Child ; Humans ; Spasms, Infantile/drug therapy* ; Electroencephalography ; China

OBJECTIVE: To investigate the factors in first-time adrenocorticotropic hormone (ACTH) therapy and their influence on spasm control time in infants with infantile spasms. METHODS: A total of 72 infants with infantile spasms who were admitted from January 2008 to October 2013 were enrolled. Their clinical data were collected, and the exposure factors for infantile spasms were selected. A Cox proportional-hazards regression model analysis was performed for these factors to analyze their influence on spasm control time. RESULTS: Clarification of the etiology (known or unexplained etiology), frequency of spasms before treatment, and presence or absence of combination therapy (ACTH used alone or in combination with magnesium sulfate) had a significant influence on spasm control time in infants with infantile spasms. The infants with a known etiology had a significantly shorter spasm control time than those with unexplained etiology, and the infants with a low frequency of spasms before treatment and receiving ACTH combined with magnesium sulfate early had a significantly longer spasm control time than their counterparts (P<0.05). CONCLUSIONS For infants with infantile spasms at initial diagnosis, etiology should be clarified, which may helpful for evaluating prognosis. A combination of ACTH and magnesium sulfate should be given as soon as possible, which may improve their prognosis.
Adrenocorticotropic Hormone ; therapeutic use ; Anticonvulsants ; Humans ; Infant ; Proportional Hazards Models ; Spasm ; Spasms, Infantile ; drug therapy

OBJECTIVES: To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis. METHODS: The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis. RESULTS: ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05). CONCLUSIONS Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.
Child ; Humans ; Infant ; Adrenocorticotropic Hormone/therapeutic use* ; Spasms, Infantile/drug therapy* ; Treatment Outcome ; Seizures ; Electroencephalography/adverse effects* ; Spasm/drug therapy*

OBJECTIVETo investigate the immunological mechanism of prednisone in the treatment of infantile spasm (IS) by evaluating the immune function of IS children before and after treatment.

METHODSThirty children with IS were enrolled as IS group. Thirty healthy infants who underwent physical examination were enrolled as healthy control group. Fasting venous blood was collected for both groups before and after prednisone treatment. Chemiluminescence was used to measure serum levels of interleukin-1B (IL-1B), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Immunoturbidimetric assay was used to measure serum levels of immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG). Flow cytometry was used to measure the percentages of T lymphocyte subsets (CD3, CD4, and CD8). The clinical outcome and electroencephalographic findings were evaluated for all IS children after prednisone treatment.

RESULTSThe IS group had significantly higher serum levels of IL-2R, IL-8, and TNF-α than the healthy control group before treatment (P<0.05). The mean number of daily ictal clusters was positively correlated with the levels of IL-2R, IL-8, and TNF-α in IS children, the mean number of total daily seizures was positively correlated with IL-8 level, and any two indices out of IL-2R, IL-8, and TNF-α were positively correlated with each other (P<0.05). Among the 30 IS children treated with prednisone, 19 achieved seizure control; electroencephalography showed that 18 children achieved complete remission of hyperarrhythmia. After treatment, the IS group had significant reductions in the numbers of daily ictal clusters and total daily seizures, significant improvement in developmental quotient (P<0.05), and significant reductions in serum levels of IL-2R, L-8, and TNF-α, the percentage of CD4T lymphocytes, and CD4/CD8ratio (P<0.05), as well as a significant increase in the percentage of CD8T lymphocytes (P<0.05).

CONCLUSIONSIS children have immune dysfunction. Prednisone can control seizures in IS children, possibly by regulating and improving immune dysfunction.

CD4-CD8 Ratio ; Cytokines ; blood ; Electroencephalography ; Female ; Humans ; Infant ; Male ; Prednisone ; therapeutic use ; Spasms, Infantile ; drug therapy ; immunology

OBJECTIVEThe efficacy and adverse effects of conventional dose and low dose adrenocorticotrophic hormone (ACTH) therapy for West syndrome (WS) were compared in order to identify a low effective dose with few adverse effects.

METHODSA prospective randomized controlled study was conducted. Thirty children with cryptogenic (n=8) or symptomatic (n=22) WS were enrolled. They were randomly assigned to receive either conventional dose or low dose ACTH therapy. For the conventional dose group, ACTH 50 IU per day was administered for 2 weeks and tapered to zero over the subsequent 2 weeks. For the low dose group, 0.4 IU/kg per day was injected for 2 weeks. After seizures were fully controlled, ACTH was tapered to zero over the subsequent 2 weeks. If there was an absence of an effective response in the low dose group, the dosage was increased to 1 IU/kg per day for the next 2 weeks and then tapered to zero over 2 weeks. Both effectiveness and adverse effects were compared between the two groups.

RESULTSThere were no significant differences in the good initial responses between the conventional and the low dose groups, which were 53% and 60%, respectively (P> 0.05). EEG findings after ACTH therapy, the rate of relapse of spasms, and the interval to relapse were not different between the two groups (P> 0.05). The long-term outcomes were assessed in the initial 8 responders, and there were no significant differences between the two groups (follow-up duration>12 months). The rates of good efficacy and disappearance of the hypsarrhythmia were significantly higher in the cryptogenic WS group than in the symptomatic WS group (P<0.05). The incidence of ACTH therapy related-adverse effects in the conventional dose group (93%) was significantly higher than in the low dose group (20%) (P<0.01). The mild brain shrinkage was observed in one patient from the conventional dose group.

CONCLUSIONSThe short-term and long-term therapeutic effects of ACTH between 50 IU/d and 0.4 IU/kg/d doses are similar. ACTH therapy is more effective for cryptogenic WS than symptomatic WS. To reduce adverse effects, ACTH therapy should start with a low dose (0.4 IU/ kg each day).

Adolescent ; Adrenocorticotropic Hormone ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Humans ; Infant ; Male ; Prospective Studies ; Spasms, Infantile ; drug therapy

The ketogenic diet is an effective treatment for the patients with intractable epilepsy, however, the diet therapy can sometimes be discontinued by complications. Protein–losing enteropathy is a rarely reported serious complication of the ketogenic diet. We present a 16-month-old Down syndrome baby with protein-losing enteropathy during the ketogenic diet as a treatment for West syndrome. He suffered from diarrhea, general edema and hypoalbuminemia which were not controlled by conservative care for over 1 month. Esophagogastroduodenoscopy and stool alpha-1 antitrypsin indicated protein-losing enteropathy. Related symptoms were relieved after cessation of the ketogenic diet. Unexplained hypoalbuminemia combined with edema and diarrhea during ketogenic suggests the possibility of protein-losing enteropathy, and proper evaluation is recommended in order to expeditiously detect it and to act accordingly.
Diarrhea ; Diet Therapy ; Down Syndrome ; Drug Resistant Epilepsy ; Edema ; Endoscopy, Digestive System ; Humans ; Hypoalbuminemia ; Infant ; Infant, Newborn ; Ketogenic Diet* ; Protein-Losing Enteropathies* ; Spasms, Infantile

The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of difficult-to-control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. In this situation, a ketogenic diet should be considered as an alternative therapy. However, less attention has been paid to associated adverse events in the ketogenic diet. We report a case of infantile spasm associated with acute renal failure, lipoid pneumonitis and kwashiorkor after ketogenic diet. A better understanding of this adverse event profile will allow the pediatric neurologist to have a true informed consent discussion with the care giver when considering initiation of the ketogenic diet.
Acute Kidney Injury* ; Caregivers ; Child ; Diet ; Drug Therapy ; Epilepsy ; Humans ; Infant ; Infant, Newborn ; Informed Consent ; Ketogenic Diet* ; Kwashiorkor* ; Pneumonia ; Seizures ; Spasms, Infantile*

BACKGROUNDInfantile spasms is a severe epileptic encephalopathy, which is refractory to conventional antiepileptic drugs. Adrenocorticotropic hormone (ACTH) has been the major therapy for infantile spasms; however, ACTH therapy is ineffective for some patients. The variations in the receptor genes can contribute to antiepileptic drug resistance. This study was to elucidate the possible associations between the variations of the MC2R gene and ACTH responsiveness in patients with infantile spasms.

METHODSWe screened for variations in the promoter and coding region of the MC2R gene in 91 Chinese patients with infantile spasms and 94 controls, using PCR and a direct sequencing method. The frequencies of the genotypes, alleles and reconstructed haplotypes were analyzed in the cases and controls. The association between ACTH responsiveness and genetic variations of the MC2R gene was also assessed.

RESULTSFour single nucleotide polymorphisms (SNPs) were identified in the MC2R promoter, one of which was a novel specimen at position-2 from the transcription start site ATT, -2T > C. Three SNPs (rs1893220, rs2186944 and -2T > C) showed a significant difference between the cases and controls (P < 0.05 for all). The frequency of the common TCCT haplotype carrying four-SNP major alleles was significantly lower in the cases (39%) than in the controls (60%) (P = 0.00003). The homozygous carriers of the TCCT haplotype had a much lower relative risk than the non-carriers (RR = 0.42, 95% CI 0.26-0.70, P = 0.0001). ACTH responsiveness was strongly associated with the TCCT haplotype (P = 0.000082). Compared with non-carriers of the TCCT haplotype, the homozygous and heterozygous carriers were more responsive to ACTH therapy (P = 0.0002; P = 0.0003, respectively).

CONCLUSIONSOur results indicated that the TCCT haplotype in the MC2R promoter is strongly associated with the responsiveness of the ACTH therapy performed on patients with infantile spasms. The polymorphisms of the MC2R promoter might be one important factor that influences the efficacy of ACTH therapy on infantile spasms.

Adrenocorticotropic Hormone ; therapeutic use ; Female ; Haplotypes ; Humans ; Infant ; Male ; Polymorphism, Single Nucleotide ; Receptor, Melanocortin, Type 2 ; genetics ; Spasms, Infantile ; drug therapy ; genetics

Infantile spasm is an age-related refractory epilepsy. Topiramate is a new anticonvulsant with multiple mechanisms of action, and it may be effective for treating pediatric epilepsies. To evaluate the efficacy and tolerability of first-line topiramate treatment for infantile spasm, 20 patients received topiramate monotherapy during this study. They were treated with an initial dose of 1mg/kg/day, with a progressive titration of 1 mg/kg a week until their spasms were controlled and a maximum dose of 12mg/kg/day was achieved. The evaluation of the treatment efficacy was based on the spasm frequency data that was obtained by the scalp and video-EEG, and by the parental count of spasm. Thirty percent of the subjects became spasm-free during the study. Six of 20 subjects (30%) had cessation of spasm and disappearance of hypsarrhythmia as seen via the video EEG; four (50%) of eight idiopathic patients had a response, whereas two (17%) of 12 patients with symptomatic infantile spasm responded. Seventy of the patients, including the spasm-free patients, had a reduction in their seizure frequency of more than 50%, and 10% of the patients had a reduction in their seizure frequency of less than 50%. The clusters of spasm frequency decreased from 10.6 +/- 8.5 to 3.5 +/- 1.4 clusters/day. Topiramate is effective and tolerated in those patients suffering from infantile spasm. Our results suggest that this drug should be considered as a new first-line drug for treating infantile spasm.
Treatment Outcome ; Spasms, Infantile/*drug therapy ; Male ; Infant ; Humans ; Fructose/*analogs & derivatives/therapeutic use ; Female ; Electroencephalography ; Child, Preschool ; Anticonvulsants/*therapeutic use ; Age of Onset

Aicardi syndrome is a severe congenital disorder characterized by infantile spasms, chorioretinal lacunae, and agenesis or hypogenesis of the corpus callosum. A 6 month old female had developed abnormal eye movement and seizures of the complex partial type and myoclonic type. MRI pictures of the patient revealed the presence of genu associated with agenesis of the rest of corpus callosum. A funduscopic examination revealed bilateral small, solitary, pale areas with sharp borders, some of which had minimal surrounding pigmentation (chorioretinal lacunae), especially clustered around the disc, and they were more prominent on the left side. We report here on the unusual findings of a complex partial seizure, myoclonic seizure and the atypical EEG finding in addition to the well-known characteristic clinical and imaging findings of a patient with Aicardi syndrome.
Anticonvulsants/therapeutic use ; Arachnoid Cysts/*pathology ; Corpus Callosum/*abnormalities ; Electroencephalography ; Epilepsies, Myoclonic/drug therapy/*pathology ; Epilepsies, Partial/drug therapy/*pathology ; Female ; Humans ; Infant ; Magnetic Resonance Imaging ; Retinal Diseases/*pathology ; Spasms, Infantile/drug therapy/*pathology ; Syndrome