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      Can we use intraoperative high‐frequency oscillations to guide tumor‐related epilepsy surgery?

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          Abstract

          Objective

          In people with low‐grade intrinsic brain tumors, an epileptic focus is often located close to the lesion. High‐frequency oscillations (HFOs) in electrocorticography (ECoG) might help to delineate this focus. We investigated the relationship between HFOs and low‐grade brain tumors and their potential value for tumor‐related epilepsy surgery.

          Methods

          We analyzed pre‐ and postresection intraoperative ECoG in 41 patients with refractory epilepsy and a low‐grade lesion. Electrodes were designated as overlying the tumor, adjacent resected tissue (peritumoral), or outside the resection bed using magnetic resonance imaging (MRI) and intraoperative photographs. We then used a semiautomated approach to detect HFOs as either ripples (80–250 Hz) or fast ripples (250–500 Hz).

          Results

          The rate of fast ripples was higher in electrodes covering tumor and peritumoral tissue than outside the resection ( p = .04). Mesiotemporal tumors showed more ripples ( p = .002), but not more fast ripples ( p = .07), than superficial tumors. Rates of fast ripples were higher in glioma and extraventricular neurocytoma than in ganglioglioma or dysembryoplastic neuroepithelial tumor (DNET). The rate of ripples and fast ripples in postresection ECoG was not higher in patients with residual tumor tissue on MRI than those without. The rate of ripples in postresection ECoG was higher in patients with good than bad seizure outcome ( p = .03). Fast ripples outside the resection and in post‐ECoG seem related to seizure recurrence.

          Significance

          Fast ripples in intraoperative ECoG can be used to help guide resection in tumor‐related epilepsy surgery. Preresection fast ripples occur predominantly in epileptogenic tumor and peritumoral tissue. Fast ripple rates are higher in glioma and extraventricular neurocytoma than in ganglioglioma and DNET.

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          Most cited references31

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          High-frequency oscillations as a new biomarker in epilepsy.

          The discovery that electroencephalography (EEG) contains useful information at frequencies above the traditional 80Hz limit has had a profound impact on our understanding of brain function. In epilepsy, high-frequency oscillations (HFOs, >80Hz) have proven particularly important and useful. This literature review describes the morphology, clinical meaning, and pathophysiology of epileptic HFOs. To record HFOs, the intracranial EEG needs to be sampled at least at 2,000Hz. The oscillatory events can be visualized by applying a high-pass filter and increasing the time and amplitude scales, or EEG time-frequency maps can show the amount of high-frequency activity. HFOs appear excellent markers for the epileptogenic zone. In patients with focal epilepsy who can benefit from surgery, invasive EEG is often required to identify the epileptic cortex, but current information is sometimes inadequate. Removal of brain tissue generating HFOs has been related to better postsurgical outcome than removing the seizure onset zone, indicating that HFOs may mark cortex that needs to be removed to achieve seizure control. The pathophysiology of epileptic HFOs is challenging, probably involving populations of neurons firing asynchronously. They differ from physiological HFOs in not being paced by rhythmic inhibitory activity and in their possible origin from population spikes. Their link to the epileptogenic zone argues that their study will teach us much about the pathophysiology of epileptogenesis and ictogenesis. HFOs show promise for improving surgical outcome and accelerating intracranial EEG investigations. Their potential needs to be assessed by future research. Copyright © 2012 American Neurological Association.
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            Epilepsy in patients with brain tumours: epidemiology, mechanisms, and management.

            Epilepsy is common in patients with brain tumours and can substantially affect daily life, even if the tumour is under control. Several factors affect the mechanism of seizures in brain tumours, including tumour type, tumour location, and peritumoral and genetic changes. Prophylactic use of antiepileptic drugs is not recommended, and potential interactions between antiepileptic and chemotherapeutic agents persuades against the use of enzyme-inducing antiepileptic drugs. Multidrug-resistance proteins prevent the access of antiepileptic drugs into brain parenchyma, which partly explains why seizures are frequently refractory to treatment. Lamotrigine, valproic acid, and topiramate are first-line treatments of choice; if insufficient, add-on treatment with levetiracetam or gabapentin can be recommended. On the basis of clinical studies, we prefer to start treatment with valproic acid, adding levetiracetam if necessary. Risks of cognitive side-effects with antiepileptic drugs can add to previous damage by surgery or radiotherapy, and therefore appropriate choice and dose of antiepileptic drug is crucial.
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              Epileptic seizures in diffuse low-grade gliomas in adults.

              Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.
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                Author and article information

                Contributors
                n.vanklink-2@umcutrecht.nl
                Journal
                Epilepsia
                Epilepsia
                10.1111/(ISSN)1528-1167
                EPI
                Epilepsia
                John Wiley and Sons Inc. (Hoboken )
                0013-9580
                1528-1167
                22 February 2021
                April 2021
                : 62
                : 4 ( doiID: 10.1111/epi.v62.4 )
                : 997-1004
                Affiliations
                [ 1 ] Department of Neurology and Neurosurgery University Medical Center Utrecht Brain Center Utrecht the Netherlands
                [ 2 ] Department of Neurosurgery Mayo Clinic Rochester Minnesota USA
                [ 3 ] Department of (Neuro)Pathology, Amsterdam Neuroscience Amsterdam University Medical Center Amsterdam the Netherlands
                [ 4 ] Epilepsy Institutes of the Netherlands Foundation (SEIN) Heemstede the Netherlands
                Author notes
                [*] [* ] Correspondence

                Nicole van Klink, Department of Neurology and Neurosurgery, Brain Center University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.

                Author information
                https://orcid.org/0000-0002-6773-985X
                https://orcid.org/0000-0002-0720-7878
                https://orcid.org/0000-0003-1258-5678
                Article
                EPI16845
                10.1111/epi.16845
                8248094
                33617688
                5fef3a35-80c5-4d00-b511-79346bae0516
                © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 27 January 2021
                : 16 November 2020
                : 27 January 2021
                Page count
                Figures: 3, Tables: 1, Pages: 10, Words: 5182
                Funding
                Funded by: Dutch Brain Foundation
                Award ID: 2013‐139
                Funded by: Alexandre Suerman Stipendium
                Funded by: Van Wagenen Foundation
                Funded by: the AMC Foundation
                Funded by: ZonMw
                Award ID: 91615149
                Funded by: ERC Starting
                Award ID: 803880
                Categories
                Full‐length Original Research
                Full‐length Original Research
                Custom metadata
                2.0
                April 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:01.07.2021

                Neurology
                corticography,epilepsy surgery,high‐frequency oscillations,tumor‐related epilepsy

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