4 outcomes. We recognize that a survey requiring entries for individual queries may not reflect the complexity of the analyses that go into surgical decision‐making. In addition to the results of clinical tests, factors such as seizure burden, patient age, or coexisting encephalopathy also play a role; family preference or palliative goals are also important factors in the complex decision‐making process in epilepsy surgery. Furthermore, there will always be exceptional cases that require deviation from preestablished practice. However, we feel that in the more normative or routine cases and given the lack of class I or II evidence to guide practice, recommendations derived from expert opinion help to standardize surgical strategies in pediatrics…

The survey demonstrates that there is variation among the major epilepsy surgery centers in the process of defining the EZ and EC, acceptable outcomes, and the use of protective strategies. Our recommendations include using the full spectrum of tools to educate families on all potential functional losses that may result from a proposed resection as what is deemed “critical” by practitioners is not consistent among centers. Multimodal mapping should be implemented to ensure that maximum EC is spared while removing the EZ. Staged surgeries with function‐sparing resections should be considered when the perceived EZ involves EC, especially in MRI‐negative cases. Finally, standardized reporting of deficits using the recommended classification will facilitate shifting the focus of surgical outcomes to overall well‐being of the patient from both a seizure and a functional perspective.

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