Infantile Spasms Group Research Articles

Application of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm

To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS). A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity. Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05). Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.

Application of High-Frequency Oscillations on Scalp EEG in Infant Spasm: A Prospective Controlled Study.

ObjectiveWe quantitatively analyzed high-frequency oscillations (HFOs) using scalp electroencephalography (EEG) in patients with infantile spasms (IS).MethodsWe enrolled 60 children with IS hospitalized from January 2019 to August 2020. Sixty healthy age-matched children comprised the control group. Time–frequency analysis was used to quantify γ, ripple, and fast ripple (FR) oscillation energy changes.Resultsγ, ripple, and FR oscillations dominated in the temporal and frontal lobes. The average HFO energy of the sleep stage is lower than that of the wake stage in the same frequency bands in both the normal control (NC) and IS groups (P < 0.05). The average HFO energy of the IS group was significantly higher than that of the NC group in γ band during sleep stage (P < 0.01). The average HFO energy of S and Post-S stage were higher than that of sleep stage in γ band (P < 0.05). In the ripple band, the average HFO energy of Pre-S, S, and Post-S stage was higher than that of sleep stage (P < 0.05). Before treatment, there was no significant difference in BASED score between the effective and ineffective groups. The interaction of curative efficacy × frequency and the interaction of curative efficacy × state are statistically significant. The average HFO energy of the effective group was lower than that of the ineffective group in the sleep stage (P < 0.05). For the 16 children deemed “effective” in the IS group, the average HFO energy of three frequency bands was not significantly different before compared with after treatment.SignificanceScalp EEG can record HFOs. The energy of HFOs can distinguish physiological HFOs from pathological ones more accurately than frequency. On scalp EEG, γ oscillations can better detect susceptibility to epilepsy than ripple and FR oscillations. HFOs can trigger spasms. The analysis of average HFO energy can be used as a predictor of the effectiveness of epilepsy treatment.

Investigation of the association between imbalance of the intestinal flora and infantile spasms: a pilot case-control study.

BackgroundThe intestinal flora (IF) regulates brain function via the neuroendocrine and neuroimmune systems and influences the development of several neuropsychiatric diseases, including epilepsy. Here, we investigated the specific relationship between the IF and infantile spasms (IS), a specific form of epilepsy.MethodsTwenty-three children suffering from IS were recruited from the Chinese PLA General Hospital. According to patient response to adrenocorticotropic hormone (ACTH) treatment, the cohort was subdivided into 2 groups: an ACTH-response group and an ACTH-no response (NR) group. A total of 21 healthy children were recruited as a control group (healthy controls: HCs) during the same time period. Fecal samples were collected from infants in the IS and HC groups, and the population of fecal microorganisms was analyzed by 16s ribosomal DNA sequencing. The α and β diversity of the fecal microflora was determined, and the relative abundance of each species was classified. Tax4Fun2 was used to analyze the metabolic pathways utilized by the microflora, and the Kyoto Encyclopedia of Genes and Genomes database was used to analyze differentially expressed genes and pathways.ResultsNo significant differences existed in α or β diversity when compared between the IS and HC groups, nor between the ACTH-response and ACTH-NR groups which were separated before and after ACTH treatment. Although there was no significant difference between the ACTH-response and ACTH-NR groups with respect to α diversity, there was a significant difference in β diversity. Compared with that of the HCs, the IF of the IS group featured lower proportions of Lactobacillus, Roseburia, and Lachnospira, and a higher proportion of Clostridium. In the IS group, the proportion of Staphylococcus in the IF was higher before treatment than after treatment. Compared with the ACTH-NR group, the ACTH-response group had reduced populations of Odoribacter, Phascolarctobacterium, Anaerotruncus, Mitsuakella, and Robinsoniella. However, an increase was observed in the population of Bifidobacterium. A significant difference was also identified between the IS and HC groups with regard to the expression levels of genes associated with lipoic acid synthesis.ConclusionsOur analysis demonstrated that imbalance of the IF may be involved in the pathogenesis of IS and is related to response to ACTH. Regulating the composition of the IF may pave the way to developing a potential adjuvant therapy for patients with IS.

Risk factors for recurrence after drug withdrawal in childhood epilepsy

BackgroundSeveral studies have been conducted to determine the risk of recurrence after withdrawal of antiepileptic drugs (AEDs) in recent years. There is no consensus concerning the circumstances affecting discontinuation of AEDs. This study was designed to determine the recurrence rate of epilepsy after withdrawal of AEDs and the risk factors related with recurrence. MethodsChildren with epilepsy onset between 1 month and 16 years of age who were followed up at least 3 years after AED treatment withdrawal were enrolled. Patients were classified into groups according to defined risk factors for recurrence. ResultsA total of 284 patients, 137 (48.2%) girls and 147 (51.8%) boys were included, and seizures recurred after withdrawal in 51 patients (18%). Thirty-three (64.7%) patients had recurrence in the first year after withdrawal. The recurrence risk was calculated based on the electro-clinical syndromes classification; the recurrence risk was the highest in the juvenile myoclonic/absence group and lowest in the benign infantile seizure group. No recurrence was observed in the infantile spasm group. Data evaluated by multivariable analysis showed that having the structural-metabolic and unknown epilepsy and <3 years seizure free period before withdrawal of AEDs were the main risk factors for recurrence after AED withdrawal in our study. ConclusionWe suggest a seizure-free period of at least 3 years under AED medication and we must be cautious in patients with structural-metabolic and unknown epilepsy before AED withdrawal.

Altered regional homogeneity in epileptic patients with infantile spasm: A resting-state fMRI study.

Infantile spasm (IS) syndrome is an age-related epileptic encephalopathy that occurs in children. The purpose of this study was to investigate regional homogeneity (ReHo) changes in IS patients. Resting-state fMRI was performed on 11 patients with IS, along with 35 age- and sex-matched healthy subjects. Group comparisons between the two groups demonstrate that the pattern of regional synchronization synchronization in IS patients is changed. Decreased ReHo values were found in default mode network, bilateral motor-related areas and left occipital gyrus of the patient group. Increased ReHo was found in regions of cingulum, cerebellum, supplementary motor area and brain deep nucleus, such as hippocampus, caudate, thalamus and insula. The significant differences might indicate that epileptic action have some injurious effects on the motor, executive and cognitive related regions. In addition, ReHo values of left precuneus and right superior frontal gyrus were associated with the epilepsy duration in the IS group. The correlation results indicate that the involvement of these regions may be related to the seizure generation. Our results suggest that IS may have an injurious effect on the brain activation. The findings may shed new light on the understanding the neural mechanism of IS epilepsy.

Changes in the ERG d-wave with vigabatrin treatment in a pediatric cohort.

Vigabatrin (VGB), a treatment for the childhood epilepsy, infantile spasms (IS), is implicated in visual field constriction. Electroretinograms (ERGs) are used as a substitute for visual field testing in infants. We use the VGB-associated ERG reduction (VAER), defined as reduction in age-corrected light adapted 30 Hz flicker amplitude from a pre-treatment measurement in the absence of other retinal defects, as an indicator of retinal toxicity resulting from VGB use. The d-wave ERG response is predominantly the result of OFF-bipolar cell depolarization response to light offset. The purpose of this study is to evaluate the ERG d-wave response as a marker for VAER toxicity in an infant population. One hundred children with IS treated with VGB (median age at baseline: 7.6 months; range 1.7-38.4) were tested for the cone-OFF response elicited to a 250 cd s m(2) flash with 200 ms duration (long flash ERG). Diagnosis of VAER requires baseline testing of the flicker ERG and at least one follow up ERG; Fifty-one patients fulfilled this criteria. Fifty-eight children received the long flash ERG at baseline. Thirteen retinally normal controls with a median age of 32 months (5.7-65) were also tested. Amplitude and implicit time of the d-wave response were measured manually. Longer duration of treatment was associated with reduced d-wave amplitude (ANOVA p < 0.05) in patients taking VGB. Nine patients demonstrated VAER during the course of the study. D-wave amplitude was reduced in the IS group with VAER compared to those without VAER (p < 0.05). Vigabatrin associated retinal defects may be reflected in reduction of the cone d-wave amplitude.

G339(P) Seizure and Developmental Outcome of Infantile (epileptic) Spasms Starting as FE in Early Infancy

ObjectiveThis study sought to compare the clinical course, seizure and developmental outcome of infantile spasms (IS) that start off as focal epilepsy (FE) with those who present with IS from...

Association Between Prenatal Stress and Infantile Spasms: A Case-Control Study in China

The present study investigated a possible correlation between prenatal stress and the onset of infantile spasms. A total of 120 infants (60 cases, 30 positive controls, and 30 negative controls) went through routine etiologic screening. The Pregnant Woman Life Event Scale was used to investigate and evaluate the degree of prenatal stress of the mothers in the three infant groups. Etiologic analyses indicated no statistical difference between the infantile spasms group and the other epilepsy control group. There was a significant difference in the degree of prenatal stress among mothers of the three infant groups, with higher maternal prenatal stress levels in the infantile spasms group than in the other epilepsy group (positive control) or the normal control group (P < 0.05). Regression analysis with the dummy variable indicated that the onset risk of infantile spasms correspondingly increased with the degree of maternal prenatal stress for stress levels 1-3 (out of four levels) (P < 0.05). Within a certain range, the onset risk of infantile spasms increases with the degree of prenatal stress.

Head Growth in Infants With Infantile Spasms May Be Temporarily Reduced

Epileptic activity, as a component of epileptic encephalopathies, can interfere with brain growth and development. Infantile spasms as a syndrome represent such epileptic activity during the period of spasms and hypsarrhythmia. The rate of head growth in infants with infantile spasms during the period of spasms has not been studied previously. A retrospective study of head growth in 38 infants with infantile spasms and no other cause of abnormal head growth is presented. Mental outcome was assessed at follow-up. The mean head circumference of infants with infantile spasms was not significantly smaller than in the normal population, but the proportion of head circumference below the tenth percentile in the infantile spasms group was higher (27%). Head circumference below the tenth percentile in the fourth and fifth month after the onset of infantile spasms was significantly associated with later mental retardation (P = 0.004). There was no correlation with specific treatment of infantile spasms. Transiently diminished head growth in infants with infantile spasms coincides temporally with the onset of infantile spasms and "catches up" during remission of infantile spasms in favorable cases. This pattern can reflect the negative influence of epileptic activity on brain growth during the sensitive period. Head circumference can provide a reliable predictive value of mental outcome in children with infantile spasms.

Seizure frequency and characteristics in children with Down syndrome

Seizures have not historically been considered a major component of Down syndrome. We examined the prevalence of epileptic seizures in 350 children and adolescents with Down syndrome evaluated at a regional center between 1985 and 1997. Results showed that 28 patients (8%) had epileptic seizures: 13 (47%) partial seizures; 9 (32%) infantile spasms, and 6 (21%) generalized tonic–clonic seizures. In the infantile spasm group, there was no relationship between the initial electroencephalogram (EEG) pattern and response to treatment or long-term seizure control, or between type of pharmacologic treatment (valproic acid, adrenocorticotropic hormone or both) and clinical remission, EEG normalization or long-term seizure control. Neurodevelopmental outcome was poor despite good seizure control in the infantile spasm group. This regional study reinforces the relative association of seizures and Down syndrome. A prospective study including a national/international registry with emphasis on developmental assessment and long-term follow up is warranted.

Contribution of the MHC class II antigens to the etiology of infantile spasm in Mexican Mestizos.

Infantile spasms (ISs) are age-dependant epileptic seizures, which may be flexor, extensor, lightning or nods, or mixed. The aim of this study was the analysis of genetic factors within the human leukocyte antigen (HLA) complex associated with ISs. Sixty-five patients diagnosed according to the established international criteria were compared with 229 healthy individuals; all of them were Mexican Mestizos. Five families were also analyzed (seven affected and five healthy sibs); HLA class I and class II antigens were typed using the standard microlymphocytotoxicity methods. The findings showed female gender preference (2:1). Two thirds were symptomatic, and prevalent seizures were of mixed type (67%). A strong association with HLA-DR17 was detected in the IS group (pc < 0.01; OR = 3.6; EF = 0.20). DR17 was also found increased in the symptomatic patients (p = 0.009; OR = 3.16) and in those with other types of seizures (p = 0.001; OR = 2.0). Conversely, HLA-DQ6 was significantly decreased (pc < 0.002; PF = 0.37) in the total and in the symptomatic groups (p < 0.01). Haplotype linkage was not confirmed in the families; however, those with more than one affected sib shared at least one haplotype. These findings suggest the contribution of DR locus to the susceptibility and the participation of DQ region in the resistance to IS. Severity seems also to be influenced by HLA-DR17, and therefore class II typing may be a helpful tool for disease prognosis.

Contribution of the MHC Class II Antigens to the Etiology of Infantile Spasm in Mexican Mestizos

Summary Purpose: Infantile spasms (ISs) are age‐dependant epileptic seizures, which may be flexor, extensor, lightning or nods, or mixed. The aim of this study was the analysis of genetic factors within the human leukocyte antigen (HLA) complex associated with ISs. Methods: Sixty‐five patients diagnosed according to the established international criteria were compared with 229 healthy individuals; all of them were Mexican Mestizos. Five families were also analyzed (seven affected and five healthy sibs); HLA class I and class II antigens were typed using the standard microlymphocytotoxicity methods. Results: The findings showed female gender preference (2:1). Two thirds were symptomatic, and prevalent seizures were of mixed type (67%). A strong association with HLA‐DR17 was detected in the IS group (pc &lt;0.01; OR = 3.6; EF = 0.20). DR17 was also found increased in the symptomatic patients (p = 0.009; OR = 3.16) and in those with other types of seizures (p = 0.001; OR = 2.0). Conversely, HLA‐DQ6 was significantly decreased (pc &lt;0.002; PF = 0.37) in the total and in the symptomatic groups (p &lt;0.01). Haplotype linkage was not confirmed in the families; however, those with more than one affected sib shared at least one haplotype. Conclusions: These findings suggest the contribution of DR locus to the susceptibility and the participation of DQ region in the resistance to IS. Severity seems also to be influenced by HLA‐DR17, and therefore class II typing may be a helpful tool for disease prognosis.

Serologic HLA typing in infantile spasms.

Serologic HLA typing was performed on 29 patients with infantile spasms and hypsarrhythmic patterns in their electroencephalograms (EEGs). There were no significant increases in the frequencies of HLA-A, B, and C antigens in the infantile spasm group as compared with controls. However, there was a significant increase in the frequency of DRw52 in the infantile spasm patients (90%) as compared with controls (72%) (p less than 0.05). In addition, 3 of 12 white infantile spasm patients demonstrated the complete B18,DR3 (DRw52) haplotype; none of 150 control white subjects showed this haplotype. These findings contribute to evidence that immunological mechanisms may be involved in the pathophysiology of infantile spasms.

Cerebrospinal fluid monoamine metabolites in patients with infantile spasms

We measured CSF levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) by high-performance liquid chromatography in seven children with infantile spasms and in a group of age- and sex-matched controls. The mean concentration of the serotonin metabolite 5-HIAA was 40% (p less than 0.01) lower in the infantile spasms group as compared with controls; HVA levels were similar in both groups. The data provide additional evidence that serotonin metabolism is abnormal in patients with infantile spasms.

PRELIMINARY STUDIES IN PLASMA AND CEREBROSPINAL FLUID CORTISOL IN CHILDREN WITH DIFFERENT DISEASES

Corticosteroids and ACTH can successfully be used for therapy of infantile spasms, especially when spasms are of idiopathic origin. Therefore we are interested in the amount of cerebrospinal fluid (CSF) cortisol and the ratio of plasma to CSF cortisol. Using a protein binding technique we studied plasma and CSF cortisol in 5 children with infantile spasms (West syndrome) and 48 other children, from the neonatal period up to 14 years. In the infantile spasms group we found elevated cortisol levels, in the plasma exceeding 260 ng/ml and in the CSF higher than 26 ng/ml, and CSF cortisol relatively more elevated than plasma cortisol, the ratio plasma to CSF cortisol was therefore below 10. Similar findings were observed in 15 other patients with different diseases. All the other patients showed a normal plasma cortisol level and a ratio plasma to CSF cortisol higher than 10. Our results seem to be in correlation with the experiments of Ortiz-Galvan and Morell who suggested that cortisol might have a protecting function in the central nervous system. Low suspected that cortisol might act by stimulation of enzyme activity. Karl son and Sekeris and also Kroger demonstrated the induction of enzymes by cortisol and synthetic corticoids. Therefore it may be that there exists a correlation between the disease of the central nervous system and the CSF cortisol levels. Further studies will give us more information on this matter.

Preliminary studies in plasma and cerebrospinal fluid cortisol in children with different diseases

A protein binding technique for cerebrospinal fluid (CSF) cortisol detection is described. Using this technique and a protein binding method for plasma cortisol measurement, we studied plasma and CSF cortisol in 5 children with infantile spasms (West syndrome) and in 48 children, from the neonatal period up to 14 years of age, with other diseases (in total 35 boys and 18 girls). In the infantile spasm group we found elevated cortisol levels in the plasma exceeding 260 ng/ml, and in the CSF, levels higher than 20 ng/ml. The quotient plasma cortisol to CSF cortisol was under 10.6. Similar findings were made in 15 patients with other pathologic conditions.