Adrenocorticotropic Hormone Treatment Research Articles

Dysregulation of circadian clock gene expression patterns in a treatment-resistant animal model of depression.

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances. In this study, we investigate the potential of adrenocorticotropic hormone (ACTH)-treated animals as a disease model for research in CR disturbances in treatment-resistant depression. For this purpose, we evaluate the changes in several circadian phase markers, including plasma concentrations of corticosterone, ACTH, and melatonin, as well as gene expression patterns of 13 selected ccgs at 3 different time points, in both peripheral and central tissues. We observed no impact on plasma corticosterone and melatonin concentrations in the ACTH rats compared to vehicle. However, the expression pattern of several ccgs was affected in the ACTH rats compared to vehicle. In the hippocampus, 10 ccgs were affected by ACTH treatment, whereas in the adrenal glands, 5 ccgs were affected and in the prefrontal cortex, hypothalamus and liver 4 ccgs were regulated. In the blood, only 1 gene was affected. Individual tissues showed changes in different ccgs, but the expression of Bmal1, Per1, and Per2 were most generally affected. Collectively, the results presented here indicate that the ACTH animal model displays dysregulation of a number of phase markers suggesting the model may be appropriate for future studies into CR disturbances.

Role of TRAK1 variants in epilepsy: genotype-phenotype analysis in a pediatric case of epilepsy with developmental disorder.

The TRAK1 gene is mapped to chromosome 3p22.1 and encodes trafficking protein kinesin binding 1. The aim of this study was to investigate the genotype-phenotype of TRAK1-associated epilepsy. Trio-based whole-exome sequencing was performed on a cohort of 98 patients with epilepsy of unknown etiologies. Protein modeling and the VarCards database were used to predict the damaging effects of the variants. Detailed neurological phenotypes of all patients with epilepsy having TRAK1 variants were analyzed to assess the genotype-phenotype correlations. A novel TRAK1 compound heterozygous variant comprising variant c.835C > T, p.Arg279Cys and variant c.2560A > C, p.Lys854Gln was identified in one pediatric patient. Protein modeling and VarCards database analyses revealed that the variants were damaging. The patient received a diagnosis of early infantile epileptic spasms with a developmental disorder; he became seizure-free through valproate and adrenocorticotropic hormone treatment. Further results for six variants in 12 patients with epilepsy indicated that biallelic TRAK1 variants (including homozygous or compound heterozygous variants) were associated with epilepsy with developmental disorders. Among these patients, eight (67%) had epileptic spasms and seven (58%) were intractable to anti-seizure medicines. Moreover, eight patients experienced refractory status epilepticus, of which seven (88%) died in early life. To our knowledge, this is the first reported case of epilepsy caused by TRAK1 compound heterozygous variants. Biallelic TRAK1 variants can cause epilepsy and developmental disorders. In these patients, seizures progress to status epilepticus, suggesting a high risk for poor outcomes and the requirement of early treatment.

SYK-623, a δ Opioid Receptor Inverse Agonist, Mitigates Chronic Stress-Induced Behavioral Abnormalities and Disrupted Neurogenesis.

The δ opioid receptor (DOR) inverse agonist has been demonstrated to improve learning and memory impairment in mice subjected to restraint stress. Here, we investigated the effects of SYK-623, a new DOR inverse agonist, on behavioral, immunohistochemical, and biochemical abnormalities in a mouse model of imipramine treatment-resistant depression. Male ddY mice received daily treatment of adrenocorticotropic hormone (ACTH) combined with chronic mild stress exposure (ACMS). SYK-623, imipramine, or the vehicle was administered once daily before ACMS. After three weeks, ACMS mice showed impaired learning and memory in the Y-maze test and increased immobility time in the forced swim test. SYK-623, but not imipramine, significantly suppressed behavioral abnormalities caused by ACMS. Based on the fluorescent immunohistochemical analysis of the hippocampus, ACMS induced a reduction in astrocytes and newborn neurons, similar to the reported findings observed in the postmortem brains of depressed patients. In addition, the number of parvalbumin-positive GABA neurons, which play a crucial role in neurogenesis, was reduced in the hippocampus, and western blot analysis showed decreased glutamic acid decarboxylase protein levels. These changes, except for the decrease in astrocytes, were suppressed by SYK-623. Thus, SYK-623 mitigates behavioral abnormalities and disturbed neurogenesis caused by chronic stress.

Comparison of Different Doses of ACTH Used in ACTH Stimulation Test to Determine the Subtypes of Primary Aldosteronism

To compare the diagnostic value of adrenocorticotropic hormone (ACTH) stimulation test (AST) with different doses of ACTH combined with midnight administration of 1 mg dexamethasone for the determination of the subtypes of primary hyperaldosteronism (PA). This is a prospective observational study. Patients diagnosed with PA in the Department of Endocrinology, the First Medical Center of of Chinese PLA General Hospital from January 1, 2020 to September 30, 2022 underwent AST with different doses of ACTH. All patients received 1 mg dexamethasone at midnight for inhibition. Then, the patients were randomly assigned to 25-unit and 50-unit ACTH treatment groups by a ratio of 1:2. Subtype classification and diagnosis of aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) was made on the basis of adrenal venous blood samples and/or postoperative pathology and clinical follow-up findings. Receiver operating characteristics (ROC) curves were plotted to examine the diagnostic efficacy and the difference of AST by varying doses of ACTH in distinguishing APA and IHA. A total of 82 patients, including 49 patients with APA (59.8%) and 33 patients with IHA (40.2%), were enrolled. There were 29 patients in the 25-unit ACTH group (35.4%) and 53 patients in the 50-unit ACTH group (64.6%). There were no significant differences in age, sex, blood pressure, minimum serum potassium, and biochemical parameters between the 25-unit and 50-unit groups. After ACTH stimulation, plasma aldosterone concentration (PAC), cortisol (F), and PAC/F at different points of time showed no statistical difference between the two groups (P>0.05). The area under the curve (AUC) of PAC in the 25-unit group was higher than that of PAC/F. The AUC of PAC reached the maximum at 90 minutes (0.948, 95% confidence interval [CI]: 0870-1.000) and the optimal cutoff was 38.0 ng/dL, which had a sensitivity of 92.9% and a specificity of 86.7% for differentiating APA and IHA. Similar to the 25-unit group, the maximum AUC of PAC in the 50-unit group was greater than that of PAC/F. The AUC of PAC reached the maximum 90 minutes (0.930, 95% CI: 0.840-0.994) and the optimal cutoff was 39.6 ng/dL, which had a sensitivity of 91.2% and a specificity of 83.3%. The AUC of PAC at different points of time in the 25-unit ACTH group (0.862-0.948) was greater than that of 50-unit ACTH group (0.823-0.930), but the difference was not statistical significance. AST with 25-unit or 50-unit ACTH combined with small-dose dexamethasone can be used in PA subtype determination, ie, differentiation between APA and IHA. The optimal PAC cut-off values for 25-unit or 50-unit ACTH are similar, being 38.0 ng/dL and 39.6 ng/dL, respectively, and both cutoff values show higher sensitivity and specificity at 90 min. The AST with 25-unit ACTH has the smaller dose and the better safety. Therefore, it is recommended for the diagnosis of PA subtypes.

The Response of Synthetic Adrenocorticotropic Hormone (ACTH) Treatment in Pediatric Drug-Resistant Epilepsy Other Than Infantile Epileptic Spasms Syndrome: A Retrospective Observational Study.

Adrenocorticotropic hormone (ACTH) is a tropic hormone naturally secreted by the anterior pituitary gland to stimulate the secretion of cortisol and androgens.ACTH is used innon-tuberous sclerosis infantile epileptic spasms syndrome (IESS), and ithas shown significant, promising results in epilepsy syndromes with possible inflammatory processes.However, many studies have also demonstrated a promising potential even in other types of drug-resistant epilepsy. Material and method: This study is a retrospective observational study that follows the clinical characteristics and outcomes of nine pediatric patients with drug-resistant epilepsy treated with short-term synthetic ACTH in Saudi Arabia. The response was assessed during the ACTH infusion and after three months. During infusion, six of the nine (66%) patients had a short-term (within two weeks) favorable response, with a more than 50% reduction in seizure frequency. Four of the nine (44%) patients had complete responses with seizure freedom. After three months, four patients (44%) had a three-month seizure frequency reduction of more than 30% attributed to ACTH, including one patient with an IESS history who had a 70% reduction in seizure frequency. Of the four patients who had a complete response, three (75%) had a seizure relapse after tapering in the following three months. Conclusion: This case series adds to the literature to suggest ACTH treatment of drug-resistant epilepsies other than IESS might benefit some patients in the acute settingbut they are less likely to maintain a sustained treatment response. Randomized and large sample size studies are necessary to assess treatment response and accurately aid in appropriate patient selection.

Abnormalities in Clostridioides and related metabolites before ACTH treatment may be associated with its efficacy in patients with infantile epileptic spasm syndrome.

Adrenocorticotropic hormone (ACTH) is the first-line treatment of infantile epileptic spasm syndrome (IESS). Its reported effectiveness varies, and our current understanding regarding the role of gut microbiota composition in IESS treatment response is limited. This study assessed the microbiome-metabolome association to understand the role and mechanism of gut microbiota composition in IESS treatment outcomes. Children with IESS undergoing ACTH treatment were enrolled. Pre-treatment stool and serum samples were collected for 16S rRNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively. The children were divided into "responsive" and "non-responsive" groups, and gut microbiota and serum metabolome differences were analyzed. Of the 30 patients with IESS, 14 responded to ACTH and 16 did not. The "non-responsive" group had larger maleficent Clostridioides and Peptoclostridium_phage_p630P populations (linear discriminant analysis >2; false discovery rate q < 0.05). Ten metabolites were upregulated (e.g., xanthurenic acid) and 15 were downregulated (e.g., vanillylmandelic acid) (p < 0.05). Association analysis of the gut microbiome and serum metabolome revealed that Clostridioides and Peptoclostridium_phage_p630P2 were positively correlated with linoleic and xanthurenic acids, while Clostridioides was negatively correlated with vanillylmandelic acid (p < 0.05). A classifier using differential gut bacteria and metabolites achieved an area under the receiver operating characteristic curve of 0.906 to distinguish responders from non-responders. This study found significant differences in pre-treatment gut microbiota and serum metabolome between children with IESS who responded to ACTH and those who did not. Additional exploration may provide valuable information for treatment selection and potential interventions. Our results suggest that varying ACTH responses in patients with IESS may be associated with increased gut Clostridioides bacteria and kynurenine pathway alteration, but additional experiments are needed to verify this association.

Early-Life Cooling Alters Later Corticosterone Response to Restraint in Prefledging Eastern Bluebirds (Sialia sialis) but Does Not Alter Adrenal Sensitivity to ACTH.

AbstractEnvironmental challenges faced early in life can both activate and shape the development of the hypothalamic-pituitary-adrenal axis. Activation of this axis is characterized in part by elevated levels of glucocorticoids, exposure to which can have profound effects throughout an animal's life. We have demonstrated that in nestling eastern bluebirds (Sialia sialis), bouts of environmentally relevant cooling result in elevations of corticosterone (the primary avian glucocorticoid) very early in life. Nestlings repeatedly exposed to cooling also exhibit dampened corticosterone secretion later in life in response to restraint compared to control nestlings. We explored the mechanistic basis of this phenomenon. Specifically, we asked whether early-life cooling alters adrenal sensitivity to adrenocorticotropic hormone (ACTH), the primary controller of corticosterone synthesis and release. To this end, we subjected nestlings to repeated bouts of cooling (cooled nestlings) or brooding temperatures (control nestlings) early in life and, before fledging, assessed (1) the capacity of the nestlings' adrenals to produce corticosterone following ACTH injection, (2) the effect of cooling on corticosterone responses to restraint, and (3) the effect of cooling on adrenal sensitivity to ACTH. We found that both cooled and control nestlings secreted substantially higher levels of corticosterone following ACTH treatment than they did following restraint. We also confirmed that cooled nestlings had reduced corticosterone secretion in response to restraint compared to control nestlings; however, sensitivity to exogenous ACTH did not differ between temperature treatments. We hypothesize that early-life cooling alters later corticosterone secretion by affecting higher levels of the hypothalamic-pituitary-adrenal axis.

Real-word adrenocorticotropic hormone treatment for childhood-onset nephrotic syndrome.

Current first-line anti-proteinuric treatments do not produce a satisfactory therapeutic effect in a considerable number of patients with nephrotic syndrome (NS). Interest in adrenocorticotropic hormone (ACTH) for the treatment of NS has recently been revived. The present study investigated the efficacy and safety of ACTH treatment in children with frequent relapsing NS (FRNS), steroid-dependent NS (SDNS), and steroid-resistant NS (SRNS). The ACTH treatment group was comprised of NS patients receiving ACTH treatment. Patients with serum cortisol concentrations <85.3 nmol/L and who had not received ACTH treatment previously were enrolled in the control group from January 2018 to January 2021. The maintenance dose of prednisone, the number of disease recurrences, the time of first disease relapse, immunosuppressant use, serum cortisol levels, and adverse events were recorded in both groups. Fifty-one patients were included in the ACTH group, and twenty-one patients were enrolled in the control group. Concurrent treatment with one or more immunosuppressive and/or cytotoxic treatments occurred in 92.2% and 85.7% of patients in the ACTH and control groups, respectively, throughout the study period. A greater reduction in the prednisone maintenance dose was observed in the ACTH group compared with the control group after 1 year of follow up (0.603 ± 0.445 mg/kg vs. 0.267 ± 0.500 mg/kg, p = 0.006). During the one-year study period, fewer participants experienced one or more disease relapses in the ACTH group (45.1%) compared to the control group (76.2%, odds ratio = 3.896, p = 0.016). The number of disease recurrences per patient in the ACTH group was less than that in the control group (median difference = -1, p = 0.006). The mean length of remission was 8.902 m and 7.905 m in the ACTH group and control group, respectively. A log-rank test showed a longer relapse free survival for patients in the ACTH group (p = 0.046), but the Breslow test showed no significant difference between groups (p = 0.104). Ten patients in the ACTH group successfully discontinued all drug therapies. No patients in the control group were able to discontinue drug therapy as of February 2022. ACTH, combined with multiple drugs, is effective at reducing the prednisone maintenance dose and may effectively prevent disease relapses in childhood NS.

Magnesium suppresses in vivo oxidative stress and ex vivo DNA damage induced by protracted ACTH treatment in rats.

Oxidative stress, arising from disrupted balance between reactive oxygen/nitrogen species (ROS/RNS) and antioxidant defences, has been implicated in the pathogenesis of stress-related disorders. There is a growing body of evidence that supports the relationship between the activity of the hypothalamic-pituitary-adrenal (HPA) stress system, oxidative stress and magnesium (Mg) homeostasis. The present study aimed to explore the gap in our current understanding of antigenotoxic and protective effects of Mg supplementation against excessive ROS production in male rats during chronic treatment with adrenocorticotropic hormone (ACTH). Our findings show that exposure to exogenous ACTH (10μg/day, s.c., for 21 days), as one of the key mediators of the HPA axis and stress response, produced an increase in superoxide anion levels and a decrease in superoxide dismutase activity in plasma. We observed that Mg supplementation, starting seven days prior to ACTH treatment and lasting 28 days (300mg/L of drinking water, per os), abolished these effects in experimental animals. Moreover, our study reveals that ACTH increased the susceptibility of peripheral blood lymphocytes to ex vivo H2O2-induced total and high-level oxidative DNA damage, while Mg completely reversed these effects. Collectively, these results highlight the promising role of Mg in stress-related conditions accompanied by increased oxidative stress in animals and support further investigation using human dietary trials.

Epileptik ensefalopatide kullanılan adrenokortikotropik hormonun kemik mineral metabolizması ve adrenal yolak üzerine kısa dönem etkilerinin değerlendirilmesi

Background: We aimed to investigate the short-term effects of adrenocorticotropic hormone (ACTH) treatment on the adrenal pathway and bone metabolism in patients with epileptic encephalopathy.&#x0D; Methods: Two groups with 16 patients and 16 controls were formed. Before the treatment, all patients and controls were tested for bone and adrenal metabolism. Twenty doses of ACTH therapy were given to the patient group over 3 months. The tests on the patient group were repeated 1 month after the end of the treatment.&#x0D; Results: In the patient group, serum calcium, phosphorus and parathyroid hormone levels increased significantly after treatment compared with before treatment. Comparing the bone metabolism of the patient and control groups, urinary calcium/creatinine ratio was higher before treatment; serum phosphorus level, bone-specific alkaline phosphatase level and the urinary calcium/creatinine ratio were higher after treatment in the patient group. In the evaluation of the adrenal pathway, no significant differences were found between fasting serum glucose, sodium, potassium, cortisol and ACTH levels before and after treatment and in the comparison of the patient and control groups.&#x0D; Conclusion: Our study investigated the short-term effect of ACTH on the adrenal pathway and bone metabolism. The results show that ACTH treatment did not have a negative effect on the adrenal pathway in the early period but, its effects on bone metabolism have not been adequately clarified.

Immunological markers of drug resistant epilepsy and its response to immunomodulatory therapy with ACTH in children.

Drug-resistant epilepsy in infancy and childhood is a devastating condition, frequently associated with neuropsychiatric comorbidities. West syndrome is one of the most severe epilepsy syndromes. Adrenocorticotropic hormone (ACTH) treatment is recommended in such cases, but its mechanism of action is still unknown. We prospectively observed levels of selected cytokines in order to identify biomarkers of response to ACTH and the potential mechanism of its antiseizure effect. Fifty-three infants and young children with pharmacoresistant epilepsy receiving ACTH 1-24 were included. There were 2 control groups - children with epilepsy responding to the first medication and children with no history of epilepsy. Blood concentrations of IL-1b, IL-1Ra, IL-6, IL-8, IL-10, TNF-a, IFN-g, MCP-1 and MIP-1a were analyzed at three time points: T0 (before ACTH), T1 (after intensive ACTH treatment) and at T2 (at the end of ACTH withdrawal). The results were correlated with the response to treatment, dose of ACTH and concomitant medications. We found statistically significantly higher concentrations of IL-1, IL-8 and MIP-1a at baseline (T0) in the study group compared to the control groups. ACTH significantly lowered levels of IL-6, IFN-g and MCP from time T0 to T1. This effect was short lasting and no significant changes in cytokine levels were found between T2 and T0. We did not find any differences in immunological markers between the responders and non-responders to ACTH. Our research did not allow us to identify any reliable immunological marker of response to ACTH treatment. We did not observe a positive effect of higher ACTH doses on the response rate in the patients. Our study showed significantly lower concentrations of IL-10 and IFN in the group of patients receiving levetiracetam. The concentration of TNF was higher and the concentration of MIP was lower in the group receiving valproic acid. Our study indicates that increased levels of IL-1, IL-8 and MIP-1a are associated with drug-resistant epilepsy in infants and young children and might be considered immunological markers. IL-6, IFN-g and MCP-1 take part in the effect of ACTH. Immunological mechanisms seem also to be involved in the mechanism of action of classical antiseizure drugs.

Validation of complementary non-invasive tools for stress assessment in spotted paca (Cuniculus paca).

Monitoring the concentration of glucocorticoid metabolites (GCMs) in faecal samples is a non-invasive tool for physiological stress evaluation, particularly useful when studying wild species. However, both negative and positive stimuli (distress and eustress, respectively) can lead to a rise in glucocorticoids. Thus, besides validating whether GCM concentration in faeces reflects endogenous adrenal activity, we also need to identify behavioural indicators of distress to avoid misinterpretation. Therefore, we submitted four adult male spotted pacas (Cuniculus paca) to an exogenous adrenocorticotropic hormone (ACTH) challenge-test in a Latin square design (4 × 4) to monitor changes in the GCM concentration in faeces. We also aimed to describe behaviours potentially indicative of distress. We collected excreted faeces and video-recorded the animals' behaviours for five consecutive days, one day before and four days after application of the following four treatments: 1st control (no-handling); 2nd control (intra-muscular [IM] injection of saline solution); low-dose ACTH (IM injection of 0.18 ml ACTH); and high-dose ACTH (IM injection of 0.37 ml ACTH). There was a peak in the concentration of GCM in faeces collected 24 h after the injection of the high-dose ACTH treatment. Additionally, independent of the treatments, spotted pacas spent less time on exploration and feeding states, while spending more time in the inactive but awake (IBA) state following the treatment application (challenge day). The use of GCM concentration in faecal samples together with the behavioural changes (less exploration and feeding, and more IBA) showed to be efficient as a non-invasive tool for welfare assessment of farmed spotted paca.

Adrenocorticotropic Hormone-Induced Dyskinesia and Probable Sudden Unexpected Death in an Infant with Early Infantile Developmental and Epileptic Encephalopathy—Infantile Epileptic Spasm Syndrome Overlap

AbstractA 2.5-month-old infant with global developmental delay, initially had generalized tonic spasms followed by appearance of infantile spasms from 4.5 months of age. Thus, he had evolution from early infantile developmental and epileptic encephalopathy (EIDEE) to infantile epileptic spasm syndrome (IESS). Neuroimaging and screening of inborn errors of metabolism were normal, but sleep electroencephalogram showed suppression-burst pattern. Treatment with intramuscular injections of adrenocorticotropic hormone (ACTH) was associated with significant control of infantile spasms, but was followed by development of right hemichoreiform movements 2 days later. Upon continuing ACTH treatment, the dyskinesia generalized, prompting us to stop it and shift to vigabatrin which resulted in partial control of his spasms. Whole-exome sequencing revealed an autosomal dominant heterozygous variation of uncertain significance in the NPRL3 gene. At 6 months of age, he suffered of a probable sudden unexpected death, without any notable illness. The case is unique because both the phenomena—ACTH-induced dyskinesia and probable sudden unexpected death in infancy—are rarely described in the EIDEE-IESS continuum.

Integration of multiscale entropy and BASED scale of electroencephalography after adrenocorticotropic hormone therapy predict relapse of infantile spasms.

Even though adrenocorticotropic hormone (ACTH) demonstrated powerful efficacy in the initially successful treatment of infantile spasms (IS), nearly half of patients have experienced a relapse. We sought to investigate whether features of electroencephalogram (EEG) predict relapse in those IS patients without structural brain abnormalities. We retrospectively reviewed data from children with IS who achieved initial response after ACTH treatment, along with EEG recorded within the last twodays of treatment. The recurrence of epileptic spasms following treatment was tracked for 12months. Subjects were categorized as either non-relapse or relapse groups. General clinical and EEG recordings were collected, burden of amplitudes and epileptiform discharges (BASED) score and multiscale entropy (MSE) were carefully explored for cross-group comparisons. Forty-one patients were enrolled in the study, of which 26 (63.4%) experienced a relapse. The BASED score was significantly higher in the relapse group. MSE in the non-relapse group was significantly lower than the relapse group in the γ band but higher in the lower frequency range (δ, θ, α). Sensitivity and specificity were 85.71% and 92.31%, respectively, when combining MSE in the δ/γ frequency of the occipital region, plus BASED score were used to distinguish relapse from non-relapse groups. BASED score and MSE of EEG after ACTH treatment could be used to predict relapse for IS patients without brain structural abnormalities. Patients with BASED score ≥ 3, MSE increased in higher frequency, and decreased in lower frequency had a high risk of relapse.

Hypsarrhythmia paroxysm intensities that initiate and render physical and mental retardation irreversible in West syndrome

Purpose The present study would like to investigate the effect of hypsarrhythmia paroxysms on neurological examination findings. Material and Method This study enrolled 48 children with normal cranial magnetic resonance imaging (cMRI) findings who were previously untreated with adrenocorticotropic hormone (ACTH) and had no history of asphyxia or anoxia at birth, no underlying disease, and no history of head trauma or central nervous system infection. In these children, duration of treatment delay (DTD) was calculated, HPs in NREM sleep were counted, and neurological examination findings were identified. During the study, sometimes the ‘countable hypsarrhythmia paroxysms index’ (cHPI) and sometimes the ‘durational hypsarrhythmia paroxysm index (dHPI)’ was estimated. The onset of neurological examination findings, the onset of physical and mental retardation and the time when physical and mental retardation became irreversible were investigated. The children were stratified into 5 groups based on DTD and attempts were made to prevent the recurrence of aborted ISs by ACTH treatment. Results I- When ‘cHPI = 4/min’; mild growth retardation may be noticed. II- When ‘cHPI = 6/min’ and ‘dHPI = 25%’; reduced eye tracking and reduced movement may be observed. III- When ‘cHPI = 8/min’ and ‘dHPI >32%’; reduced eye tracking and reduced movement become evident, and neurological examination findings are reversible. IV- When ‘dHPI = 45%’; partially permanent, mild motor and psychiatric sequelae develop. V- When ‘dHPI >49%’; neurological examination findings become irreversible. VI- No relationship was found between neurological examination findings the early onset of ISs. Conclusion WS cannot be treated unless DCHP is elucidated.

Assessing Risk for Relapse among Children with Infantile Spasms Using the Based Score after ACTH Treatment: A Retrospective Study.

IntroductionEven though adrenocorticotropic hormone (ACTH) demonstrated powerful efficacy in the initially successful treatment of infantile spasms (IS), nearly one-half of patients whose spasms were once suppressed experienced relapse. There is currently no validated method for the prediction of the risk of relapse. The Burden of Amplitudes and Epileptiform Discharges (BASED) score is an electroencephalogram (EEG) grading scale for children with infantile spasms. We sought to determine whether an association exists between the BASED score after ACTH treatment and relapse after initial response with ACTH.MethodsChildren with IS who achieved initial response after ACTH treatment were selected as the study subjects. Those who experienced relapse within 12 months after ACTH treatment were categorized as the relapse group, and those who did not were categorized as the non-relapse group. Their general clinical data and EEG data (using BASED scoring) after ACTH treatment were collected, and compared between groups. Cox proportional hazards models were fit to determine factors associated with relapse.ResultsA total of 64 children with IS were enrolled in the study, of which 37 (57.8%) experienced a relapse, and the median duration after ACTH treatment was 3 (1.5, 6) months. The BASED score was significantly higher in the relapse group than in the non-relapse group. Cox modeling demonstrated that BASED score was independently associated with relapse. The patients with a score greater than or equal to 3 showed a high rate (89.3%) of relapse. The relapse group had stronger, more stable EEG functional networks than the non-relapse group, and there were obvious correlations between BASED score and functional connectivity.ConclusionThis study suggests the BASED score after ACTH treatment has potential value as a predictor for relapse after initial response. Children with IS who have a BASED score greater than or equal to 3 after the initial response of ACTH carry a high risk of relapse within 1 year.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00347-7.

Long-Term Health Outcomes of Infantile Spasms Following Prednisolone vs. Adrenocorticotropic Hormone Treatment Characterized Using Phenome-Wide Association Study.

ObjectiveTo determine differences in long-term health and neurological outcomes following infantile spasms (IS) in patients treated with adrenocorticotropic hormone (ACTH) vs. prednisolone/prednisone (PRED).MethodsA retrospective, case-control study of patients with an International Classification of Diseases, Ninth Revision, Clinical Modifications (ICD-9) diagnosis of IS, identified over a 10-year period from a national administrative database, was conducted. IS patients treated with ACTH or PRED were determined and cohorts established by propensity score matching. Outcomes, defined by hospital discharge ICD codes, were followed for each patient for 5 years. Related ICD codes were analyzed jointly as phenotype codes (phecodes). Analysis of phecodes between cohorts was performed including phenome-wide association analysis.ResultsA total of 5,955 IS patients were identified, and analyses were subsequently performed for 493 propensity score matched patients, each in the ACTH and PRED cohorts. Following Bonferroni correction, no phecode was more common in either cohort (p < 0.001). However, assuming an a priori difference, one phecode, abnormal findings on study of brain or nervous system (a category of abnormal neurodiagnostic tests), was more common in the PRED cohort (p <0.05), and was robust to sensitivity analysis. Variability in outcomes was noted between hospitals.SignificanceWe found that long-term outcomes for IS patients following ACTH or PRED treatment were very similar, including for both neurological and non-neurological outcomes. In the PRED-treated cohort there was a higher incidence of abnormal neurodiagnostic tests, assuming an a priori statistical model. Future studies can evaluate whether variability in outcomes between hospitals may be affected by post-treatment differences in care models.

Adrenal glands and diabetes

Adrenal glands and diabetes

The Effectiveness of Synthetic Adrenocorticotropic Hormone (ACTH) Treatment for Pediatric Intractable Epilepsy Other than Infantile Spasms, Case-Series

The Effectiveness of Synthetic Adrenocorticotropic Hormone (ACTH) Treatment for Pediatric Intractable Epilepsy Other than Infantile Spasms, Case-Series

Effects of ACTH and Acute Heat Stress on Oxidative Stress in an Early Environmentally Enriched Broilers

Objective: In this study, the effects of early (≤21. d) environmental enrichment and acute heat stress on oxidative stress were investigated and the ability of broilers to cope with later heat stress and adrenocorticotropic hormone (ACTH) treatments were determined. Material and Methods: Six hundred day-old chicks were randomly assigned to 3 experimental groups as a control (C), environmental enrichment (EE) and environmental enrichment plus heat stress (EE+HS). At 21 d of age, broilers in EE+HS group were exposed to acute heat stress at 38±1 ˚C for 3 h. On the day 42nd, C and EE groups were divided into 2 subgroups as well Control, Control+ACTH, EE, EE+ACTH. While 50 IU ACTH/kg body weight was injected to Control+ACTH and EE+ACTH groups intramuscularly, broilers in C, EE and EE+HS groups were exposed to heat stress and oxidative stress responses of birds were evaluated. Results: Environmental enrichment did not affect blood corticosterone (CORT), malondialdehyde (MDA) and liver superoxide dismutase (SOD) levels of broilers at 21 d of age. ACTH treatment caused a significant decrease in CORT and MDA concentrations in EE broilers compared to the control group. Exposing birds to heat stress (42nd day) significantly increased CORT, MDA and decreased liver SOD levels in control as compared to EE and EE+HS groups. No significant differences were found in the SOD serum levels between groups. ACTH treatment caused more stress reactions than heat stress. Conclusion: The results obtained from this study show that exposure of broilers to acute heat stress or treatment of experimental adrenocorticotropic hormone causes preferable reactions in oxidative metabolism. It was concluded that rearing in an enrichment environment beginning from early ages can be recommended as a useful method for adaptation to stress.