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Background: Epileptogenesis and glioma growth have a bidirectional relationship. We hypothesized people with gliomas can benefit from the removal of epileptic tissue and that tumor-related epileptic activity may signify tumor infiltration in peritumoral regions. We investigated whether intraoperative electrocorticography (ioECoG) could improve seizure outcomes in oncological glioma surgery, and vice versa, what epileptic activity (EA) tells about tumor infiltration. Methods: We prospectively included patients who underwent (awake) ioECoG-assisted diffuse-glioma resection through the oncological trajectory. The IoECoG-tailoring strategy relied on ictal and interictal EA (spikes and sharp waves). Brain tissue, where EA was recorded, was assigned for histopathological examination separate from the rest of the tumor. Weibull regression was performed to assess how residual EA and extent of resection (EOR) related to the time-to-seizure recurrence, and we investigated which type of EA predicted tumor infiltration. Results: Fifty-two patients were included. Residual spikes after resection were associated with seizure recurrence in patients with isocitrate dehydrogenase (IDH) mutant astrocytoma or oligodendroglioma (HRâ =â 7.6[1.4-40.0], P-valueâ =â .01), independent from the EOR. This was not observed in IDH-wildtype tumors. All tissue samples resected based on interictal spikes were infiltrated by tumor, even if the MRI did not show abnormalities. Conclusions: Complete resection of epileptogenic foci in ioECoG may promote seizure control in IDH-mutant gliomas. The cohort size of IDH-wildtype tumors was too limited to draw definitive conclusions. Interictal spikes may indicate tumor infiltration even when this area appears normal on MRI. Integrating electrophysiology guidance into oncological tumor surgery could contribute to improved seizure outcomes and precise guidance for radical tumor resection.
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BACKGROUND: Deuterium metabolic imaging (DMI) is an innovative, noninvasive metabolic MR imaging method conducted after administration of 2H-labeled substrates. DMI after [6,6'-2H2]glucose consumption has been used to investigate brain metabolic processes, but the impact of different [6,6'-2H2]glucose doses on DMI brain data is not well known. PURPOSE: To investigate three different [6,6'-2H2]glucose doses for DMI in the human brain at 7 T. STUDY TYPE: Prospective. POPULATION: Six healthy participants (age: 28 ± 8 years, male/female: 3/3). FIELD STRENGTH/SEQUENCE: 7 T, 3D 2H free-induction-decay (FID)-magnetic resonance spectroscopic imaging (MRSI) sequence. ASSESSMENT: Three subjects received two different doses (0.25 g/kg, 0.50 g/kg or 0.75 g/kg body weight) of [6,6'-2H2]glucose on two occasions and underwent consecutive 2H-MRSI scans for 120 minutes. Blood was sampled every 10 minutes during the scan, to determine plasma glucose levels and plasma 2H-Glucose atom percent excess (APE) (part-1). Three subjects underwent the same protocol once after receiving 0.50 g/kg [6,6'-2H2]glucose (part-2). STATISTICAL TEST: Mean plasma 2H-Glucose APE and glucose plasma concentrations were compared using one-way ANOVA. Brain 2H-Glc and brain 2H-Glx (part-1) were analyzed with a two-level Linear Mixed Model. In part-2, a General Linear Model was used to compare brain metabolite signals. Statistical significance was set at P < 0.05. RESULTS: Between 60 and 100 minutes after ingesting [6,6'-2H2]glucose, plasma 2H-Glc APE did not differ between 0.50 g/kg and 0.75 g/kg doses (P = 0.961), but was significantly lower for 0.25 g/kg. Time and doses significantly affected brain 2H-Glucose levels (estimate ± standard error [SE]: 0.89 ± 0.01, 1.09 ± 0.01, and 1.27 ± 0.01, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively) and brain 2H-Glutamate/Glutamine levels (estimate ± SE: 1.91 ± 0.03, 2.27 ± 0.03, and 2.46 ± 0.03, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively). Plasma 2H-Glc APE, brain 2H-Glc, and brain 2H-Glx levels were comparable among subjects receiving 0.50 g/kg [6,6'-2H2]glucose. DATA CONCLUSION: Brain 2H-Glucose and brain 2H-Glutamate/Glutamine showed to be [6,6'-2H2]glucose dose dependent. A dose of 0.50 g/kg demonstrated comparable, and well-detectable, 2H-Glucose and 2H-Glutamate/Glutamine signals in the brain. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.
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OBJECTIVE: We aimed to evaluate determinants of functional outcome after pediatric hemispherotomy in a large and recent multicenter cohort. METHODS: We retrospectively investigated the functional outcomes of 455 children who underwent hemispherotomy at 5 epilepsy centers in 2000-2016. We identified determinants of unaided walking, voluntary grasping with the hemiplegic hand, and speaking through Bayesian multivariable regression modeling using missing data imputation. RESULTS: Seventy-five percent of children were seizure-free, and 44% stopped antiseizure medication at a 5.1-year mean follow-up (range = 1-17.1). Seventy-seven percent of children could walk unaided, 8% could grasp voluntarily, and 68% could speak at the last follow-up. Children were unlikely to walk when they had contralateral magnetic resonance imaging (MRI) abnormalities (40/73, p = 0.04), recurrent seizures following hemispherotomy (62/109, p = 0.04), and moderately (50/61, p = 0.03) or severely impaired (127/199, p = 0.001) postsurgical intellectual functioning, but were likely to walk when they were older at outcome determination (p = 0.01). Children were unlikely to grasp voluntarily with the hand contralateral to surgery when they had Rasmussen encephalitis (0/61, p = 0.001) or Sturge-Weber syndrome (0/32, p = 0.007). Children were unlikely to speak when they had contralateral MRI abnormalities (30/69, p = 0.002) and longer epilepsy duration (p = 0.01), but likely to speak when they had Sturge-Weber syndrome (29/35, p = 0.01), were older at surgery (p = 0.04), and were older at outcome determination (p < 0.001). INTERPRETATION: Etiology and bilaterality of structural brain abnormalities were key determinants of functional outcome after hemispherotomy. Longer epilepsy duration affected language outcomes. Not surprisingly, walking and talking ability increased with older age at outcome evaluation. ANN NEUROL 2024;95:377-387.
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Epilepsia , Hemisferectomía , Síndrome de Sturge-Weber , Niño , Humanos , Estudios Retrospectivos , Síndrome de Sturge-Weber/cirugía , Teorema de Bayes , Resultado del Tratamiento , Hemisferectomía/métodos , Epilepsia/cirugíaRESUMEN
Introduction: Constitutive activation of the mTOR pathway, as observed in Tuberous Sclerosis Complex (TSC), leads to glial dysfunction and subsequent epileptogenesis. Although astrocytes are considered important mediators for synaptic clearance and phagocytosis, little is known on how astrocytes contribute to the epileptogenic network. Methods: We employed singlenuclei RNA sequencing and a hybrid fetal calf serum (FCS)/FCS-free cell culture model to explore the capacity of TSC-derived astrocytes to maintain glutamate homeostasis and clear debris in their environment. Results: We found that TSC astrocytes show reduced maturity on RNA and protein level as well as the inability to clear excess glutamate through the loss of both enzymes and transporters complementary to a reduction of phagocytic capabilities. Discussion: Our study provides evidence of mechanistic alterations in TSC astrocytes, underscoring the significant impairment of their supportive functions. These insights enhance our understanding of TSC pathophysiology and hold potential implications for future therapeutic interventions.
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Brain surgery is the only curative treatment for people with focal epilepsy, but it is unclear whether this induces active disease in multiple sclerosis (MS). This creates a barrier to evaluate MS patients for epilepsy surgery. We present two cases of successful epilepsy surgery in patients with pharmacoresistant epilepsy and stable MS and give an overview of the existing literature. (1) a 28-year-old woman with seizures arising from a right basal temporo-occipital ganglioglioma was seizure-free after surgery, without MS relapse but with one new MS lesion postsurgically. (2) a 46-year-old woman with seizures arising from a natalizumab-associated progressive multifocal leukoencephalopathy (PML) lesion in the right frontal lobe was seizure-free after surgery preceded by extraoperative subdural electrocorticography, with new subclinical MS lesions. We are the first to report brain surgery in a PML survivor. Both patients stabilized radiologically after initiating second-line therapies. Successful epilepsy surgery can substantially increase the quality of life in patients with pharmacoresistant epilepsy and MS. With increasing survival rates of brain tumors and PML, the risk-benefit ratio of epilepsy surgery compared to a potential MS relapse after surgery becomes critically important. Shared decision-making is valuable for balancing the risks related to both diseases.
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Epilepsia , Leucoencefalopatía Multifocal Progresiva , Esclerosis Múltiple , Femenino , Humanos , Adulto , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/cirugía , Esclerosis Múltiple/tratamiento farmacológico , Calidad de Vida , Recurrencia Local de Neoplasia , Leucoencefalopatía Multifocal Progresiva/patología , Convulsiones , RecurrenciaRESUMEN
BACKGROUND: Glioblastoma (GBM) is the most common primary, malignant brain tumour with a 5-year survival of 5%. If possible, a glioblastoma is resected and further treated with chemoradiation therapy (CRT), but resection is not feasible in about 30% of cases. Current standard of care in these cases is a biopsy followed by CRT. Magnetic resonance (MR) imaging-guided laser interstitial thermal therapy (LITT) has been suggested as a minimally invasive alternative when surgery is not feasible. However, high-quality evidence directly comparing LITT with standard of care is lacking, precluding any conclusions on (cost-)effectiveness. We therefore propose a multicenter randomized controlled study to assess the (cost-)effectiveness of MR-guided LITT as compared to current standard of care (EMITT trial). METHODS AND ANALYSIS: The EMITT trial will be a multicenter pragmatic randomized controlled trial in the Netherlands. Seven Dutch hospitals will participate in this study. In total 238 patients will be randomized with 1:1 allocation to receive either biopsy combined with same-session MR-guided LITT therapy followed by CRT or the current standard of care being biopsy followed by CRT. The primary outcomes will be health-related quality of life (HR-QoL) (non-inferiority) using EORTC QLQ-C30 + BN20 scores at 5 months after randomization and overall survival (superiority). Secondary outcomes comprise cost-effectiveness (healthcare and societal perspective) and HR-QoL of life over an 18-month time horizon, progression free survival, tumour response, disease specific survival, longitudinal effects, effects on adjuvant treatment, ablation percentage and complication rates. DISCUSSION: The EMITT trial will be the first RCT on the effectiveness of LITT in patients with glioblastoma as compared with current standard of care. Together with the Dutch Brain Tumour Patient association, we hypothesize that LITT may improve overall survival without substantially affecting patients' quality of life. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05318612).
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Glioblastoma , Hipertermia Inducida , Humanos , Calidad de Vida , Glioblastoma/diagnóstico , Glioblastoma/terapia , Biopsia , Adyuvantes Inmunológicos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
The structure of the human connectome develops from childhood throughout adolescence to middle age, but how these structural changes affect the speed of neuronal signaling is not well described. In 74 subjects, we measured the latency of cortico-cortical evoked responses across association and U-fibers and calculated their corresponding transmission speeds. Decreases in conduction delays until at least 30 years show that the speed of neuronal communication develops well into adulthood.
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Conectoma , Sustancia Blanca , Persona de Mediana Edad , Adolescente , Humanos , Niño , Encéfalo/fisiología , Neuronas , Transducción de SeñalRESUMEN
MRI and intraoperative electrocorticography are often used in tandem to delineate epileptogenic tissue in resective surgery for focal epilepsy. Both the resection of the MRI lesion and tissue with high rates of electrographic discharges on electrocorticography, e.g. spikes and high-frequency oscillations (80-500â Hz), lead to a better surgical outcome. How MRI and electrographic markers are related, however, is currently unknown. The aim of this study was to find the spatial relationship between MRI lesions and spikes/high-frequency oscillations. We retrospectively included 33 paediatric and adult patients with lesional neocortical epilepsy who underwent electrocorticography-tailored surgery (14 females, median age = 13.4 years, range = 0.6-47.0 years). Mesiotemporal lesions were excluded. We used univariable linear regression to find correlations between pre-resection spike/high-frequency oscillation rates on an electrode and its distance to the MRI lesion. We tested straight lines to the centre and the edge of the MRI lesion, and the distance along the cortical surface to determine which of these distances best reflects the occurrence of spikes/high-frequency oscillations. We conducted a moderator analysis to investigate the influence of the underlying pathology type and lesion volume on our results. We found spike and high-frequency oscillation rates to be spatially linked to the edge of the MRI lesion. The underlying pathology type influenced the spatial relationship between spike/high-frequency oscillation rates and the MRI lesion (P spikes < 0.0001, P ripples < 0.0001), while the lesion volume did not (P spikes = 0.64, P ripples = 0.89). A higher spike rate was associated with a shorter distance to the edge of the lesion for cavernomas [F(1,64) = -1.37, P < 0.0001, η 2 = 0.22], focal cortical dysplasias [F(1,570) = -0.25, P < 0.0001, η 2 = 0.05] and pleomorphic xanthoastrocytomas [F(1,66) = -0.18, P = 0.01, η 2 = 0.09]. In focal cortical dysplasias, a higher ripple rate was associated with a shorter distance [F(1,570) = -0.35, P < 0.0001, η 2 = 0.05]. Conversely, low-grade gliomas showed a positive correlation; the further an electrode was away from the lesion, the higher the rate of spikes [F(1,75) = 0.65, P < 0.0001, η 2 = 0.37] and ripples [F(1,75) = 2.67, P < 0.0001, η 2 = 0.22]. Pathophysiological processes specific to certain pathology types determine the spatial relationship between the MRI lesion and electrocorticography results. In our analyses, non-tumourous lesions (focal cortical dysplasias and cavernomas) seemed to intrinsically generate spikes and high-frequency oscillations, particularly at the border of the lesion. This advocates for a resection of this tissue. Low-grade gliomas caused epileptogenicity in the peritumoural tissue. Whether a resection of this tissue leads to a better outcome is unclear. Our results suggest that the underlying pathology type should be considered when intraoperative electrocorticography is interpreted.
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BACKGROUND: Intraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year. METHODS: The HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom [defined as Engel 1A-B] vs seizure recurrence [Engel 1C-4]). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673. FINDINGS: Between Oct 10, 2014, and Jan 31, 2020, 78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference -23·5%, 90% CI -39·1 to -7·9; for the 48 patients with temporal lobe epilepsy, the risk difference was -25·5%, -45·1 to -6·0, and for the 30 patients with extratemporal lobe epilepsy it was -20·3%, -46·0 to 5·4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of -7·9% (90% CI -20·7 to 4·9; adjusted risk difference -12·5%, -31·0 to 5·9, for temporal lobe epilepsy and 5·8%, -7·7 to 19·5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died. INTERPRETATION: HFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy. FUNDING: UMCU Alexandre Suerman, EpilepsieNL, RMI Talent Fellowship, European Research Council, and MING Fund.
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Epilepsias Parciales , Epilepsia del Lóbulo Temporal , Epilepsia , Adulto , Niño , Humanos , Electrocorticografía , Método Simple Ciego , Países Bajos , Epilepsia/cirugía , Convulsiones/cirugía , Epilepsias Parciales/cirugíaRESUMEN
Mesial temporal lobe epilepsy (mTLE) is a chronic disease characterized by recurrent seizures that originate in the temporal lobes of the brain. Anti-epileptic drugs (AEDs) are the standard treatment for managing seizures in mTLE patients, but are frequently ineffective. Resective surgery is an option for some patients, but does not guarantee a postoperative seizure-free period. Therefore, further insight is needed into the pathogenesis of mTLE to enable the design of new therapeutic strategies. Circular RNAs (circRNAs) have been identified as important regulators of neuronal function and have been implicated in epilepsy. However, the mechanisms through which circRNAs contribute to epileptogenesis remain unknown. Here, we determine the circRNA transcriptome of the hippocampus and cortex of mTLE patients by using RNA-seq. We report 333 differentially expressed (DE) circRNAs between healthy individuals and mTLE patients, of which 23 circRNAs displayed significant adjusted p-values following multiple testing correction. Interestingly, hippocampal expression of circ_Satb1, a circRNA derived from special AT-rich sequence binding protein 1 (SATB1), is decreased in both mTLE patients and in experimental epilepsy. Our work shows that circ_Satb1 displays dynamic patterns of neuronal expression in vitro and in vivo. Further, circ_Satb1-specific knockdown using CRISPR/CasRx approaches in hippocampal cultures leads to defects in dendritic spine morphology, a cellular hallmark of mTLE. Overall, our results identify a novel epilepsy-associated circRNA with disease-specific expression and previously unidentified cellular effects that are relevant for epileptogenesis.
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OBJECTIVE: We retrospectively assessed the localizing value of patient-history-based semiology (PHS), video-based semiology (VS), long-term monitoring video electroencephalography (LTM-VEEG) and interictal high resolution electric source imaging (HR-ESI) in the presurgical workup of patients with tuberous sclerosis complex (TSC). METHODS: Data from 24 consecutive TSC surgical candidates who underwent both HR-ESI and LTM-VEEG was retrospectively collected. PHS and VS were analyzed to hypothesize the symptomatogenic zone localization. LTM-VEEG and HR-ESI localization results were extracted from the diagnostic reports. Localizing value was compared between modalities, taken the resected/disconnected area of surgical patients in consideration. HR-ESI's impact on the epileptogenic zone hypothesis and surgical workup was evaluated. RESULTS: Semiology, interictal EEG, ictal EEG and HR-ESI were localizing in 25%, 54%, 63% and 79% of patients. Inter-modality concordance ranged between 33-89%. In good surgical outcome patients, PHS, VS, interictal EEG, ictal EEG and HR-ESI showed concordance with resected area in 1/9 (11%), 0/9 (0%), 4/9 (44%), 3/9 (33%) and 6/9 patients (67%). HR-ESI positively impacts clinical management in 50% of patients. CONCLUSIONS: In presurgical evaluation of TSC patients, semiology often has limited localizing value. Presurgical work-up benefits from HR-ESI. SIGNIFICANCE: Our findings may advice future presurgical epilepsy workup of TSC patients with the ultimate aim to improve outcome.
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Mapeo Encefálico/métodos , Encéfalo/fisiopatología , Epilepsia/fisiopatología , Cuidados Preoperatorios/métodos , Esclerosis Tuberosa/fisiopatología , Adolescente , Adulto , Encéfalo/cirugía , Niño , Preescolar , Electroencefalografía , Epilepsia/cirugía , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Esclerosis Tuberosa/cirugía , Adulto JovenRESUMEN
MRI is a cornerstone in presurgical evaluation of epilepsy. Despite guidelines, clinical practice varies. In light of the E-PILEPSY pilot reference network, we conducted a systematic review and meta-analysis on the diagnostic value of MRI in the presurgical evaluation of epilepsy patients. We included original research articles on diagnostic value of higher MRI field strength and guideline-recommended and additional MRI sequences in detecting an epileptogenic lesion in adult or paediatric epilepsy surgery candidates. Lesion detection rate was used as a metric in meta-analysis. Eighteen studies were included for MRI field strength and 25 for MRI sequences, none were free from bias. In patients with normal MRI at lower-field strength, 3T improved lesion detection rate by 18% and 7T by 23%. Field strengths higher than 1.5T did not have higher lesion detection rates in patients with hippocampal sclerosis (HS). The lesion detection rate of epilepsy-specific MRI protocols was 83% for temporal lobe epilepsy (TLE) patients. Dedicated MRI protocols and evaluation by an experienced epilepsy neuroradiologist increased lesion detection. For HS, 3DT1, T2, and FLAIR each had a lesion detection rate at around 90%. Apparent diffusion coefficient indices had a lateralizing value of 33% for TLE. DTI fractional anisotropy and mean diffusivity had a localizing value of 8% and 34%. A dedicated MRI protocol and expert evaluation benefits lesion detection rate in epilepsy surgery candidates. If patients remain MRI negative, imaging at higher-field strength may reveal lesions. In HS, apparent diffusion coefficient indices may aid lateralization and localization more than increasing field strength. DTI can add further diagnostic information. For other additional sequences, the quality and number of studies is insufficient to draw solid conclusions. Our findings may be used as evidence base for developing new high-quality MRI studies and clinical guidelines.
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Epilepsia del Lóbulo Temporal , Epilepsia , Adulto , Niño , Epilepsia/diagnóstico , Epilepsia/patología , Epilepsia/cirugía , Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
OBJECTIVE: High frequency oscillations (HFOs) in intraoperative electrocorticography (ioECoG) are thought to be generated by hyperexcitable neurons. Inflammation may promote neuronal hyperexcitability. We investigated the relation between HFOs and inflammation in tumor-related epilepsy. METHODS: We identified HFOs (ripples 80-250 Hz, fast ripples 250-500 Hz) in the preresection ioECoG of 32 patients with low-grade tumors. Localization of recorded HFOs was classified based on magnetic resonance imaging reconstructions: in tumor, in resected non-tumorous area and outside the resected area. We tested if the following inflammatory markers in the tumor or peritumoral tissue were related to HFOs: activated microglia, cluster of differentiation 3 (CD3)-positive T-cells, interleukin 1-beta (IL1ß), toll-like receptor 4 (TLR4) and high mobility group box 1 protein (HMGB1). RESULTS: Tumors that generated ripples were infiltrated by more CD3-positive cells than tumors without ripples. Ripple rate outside the resected area was positively correlated with IL1ß/TLR4/HMGB1 pathway activity in peritumoral area. These two areas did not directly overlap. CONCLUSIONS: Ripple rates may be associated with inflammatory processes. SIGNIFICANCE: Our findings support that ripple generation and spread might be associated with synchronized fast firing of hyperexcitable neurons due to certain inflammatory processes. This pilot study provides arguments for further investigations in HFOs and inflammation.
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Neoplasias Encefálicas/fisiopatología , Ondas Encefálicas/fisiología , Encéfalo/fisiopatología , Epilepsia/fisiopatología , Enfermedades Neuroinflamatorias/fisiopatología , Adolescente , Adulto , Encéfalo/cirugía , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Niño , Preescolar , Electrocorticografía , Epilepsia/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Neuroinflamatorias/etiología , Adulto JovenRESUMEN
OBJECTIVE: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit). RESULTS: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE). INTERPRETATION: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.
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Mapeo Encefálico/métodos , Electroencefalografía/métodos , Epilepsia/cirugía , Procedimientos Neuroquirúrgicos/métodos , Convulsiones/cirugía , Técnicas Estereotáxicas , Adulto , Electrodos Implantados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy and is often associated with hippocampal sclerosis (HS) and cognitive disturbances. Over the last decade, high frequency oscillations (HFOs) in the intraoperative electrocorticography (ioECoG) have been proposed to be biomarkers for the delineation of epileptic tissue but hippocampal ripples have also been associated with memory consolidation. Healthy hippocampi can show prolonged ripple activity in stereo- EEG. We aimed to identify how the HFO rates [ripples (80-250 Hz, fast ripples (250-500 Hz); prolonged ripples (80-250 Hz, 200-500 ms)] in the pre-resection ioECoG over subtemporal area (hippocampus) and lateral temporal neocortex relate to presence of hippocampal sclerosis, the hippocampal volume quantified on MRI and the severity of cognitive impairment in TLE patients. Volumetric measurement of hippocampal subregions was performed in 47 patients with TLE, who underwent ioECoG. Ripples, prolonged ripples, and fast ripples were visually marked and rates of HFOs were calculated. The intellectual quotient (IQ) before resection was determined. There was a trend toward higher rates of ripples and fast ripples in subtemporal electrodes vs. the lateral neocortex (ripples: 2.1 vs. 1.3/min; fast ripples: 0.9 vs. 0.2/min). Patients with HS showed higher rates of subtemporal fast ripples than other patients (Z = -2.51, p = 0.012). Prolonged ripples were only found in the lateral temporal neocortex. The normalized ratio (smallest/largest) of hippocampal volume was correlated to pre-resection IQ (r = 0.45, p = 0.015). There was no correlation between HFO rates and hippocampal volumes or HFO rates and IQ. To conclude, intra-operative fast ripples were a marker for HS, but ripples and fast ripples were not linearly correlated with either the amount of hippocampal atrophy, nor for pre-surgical IQ.
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Signal analysis biomarkers, in an intra-operative setting, may be complementary tools to guide and tailor the resection in drug-resistant focal epilepsy patients. Effective assessment of biomarker performances are needed to evaluate their clinical usefulness and translation. We defined a realistic ground-truth scenario and compared the effectiveness of different biomarkers alone and combined to localize epileptogenic tissue during surgery. We investigated the performances of univariate, bivariate and multivariate signal biomarkers applied to 1 min inter-ictal intra-operative electrocorticography to discriminate between epileptogenic and non-epileptogenic locations in 47 drug-resistant people with epilepsy (temporal and extra-temporal) who had been seizure-free one year after the operation. The best result using a single biomarker was obtained using the phase-amplitude coupling measure for which the epileptogenic tissue was localized in 17 out of 47 patients. Combining the whole set of biomarkers provided an improvement of the performances: 27 out of 47 patients. Repeating the analysis only on the temporal-lobe resections we detected the epileptogenic tissue in 29 out of 30 combining all the biomarkers. We suggest that the assessment of biomarker performances on a ground-truth scenario is required to have a proper estimate on how biomarkers translate into clinical use. Phase-amplitude coupling seems the best performing single biomarker and combining biomarkers improves localization of epileptogenic tissue. Performance achieved is not adequate as a tool in the operation theater yet, but it can improve the understanding of pathophysiological process.
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Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/cirugía , Electrocorticografía/métodos , Epilepsia del Lóbulo Temporal/fisiopatología , Epilepsia del Lóbulo Temporal/cirugía , Adolescente , Adulto , Anciano , Biomarcadores , Niño , Preescolar , Epilepsia Refractaria/epidemiología , Epilepsia del Lóbulo Temporal/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Retrospectivos , Convulsiones/fisiopatología , Lóbulo Temporal/fisiopatología , Lóbulo Temporal/cirugía , Adulto JovenRESUMEN
Recent studies suggested a possible association between malformations of cortical development and microvascular density. In this study we aimed to further elucidate the relation between microvascular density and cortical developmental abnormalities in a cohort of 97 patients with epilepsy and histologically proven mild malformation of cortical development (mMCD), focal cortical dysplasia (FCD) or tuberous sclerosis complex (TSC). Surgical tissue samples were analyzed with quantitative measures of vessel density, T-cell response, microglial activation and myelin content. Subsequently, the results were compared to an age- and localization matched control group. We observed an increase in microvasculature in white matter of TSC cortical tubers, which is linked to inflammatory response. No increase was seen in mMCD or FCD subtypes compared to controls. In mMCD/FCD and tubers, lesional cortex and white matter showed increased vascular density compared to perilesional tissues. Moreover, cortical vessel density increased with longer epilepsy duration and older age at surgery while in controls it decreased with age. Our findings suggest for that the increase in white matter vascular density might be pathology-specific rather than a consequence of ongoing epileptic activity. Increased cortical vessel density with age and with longer epilepsy duration in mMCD/FCD's and tubers, however, could be a consequence of seizures.
Asunto(s)
Corteza Cerebral/patología , Epilepsia/patología , Malformaciones del Desarrollo Cortical de Grupo I/patología , Malformaciones del Desarrollo Cortical/patología , Microvasos/patología , Esclerosis Tuberosa/patología , Adolescente , Adulto , Corteza Cerebral/cirugía , Niño , Preescolar , Epilepsia/cirugía , Femenino , Humanos , Lactante , Masculino , Malformaciones del Desarrollo Cortical/cirugía , Malformaciones del Desarrollo Cortical de Grupo I/cirugía , Persona de Mediana Edad , Esclerosis Tuberosa/cirugía , Adulto JovenRESUMEN
Expert panel consultations are heavily regulated. To such an extent that they impede doctors from obtaining expert advice for their patients in practically feasible ways, i.e. by phone call. We argue that this is emblematic of the fact that the legal and the medical domain have increasingly become "non-overlapping magisteria"; two world views that each have their own - completely separate - dynamics and have very little in common. There was a time when intuitive moral ideas of doctors and patients about privacy and confidentiality, about responsibilities and expedience closely approximated the legal framework. Those days are over, and doctors have to ask themselves whether they want to be part of the legal or the medical magisterium. We choose the latter and are willing to face the consequences.
Asunto(s)
Confidencialidad/legislación & jurisprudencia , Abogados/legislación & jurisprudencia , Principios Morales , Relaciones Médico-Paciente/ética , Médicos/legislación & jurisprudencia , Privacidad/legislación & jurisprudencia , HumanosRESUMEN
Mild malformation of cortical development (mMCD) and focal cortical dysplasia (FCD) subtypes combined are by far the most common histological diagnoses in children who undergo surgery as treatment for refractory epilepsy. In patients with refractory epilepsy, a substantial burden of disease is due to cognitive impairment. We studied intelligence quotient (IQ) or developmental quotient (DQ) values and their change after epilepsy surgery in a consecutive series of 42 children (median age at surgery: 4.5, range: 0-17.0â¯years) with refractory epilepsy due to mMCD/FCD. Cognitive impairment, defined as IQ/DQ below 70, was present in 51% prior to surgery. Cognitive impairment was associated with earlier onset of epilepsy, longer epilepsy duration, and FCD type I histology. Clinically relevant improvement of ≥10 IQ/DQ points was found in 24% of children and was related to the presence of presurgical epileptic encephalopathy (EE). At time of postsurgical cognitive testing, 59% of children were completely seizure-free (Engel 1A). We found no association between cognitive outcome and seizure or medication status at two years of follow-up. Epilepsy surgery in children with mMCD or FCD not only is likely to result in complete and continuous seizure freedom, but also improves cognitive function in many.
Asunto(s)
Disfunción Cognitiva/cirugía , Epilepsia/cirugía , Malformaciones del Desarrollo Cortical/cirugía , Evaluación de Resultado en la Atención de Salud , Adolescente , Niño , Preescolar , Disfunción Cognitiva/etiología , Anomalías Craneofaciales/complicaciones , Anomalías Craneofaciales/cirugía , Epilepsia Refractaria/complicaciones , Epilepsia Refractaria/cirugía , Epilepsias Parciales/complicaciones , Epilepsias Parciales/cirugía , Epilepsia/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Malformaciones del Desarrollo Cortical/complicacionesRESUMEN
Focal cortical dysplasia (FCD) and mild malformation of cortical development (mMCD) are frequent histopathologic diagnoses in patients who undergo surgery for refractory epilepsy. Literature concerning surgical outcome in patients with mMCD, as well as its contrast with FCD, has been scarce. We studied 88 patients with a histopathologic diagnosis of isolated FCD (n = 57) or mMCD (n = 31), revised according to the latest International League Against Epilepsy (ILAE) guidelines, who underwent resective or disconnective surgery. Our findings suggest differences between mMCD and FCD in clinical presentation and surgical outcome after surgery. Patients with mMCD developed seizures later in life, and their lesions had a predilection for location in the temporal lobe and remained undetected by magnetic resonance imaging (MRI) more frequently. A diagnosis of mMCD has a less favorable surgical outcome. Still, 32% of these patients reached continuous seizure freedom (Engel class 1A) at a latest median follow-up duration of 8 years, compared to 59% in FCD. A histopathologic diagnosis of mMCD, extratemporal surgery, and indication of an incomplete resection each were independent predictors of poor outcome.