Focal epilepsy caused by single cerebral cavernous malformation (CCM) is associated with regional and global resting state functional connectivity (FC) disruption

D’Cruz, Jason; Hefner, Matthew; Ledbetter, Christina; Frilot, Clifton; Howard, Brady; Zhu, Peimin; Riel-Romero, Rosario Maria S.; Notarianni, Christina; Toledo, Eduardo Gonzalez; Nanda, Anil; Sun, Hai

doi:10.1016/j.nicl.2019.102072

Cited by 8 publications

(5 citation statements)

References 55 publications

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“…With a second surgery, for the majority, the pathology is nonspecific gliosis, and this trend continues to exaggerate with subsequent surgeries. Again, this indicates a challenging epileptic network, well described in recent years, [32][33][34][35] involving not only the lesion but other accessory nodes, perilesional and distant, which have the potential to develop subsequent hyperexcitability.…”

Section: Possible Reasons For Failure Of First Surgerymentioning

confidence: 79%

Long‐term outcomes of reoperations in epilepsy surgery

et al. 2020

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Objective To analyze longitudinal seizure outcomes following epilepsy surgery, including reoperations, in patients with intractable focal epilepsy. Methods Clinicoradiological characteristics of patients who underwent epilepsy surgery from 1995 to 2016 with follow‐up of ≥1 year were reviewed. In patients undergoing reoperations, the latest resection was considered the index surgery. The primary outcome was complete seizure freedom (Engel I) at last follow‐up. Potentially significant outcome variables were first identified using univariate analyses and then fit in multivariate Cox proportional hazards models. Results Of 898 patients fulfilling study criteria, 110 had reoperations; 92 had one resection prior to the index surgery and 18 patients had two or more prior resective surgeries. Two years after the index surgery, 69% of patients with no prior surgeries had an Engel score of I, as opposed to only 42% of those with one prior surgery, and 33% of those with two or more prior resections (P < .001). Among surgical outcome predictors, the number of prior epilepsy surgeries, female sex, lesional initial magnetic resonance imaging, no prior history of generalization, and pathology correlated with better seizure outcomes on univariate analysis. However, only sex (P = .011), history of generalization (P = .016), and number of prior surgeries (P = .002) remained statistically significant in the multivariate model. Significance Although long‐term seizure control is possible in patients with failed prior epilepsy surgery, the chances of success diminish with every subsequent resection. Outcome is additionally determined by inherent biological markers (sex and secondary generalization tendency), rather than traditional outcome predictors, supporting a hypothesis of “surgical refractoriness.”

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Section: Possible Reasons For Failure Of First Surgerymentioning

confidence: 79%

Long‐term outcomes of reoperations in epilepsy surgery

et al. 2020

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“…193,194 While this incidence is higher postrupture, AVMs and CCMs themselves can also pose elevated risk of epilepsy. 195,196…”

Section: Neuroinflammation Seizures and Cognitive Declinementioning

confidence: 99%

“…193,194 While this incidence is higher postrupture, AVMs and CCMs themselves can also pose elevated risk of epilepsy. 195,196 A major contributor to seizure onset, at least in SAH, is cortical deposition of hemoglobin and other blood-related products. Direct intracortical administration of hemoglobin is sufficient to induce seizures in rodent models, and vascular dysfunction is associated with epileptic foci.…”

Section: Complications Of Cerebrovascular Anomalies: Contributions Fr...mentioning

confidence: 99%

Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow

2021

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Appropriate vascular function is essential for the maintenance of central nervous system homeostasis and is achieved through virtue of the blood-brain barrier; a specialized structure consisting of endothelial, mural, and astrocytic interactions. While appropriate blood-brain barrier function is typically achieved, the central nervous system vasculature is not infallible and cerebrovascular anomalies, a collective terminology for diverse vascular lesions, are present in meningeal and cerebral vasculature supplying and draining the brain. These conditions, including aneurysmal formation and rupture, arteriovenous malformations, dural arteriovenous fistulas, and cerebral cavernous malformations, and their associated neurological sequelae, are typically managed with neurosurgical or pharmacological approaches. However, increasing evidence implicates interacting roles for inflammatory responses and disrupted central nervous system fluid flow with respect to vascular perturbations. Here, we discuss cerebrovascular anomalies from an immunologic angle and fluid flow perspective. We describe immune contributions, both common and distinct, to the formation and progression of diverse cerebrovascular anomalies. Next, we summarize how cerebrovascular anomalies precipitate diverse neurological sequelae, including seizures, hydrocephalus, and cognitive effects and possible contributions through the recently identified lymphatic and glymphatic systems. Finally, we speculate on and provide testable hypotheses for novel nonsurgical therapeutic approaches for alleviating neurological impairments arising from cerebrovascular anomalies, with a particular emphasis on the normalization of fluid flow and alleviation of inflammation through manipulations of the lymphatic and glymphatic central nervous system clearance pathways.

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“…Previously, our research team identified voxel-based metrics associated with a regional and global disruption in restingstate functional connectivity that may elucidate the epileptogenic focus and guide resection of cerebral cavernous malformations in patients with focal epilepsy (23). Despite single-institutional studies and observational cohorts utilizing administrative databases having identified the impact of seizures on short and long-term outcomes in patients undergoing intracranial tumor resection (4,5,(24)(25)(26)(27), meaningful clinical literature quantifying morphometric or volumetric analysis in tumor patients with seizures are limited.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers of Seizure Activity in Patients With Intracranial Metastases and Gliomas: A Wide Range Study of Correlated Regions of Interest

et al. 2020

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Introduction: Studies quantifying cortical metrics in brain tumor patients who present with seizures are limited. The current investigation assesses morphometric/volumetric differences across a wide range of anatomical regions, including temporal and extra-temporal, in patients with gliomas and intracranial metastases (IMs) presenting with seizures that could serve as a biomarker in the identification of seizure expression and serve as a neuronal target for mitigation. Methods: In a retrospective design, the MR sequences of ninety-two tumor patients [55% gliomas; 45% IM] and 34 controls were subjected to sophisticated morphometric and volumetric assessments using BrainSuite and MATLAB modules. We examined 103 regions of interests (ROIs) across eight distinct cortical categories of interests (COI) [gray matter, white matter; total volume, CSF; cortical areas: inner, mid, pial; cortical thickness]. The primary endpoint was quantifying and identifying ROIs with significant differences in z-scores based upon the presence of seizures. Feature selection employing neighborhood component analysis (NCA) determined the ROI within each COI having the highest significance/weight in the differentiation of seizure vs. non-seizure patients harboring brain tumor. Results: Overall, the mean age of the cohort was 58.0 ± 12.8 years, and 45% were women. The prevalence of seizures in tumor patients was 28%. Forty-two ROIs across the eight pre-defined COIs had significant differences in z-scores between tumor patients presenting with and without seizures. The NCA feature selection noted the volume of pars-orbitalis and right middle temporal gyrus to have the highest weight in differentiating tumor patients based on seizures for three distinct COIs [GM, total volume, and CSF volume] and white matter, respectively. Left-sided transverse temporal gyrus, left precuneus, left transverse temporal, and left supramarginal gyrus were associated with having the highest weight in the differentiation of seizure vs. non-seizure in tumor patients for morphometrics relating to cortical areas in the pial, inner and mid regions and cortical thickness, respectively. Kalakoti et al. Biomarkers in Gliomas and Metastasis Conclusion: Our study elucidates potential biomarkers for seizure targeting in patients with gliomas and IMs based upon morphometric and volumetric assessments. Amongst the widespread brain regions examined in our cohort, pars orbitalis, supramarginal and temporal gyrus (middle, transverse), and the pre-cuneus contribute a maximal potential for differentiation of seizure patients from non-seizure.

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Focal epilepsy caused by single cerebral cavernous malformation (CCM) is associated with regional and global resting state functional connectivity (FC) disruption

Cited by 8 publications

References 55 publications

Long‐term outcomes of reoperations in epilepsy surgery

Long‐term outcomes of reoperations in epilepsy surgery

Cerebrovascular Anomalies: Perspectives From Immunology and Cerebrospinal Fluid Flow

Biomarkers of Seizure Activity in Patients With Intracranial Metastases and Gliomas: A Wide Range Study of Correlated Regions of Interest

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