The reliability and quality of YouTube videos as a source of breath holding spell.

BACKGROUND: Breath holding spells (BHS) are an important non-epileptic condition that is common in childhood and causes concern to families. YouTube is a powerful social media tool for accessing diseases and information such as BHS in child health. The aim of the study was to measure of the quality and reliability levels of the videos published in English on BHS uploaded on YouTube. METHODS: The key words "infant", "cry", "breath holding spells", holding spells" and "breath spells" were searched on the YouTube on November 14, 2022, in this study. Along with the general features of the videos, their quality and reliability were evaluated according to the global quality score (GQS), mDISCERN score. RESULTS: Fifty-five videos were evaluated. The mDISCERN and GQS scores of the videos in the useful group were higher than those in the misleading group (p < 0.001, p < 0.001). In the useful group, 87.5% of academic institutions and 93.3% of medical doctors (MDs) uploaded high-score GQS videos, while this rate was 16.7% in independent users (p = 0.005). The positive correlation was found between mDISCERN and GQS scores (p < 0.001). CONCLUSION: The majority of YouTube videos on BHS contained useful information with sufficient quality. Professional associations such as universities and academic institutes need to produce better quality videos to provide families/users with more accurate and up-to-date information about BHS. We emphasize that YouTube should analyse videos published in the field of health, especially in the field of pediatrics, such as BHS, with committees consisting of expert health professionals, and publish them after evaluation. YouTube should consider collaborating with professional pediatrics health organizations such as American Academy of Pediatrics (AAP), academic institutes and universities in the field of BHS to produce high-quality videos.

Overuse of EEG and ECG in children with breath-holding spells and its implication for the management of the spells.

AIM: Breath-holding spells (BHS) are common in children, but evidence-based clinical guidelines are lacking. We investigated a large population-based cohort of BHS patients, to propose a refined description of typical BHS and guidelines for its management. METHODS: In a cross-sectional retrospective study, patients diagnosed with BHS in Southern Sweden 2004-2018 were recruited. Disease characteristics and diagnostic data were collected from patient medical records. RESULTS: In total, 519 patients, mean age at diagnosis 19.8 ± 13.8 months with equal gender distribution, were included. In 48.3%, BHS had already been diagnosed after one spell. During spells, 78.0% of patients were unresponsive. For 71.5%, atonic, tonic, tonic-clonic or myoclonic seizures were reported, and 78.0% of patients had a spell lasting less than 1 min. Electroencephalography was conducted in 30.4% and Electrocardiography in 45.1%. Six children (3.8%) had a pathological electroencephalogram, four of which had concomitant epilepsy and only 0.9% of children had electrocardiogram findings suggesting pathology, none showing long QT syndrome. CONCLUSION: Children with BHS were frequently subjected to unnecessary diagnostic interventions. We characterise a typical presentation of BHS and propose a management-algorithm, which is expected to reduce unnecessary usage of electroencephalography and electrocardiography.

Evaluation of the Effectiveness of Risperidone in Treating Breath-Holding Spells in Children.

Objectives: Breath holding spells (BHS) are a type of syncope in children that is commonly seen in the first years of life. Although these attacks do not cause serious damage to the child's brain, in severe or repeated cases, they expose the brain to hypoxia and cause a lot of stress in parents. In these cases, the clinician should consider therapy. The purpose of this study is to investigate the effectiveness of Risperidone in the treatment of BHS in children visiting the neurology clinic of the Children's Medical Center Hospital. Materials & Methods: In this randomized clinical trial, the statistical population included patients with the history of Breath Holding spells grades 2 to 3 (after ruling out of seizure disorders) over one year old, visiting the neurology clinic of Tehran Children's Medical Center in 2019. The subjects were randomly selected from patients visiting the clinic using a table of random numbers from the admit ion list. After providing the necessary explanations and obtaining informed consent from their parents, they were treated with low-dose Risperidone (maximum 1 mg) for three months. The patients were observed for three months in terms of frequency and severity of spells monthly. Results: In this study, the median (25th and 75th percentile) age of subjects was 2.3 (2.0-2.6) years. Both the number and severity of seizures in the subjects had a statistically significant decrease in the period after treatment with Risperidone (P<0.001). The studied boys and girls experienced statistically significant decrease in terms of both the frequency of spells (P-value of 0.002 and 0.039) and intensity of seizures (P=0.016) and P=0.008), respectively after treatment with Risperidone. Also, in the studied children under 2 years old and over 2 years old, both the frequency (P=0.021 and P=0.004) and intensity of spells (P=0.008) 0.016 for subjects under and over 2 years, respectively) had a statistically significant decrease after treatment with risperidone compared to pretreatment. Conclusion: According to the results of this study, it seems that both the frequency and the intensity of spells in children (regardless of gender and age group), experienced a statistically significant decrease after treatment with Risperidone. We suggest conducting a more comprehensive study considering a larger sample size in order to estimate this issue more correctly.

Assessing the Level of Awareness About Breath-Holding Spells Among the General Population in the Makkah Region, Saudi Arabia.

Background and objective Breath-holding spell (BHS) is a serious condition that affects healthy and normal children. It is a paroxysmal non-epileptic disorder and usually occurs after the child gets angry, annoyed, or aroused. In such a scenario, an episode of crying and silent expiration associated with color changes, either cyanosis or pallor, leads to loss of consciousness in the child. In Saudi Arabia, studies assessing the awareness among parents about BHS have been scarce. In light of this, this study aimed to evaluate the awareness of BHS among parents in Makkah, Saudi Arabia, in 2023. Methodology This was a cross-sectional study conducted between June and October 2023 by using Google Forms to collect data about awareness of risk factors of BHS among the general population in Makkah. We employed a validated and self-generated survey that was distributed through social media platforms. Results The study included 602 participants; 138 (22.9%) of them had witnessed BHS episodes. Of note, 407 (67.6%) thought that there was a connection between BHS and iron deficiency anemia. A significant majority (n=565, 93.9%) mentioned that spells can lead to passing out and seizures, and 542 (90%) thought that spells are dangerous. The majority (n=479, 79.6%) reported that the actions required during spells involve laying the child on the floor, keeping the child away from anything sharp, staying with the child, and calling 911 if the child remains blue or is not breathing for longer than a minute. The most common source of information for the participants was the Ministry of Health (n=182, 30.2%). Conclusions This study found a generally low level of awareness among parents regarding several aspects of BHS. Hence, we recommend conducting educational campaigns to ensure parents have accurate information about BHS so that they can respond appropriately to its occurrence in children.

Docosahexaenoic Acid Plus Piracetam Versus Piracetam Alone for Treatment of Breath-Holding Spells in Children: A Randomized Clinical Trial.

BACKGROUND: Piracetam is the most widely used drug in breath-holding spells (BHS); however, its efficacy might not be satisfying to parents. This study aimed to compare the efficacy of docosahexaenoic acid (DHA) plus piracetam with piracetam alone in reducing the frequency and severity of BHS in infants and preschool children. METHODS: This randomized clinical trial included two groups diagnosed with BHS. Group I included 50 patients who received DHA plus piracetam. Group II (control group) included 50 children who were managed with piracetam plus a placebo. Children were re-evaluated at one, three, and six months after treatment. Occurrences of BHS and drug side effects were recorded. The primary outcome was to evaluate the effect of the combined treatment of piracetam and DHA on the frequency and severity of spells. RESULTS: BHS were reported in only 16% of children six months after treatment with piracetam and DHA compared with 50% of those treated with piracetam only (P value = 0.001). CONCLUSION: DHA plus piracetam is more effective than piracetam alone in decreasing the frequency and severity of BHS in children.

Postoperative Breath-Holding Spells Requiring Cardiopulmonary Resuscitation After Cardiopulmonary Bypass.

Breath-holding spells are common in childhood and can be associated with bradycardia and pulselessness. This report details severe breath-holding spells complicating postoperative management after atrial septal defect closure. The patient required cardiopulmonary resuscitation despite the use of a temporary pacemaker to prevent bradycardia. After multiple episodes of chest compressions, the decision was made to not intervene immediately to pulselessness and the patient was able to recover without further intervention.

A case of Bainbridge-Ropers syndrome with breath holding spells and intractable epilepsy: challenges in diagnosis and management.

BACKGROUND: Bainbridge-Ropers syndrome is caused by monoallelic ASXL3 variants on chromosome 18. Clinical features include dysmorphic facies, developmental delay, intellectual disability, autistic traits, hypotonia, failure to thrive, seizures and hyperventilation. Breath-holding spells with choreathetoid movements have been previously described. CASE PRESENTATION: We describe an 11-year old boy who has daily intractable seizures reported since birth, developmental delay, autistic features and feeding difficulties. He was eventually found to have de novo, heterozygous pathogenic variant (c.1612G > T, p.E538*) in the ASXL3 gene. He has frequent episodes of breath-holding accompanied by dystonic posturing with right leg extension and head turning without ictal EEG correlate. The breath-holding spells have been refractory to several medication trials including iron supplementation, acetazolamide, and desipramine. CONCLUSIONS: This case represents a more severe phenotype of Bainbridge-Ropers Syndrome than previously described with refractory breath-holding spells with dystonia, intractable epilepsy, and progressive cerebral/cerebellar atrophy. Breath-holding spells cause significant morbidity, are poorly understood, and have very limited treatment options.

Breath-holding spells after endoscopic third ventriculostomy in a post-ventriculoperitoneal shunted patient.

Breath-holding spells (BHS) are commonly observed in children as a result of an autonomic nervous system disorder triggered by crying, emotional distress, or pain. There are several types of BHS and cyanotic type is one of them. We encountered a case of 3-year-old girl who presented with a delayed adaptation period and BHS 2 weeks after an endoscopic third ventriculostomy (ETV). She experienced severe headache due to increased intracranial pressure (ICP) during the delayed adaptation period, which may have contributed to the onset of BHS. Management of BHS warrants treatment of the symptoms and removal of the causative factors; in our case, intensive pain control and resolution of the increased ICP after the adaptation period were effective. While BHS are usually described as a benign condition that improves spontaneously, we highlighted the importance of recognizing and monitoring atypical symptoms such as BHS in pediatric cases.

Non-Epileptic Paroxysmal Events: Clinical features and diagnostic differences with epileptic seizures. A Single Tertiary Centre Study.

BACKGROUND: Non-Epileptic Paroxysmal Events (NEPE) are common clinical manifestations in pediatric age presenting with dysfunction of motor and behavioral activity mimicking features of epileptic seizures. OBJECTIVE: To present and analyze number and clinical characteristic of a group of children/adolescents presenting with various types of NEPE; to compare clinical data of this group of NEPE affected children/adolescents with a group of children/adolescents affected by Epileptic Seizures (ES). METHODS: The retrospective study was conducted at the Pediatric Clinic of University of Catania, Catania, Italy, in a period ranging from January 2005 and January 2018. Two groups of children/adolescents, aged from 1 month to 15 years, were selected: 312 affected by NEPE and 192 by ES. Number and percentage of the single type of NEPE were reported. Then, demographic characteristics, clinical manifestations, duration of the events, time of diagnosis, and age of onset of each type of NEPE and ES affected children/adolescents were analyzed and compared. Results of statistical analysis of the data were carried out between ES and some type of NEPEs including Sandifer syndrome, breath-holding spells, paroxysmal tremors, vertigo, and syncope. RESULTS: Among the group of NEPE, vertigo, type of paroxysmal event clinically not classifiable, syncope, and Sandifer syndrome were the most common events; In the comparative analyzed samples, variability between NEPE and ES was found in the duration of the paroxysmal events, in number of episodes, in lag-time between the onset of symptoms and the diagnosis, and in age of onset. Analyzing clinical data of ES with some type of NEPE, statistical significant results were obtained in vertigo as regards the duration and average duration event, in paroxysmal tremors as number of events, in Sandifer syndrome as lag-time of diagnosis, and finally in all the types of NEPE as regards the age of onset, and loss of consciousness. CONCLUSIONS: Analyzing the clinical features of each type of NEPE differences with ES are found. However, globally considered diagnostic differences between NEPE and ES remain difficult, questionable, and unrealizable without the support of correct parental report, direct clinical observations, and video-EEG monitoring.

Non-epileptic paroxysmal events in paediatric patients: A single tertiary centre study in Egypt.

PURPOSE: The misdiagnosis of non-epileptic seizures (NES) as epilepsy is one of the most common pitfalls in neuropsychiatric practice. This study aimed to describe the percentage and types of NES among children who were referred for a diagnosis of epilepsy in Upper Egypt. METHODS: We recruited a total of 876 patients who were referred to Sohag University Hospital, a tertiary referral centre in Upper Egypt, for the evaluation of suspected epilepsy. Relevant methods for the diagnosis of epilepsy, including medical history and examination, EEG, video-EEG, laboratory investigations, and brain imaging, were performed for all study participants. RESULTS: Among the 876 patients who were referred for the diagnosis of suspected epilepsy during the period from June 2017 to October 2018, 171 patients (19.5 %) were diagnosed as having NES. In general, we found that NES in the paediatric age groups did not differ from that reported in various studies across several different populations. The most prevalent NES in our study was breath-holding spells (32.2 %), followed by syncope (17.5 %), psychogenic nonepileptic seizures (12.3 %), motor tics (9.9 %), and benign sleep myoclonus (7.6 %). Other less frequent NES included infantile masturbation (7 %), spasmus nutans (5.3 %), migraine (2.9 %), benign paroxysmal torticollis (2.9 %), night terrors (1.8 %), and shuddering attacks (0.6 %). CONCLUSION: Ideally, neurologists should not misdiagnose NES as epilepsy, and whenever the diagnosis of NES is uncertain, an accurate diagnosis should be made using long-term video-EEG monitoring, especially in younger paediatric patients.

Severe pallid breath-holding spells treated with low-dose theophylline.

BACKGROUND: The medical treatment for severe pallid breath-holding spells accompanied with severe bradycardia or transient cardiac arrest is controversial. Although various medications have been reported to be effective, patients treated with pacemaker insertion are not always evaluated for pharmacological therapy beforehand. CASE REPORT: A 9-month-old boy developed pallid breath-holding spells. At 15 months of age, a Holter electrocardiogram revealed 12 s of asystole during a breath-holding spell. Treatment with low-dose theophylline sustained-release dry syrup (5.3 mg/kg/day) led to complete control of the spells. The peak concentration of theophylline was 4.4 µg/mL which was below the therapeutic range for bronchial asthma. When he turned 3 years and 5 months of age, theophylline treatment was discontinued without recurrence of pallid breath-holding spells. DISCUSSION: Theophylline is now infrequently used to treat pediatric bronchial asthma due to its limited effect coupled with its side effects, which include headache, digestive symptoms, and theophylline-associated convulsions. The effectiveness of theophylline as a treatment for pallid breath-holding spells has been reported in several reports. In our case, the theophylline dosage was approximately half the amount described in previous reports. CONCLUSIONS: In this case, low-dose theophylline was adequate in controlling the pallid breath-holding spells. Because theophylline-associated seizures are a major concern, we suggest an evaluation of low-dose theophylline for treating patients with severe pallid breath-holding spells without febrile convulsions or epilepsy before proceeding with permanent pacemaker insertion. Further development of preventive strategies for theophylline-associated seizures and characterization of patients who respond well to theophylline treatment is required.

Clinical features of infants with breath-holding spells and the characteristics of electroencephalogram as well as heart rate during the episode / 中华实用儿科临床杂志

Objective:To analyze the electroencephalogram (EEG) characteristics, heart rate (HR) changes and clinical characteristics during the episode of breath-holding spells(BHS), thus providing refe-rences for the differential diagnosis of infants with BHS.Methods:This was a retrospective single-center analysis involving consecutive 14 infants with HBS admitted in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from November 2016 to December 2019.Results:A total of 16 episodes of crying-induced BHS were detected in the EEG of 14 infants, of which 3 were mild episodes without loss of consciousness and 13 were severe episodes with loss of consciousness.During the mild episodes, EEG presented a phase with slow-slow mode, and the average duration of each phase was (23.3±5.8) s and (16.7±5.8) s, respectively.In addition, the average recovery time from unconsciousness in 13 severe episodes was (16.7±12.3) s. Among the 13 severe episodes, EEG of 12 episodes presented a phase with slow-flat-slow mode, and the average duration of each phase was (26.4±8.5) s, (8.0±5.1) s and (84.6±46.6) s, respectively.Besides, the second slow wave phase usually started by the generalized delta rhythm with predominance in leads of anterior brain, with the average duration at (6.7±1.5) s. During the 16 episodes of BHS, cyanosis occurred in the first phase of slow wav, and loss of consciousness occurred in the flat phase.Transient bradycardia was observed in the second slow wave phase of 7 episodes, the first slow wave phase of 4 episodes and the flat phase of 2 episodes.Conclusions:Typical EEG pattern of in infants with mild BHS is slow-slow mode, and most of them with severe BHS is slow-flat-slow mode.In the first slow wave phase, slow wave always evolves rapidly.The unconsciousness mostly occurs in the flat period, the lasting time of which is closely related to the duration of the flat phase.The generalized delta rhythm with predominance in leads of anterior brain mostly starts in the second slow wave phase.A brief bradycardia often accompanies with the episodes of BHS in infants.

Evaluation of the Efficacy of LevetiracetamPlus Iron in Comparison With Iron Alone in Controlling and Reducing the Frequency of Breath-Holding Spells in Children Aged 6 Months to 5 Years.

OBJECTIVE: A breath-holdingspell (BHS) is defined as an apnea attack following an initial stressful event like anger, sadness, and fear, a painful event like falling or head trauma or any stressful psychology event. This study was designed to assessthe comparative efficacy of levetiracetam plus iron and iron alone in reducingthe BHS frequency in children aged 6 months to 5 years. MATERIALS &METHOD: This study was designed asa double-blinded randomized clinical trial. Sixty patients aged 6 months to 5 years were assigned into two groups, withthe first group (A) receiving onlyiron and the second group (B)receiving levetiracetam plus iron. At the end of the study, the efficacy of therapywas analyzed comparatively in these groups. RESULTS: In this study, the mean number of attacks was 3.94 ± 2.69 before treatment and 1.71 ± 1.99after treatmentin the group A,while it was 6.39 ± 5.7 before treatment and 0.37 ± 1.03after treatment in the group B.The mean number of attacksafter treatment was lower in group B than in group A. In fact, there was a significant difference between the two groups in terms of the number of attacks after treatment (P = 0.003). CONCLUSION: Levetiracetam plus iron is more effective than iron alone in reducing BHSs in children aged 6 months to 5 years.

Evaluation of the effectiveness of valproic acid for treating cyanotic breath holding spells: A Pilot prospective study.

BACKGROUND: Cyanotic breath-holding spells (CBHS) are self-limited conditions among younger children. Frequent spells cause parents' fear and anxiety. Seizures, brain damage and sudden death have been rarely reported with BHS. Some reported spells' frequency reduction with iron or piracetam. We evaluated the effectiveness of valproic acid (VPA) to treat CBHS and predictors of improvement. METHODS: Participants were 90 children with CBHS (≥4/week) (age: 1.6±0.4yrs). They were treated with VPA (5 mg/kg/d). Follow-ups occurred after 3-≥6 months. Autonomic nervous system functions were evaluated. RESULTS: The majority (74.4%) had daily spells and 19% had ≥2 spells/d. Crying or anger provoked spells. Postural hypotension was found in 46.7%. They had normal electroencephalography and QT, QTc interval or QTd or QTcd and heart rate. Compared to controls, postural fall in systolic (>20mmHg) and diastolic (>10mmHg) blood pressures and mean arterial pressure (>10mmHg) were observed in 46.7%, 74.4% and 72.2% and miosis observed with 0.125% pilocarpine in 28.9% (P=0.001). Spells' frequency reduction (P=0.001) occurred within 3 months with VPA. The independent prdictors for spell' frequency reduction were reduction of anger and crying [OR=4.52(95%CI=2.35-6.04), P =0.01]. CONCLUSION: VPA therapy reduces CBHS' frequency. Mood improvement is a suggestive effective mechanism. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT04482764.

Spectrum of Nonepileptic Paroxysmal Events in Children from Southern India.

Background Nonepileptic paroxysmal events (NEPEs) present with episodes similar to epileptic seizures but without abnormal electrical discharge on electroencephalogram (EEG). NEPEs are commonly misdiagnosed as epilepsy. Epilepsy is diagnosed on the basis of a detailed history and examination. Emphasis during history to rule out the possibility of NEPE is important. The wrong diagnosis of epilepsy can lead to physical, psychological, and financial harm to the child and the family. Hence, this study was planned. Objective The objective of the study is to evaluate clinical profile, frequency, and spectrum of NEPE in children. Materials and Methods This is a prospective observational study. Patients with NEPE between January 2014 and August 2016 aged < 18 years were enrolled. NEPEs were diagnosed on the basis of history, home video, and EEG recordings. Patients were divided into different categories according to age, specific type of disorder, and system responsible. Patients were followed for their NEPE frequency and outcome. Results A total of 3,660 children presented with paroxysmal events; of them 8% were diagnosed with NEPE. Patients diagnosed with NEPE were classified into three age groups on the basis of their age of onset of symptom; of the total 285 patients, there were 2 neonates (0.7%), 160 infants (56%), and 123 children and adolescents (43.1%). Fifty-eight percent patients were boys. The most common diagnoses were breath-holding spells 113 (39%), followed by syncope 38 (13.3%) and psychogenic nonepileptic seizures 37 (12.9%). About 9 and 5% of patients had concomitant epilepsy and developmental delay, respectively. Conclusions NEPEs account for 8% of paroxysmal events. Most common NEPEs were breath-holding spells among infants and syncope and "psychogenic nonepileptic seizures" in children and adolescents.

Effectiveness of Iron Therapy on Breath Holding Spells in the Children.

OBJECTIVES: The pathophysiology and mechanism of Breath-Holding Spells (BHS) remain controversial, and the relationship between BHS and anemia has not been clarified, although iron supplementation appears to be effective in many patients. We aimed to assess the probable relation of iron level with initiation of these spells in children. MATERIALS & METHODS: Overall, 42 children with a diagnosis of BHS, aged between 6 months to 2 yr were enrolled during Mar 2015 to Dec 2016 at Rasht 17th Shahrivar Hospital, Rasht, northern Iran. Ferrous sulfate solution prescribed 6 mg/kg/d, 3 times daily, for all of cases, regardless of their iron levels, and the response to the treatment was evaluated. RESULTS: Twenty-five patients were boys (59.52%). The mean age for all patients was 11.71±4.63 months. Positive family history detected in 33.33%; iron deficiency anemia in 21.42%, depletion of iron stores in 52.38%, and normal iron status in 26.19% of cases. Simple spells showed significantly higher mean of Hb in comparison with severe spells (P=0.008); also increased number of spells per month significantly decreased the mean of Hb (P=0.007). Mean frequency of spells was 40.14±47.08 before and 11.14±31.10 after iron therapy, per month (P<0.0001). Overall, 32 patients (76.19%) had complete control of spells, 7 patients (16.66%) partial, 2 cases (4.76%) weak, and 1 child (2.38%) no response after iron therapy. CONCLUSION: Iron deficiency anemia may have an important role in BHS, and treatment of anemia may decrease number of the spells.

Ventricular repolarization changes in children with breath holding spells.

OBJECTIVE: Breath holding spells is a non-epileptic paroxysmal disease which is frequently seen in childhood. In this study, we aimed to investigate electrocardiographic atrial conduction and ventricular repolarization changes in children with breath holding spells. MATERIALS AND METHODS: We reviewed the electrocardiograms of 58 patients with breath holding spells who admitted to SBU Okmeydani SUAM Pediatric Cardiology Clinic between November 2018 and February 2019. QT, QTc (calculated with Bazett formula), T peak-end (Tp-e), QT dispersion (QTd), QTc dispersion (QTcd), Tp-e/QT ratio, Tp-e/QTc ratio, JT interval, JTc (calculated with Bazett formula), Tp-e/JT ratio, Tp-e/JTc ratio and P dispersion (Pd) were measured and compared with the control group of 44 healthy children. RESULTS: In the control and the case groups, mean QTd was 19.86 ms and 38.57 ms, QTcd was 28.34 ms and 58.03 ms, Tp-e/QT ratio was 0.16 and 0.26, Tp-e/QTc ratio was 0.11 and 0.17, JT interval was 204.09 ms and 224.52 ms, JTc value was 290.00 ms and 333.72 ms, Tp-e/JT ratio was 0.23 and 0.35, Tp-e/JTc ratio was 0.16 and 0.24, Pd was 29.32 ms and 40.53 ms respectively. Differences between two groups were statistically significant (p < 0,001). CONCLUSION: QTd, QTcd, Tp-e, Tp-e/QT ratio, Tp-e/QTc ratio, JT, JTc, Tp-e/JT, Tp-e/JTc ratio and Pd were increased significantly compared to healthy children. Based on the results, ventricular repolarization and atrial conduction were affected in patients with breath holding spells. These patients may be under the risk of developing rhythm disorders.

A Chinese pedigree with Brown-Vialetto-Van Laere syndrome due to two novel mutations of SLC52A2 gene: clinical course and response to riboflavin.

BACKGROUND: Brown-Vialetto-Van Laere Syndrome (BVVLS), a rare neurological disorder characterized by motor, sensory, and cranial neuronopathies, is mainly associated with defective riboflavin transporters encoded by SLC52A2 and SLC52A3 genes. Clinical outcomes have been shown to be improved significantly by high-dose riboflavin supplementation. The aim of this study was to identify genetic causes and further evaluate the clinical course and response to riboflavin in a Chinese pedigree with BVVLS. CASE PRESENTATION: We report the novel compound heterozygous variants c.1328G>A p.(Cys443Tyr) and c.1022_1023insC p. (Leu341Profs*103) of SLC52A2 gene in a female proband who presented in our out-patient clinic at the age of one-year-old with progressive mental and motor regression, breath holding, and brain stem dysfunction including facial weakness, hearing loss, dysphagia. Following high-dose riboflavin supplementation, the respiratory insufficiency and mental, motor, and bulbar function improved. However, sensorineural hearing loss was not improved. The missense variant site was highly conserved. Both variants were not found in the population database gnomAD. The two variants were inherited from her mother and father, respectively. Both variants were predicted to be deleterious by Polyphen2, Mutation taster, and SIFT and were classified as likely pathogenic according to the ACMG guideline. CONCLUSIONS: Two novel pathogenic variations of SLC52A2 gene were firstly found from a Chinese pedigree with BVVLS. Clinical outcomes could be improved by early diagnosis and riboflavin supplementation.

Iron deficiency and cyanotic breath-holding spells: The effectiveness of iron therapy.

Aim: Frequent cyanotic breath holding spells cause fear and severe anxiety to parents. This study aimed to evaluate clinical, laboratory and treatment characteristics of children with cyanotic breath holding spells. Methods: Included were 180 children (mean age: 1.82 ± 0.53 years) with cyanotic breath holding spells. They were divided into three groups: with iron deficiency, with iron deficiency anemia and without iron deficiency. Blood hemoglobin (HB), ferritin and iron concentrations were measured at baseline and after 3 and 6 months of iron treatment. Results: The mean spell frequency was 24.57 ± 7.31/months, 83% had spells after the age of 1 year, 37% had daily spells, 16% had family history of spells, and 61% had Iron deficiency/Iron deficiency anemia (p = .001). No significant difference in the frequency of spells between children with iron deficiency and those with Iron deficiency anemia. Compared to patients without iron deficiency, there was significant reduction of spells frequency, increased hemoglobin, ferritin and iron levels after 3 and 6 months of iron therapy (p = .0001). Negative correlations were observed between spell frequency with hemoglobin (p = .001), ferritin (p = .0001) and iron (p = .001) levels. Conclusion: Not only Iron deficiency anemia but also iron deficiency alone without anemia is associated with a risk of high-frequency cyanotic breath holding spells. Iron therapy results in reduction in spells' frequency which was correlated with increasing ferritin and iron levels.

Efficacy of treatment with belladonna in children with severe pallid breath-holding spells.

IntroductionPallid breath-holding spells are common and dramatic forms of recurrent syncope in infancy. They are very stressful despite their harmless nature and sometimes require treatment. OBJECTIVE: The objective of this study was to evaluate the efficacy of belladonna in severe breath-holding spells. METHODS: This is a multicentric, retrospective series involving 84 children with severe pallid breath-holding spells. Inclusion criteria were >1 pallid breath-holding spell with loss of consciousness, paediatric cardiology evaluation, and follow-up >6 months. In total, 45 patients received belladonna and 39 patients did not receive treatment, according to physician preference. RESULTS: Mean age was 11 months, ranging from 4 to 18 months, with 54% of males. Mean spell duration was 30 seconds (interquartile range 15, 60), and the frequency was four episodes per month (interquartile range 0.5, 6.5). Comparison of baseline characteristics between groups showed similar demographics, with the single difference in the severity of the spells, being more severe in the treated group. When comparing the treated and non-treated groups at 3 months, only two (5%) patients had a complete remission in the first group, whereas 20 (44%) had remission in the belladonna group (p<0.01). When considering the characteristics of the spells before and after the initiation of treatment with belladonna, 75% of the patients presented a positive response, with 44% of the patients presenting with complete resolution of the spells (p<0.01). No major adverse reaction was reported, with only 5% minor adverse events. CONCLUSIONS: Belladonna is highly effective to alleviate severe breath-holding spells in young children, without any major adverse effects.