BACKGROUND: Research has shown gene ATN1 to be associated with the nuclear receptor signaling. Its mutations in an evolutionarily conserved histidine-rich motif may cause CHEDDA, short for congenital hypotonia, epilepsy, developmental delay and digital anomalies, a recently identified neurodevelopmental syndrome that could evolve into developmental and epileptic encephalopathy (DEE). Up to date, there have been reported less than 20 cases, whose clinical features and treatment are worth in-depth exploring.
METHODS: The clinical characteristics and genetic data of an infant with CHEDDA and further DEE were analyzed, who carried a de novo ATN1 variant identified by trio whole-exome sequencing. The alike patients with such a neurodevelopmental syndrome and epileptic seizures were reviewed on the literature.
RESULTS: The infant harboring a de novo missense mutation in ATN1 (c.3155A>C; p.His1052Pro) held almost all features of CHEDDA and presented with drug-resistant epileptic spasms, differing from one case previously reported with the same gene variant exhibiting milder seizures controlled easily. We further reviewed 11 CHEDDA patients with epileptic seizures in the literature and compared the correlation between abnormal cerebral structure and the incidence of intractable epilepsy among CHEDDA patients. Fortunately, this patient\'s seizures decreased remarkably after administering ketogenic diet (KD).
CONCLUSIONS: CHEDDA patients have significant phenotypic differences, especially in the epilepsy severity and their drug resistance, even if they carry the same mutation hotspot. Ketogenic diet and other treatments like Topiramate should be recommended for ATN1-related refractory epilepsy based on their regulation on expression of cation-chloride cotransporters and cellular hyperpolarization.

Epileptic spasms (ES) occur mostly between age 3 months and 24 months. ES beginning before 3 months of age were called early-onset ES in previous studies. The aim of this study was to identify clinical and electroencephalographic characteristics of patients with ES onset before 3 months of age. In total, 34 ES patients were retrospectively identified at Children\'s Hospital of Chongqing Medical University from January 1, 2020 to October 1, 2022. Our patients had diverse etiologies, including genetic (32.3 %), genetic-structural (11.8 %), structural-acquired (11.8 %), structural-congenital (8.8 %), and metabolic (5.9 %), with 29.4 % of patients having unknown etiology. Some patients experienced ES in clusters (either symmetrical or flexional) that occurred most often during awakening after sleep, and a minority of ES were characterized as isolated or asymmetrical, occurred during sleep, and could also manifest as relatively subtle. Approximately 35.3 % of patients also experienced other seizure types concurrently, including 10 focal seizures and 2 generalized seizures, and only half of the focal seizures had structural causes. The other seizure types occurred alone or sequentially with ES. Interictal electroencephalography revealed hypsarrhythmia or its variants, multifocal discharge, or burst suppression. 18 patients had no seizures lasting for more than 2 months, however, at the last follow-up visit, 5 of them had relapsed. All patients had different degrees of psychomotor retardation.

UNASSIGNED: To analyze the clinical features, treatment, and prognosis of patients with vitamin B6-responsive infantile spasms (IS).
UNASSIGNED: The clinical features, genetics, and follow-up data of 30 patients were collected and analyzed.
UNASSIGNED: The age of epileptic spasms (ES) onset was from 3 months to 12 months. They all received high doses of vitamin B6 at different times after the onset of ES, ranging from 1 day to 5 months. ES were controlled within 11 days in 93% (28/30) patients, and as late as 1 month and 2 months in the other two patients. In the course of treatment, 28 patients were seizure-free all the time, and seizures of other two patients recurred due to withdrawal of vitamin B6. The available follow-up EEG results of 28 patients were normal in 26 cases, and 81% (21/26) had suppressed epileptic discharges within 6 months. Of the 26 cases with normal follow up EEG, 4 had developmental delay and 22 had normal development. The time for EEG to return to normal in 22 patients with normal development ranged from 14 days to 2 years (mean = 111.5 days; median = 52.5 days). The time for EEG to return to normal in the other 4 patients with development delay ranged from 4 months to 2 years (mean = 375 days; median = 330 days). To the last follow-up, seizures were controlled well in 29 surviving patients, and 21 patients were able to deactivate from all medications without seizures recurrence. Sixteen patients showed varying degrees of developmental delay after onset. After seizure control, the psychomotor development was delayed in 7 patients (one died) until the last follow-up. Genetic analysis did not show any meaningful results.
UNASSIGNED: An observation period of 1-2 weeks is essential to identify patients with vitamin B6-responsive IS. The treatment time could be extended according to the treatment response and EEG changes. It might take a longer time for EEG to return to normal and to stop taking drugs in patients with persistent or unimproved developmental delay. Neurodevelopmental outcomes and prognosis of vitamin B6-responsive IS were relatively favorable.

The human dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene encodes a large subunit of the cytoplasmic dynein complex. DYNC1H1 mutations are associated with various neurological diseases involving both the peripheral and central nervous systems.
The clinical characteristics and genetic data of an infant carrying the de novo DYNC1H1 variant identified by trio exome sequencing were analyzed. Patients with epilepsy with DYNC1H1 mutations were summarized by reviewing the literature.
We first identified an infant presenting with epileptic spasms harboring a de novo missense mutation in DYNC1H1 (c.874C>T; p. Arg292Trp), once reported in an adult case, and further summarized another 54 patients with seizures or epilepsy caused by DYNC1H1 pathogenic variants in the literature. Refractory epilepsy, intellectual disability, and cortical developmental malformations are crucial characteristics of patients with developmental and epileptic encephalopathy (DEE) caused by DYNC1H1 variants. Notably, epileptic spasms in this case were resistant to multiple anti-seizure medications, corticosteroids, ketogenic diet, and vagus nerve stimulation treatment. The child also showed cortical gyrus malformation and global developmental delay.
DYNC1H1 variants can cause infantile developmental and epileptic encephalopathy, in which Arg292Trp is a mutation hotspot of the DYNC1H1 gene. Epileptic seizures in this type of DYNC1H1-related DEE are mostly resistant to multiple antiepileptic strategies and need to explore optimized treatments.

To investigate surgical prognostic factors in order to establish a surgical plan for children with drug-resistant epileptic spasms. We retrospectively analysed 64 children with drug-resistant spasms who were operated on in Beijing; the electroclinical features, surgical procedures, and surgical outcomes of these children were discussed in detail. We divided the seizure-free patients into several groups according to imaging, aetiology, and application of stereo-electroencephalography in order to investigate the extent of the various influencing factors. Fifty-three (82.8%) patients had favourable outcome, and 11 (17.2%) had unfavourable outcome. Based on the univariate analysis, the factors associated with favourable seizure outcome were interictal high γ frequency (χ 2 = 4.161; p = 0.041), concordance between MRI and interictal epileptic discharges (IEDs) (χ 2 = 6.148; p =0.013), and concordance between PET and IEDs (χ 2 = 4.281; p = 0.039). Concordance between MRI and IEDs (OR = 0.083, 95% CI = 0.014-0.483; p = 0.006) and continuous discharges on electrocorticography (OR = 0.109, 95% CI = 0.019-0.639; p = 0.014) were important factors associated with a favourable surgical outcome. Resective surgery is an effective treatment for drug-resistant ES in children. A deeper understanding of the predictors of seizure outcome is beneficial for establishing a standard, one-stage resection procedure for spasms in order to benefit more patients who have not previously considered surgery. We propose a workflow for presurgical evaluation in children with epileptic spasms.

OBJECTIVE: Viral encephalitis (VE) or bacterial meningoencephalitis (BME) in early childhood may cause brain injury and neurological sequelae, including epilepsy. Postencephalitic epilepsy (PEE) characterized by epileptic spasms (ES) is a rare but serious condition; there is an urgent need to develop new methods to evaluate the characteristics of these children and select appropriate treatments.
METHODS: We conducted an observational study of 20 patients (11 males, 9 females) who experienced ES after VE or BME at the Chinese PLA General Hospital. Patients were followed up for over 12 months, and outcomes were analyzed.
RESULTS: The median ages at the onset of encephalitis and ES were 5.5 and 11.5 months, respectively. The median age at follow-up was 35.5 months. Sixteen (80 %) patients developed drug-resistant epilepsy (DRE), including all 12 patients with VE and 4 of 8 patients with BME. Epileptiform discharges were detected on electroencephalography, including 15 patients with hypsarrhythmia and 5 without. Fifteen of the patients were treated with a 14-day intravenous infusion of adrenocorticotropic hormone (ACTH) at a dose 2.5 U/kg (≤25 U); 12 showed a short-term response but 10 experienced recurrence. Three patients received vigabatrin, and none of these patients responded to treatment. Six patients started a ketogenic diet (KD); five failed to respond and the outcome was not known in one. Four patients were treated by vagus nerve stimulation (VNS), and all showed a partial response.
CONCLUSIONS: Children with PEE characterized by ES are more likely to develop DRE. The prognosis was worse for patients with VE compared to those with BME. Clarifying the efficacies of treatments involving ACTH (low-dose), KD, vigabatrin, and VNS will require further investigation.

OBJECTIVE: To analyze diurnal cortisol (COR) rhythms among children with epileptic spasms (ESs) and explore the relationship between endocrine factors, circadian rhythm, and ES.
METHODS: This study assessed the COR and adrenocorticotropic hormone (ACTH) levels at 08:00 and 16:00, and COR values at 00:00 among children with ESs. Additionally, the etiology of ESs was analyzed. All cases were divided into the following three etiology groups: genetic group, structural etiology group, and unknown etiology group. ACTH was administered to 24 patients, who were divided into the positive electroclinical outcome group and negative electroclinical outcome group. All data were analyzed using a two-way repeated measures analysis of variance.
RESULTS: All children showed a COR rhythm. Controls displayed a significantly different COR rhythm from that in the ES group (Fgroup*COR =24.100, p = 0.000). It was observed that the ACTH levels at 08:00 (t = -3.720) and 16:00 (t=-3.794) and COR levels at 16:00 (t = -2.264) and 00:00 (t = -4.607) in the ES group were significantly higher than those in the control group (p < 0.05); COR levels at 08:00 were significantly lower among individuals in the structural etiology group (F = 3.828, p < 0.05). COR levels at 08:00 in the negative electroclinical outcome group (668.30 ± 227.42) nmol/L were higher than those in the positive electroclinical outcome group (462.25 ± 249.71) nmol/L.
CONCLUSIONS: Our results suggest that the change in COR rhythm is an important pathophysiological characteristic of ESs, suggesting that hypothalamus-pituitary-adrenal axis dysfunction possibly leads to the different manifestations of ESs.

Epileptic spasms are a catastrophic form of epilepsy. When epileptic spasms occur under 2-year-old, they may be also called \"infantile spasms\". Adrenocorticotropic hormone (ACTH) is recommended as first line intervention for the treatment of epileptic spasms without tuberous sclerosis complex. The chief risks of ACTH therapy are immunosuppression and hypertension. We reported rare cases of abnormal high blood pressure in two male epileptic spasms patients during ACTH therapy. Both patients\' blood pressure reached a high blood pressure stage 2 on the 9th day and 10th day of ACTH treatment, respectively. The blood pressure returned to normal range after the drug dosage was reduced or stopped. The lower level of neutrophil%, neutrophil count, and a higher level of lymphocyte%, lymphocyte count and prealbumin than normal range were observed in both patients before ACTH therapy. The neutrophil to lymphocyte rate might be a predictor for high blood pressure among patients treated with ACTH. The rates of both patients were under 0.50 (0.42 for Case 1 and 0.17 for Case 2). We reported the documented cases in two Chinese pediatric patients who suffered from epileptic spasms treated with ACTH resulted in abnormal high blood pressure, which could be predicted by using neutrophil to lymphocyte rate. We also mentioned serum prealbumin might be another predictor. More clinical data is required to elucidate the relationship between serum prealbumin level and blood pressure.

Background: Epileptic spasms (ES) is a severe seizure type and lack of adequate methods for controlling of clinical attacks. Previous studies have indicated that cathodal transcranial direct current stimulation (tDCS) reduces seizure frequency for patients with epilepsy. ES are proposed to have a focal cortical origin. We hypothesized that patients with ES exhibit hyperactive network hubs in the parietal lobe, and that cathodal tDCS targeting the bilateral parietal region can reduce seizure frequency in patients with pharmacoresistant ES. Materials and Methods: The present study consisted of three basic phases: (a) a pre-treatment monitoring period for 14 days; (b) a consecutive 14-day treatment period during which patients were treated with 1 or 2 mA cathode tDCS for 40 min once per day; (c) and a follow-up period for at least 28 days. During the first 20 min of treatment, the cathode was placed over the right parietal lobe (P4) with the reference electrode over the contralateral supra-orbital area. In the second 20 min, the cathode was placed over the left parietal lobe (P3), with the reference electrode over the contralateral supra-orbital area. All patients received active tDCS treatment, and some patients underwent more than one treatment block. Patients maintained a seizure diary throughout the study. Antiepileptic drug therapy remained unchanged throughout the study. K-related samples Friedman tests and two-related samples tests were used to analyze data from all patients. Results: Seven patients with pharmacoresistant ES were included, receiving a total of eighteen 14-day blocks of tDCS treatment. We observed a significant difference in seizure frequency at the second month (p = 0.028, unadjusted), as well as a trend toward decreased seizure frequency at the fourth month (p = 0.068, unadjusted) of the first follow-up, relative to baseline. Three of seven patients (42.9%) exhibited sustained seizure reduction, while one (14.3%) experienced a short-term reduction in seizure frequency following cathodal tDCS treatment. Treatment was well tolerated in all patients. Conclusions: Repeated tDCS with the cathode placed over the bilateral parietal region is safe and may be effective for reducing seizure frequency in a subgroup of patients with pharmacoresistant ES.

The aim of this study was to evaluate the electro-clinical features, etiology, treatment, and postsurgical seizure outcomes in patients with intractable epileptic spasms (ESs).
The authors retrospectively studied the medical records of all patients who had presented with medically intractable ESs and had undergone surgery in the period between October 2009 and August 2015. The interictal electroencephalography (EEG) pattern, MRI studies, magnetoencephalography findings, and postsurgical seizure outcomes were compared.
Twenty-six patients, 12 boys and 14 girls (age range 3-22 years), were eligible for study inclusion. Of these 26 patients, 84.6% (22) presented with multiple seizure types including partial seizures (PSs) independent of the ESs (30.8%); ESs followed by tonic seizures (30.8%); myoclonic seizures (19.2%); tonic seizures (19.2%); ESs followed by PSs (19.2%); focal seizures with secondary generalization (15.4%); atypical absence (11.5%); PSs followed by ESs (7.7%); and myoclonic followed by tonic seizures (7.7%). Seventeen patients underwent multilobar resection and 9 underwent unilobar resection. At the last follow-up (mean 36.6 months), 42.3% of patients were seizure free (outcome classification [OC] 1), 23.1% had > 50% reduction in seizure frequency (OC2-OC4), and 34.6% had < 50% reduction in seizure frequency or no improvement (OC5 and OC6). Predictors of favorable outcomes included an interictal focal EEG pattern and concordance between interictal EEG and MRI-demonstrated lesions (p = 0.001 and 0.004, respectively).
A favorable surgical outcome is achievable in a highly select group of patients with ESs secondary to structural lesions. Interictal EEG can help in identifying patients with the potential for favorable resective outcomes.