Epilepsy Syndromes: Pathophysiology and Managements

Editorial

13 November 2023

Editorial: Epilepsy syndromes: pathophysiology and managements

Hua-Jun Feng

Tao Sun

and

Bo Xiao

1,985 views

0 citations

Editors

Hua-Jun Feng

Massachusetts General Hospital, Harvard Medical School

Tao Sun

Ningxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical University

Bo Xiao

Xiangya Hospital, Central South University

Impact

Original Research

03 August 2023

Structural and functional changes of the cerebellum in temporal lobe epilepsy

Ge Wang

, 9 more and

Lili Long

Correlation between clinical assessments and altered functional connectivity (A) Correlation between disease duration and increased FC. (B) Correlation between neuropsychological assessment and altered FC.

Aims: This study aimed to comprehensively explore the cerebellar structural and functional changes in temporal lobe epilepsy (TLE) and its association with clinical information.

Methods: The SUIT toolbox was utilized to perform cerebellar volume and diffusion analysis. In addition, we extracted the average diffusion values of cerebellar peduncle tracts to investigate microstructure alterations. Seed-based whole-brain analysis was used to investigate cerebellar–cerebral functional connectivity (FC). Subgroup analyses were performed to identify the cerebellar participation in TLE with/without hippocampal sclerosis (HS)/focal-to-bilateral tonic–clonic seizure (FBTCS) and TLE with different lateralization.

Results: TLE showed widespread gray matter atrophy in bilateral crusII, VIIb, VIIIb, left crusI, and left VIIIa. Both voxel and tract analysis observed diffusion abnormalities in cerebellar afferent peduncles. Reduced FC between the right crus II and the left parahippocampal cortex was found in TLE. Additionally, TLE showed increased FCs between left lobules VI–VIII and cortical nodes of the dorsal attention and visual networks. Across all patients, decreased FC was associated with poorer cognitive function, while increased FCs appeared to reflect compensatory effects. The cerebellar structural changes were mainly observed in HS and FBTCS subgroups and were regardless of seizure lateralization, while cerebellar–cerebral FC alterations were similar in all subgroups.

Conclusion: TLE exhibited microstructural changes in the cerebellum, mainly related to HS and FBTCS. In addition, altered cerebellar–cerebral functional connectivity is associated with common cognitive alterations in TLE.

2,582 views

9 citations

Clinical features categorized based on ASM response.

Original Research

07 August 2023

Effect of clinical features on antiseizure medication doses in patients with newly diagnosed epilepsy

Hire Hersi

, 2 more and

Jukka T. Saarinen

1,143 views

0 citations

Original Research

14 July 2023

Prediction model for long-term seizure and developmental outcomes among children with infantile epileptic spasms syndrome

Yuto Arai

, 7 more and

Yoshihiro Maegaki

Introduction: Children with infantile epileptic spasms syndrome (IESS) are likely to experience poor outcomes. Researchers have investigated the factors related to its long-term prognosis; however, none of them developed a predictive model.

Objective: This study aimed to clarify the factors that influence the long-term prognosis of seizures and their development and to create a prediction model for IESS.

Materials and methods: We conducted a retrospective cohort study enrolling participants diagnosed with IESS at the Tottori University Hospital. We examined the seizure and developmental status at 3 and 7 years after the IESS onset and divided the participants into favorable and poor outcome groups. Subsequently, we analyzed the factors associated with the poor outcome group and developed a prediction model at 3 years by setting cutoff values using the receiver operating characteristic curve.

Results: Data were obtained from 44 patients with IESS (19 female patients and 25 male patients). Three years after epileptic spasms (ES) onset, seizure and development were the poor outcomes in 15 (34.9%) and 27 (61.4%) patients, respectively. The persistence of ES or tonic seizures (TS) after 90 days of onset, moderate or severe magnetic resonance imaging abnormalities, and developmental delay before IESS onset were significantly associated with poor outcomes. Seven years after the onset of ES, seizures and development were the poor outcomes in 9 (45.0%) and 13 (72.2%) patients, respectively. We found that no factor was significantly associated with poor seizure outcomes, and only developmental delay before IESS onset was significantly associated with poor developmental outcomes. Our prediction model demonstrated 86.7% sensitivity and 64.3% specificity for predicting poor seizure outcomes and 88.9% sensitivity and 100% specificity for predicting poor developmental outcomes.

Conclusion: Our prediction model may be useful for predicting the long-term prognosis of seizures and their development after 3 years. Understanding the long-term prognosis during the initial treatment may facilitate the selection of appropriate treatment.

2,200 views

4 citations

Pedigree figure of the Chinese Tujia ethnic family with genetic epilepsy with febrile seizures plus (GEFSP) and the variant analysis. (A) A pedigree figure of the family. (B) SCN1A sequence of the proband (III:1) with heterozygous c.5725A>G (p.T1909A) variant. (C) Normal SCN1A sequence of the unaffected member (II:2). (D) SCN1A p.T1909 amino acid residue is conserved in multiple species. (E) Schematic structure of SCN1A protein and the location of the p.T1909A variant. S1–S6 represent six alpha-helical transmembrane segments, and DI–DIV represent four homologous domains.

Brief Research Report

27 July 2023

An SCN1A gene missense variant in a Chinese Tujia ethnic family with genetic epilepsy with febrile seizures plus

Ling Li

, 5 more and

Hao Deng

1,677 views

0 citations

Original Research

23 June 2023

Electrophysiological network predicts clinical response to vigabatrin in epileptic spasms

Junhyung Kim

, 3 more and

Tae-Sung Ko

Purpose: This study aimed to discover electrophysiologic markers correlated with clinical responses to vigabatrin-based treatment in infants with epileptic spasms (ES).

Method: The study involved a descriptive analysis of ES patients from a single institution, as well as electroencephalogram (EEG) analyses of 40 samples and 20 age-matched healthy infants. EEG data were acquired during the interictal sleep state prior to the standard treatment. The weighted phase-lag index (wPLI) functional connectivity was explored across frequency and spatial domains, correlating these results with clinical features.

Results: Infants with ES exhibited diffuse increases in delta and theta power, differing from healthy controls. For the wPLI analysis, ES subjects exhibited higher global connectivity compared to control subjects. Subjects who responded favorably to treatment were characterized by higher beta connectivity in the parieto-occipital regions, while those with poorer outcomes exhibited lower alpha connectivity in the frontal regions. Individuals with structural neuroimaging abnormalities exhibited correspondingly low functional connectivity, implying that ES patients who maintain adequate structural and functional integrity are more likely to respond favorably to vigabatrin-based treatments.

Conclusion: This study highlights the potential utility of EEG functional connectivity analysis in predicting early response to treatments in infants with ES.

1,691 views

5 citations

Age-dependent changes in T1post in each brain region of wild-type and Scn1a+/− rats. (A) T1post showed age-dependent changes in each region of wild-type (WT, green circle) and Scn1a+/− rats (Scn1a+/−, magenta circle). Tukey multiple-comparison test showed a significant decrease in T1post of Scn1a+/− rats during P19–22: M1(mean difference 0.205s; 95% CI 0.073–0.337s), M2 (0.198s; 0.066–0.330s), CPu (0.355s;−0.203–0.467s), LGP (0.247s; 0.115–0.380s), RSGb (0.318s; 0.203–0.467s), DG (-0.272s; 0.140–0.404s), S1BF (0.299s; 0.167–0.431s), Au1 (0.269s; 0.137–0.401s), VPM (0.286s; 0.154–0.419s), VPL (0.316s; 0.184–0.448s), nRT (0.280s; 0.142–0.418s), LHb (0.202s; 0.070–0.334s), CA3 (0.277s; 0.145–0.409s), V1B (0.278s; 0.147–0.410s), V2L (0.291s; 0.159–0.423s), Vermis (0.126s;−0.006–0.258s), and Hemisphere (0.229s; 0.097–0.361s). These differences disappeared after P23, but are significantly decreased during P35–38: CPu (0.148s; 0.028–0.268s), LGP (0.120s; 0.000–0.240s), LHb (0.136s; 0.012–0.260s), and CA3 (0.143s; 0.023–0.263s). Tukey's multiple-comparison test; *p < 0.05, ** p < 0.01, *** p < 0.001. Data are presented as mean ± standard error of the mean (SEM). Dots represent individual data points. (B) Representative MEMRI T1 map at P21. Yellow lines show part of regions of interest. MEMRI, manganese-enhanced magnetic resonance imaging; M1, primary motor cortex; CI, confidence interval; M2, secondary motor cortex; CPu, caudate-putamen (striatum); LGP, lateral globus pallidus; RSGb, retrosplenial granular b cortex; DG, dentate gyrus; S1BF, primary somatosensory cortex, barrel field; Au1, primary auditory cortex; VPM, ventral posteromedial thalamic nucleus; VPL, ventral posterolateral thalamic nucleus; nRT, reticular thalamic nucleus; LHb, lateral habenular nucleus; CA3, CA3 field of the hippocampus; V1B, primary visual cortex, binocular area; V2L, secondary visual cortex, lateral area; Vermis, cerebellar vermis; Hemisphere, cerebellar hemisphere; P, postnatal day.

Original Research

14 March 2023

Developmental changes in brain activity of heterozygous Scn1a knockout rats

Mayu Tahara

, 9 more and

Hirotaka James Okano

3,023 views

2 citations

Original Research

02 March 2023

Clinical phenotypic and genotypic characterization of NPRL3-related epilepsy

Hongwei Zhang

, 5 more and

Fang Fang

Background: As one of the assembly factors of the GATOR1 protein complex in the mechanism of rapamycin pathway, NPRL3 plays an important role in the pathogenesis of epilepsy. However, the correlation between genotype and clinical phenotype in patients with NPRL3-related epilepsy has not been clarified.

Methods: A total of 11 Chinese children with NPRL3-related epilepsy were identified through whole-exome sequencing (WES). The data from the clinical presentation, laboratory data, brain imaging findings, genetic results, and treatment methods were collected. All previously reported cases with NPRL3-related epilepsy were collected and reviewed through PubMed search.

Results: Among the 11 children, eight have not been reported, and two of them presented infantile spasms (ISs) as a new phenotype of NPRL3-related epilepsy. In addition, WES identified five frameshift mutations, three nonsense mutations, two missense mutations, and one exon deletion. Based on bioinformatics analysis, it was found that two missense mutation sites were highly conserved, and the c.400G>A mutation site of the NPRL3 gene caused the alteration of the protein structure. To date, 88 patients have been reported with NPRL3-related defects, including our 11 cases. The most common presentations were sleep-related hypermotor epilepsy (SHE), frontal lobe epilepsy (FLE), and temporal lobe epilepsy. A majority of patients (70%) presented normal neuroimaging results, and focal cortical dysplasia was the most common neuroimaging abnormality (62.5%). Among the NPRL3 gene mutations, loss of function (nonsense mutations, frameshift mutations, and exons deletion) was the most common genetic variation (75%). For 73% of patients with NPRL3-related epilepsy, monotherapy of sodium channel blockers was effective. Surgery was effective for 75% of children with neuroimaging abnormalities. Two cases unresponsive to surgery or anti-seizure medications were treated with ketogenic diets (KD), which were effective. One case was treated with rapamycin at an early stage of epilepsy, which was effective as well.

Conclusion: NPRL3-related epilepsy has high clinical and genetic heterogeneity. SHE and FLE are the most common clinical presentations. Furthermore, ISs are the new phenotypes of NPRL3-related epilepsy, while the variants c.275G>A, c.745G>A, and c.1270C>T may be the most common NPRL3 gene mutations. Sodium channel blockers, surgery, KD, and rapamycin may be the potential treatments for these patients. Our study expanded the clinical and genetic spectrum of NPRL3-related epilepsy and provided important information for the precise treatment of patients.

3,551 views

5 citations