Severe Breath-holding Spells Research Articles

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.

The Comparison of Levetiracetam and Piracetam Effectiveness on Breath-Holding Spells in Children: A Randomized Controlled Clinical Trial.

Background:We aimed to compare the effectiveness of Levetiracetam and Piracetam on the severity and frequency of spells in children with severe breath-holding spells (BHS), i.e. bening, paroxysmal, and nonepileptic events that are common in early childhood.Materials and Methods:This study is a randomized controlled clinical trial in 71 children from 6 months to 6 years of age with BHS. They were randomly assigned to the two study groups (Levetiracetam and Piracetam group). The frequency and severity of BHS and the response to treatment were recorded on monthly visits during our 3 months follow-up.Results:There was a significant decline in the average number of frequency of spells before and after 3 months of treatment in each group in this study. Levetiracetam had significant effects on the average incidence of the loss of consciousness and seizure-like movements in our study, while Piracetam had no significant effect on the loss of consciousness. Our result showed better response in the Levetiracetam group (88.9% partial or complete response after treatment) compared with the Piracetam group (77.1% partial or complete response after treatment); however, it was not significant. It seems that Levetiracetam had better effect than Piracetam in some aspects in the treatment of BHS.Conclusions:Both Piracetam and Levetiracetam are safe and had significant effects on the frequency of BHS in our study, however, levetiracetam showed superior effects on the severity of BHS.

Therapeutic Effects of Single and Divided Doses of Piracetam for Children with Severe Breath Holding Spells

Objectives: Breath-holding spells (BHS) are common in infancy and childhood. The severe episodes are frightening events for the families. The aim of this study was to evaluate therapeutic effects of piracetam in single daily dose and twice-daily dose of 40 mg/kg/day for treatment of severe spells. Methods: In this prospective clinical trial, 50 children with severe BHS referred to our outpatient university clinics of pediatric neurology and were randomized to single-dose and divided-dose groups. The single-dose group received a single daily dose of 40 mg/kg/day piracetam in the morning, and the divided-dose group received 20 mg/kg/dose of piracetam twice daily. Patients were followed for four months. The number of severe attacks/month before and after treatments were recorded. Results: In the single-dose group, 14 cases (60.9%) showed complete recovery, and nine (39.1%) showed relative recovery. In the divided dose group, eight patients (33.3%) showed complete recovery, 11 (45.8%) showed relative recovery, and five cases (20.8%) showed no recovery. This difference was statistically significant at P = 0.03. Conclusions: Our study showed that once-daily administration of piracetam could be more effective than twice-daily dose in the management of severe spells.

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

The objective of this study was to evaluate the efficacy of belladonna in severe breath-holding spells. 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. 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. Belladonna is highly effective to alleviate severe breath-holding spells in young children, without any major adverse effects.

Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children.

Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results. We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P < .001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P = .001; motor, P = .006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P < .05). These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.

Pacemaker in complicated and refractory breath-holding spells: When to think about it?

Breath-holding spells (BHS) are benign non-epileptic paroxysmal events of infancy, rarely occurring with high frequency and complicated by prolonged syncope, convulsions and even status epilepticus. In these cases response to medical treatment is often unsatisfactory. Pacemaker implantation is a possible therapeutic option, but its indications, efficacy and complications have not been clarified yet. To report a new case of BHS treated with pacemaker and to review its indications and efficacy in patients with severe BHS. We extensively searched the literature in PubMed on cardiac pacing in patients with BHS and we described a new case. A previously healthy boy presented at the age of 4 months with frequent BHS inconstantly associated to prolonged syncope and post-anoxic non-epileptic and epileptic seizures. Parental reassurance, iron supplementation and piracetam were ineffective. After cardiac pacing at the age of 16 months, BHS and their complications disappeared. We identified 47 patients with BHS treated with pacemaker in the literature. Based on the available data, in all patients asystole or marked bradycardia were documented during BHS or stimulating maneuvers; syncope complicated BHS in 100% of cases and post-anoxic convulsions in 78.3%. Medical treatment before pacing, when administered, was ineffective or poorly tolerated. After pacing, BHS complications disappeared in 86.4% of cases, and decreased in 13.6%. Technical problems with the device were reported in 25.7% of patients and mild medical complications in 11.4%. Pacemaker could be reasonably considered in subjects with frequent and severe BHS, poor response to medications, and demonstration of cardioinhibition during spells.

Successful Treatment of Pallid Breath-holding Spells With Fluoxetine

Objective: To promote dialogue among readers and between readers and editors, we offer here brief reports and observations on topics of interest authored by members of the AAP Grand Rounds editorial team.At the severe end of the clinical spectrum, pallid breath-holding (PBH) spells can be disruptive and debilitating to the patients and families of those who are afflicted. Effective treatment options are few and include medications,1 pacemaker implantation,2 and tincture of time.3In their recent publication, Walsh and colleagues4 seek to add to our clinical armamentarium for the medical treatment of PBH spells using fluoxetine. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has been shown to be beneficial in the treatment of neurocardiogenic syncope in older children and adults.5 Hypothesizing that PBH spells are physiologically similar to vasovagal syncope, these investigators performed a retrospective review and attempted a prospective follow-up on all patients referred to their institution for severe PBH spells treated with fluoxetine after failing “medical management.” All patients had been screened for conditions associated with cardiac syncope and sudden cardiac death. Each had documented severe bradycardia or asystole during PBH episodes.The study included 6 (out of 7) patients, age 4 to 24 months, identified by retrospective chart review who were available for prospective follow-up. Four patients had failed alternative medications (propranolol, carbamazepine, and/or glycopyrrolate) prior to initiating fluoxetine. Fluoxetine treatment was maintained for 1 to 2 years and was associated with improved symptoms based on medical records review and parental report in 5 of 6 patients (3 complete resolution, 2 partial resolution). No serious adverse events from fluoxetine therapy occurred. Side effects included decreased appetite and tremors, both of which improved over time on therapy. The authors conclude that fluoxetine is a safe and effective first-line agent for the treatment of PBH spells.Though encouraging and thought-provoking, their study by its design provides little hard evidence upon which to base a treatment recommendation. Outcome measures were subjective and the treatment was uncontrolled and unblinded. Though apparently benign in the small cohort of patients treated in this study, there is no large clinical experience with the use of SSRIs in children of the age typically affected by PBH spells. As a result, the safety of these medications cannot be readily extrapolated from this small cohort. Nonetheless, when faced with pacemaker implantation as the only other valid treatment option, the notion of prescribing treatment with fluoxetine is appealing.It is often the case that pediatric diseases are too rare and varied in nature to lend themselves well to study by randomized controlled trials. However, the prevalence of severe breath-holding spells (those associated with loss of consciousness with or without convulsions) has been estimated as high as 4.6%6 and simple breath-holding spells have a prevalence as high as 27%.7 Walsh and colleagues have recommended fluoxetine be used as first-line therapy for severe PBH spells based on preliminary evidence. It is incumbent upon those of us who care for these patients to subject fluoxetine to a proper controlled trial before heeding that advice without careful consideration.

Effects of piracetam on pediatric breath holding spells: a randomized double blind controlled trial.

Breath holding spells (BHS) are common paroxysmal non-epileptic events in the pediatric population which are very stressfull despite their harmless nature. There has been no specific treatment found for the spells yet. The aim of this study was to evaluate the efficacy of piracetam (2-oxo-l-pyrrolidine) on these children. In this randomized double blind clinical trial study, 150 children with severe BHS referred to our pediatric outpatient service were enrolled from August 2011 to July 2012. The patients were randomized into two equal groups. One received 40mg/kg/day piracetam and the other group received placebo, twice daily. Patients were followed monthly for three months. The number of attacks/month before and after treatment were documented. Of the enrolled patients, 86 were boys. The mean age of the patients was 17 months (range, 6 to 24 months). In the piracetam group, 1 month after treatment an 81% response to treatment was found. In the placebo group, none of the patients had complete remission and 7% of the cases had partial remission. Overall, control of breath-holding spells was observed in 91% of the patients in the group taking piracetam as compared with 16% in the group taking placebo at the end of the study. There was no significant difference detected between the groups regarding the prevalence of drug side effects. A significant difference was detected between piracetam and placebo in prevention and controlling BHS. Piracetam (40mg/kg/day) had a good effect on our patients.

Piracetam in Severe Breath Holding Spells

Breath holding spells (BHS) are apparently frightening events occurring in otherwise healthy children. Generally, no medical treatment is recommended and parental reassurance is believed to be enough, however, severe BHS can be very stressful for the parents and a pharmacological agent may be desired in some of these children. In this prospective study aim was to determine the usefulness of piracetam as prophylactic treatment for severe BHS. Children were recruited from Neurology Clinic in Children's Hospital, Islamabad between January 2002 to December 2004. Diagnosis of BHS was based on characteristic history and normal physical examination. Piracetam was prescribed to those children who were diagnosed as severe BHS in a dose ranging from 50-100 mg/kg/day. Iron supplements were added if hemoglobin was less than 10 gm%. Patients were seen at 2-4 weeks interval and follow-up was continued until 3 months after the cessation of drug therapy. Fifty-two children were enrolled in the study, 34 boys and 18 girls. Ages ranged from 4 weeks to 5 years with mean age of 17 months. In 81% of children, spells disappeared completely and in 9% frequency was reduced to less than one per month and of much lesser intensity. Prophylaxis was given for 3-6 months (mean 5) duration. Piracetam is an effective prophylactic treatment for severe BHS.

Changes of Autonomic Nervous System Function in Patients With Breath-Holding Spells Treated With Iron

To evaluate the autonomic nervous system of patients with breath-holding spells after iron treatment, we attempted to determine whether a dysregulation of the autonomic nervous system reflexes exists in children with severe cyanotic breathholding spells. An electrocardiogram for each subject was recorded for 24 hours in the subject's home and parasympathetic activity was investigated by the fast Fourier transform method. Hematologic data and clinical symptoms of all three patients treated with iron improved and attacks of severe breath-holding spells disappeared. After iron treatment was started, the heart rate variability increased during sleep. It appears that supplementation of iron is effective in improving the dysregulation of autonomic nervous system reflexes.

Prospective Study of Breath-Holding Spells

The natural history of severe breath-holding spells (BHS) was studied prospectively in 95 children (48 boys, 47 girls) referred for neurologic consultation at Children’s Medical Center, Hartford, CT.

Prospective study of children with cyanotic and pallid breath-holding spells.

In this investigation, we sought to prospectively document the natural history of severe breath-holding spells (BHS) among children with both cyanotic and pallid BHS who were referred for neurologic consultation. Prospective cohort study. A structured interview was undertaken at the time of initial consultation and at subsequent 1-year intervals regarding type of BHS, frequency of spells, associated phenomenon, sequelae, family history, and age at termination of spells. A total of 95 children (48 boys, 47 girls) with BHS were identified and followed over a 9-year interval. There were no significant differences between genders. Median onset age was between 6 and 12 months old with 15% presenting younger than 6 months. A median frequency of spells was weekly with 30% experiencing 1 or more spells per day. The median age at peak frequency was between 12 and 18 months old with a range extending from 6 months to 4 years of age. Of the patients whose BHS had remitted for >12 months' time (n = 67), the last spell occurred at a median age of 37 to 42 months. Of those children whose BHS were still occurring, the oldest age at time of latest spell was at 7 years old. Hypoxic convulsions were associated with BHS in </=15% of all participants. A positive family history of BHS was identified in 34% of all families with equal frequency distributed between paternal and maternal sides. In this study, new data concerning the natural history of BHS have been determined. The information is important for family counseling and identifying intervention strategies, and serves as baseline data to evaluate the efficacy of future treatment approaches.

Respiratory sinus arrhythmia in children with severe cyanotic and pallid breath-holding spells.

In this study we investigated centrally mediated parasympathetic regulation of modulated cardiac vagal tone among children with severe cyanotic and pallid breath-holding spells by examining respiratory sinus arrhythmia. Respiratory sinus arrhythmia was evaluated in 41 children; 17 subjects with cyanotic breath-holding spells (6 boys, 11 girls; mean age 37.1 months), 7 subjects with pallid breath-holding spells (2 boys, 5 girls; mean age 33.0 months), and 17 controls (8 boys, 9 girls; mean age 41.2 months). Subjects had recurrent (more than 3) severe breath-holding spells. Each subject's electrocardiogram was recorded in a quiet room and digitized by an 80386 personal computer during five 1-minute periods. R-R intervals within each 1-minute period were converted to heart rate in 120 successive 0.5-second intervals. The resultant heart rate time series was converted to its underlying frequency composition by a fast Fourier transform and averaged across minutes. Respiratory sinus arrhythmia was defined as the variability in the time series over a frequency range (0.096 Hz to 0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. ANCOVA adjusting for age and sex was conducted with the subject group as the independent measure. There were no significant differences between subjects with cyanotic breath-holding spells and controls. Pallid breath-holding spell subjects had a marked difference in respiratory sinus arrhythmia from either controls or subjects with cyanotic breath-holding spells, demonstrating less variability in respiratory sinus arrhythmia (P < .042) This study supports the hypothesis that there exists autonomic dysregulation in pallid breath-holding spells, caused by a primary central parasympathetic disturbance distinct from the dysregulation found in cyanotic breath-holding spells.

Family pedigree analysis of children with severe breath-holding spells

We examined family pedigrees of children with severe breath-holding spells (SBHS). There were 57 probands (27 males, 30 females; 44 cyanotic, 13 pallid) whose families comprised 1683 individuals. We found that 31 (27%) of 114 proband parents and 9 (21%) of 43 proband siblings had current or prior SBHS. Father-to-son transmission was observed in 7 instances. There were 7 families with 2 or more affected siblings and 5 families with 3 or more affected members. From 85 nuclear families, 130 individuals had current or prior SBHS (59 males, 71 females; male/female ratio, 1:1.2). These data suggest that the most likely underlying genetic inheritance pattern in SBHS is an autosomal dominant trait with reduced penetrance. (J Pediatr 1997;130:647-51)

Autonomic nervous system function in severe breath-holding spells

This study attempted to determine noninvasively whether a dysregulation of autonomic nervous system reflexes exists in children with severe cyanotic breath-holding spells (BHS). This was a cross-sectional study performed in the neurophysiology laboratory at a tertiary care hospital. Patients, 18 months of age and older taken from a referral population of children with severe cyanotic BHS and normal controls, were studied. Fourteen children with cyanotic BHS and 12 controls were evaluated. Several noninvasive measures of parasympathetic and sympathetic reflex functions were assessed and statistically analyzed using analysis of variance and covariance, and Fisher's exact tests. The cyanotic BHS group had a significantly greater increase in pulse rate at 15 s of standing after rising from the supine position ( P<.06), with a trend toward a concomitant higher mean arterial pressure ( P<.09). After adjusting for age, sex, and mean supine systolic and diastolic blood pressures, breath-holders had a greater decrease in diastolic blood pressure ( P<.02) without an increase in systolic blood pressure after standing from the supine position. Breath-holders also had significantly abnormal 30:15 R-R interval ratios compared with controls ( P<.002). These results support the hypothesis that children with cyanotic BHS have underlying autonomic nervous system dysregulation. This dysregulation may contribute to the pathophysiology of severe BHS in these children.

Behavior profile of children with severe breath-holding spells

Thirty-two children with severe breath-holding spells and 42 control children were studied by using the Child Behavior Checklist. No single behavioral profile could identify children with breath-holding spells, and there were no group differences with respect to individual behavior categories, broad-band profiles, or total scores. No correlation was found between frequency of breath-holding spells and profile scores.

Breathholding spells in children. Differentiation from epileptic attacks

Severe breathholding spells in children follow a more or less constant clinical pattern, and the electroencephalogram is almost always normal. The spells generally appear during the first two years of life, but rarely before 6 months of age. They usually disappear spontaneously after 4 years of age and rarely recur after age 6 years. Breathholding episodes are observed almost exclusively in children with normal intelligence and do not cause demonstrable evidence of brain damage. However, they are frequently associated with or followed by behavioral disturbances. The familial incidence is high. Breathholding attacks are essentially innocuous and the general outlook is excellent. The associated unconsciousness and convulsions are very short and benign, and require no immediate care. The administration of antiepileptic or tranquilizing drugs or both is of no value. Treatment consists primarily of parent-child guidance and reassurance.

Breathholding Spells in Children Differentiation From Epileptic Attacks

Severe breathholding spells in children follow a more or less constant clinical pattern, and the electroencephalogram is almost always normal. The spells generally appear during the first two years of life, but rarely before 6 months of age. They usually disappear spontaneously after 4 years of age and rarely recur after age 6 years. Breathholding episodes are observed almost exclusively in children with normal intelligence and do not cause demonstrable evidence of brain damage. However, they are frequently associated with or followed by behavioral disturbances. The familial incidence is high. Breathholding attacks are essentially innocuous and the general outlook is excellent. The associated unconsciousness and convulsions are very short and benign, and require no immediate care. The administration of antiepileptic or tranquilizing drugs or both is of no value. Treatment consists primarily of parent-child guidance and reassurance.