Seizure‐susceptible brain regions in glioblastoma: identification of patients at risk

Cayuela, Núria; Simó, Marta; Majós, Carles; Rifà-Ros, Xavier; Pérez-Larraya, Jaime Gállego; Ripollés, Pablo; Vidal, Noemí; Miró, Júlia; Gil, Francisco; Gil-Gil, Miguel; Plans, Gerard; Graus, Francesc; Bruna, Jordi

doi:10.1111/ene.13518

Cited by 14 publications

(9 citation statements)

References 22 publications

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“…Although the temporal lobe is the most epileptogenic area in pathologic conditions, 39 it is suspected that in the case of highly infiltrative pathologies such as GBM, the connections to other lobes (as in the case of the parietal lobe, especially the associative areas [inferior parietal lobule] of the dominant hemisphere), are more frequently activated. This could explain the parietal dominance in our group.…”

Section: Discussionmentioning

confidence: 99%

IDH Wild-type Glioblastoma Presenting with Seizure: Clinical Specificity, and Oncologic and Surgical Outcomes

Pesce

Armocida

Paglia

et al. 2021

J Neurol Surg A Cent Eur Neurosurg

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Background Glioblastoma (GBM) is the most common and aggressive primary brain neoplasia in adults. Seizure is a common manifestation in GBM. Up to 25 to 60% of patients with GBM have seizures. We aim to summarize all the relevant clinical, surgical, radiologic, and molecular features of a cohort of patients suffering from GBM-related epilepsy and measure the outcome, to understand the possible existence of a clinical/phenotypical specificity of this subgroup of patients. Methods We retrospectively analyzed a cohort of 177 patients affected by isocitrate dehydrogenase wild-type (IDH-WT) GBM; 49 patients presented seizure at onset (SaO) and 128 were seizure free (SF). We investigated the relationship between seizures and other prognostic factors of GBMs. Results A statistically significant association between the location of the lesions in the parietal lobe and seizures was observed. The left side was more commonly affected. Interestingly, there was a statistical relationship between tumors involving the subventricular zone (SVZ) and SaO patients. The tumors were also smaller on average at diagnosis, and generalized SaOs were associated with longer overall survival. Conclusions The typical patient with IDH-WT GBM with SaO is a young (<55 year) male without a history of headache. The lesion is typically small to medium in size and located in the temporoparietal dominant lobe, with a high tendency to involve the SVZ.

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Section: Discussionmentioning

confidence: 99%

IDH Wild-type Glioblastoma Presenting with Seizure: Clinical Specificity, and Oncologic and Surgical Outcomes

Pesce

Armocida

Paglia

et al. 2021

J Neurol Surg A Cent Eur Neurosurg

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“…VLSM represents a robust and powerful technique in determining anatomical correlates with phenotype and has been utilized in several studies, including brain tumors, but makes several key assumptions that may result in both misleading positive findings and potentially underpowering others. 22 , 23 Here, we introduce a new WLPA technique that overcomes some of these limitations by analyzing the clustering of tumors based on tumor similarity, though it does not produce a traditional statistical map.…”

Section: Discussionmentioning

confidence: 99%

Analysis of morphological characteristics of IDH-mutant/wildtype brain tumors using whole-lesion phenotype analysis

Snyder

Huang

Bai

et al. 2021

Neuro-Oncology Advances

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Background While IDH-mutant tumors aggregate to the frontotemporal regions, the clustering pattern of IDH-wildtype tumors is less clear. As voxel-based lesion-symptom mapping (VLSM) has several limitations for solid lesion mapping, a new technique, Whole Lesion Phenotype Analysis (WLPA), is developed. We utilize WLPA to assess spatial clustering of tumors with IDH mutation from The Cancer Genome Atlas and The Cancer Imaging Archive. Methods The degree of tumor clustering segmented from T1 weighted images is measured to every other tumor by a function of lesion similarity to each other via the Hausdorff Distance. Each tumor is ranked according to the degree to which its neighboring tumors show identical phenotypes, and through a permutation technique, significant tumors are determined. VLSM was applied through a previously described method. Results   A total of 244 patients of mixed grade gliomas (WHO II-IV) are analyzed, of which 150 were IDH-wildtype, and 139 were glioblastomas. VLSM identifies frontal lobe regions that are more likely associated with the presence of IDH mutation but no regions where IDH-wildtype was more likely to be present. WLPA identifies both IDH-mutant and wildtype tumors exhibit statistically significant spatial clustering. Conclusion WLPA may provide additional statistical power as compared to VLSM without making several potentially erroneous assumptions. WLPA identifies tumors most likely to exhibit particular phenotypes, rather than producing anatomical maps, and may be used in conjunction with VLSM to understand the relationship between tumor morphology and biologically relevant tumor phenotypes.

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“…26-30 Studies investigating seizure risk in brain tumors have linked increased seizure risk to varying brain regions, including the medial temporal and frontal lobes. 6,8-10 However, there doesn’t seem to be consistent evidence on which brain regions are most susceptible for the development of lesion-induced epileptic seizures across etiologies.…”

Section: Discussionmentioning

confidence: 99%

“…However, there is no clear consensus between studies. 4,8-10 Given that focal seizures can theoretically arise from any brain region, the lack of unifying brain region associated with epilepsy across lesion etiologies is not surprising.…”

Section: Introductionmentioning

confidence: 99%

Brain lesion locations associated with secondary seizure generalization

Nordberg

Schaper

Bucci

et al. 2021

Preprint

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Background: Structural brain lesions are the most common cause of adult-onset epilepsy. The lesion location may contribute to the risk for epileptogenesis, but whether specific lesion locations are associated with a risk for secondary seizure generalization from focal to bilateral tonic-clonic seizures, is unknown. Methods: We identified patients with a diagnosis of adult-onset epilepsy caused by an ischemic stroke or a tumor diagnosed at the Turku University Hospital in 2004-2017. Lesion locations were segmented on patient-specific MR imaging and transformed to a common brain atlas (MNI space). Both region-of-interest analyses (intersection with the cortex, hemisphere, and lobes) and voxel-wise analyses were conducted to identify the lesion locations associated with focal to bilateral tonic-clonic compared to focal seizures. Results: We included 170 patients with lesion-induced epilepsy (94 tumors, 76 strokes). Lesions predominantly localized in the cerebral cortex (OR 2.50, 95% C.I. 1.21-5.15, p = 0.01) and right hemisphere (OR 2.22, 95% C.I. 1.17-4.20, p = 0.01) were independently associated with focal to bilateral tonic-clonic seizures. At the lobar-level, focal to bilateral tonic-clonic seizures were associated with lesions in the right frontal cortex (OR 4.41, 95% C.I. 1.44-13.5, p = 0.009). No single voxels were significantly associated with seizure type. These effects were independent of lesion etiology. Conclusions: Our results demonstrate that lesion location is associated with the risk for secondary generalization of epileptic seizures independent of lesion etiology. These findings may contribute to identifying patients at risk for focal to bilateral tonic-clonic seizures.

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Seizure‐susceptible brain regions in glioblastoma: identification of patients at risk

Abstract: Tumor location is a useful marker to identify patients with GBM who are at risk of suffering from seizures during follow-up. These results may help to support the use of antiepileptic prophylaxis in a selected GBM population and to improve stratification in antiepileptic clinical trials.

Cited by 14 publications

References 22 publications

IDH Wild-type Glioblastoma Presenting with Seizure: Clinical Specificity, and Oncologic and Surgical Outcomes

IDH Wild-type Glioblastoma Presenting with Seizure: Clinical Specificity, and Oncologic and Surgical Outcomes

Analysis of morphological characteristics of IDH-mutant/wildtype brain tumors using whole-lesion phenotype analysis

Brain lesion locations associated with secondary seizure generalization

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