Dataset Information

Processing speed dysfunction is associated with functional corticostriatal circuit alterations in childhood epilepsy with centrotemporal spikes: a PET and fMRI study.

ABSTRACT:

Purpose

Epilepsy with centrotemporal spikes (ECTS) is the most common epilepsy syndrome in children and usually presents with cognitive dysfunctions. However, little is known about the processing speed dysfunction and the associated neuroimaging mechanism in ECTS. This study aims to investigate the brain functional abnormality of processing speed dysfunction in ECTS patients by using the ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI).

Methods

This prospective study recruited twenty-eight ECTS patients who underwent the ¹⁸F-FDG PET, rs-fMRI, and neuropsychological examinations. Twenty children with extracranial tumors were included as PET controls, and 20 healthy children were recruited as MRI controls. The PET image analysis investigated glucose metabolism by determining standardized uptake value ratio (SUVR). The MRI image analysis explored abnormal functional connectivity (FC) within the cortical-striatal circuit through network-based statistical (NBS) analysis. Correlation analysis was performed to explore the relationship between SUVR, FC, and processing speed index (PSI).

Results

Compared with healthy controls, ECTS patients showed normal intelligence quotient but significantly decreased PSI (P = 0.04). PET analysis showed significantly decreased SUVRs within bilateral caudate, putamen, pallidum, left NAc, right rostral middle frontal gyrus, and frontal pole of ECTS patients (P < 0.05). Rs-fMRI analysis showed absolute values of 20 FCs were significantly decreased in ECTS patients compared with MRI controls, which connected 16 distinct ROIs. The average SUVR of right caudate and the average of 20 FCs were positively correlated with PSI in ECTS patients (P = 0.034 and P = 0.005, respectively).

Conclusion

This study indicated that ECTS patients presented significantly reduced PSI, which is closely associated with decreased SUVR and FC of cortical-striatal circuit. Caudate played an important role in processing speed dysfunction.

Clinical trial registration

NCT04954729; registered on July 8, 2021, public site, https://clinicaltrials.gov/ct2/show/NCT04954729.

SUBMITTER: Li Y

PROVIDER: S-EPMC9250469 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background and Purpose: To date, there is no specific treatment guideline for the benign childhood epilepsy with centrotemporal spikes (BECTS). Several countries recommend levetiracetam, carbamazepine, sodium valproate, oxcarbazepine, and lamotrigine as first-line drugs. Nevertheless, some of these drugs are associated with cognitive decline. Available studies that investigated the efficacy of levetiracetam and sodium valproate on BECTS involved small sample sizes. This study aimed to evaluate the efficacy of levetiracetam and sodium valproate on cognition, and to investigate the prognostic factors for BECTS as whole. Methods: Clinical data and treatment status of all patients with BECTS at Xiangya Hospital, Central South University followed from 2008 to 2013 were analyzed retrospectively. Since electrical status epilepticus in sleep (ESES) has been confirmed to play a role in cognitive deterioration, in order to evaluate the response to drugs and their cognitive effects, we created two groups of patients according to the levels of spike wave index (SWI): group 1; 0-50% SWI and group 2; >50% SWI at the last follow up. Results: A total of 195 cases were enrolled: 49.7% received monotherapies, 24.1% duotherapies and 27.2% polytherapies. Medications included; levetiracetam plus other drug (s) (75.9%), levetiracetam alone (32.8%), sodium valproate plus other drug (s) (31.3%), and sodium valproate alone (5.1%). After 2 years of treatment and follow up, 71% of the cases had a good seizure outcome, 15.9% had an improvement of SWI, and 91.7% had a normal DQ/IQ. Sodium valproate combined with levetiracetam, and sodium valproate alone correlated with good improvement of SWI, whereas, focal spikes were linked with poor improvement. For both groups (group 1 and group 2): monotherapy, levetiracetam alone, and a normal DQ/IQ at seizure onset correlated with good cognitive outcomes, in contrast, polytherapy, sodium valproate plus other drug (s), levetiracetam plus sodium valproate, an initial SWI of ≥85%, and multifocal spikes were linked to cognitive deterioration. Conclusions: Monotherapy, particularly levetiracetam seems to be a good first-line therapy which can help in normalizing the electroencephalograph and preventing cognitive decline. Polytherapy, mostly the administration of sodium valproate seems to relate with poor cognition, therefore, it is recommended to avoid it.

Project description:Benign childhood epilepsy with centrotemporal spikes (BECTS) is associated with cognitive and language problems. According to recent studies, disruptions in brain structure and function in children with BECTS are beyond a Rolandic focus, suggesting atypical cortical development. However, previous studies utilizing surface-based metrics (e.g., cortical gyrification) and their structural covariance networks at high resolution in children with BECTS are limited. Twenty-six children with BECTS (15 males/11 females; 10.35 ± 2.91 years) and 26 demographically matched controls (15 males/11 females; 11.35 ± 2.51 years) were included in this study and subjected to high-resolution structural brain MRI scans. The gyrification index was calculated, and structural brain networks were reconstructed based on the covariance of the cortical folding. In the BECTS group, significantly increased gyrification was observed in the bilateral Sylvain fissures and the left pars triangularis, temporal, rostral middle frontal, lateral orbitofrontal, and supramarginal areas (cluster-corrected p < 0.05). Global brain network measures were not significantly different between the groups; however, the nodal alterations were most pronounced in the insular, frontal, temporal, and occipital lobes (FDR corrected, p < 0.05). In children with BECTS, brain hubs increased in number and tended to shift to sensorimotor and temporal areas. Furthermore, we observed significantly positive relationships between the gyrification index and age (vertex p < 0.001, cluster-level correction) as well as duration of epilepsy (vertex p < 0.001, cluster-level correction). Our results suggest that BECTS may be a condition that features abnormal over-folding of the Sylvian fissures and uncoordinated development of structural wiring, disrupted nodal profiles of centrality, and shifted hub distribution, which potentially represents a neuroanatomical hallmark of BECTS in the developing brain.

Project description:ObjectiveChildhood epilepsy with centrotemporal spikes (CECTS) (formally benign epilepsy with centrotemporal spikes, BECTS) is a common childhood epilepsy syndrome characterized by psychiatric, behavioral, and cognitive abnormalities and self-limited seizures. Although CECTS is one of the most well-characterized electroclinical epilepsy syndromes, the natural history of neuropsychiatric outcomes is poorly understood. We report the psychiatric, behavioral, and cognitive profiles over the course of disease from a large, prospectively-enrolled, longitudinal cohort of children with CECTS. We further characterize the detailed seizure course and test the relationship between several proposed risk factors and neuropsychiatric and seizure outcomes in these children.MethodsPatients diagnosed with CECTS were enrolled as part of a community-based study and followed from diagnosis through disease resolution (16.0 ± 3.1 years, N = 60). Twenty sibling controls were also recruited. We report the natural history of premorbid neuropsychiatric concerns, postmorbid neuropsychiatric diagnoses, long-term neuropsychological performance, seizure course, antiseizure medication (ASM) treatment response, and the relationship between duration seizure-free and remission. Age at onset and premorbid neuropsychiatric concerns were tested as predictors of seizure count, epilepsy duration, postmorbid neuropsychiatric diagnoses, and long-term neuropsychological performance. Antiseizure medication treatment duration, seizure count, and epilepsy duration were tested as predictors of postmorbid neuropsychiatric diagnoses and long-term neuropsychological performance.ResultsChildren with CECTS had a high incidence of ADD/ADHD symptoms (18.3%) or learning difficulties (21.7%) before diagnosis. New or persistent ADHD (20%), mood disorders (23.6%), learning difficulties (14.5%), and behavioral disorders (7.3%) were common after CECTS diagnosis. At 9-year follow-up, performance on formal neuropsychological testing was comparable to population statistics and sibling controls. More than two-thirds of treated children experienced at least one seizure during treatment. Most children (61.7%) had entered terminal resolution after 12 months seizure-free. Among all children, for each month seizure-free, there was a 6-7% increase in the probability of achieving terminal remission (p < 1e-10). The presence of a premorbid neurodevelopmental concern predicted a longer epilepsy duration (p = 0.02), higher seizure count (p = 0.02), and a postmorbid psychiatric or neurodevelopmental diagnosis (p = 0.002). None of the tested features predicted long-term neuropsychological performance.SignificanceChildren are at high risk of neuropsychiatric symptoms along the course of the disease in CECTS, however, long-term cognitive performance is favorable. The majority of children had a seizure while being treated with ASMs, suggesting that CECTS is not as pharmacoresponsive as assumed or that treatment approaches are not optimized. Among treated and untreated children, future seizure-risk can be estimated from duration seizure-free. The presence of a premorbid neuropsychiatric concern predicted a more severe disease course in CECTS.