Electroencephalographic microstates as a potential neurophysiological marker differentiating bilateral from unilateral temporal lobe epilepsy.

OBJECTIVE: Electroencephalographic (EEG) microstate abnormalities have been documented in different neurological disorders. We aimed to assess whether EEG microstates are altered also in patients with temporal epilepsy (TLE) and whether they show different activations in patients with unilateral TLE (UTLE) and bilateral TLE (BTLE). METHODS: Nineteen patients with UTLE, 12 with BTLE, and 15 healthy controls were enrolled. Resting state high-density electroencephalography (128 channels) was recorded for 15 min with closed eyes. We obtained a set of stable scalp maps representing the EEG activity, named microstates, from which we acquired the following variables: global explained variance (GEV), mean duration (MD), time coverage (TC), and frequency of occurrence (FO). Two-way repeated measures analysis of variance was used to compare groups, and Spearman correlation was performed to study the maps in association with the clinical and neuropsychological data. RESULTS: Patients with BTLE and UTLE showed differences in most of the parameters (GEV, MD, TC, FO) of the four microstate maps (A-D) compared to controls. Patients with BTLE showed a significant increase in all parameters for the microstates in Map-A and a decrease in Map-D compared to UTLE and controls. We observed a correlation between Map-A, disease duration, and spatial short-term memory, whereas microstate Map-D was correlated with the global intelligence score and short-term memory performance. SIGNIFICANCE: A global alteration of the neural dynamics was observed in patients with TLE compared to controls. A different pattern of EEG microstate abnormalities was identified in BTLE compared to UTLE, which might represent a distinctive biomarker.

Neuropsychological Functioning in Bilateral versus Unilateral Temporal Lobe Epilepsy.

Although relatively specific anatomo-electro-clinical features of temporal lobe epilepsy (TLE) with bilateral ictal involvement (bitemporal epilepsy-BTLE) have been described, differentiating between BTLE and unilateral TLE (UTLE) remains challenging. Surgery is often the treatment of choice for drug-resistant UTLE, whereas its use is more controversial in BTLE. It is currently unclear whether neuropsychological assessment can contribute to the differential diagnosis. We retrospectively reviewed the neuropsychological evaluation of 46 consecutive patients with refractory TLE. Eighteen patients were diagnosed with BTLE on the basis of ictal electro-clinical data, in particular a video EEG recording of at least one seizure simultaneously involving the two temporal lobes without the possibility of lateralizing its onset or at least two different seizures independently arising from the two temporal lobes. Twenty-eight patients were classified as UTLE. Presurgery evaluation data were used in this study. Compared with UTLE, BTLE was associated with a lower intelligence quotient (IQ) and more severe impairment in long-term memory, the latter remaining significant even after controlling for IQ. No significant differences were found between right and left UTLE. In conclusion, BTLE and UTLE are associated with relatively distinct neuropsychological profiles, further supporting their classification as different disorders within the TLE spectrum.

Resting state network dynamic reconfiguration and neuropsychological functioning in temporal lobe epilepsy: An HD-EEG investigation.

Temporal lobe epilepsy (TLE) is nowadays considered a network disorder impacting several cognitive domains. In this work we investigated dynamic network reconfiguration differences in patients with unilateral TLE compared to a healthy control group, focusing on two connectivity indices: flexibility and integration. We apply these indices for the first time to high-density EEG source-based functional connectivity. We observed that patients with TLE exhibited significantly lower flexibility than healthy controls in the Control, Default Mode and Attentive Dorsal networks, expressed in the delta, theta and alpha bands. In addition, patients with TLE displayed greater integration values across the majority of the resting state networks, especially in the delta, theta and gamma bands. Relevantly, a higher integration index in the Control, Attentive Dorsal and Visual networks in the delta band was correlated with lower performance in visual attention and executive functions. Moreover, a greater integration index in the gamma band of the Control, Somatomotor and Temporoparietal networks was related to lower long-term memory performance. These results suggest that patients with TLE display dysregulated network reconfiguration, with lower flexibility in the brain areas related to cognitive control and attention, together with excessive inter-network communication (integration index). Finally, the correlation between network integration and the reduced cognitive performance suggests a potential mechanism underlying specific alterations in neuropsychological profile of patients with TLE.

Neuropsychological and behavioral profiles of self-limited epileptic syndromes of childhood: a cross-syndrome comparison.

Childhood epilepsy with centro-temporal spikes (CECTS), Childhood absence epilepsy (CAE) and Panayiotopoulos syndrome (PS) are some of the most common pediatric epileptic syndromes. Despite the relatively benign (self-limited) course of epilepsy, current evidence suggests that these conditions are associated with an increased risk of neuropsychological and behavioral comorbidities. This study provides a cross-epileptic syndromes' comparison reporting on the cognitive and behavioral profile of a cohort of 32 children with CECTS (n = 14), CAE (n = 10) and PS (n = 8), aged 6 to 15 years old. Frequent, although often subclinical cognitive difficulties involving attention, executive functions and academic abilities were found in children with CECTS and CAE, and to a lesser extent in PS. Internalizing symptoms (particularly anxiety) were more common in the PS group compared to CECTS and CAE based on parental reports. Correlational analysis revealed a significant correlation between phonemic fluency and seizure-free interval at the time of evaluation, suggesting a beneficial effect of epilepsy remission on this executive function measure in all the three groups. These results add to existing literature providing further detail on neuropsychological and behavioral peculiarities of children with CECTS, CAE, and PS. Moreover, the need for neuropsychological assessment as part of the standard childhood epilepsy evaluation is stressed. The results are discussed in the context of the current literature, highlighting areas of consensus and controversies related to the clinical management of these epileptic syndromes as well as directions for future research.

Developmental and epilepsy spectrum of Poirier-Bienvenu neurodevelopmental syndrome: Description of a new case study and review of the available literature.

AIM: To better characterize the clinical phenotype of Poirier-Bienvenu neurodevelopmental syndrome (OMIM ID: 618,732) due to pathogenic variants of the CSNK2B gene. METHOD: We reviewed the electro-clinical and developmental data of all 14 patients with de novo mutations of the CSNK2B gene reported in the literature and describe a further individual with a novel CSNK2B pathogenic variant. RESULTS: Clustered generalized tonic-clonic or myoclonic seizures with onset before the age of 18 months and delayed neurodevelopment were present in more than 75% of patients. Epilepsy was pharmaco-resistant in 40%. All the individuals (27%) with normal neurological development had pharmaco-sensitive epilepsy. The severity of cognitive and motor impairments was higher in the group with pharmaco-resistant epilepsy, and a statistically significant correlation between seizure control and the severity of cognitive impairment was documented (χ2(3) = 9.44; p = .024) INTERPRETATION: Early seizure onset, clustered seizures and delayed development in both males and females were early clinical markers in most patients with CSNK2B mutations. The entity of neurodevelopmental abnormalities was related to epilepsy severity. Prospective studies are required to better assess the relationship between epilepsy and developmental outcomes in this condition.

Implicit cognitive flexibility in self-limited focal epilepsy of childhood: An HD-EEG study.

Self-limited focal epilepsy of childhood (SFEC) is often related to mild impairments in several neuropsychological domains, including cognitive flexibility, which is generally considered a process requiring volition and attention. However, recent evidence showed that it can be implicitly adjusted exploiting simple 'stimulus-response' associations as for example, the probability of the stimulus occurrence. Here, we evaluated the capability to implicitly extract environmental patterns of regularities and use them to flexibly adjust proactive control motor control. We tested 21 children with epilepsy (total IQ > 80; 13 with Childhood epilepsy with centro-temporal spikes, 8 with Panayiotopoulos syndrome (PS); 5-13 years old) compared to a healthy age-matched control group (32 participants). We used the Dynamic Temporal Prediction (DTP) task to investigate how behavioral performance is implicitly shaped by the manipulation of the stimulus occurrence probability over time. We recorded EEG to identify neural markers to differentiate the two groups. SFEC group showed a reduction in accuracy (p = .0013) and response speed (p < .001) as well as an absence of response adjustment (p = .65) in relation to the implicit changes in stimulus probability occurrence, in comparison to the control group. The epilepsy group performance in the DTP showed a significant correlation with the phonemic fluency (r = -0.50) and the Perseverations index of the CPT test (r = 0.53). Finally, children with SFEC did not show the modulation of the contingent negative variation (CNV) evoked potential. Overall, children with SFEC showed poor implicit flexibility compared to a control group. This pattern is individually related to high-level executive function, suggesting to extend neuropsychological assessment to the implicit domain.