Cyanotic Breath-holding Spells Research Articles

Antioxidant levels in children with cyanotic breath-holding spells

Antioxidant levels in children with cyanotic breath-holding spells

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

ABSTRACT 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

Iron supplementation should be given in breath-holding spells regardless of anemia

Background/aim The purpose of this retrospective study was to determine the effectiveness of oral iron therapy in breath-holding spells and evaluation of electrocardiographical changes.Materials and methods Three hundred twelve children aged 1–48 months and diagnosed with breath-holding spells between January 2017 and April 2018 were included. Patients’ laboratory findings were compared with 100 patients who had one simple febrile seizure.Results Cyanotic breath-holding spells were diagnosed in 85.3% (n = 266) of patients, pallid spells in 5.1% (n = 16), and mixed-type spells in 9.6% (n = 30). Sleep electroencephalograms were applied for all patients, 98.2% (n = 306) of which were normal, while slow background rhythm was determined in 1.2% (n = 4). Epileptic activity was observed in only 2 patients (0.6%). The mean hemoglobin (Hb) value in the breath-holding spell group was 10.1 mg/dL. Patients’ mean corpuscular volume (MCV) was 73 fL. Patients’ Hb and MCV values were statistically significantly lower than those of the control group (P < 0.001). The difference between spell burden was not statistically significant (P = 0.691). Spell burden decreased equally in both groups.Conclusion Oral iron therapy can be administered in breath-holding seizures irrespective of whether or not the patient is anemic.

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.

Novel Findings in Breath-Holding Spells: A Cross-Sectional Study.

The mechanism of breath-holding spells (BHS) is not fully understood and most probably multifactorial; so, this study was designed to clarify the pathophysiology of BHS through assessing some laboratory parameters and electrocardiographic (ECG) changes which might be contributing to the occurrence of the attacks. Another aim of the study was to evaluate the differences in the pathophysiology between pallid and cyanotic types of BHS.This was a prospective study performed in Zagazig University Hospitals. Seventy-six children diagnosed with BHS were included as follows: 32 children with cyanotic BHS, 14 children with pallid BHS, and 30 healthy children as a control group. All children were subjected to the following: full history taking, clinical examination, and laboratory work up in the form of CBC, serum iron, ferritin, and zinc levels. Twenty-four hours ambulatory ECG (Holter) recording was also performed.No significant statistical difference was found between cyanotic and pallid groups regarding family history of BHS, severity, and precipitating factors of the attacks. Frequent runs of respiratory sinus arrhythmia (RSA) during 24 hours ECG were significantly higher in children with BHS; the frequency of RSA was significantly correlated with the frequency (severity) of the attacks. Low serum ferritin was significantly associated with BHS groups but not correlated with the severity of the attacks.Autonomic dysregulation evidenced by frequent RSA is considered to be an important cause of BHS in children and is correlated with the frequency of the attacks. Low serum ferritin is additional factor in the pathophysiology. Both pallid and cyanotic BHS are suggested to be types of the same disease sharing the same pathophysiology.

Bath-induced paroxysmal events - Notes on a case report.

To the Editor I was interested to read the case report of bathing epilepsy published by Stutchfield and Loh [1] and wish to comment on several misleading statements and factual errors. As the authors would know, we have published a comprehensive review of bath-induced events [2]. Since then, three further papers on bathing epilepsy have been published [3], [4], [5], [6] together with a letter [6] confirming that what was originally reported as neonatal-onset bathing epilepsy is in fact alternating hemiplegia of childhood. Stutchfield and Loh [1] begin their Abstract by writing that “Bath-induced events in infants and children can be triggered by various etiologies, including cardiological, neurological, and metabolic causes.” This statement reflects the general message of the paper and its conclusion that “There is a wide differential diagnosis for reduced conscious level triggered by bathing” [1]. This contradicts the findings of our very careful review [2], which found only four conditions triggered by bathing in infants, these being bathing epilepsy — by far the commonest [2], [3], [4], [5], alternating hemiplegia of childhood [6], hyperekplexia, and paroxysmal extreme pain disorder [2]. Stutchfield and Loh [1] stated that reflex anoxic seizures (reflex asystolic syncope), cyanotic breath-holding spells (prolonged expiratory apnea), and cardiac syncope from long QT syndrome might be triggered by bathing in infancy, but to my knowledge, no such reports have been published. With regard to the authors' EEG findings, readers should note that the unit of measurement for the amplitudes of the interictal background activity as well as the “slow build-up of irregular high amplitude (530 mV) delta activity” should be microvolts and not millivolts: indeed, the calibration at the top of Fig. 1. confirms this. Finally, the authors' list of references deserves comment as well. Their reference [1] – De Keyzer et al. – describes a case of bathing epilepsy (bath water was at 37 °C) and not hot water epilepsy, despite its title. Their reference [3] – Fertleman et al. – was not published in JAMA Neurol (the new name for Archives of Neurology) but rather in the journal Neurology. Lastly, their reference [4] – Mikati et al. – was published in Pediatr Neurol and not J Pediatr Neurol. Conflict of interest None.

Treatment of Cyanotic Breath-Holding Spells With Oral Theophylline in a 10-Year-Old Boy

Cyanotic breath-holding spells are generally benign and resolve spontaneously by 4 to 5 years of age. Treatment with iron and other drugs has been employed in selected cases with very frequent and severe episodes. We describe a 10-year-old boy with recent-onset cyanotic breath-holding spells that were activity limiting. He was unable to participate in physical activities with his peers as any argument or emotional upset provoked these spells. Treatment with oral iron and piracetam was ineffective. However, treatment with oral theophylline produced dramatic amelioration of symptoms, and he was once again able to participate in play activities with his peers. We believe that general central nervous system stimulant and respirogenic effects of theophylline were instrumental in control of symptoms in our child.

Diverse Presentation of Breath Holding Spells: Two Case Reports with Literature Review

Breath holding spells are a common and dramatic form of syncope and anoxic seizure in infancy. They are usually triggered by an emotional stimuli or minor trauma. Based on the color change, they are classified into 3 types, cyanotic, pallid, and mixed. Pallid breath holding spells result from exaggerated, vagally-mediated cardiac inhibition, whereas the more common, cyanotic breathholding spells are of more complex pathogenesis which is not completely understood. A detailed and accurate history is the mainstay of diagnosis. An EKG should be strongly considered to rule out long QT syndrome. Spontaneous resolution of breath-holding spells is usually seen, without any adverse developmental and intellectual sequelae. Rare cases of status epilepticus, prolonged asystole, and sudden death have been reported. Reassurance and education is the mainstay of therapy. Occasionally, pharmacologic intervention with iron, piracetam; atropine may be of benefit. Here we present 2 cases, one of each, pallid and cyanotic breath holding spells.

Permanent cardiac pacing in a 2.5 month-old infant with severe cyanotic breath-holding spells and prolonged asystole

We report the case of a 2.5 month-old infant with cyanotic breath-holding spells, loss of consciousness and seizures. Prolonged asystole up to 70 s despite cardiopulmonary resuscitation was documented by 24 hour Holter monitoring. An epicardial pacemaker was implanted followed by no further loss of consciousness and seizures during spells in a six month follow-up period.

Postoperative cyanotic breath-holding spells in a child with Worster–Drought syndrome

We report multiple cyanotic spells in the postoperative period in a child with Worster–Drought syndrome. A male child, 3.5 years old, 12 kg, who had experienced drooling of saliva since birth, was accepted for bilateral submandibular duct translocation and sublingual gland excision. He had delayed milestones (sat at 15 months and walked at 3 years). Difficulty in swallowing resulted in frequent vomiting during feeding and recurrent upper respiratory tract infections (URI). He was fed by his parents and could mainly swallow liquids or semi-solids. He did not require a nasogastric tube or gastrostomy for feeding. There was no history of epigastric pain or discomfort following feeds that would suggest a gastroesophageal reflux disorder. He was unable to protrude his tongue despite there being no tongue-tie. He could not speak despite normal hearing (normal brainstem auditory evoked responses) and communicated with signs. There was no history of seizures. Head noncontrast computerized tomography (NCCT) showed a paucity of periventricular white matter with prominent ventricles, gliotic areas, and bilateral frontoparietal volume loss. Other systems were normal. Before surgery, the patient did not have an URI, and no adventitious sounds were heard on auscultation. In the operating room, after instituting routine monitoring, anesthesia was induced with sevoflurane in oxygen and an IV access was secured. Following the administration of fentanyl and vecuronium, nasotracheal intubation was accomplished using a 4-mm-ID uncuffed endotracheal tube and the oropharynx packed. Paracetamol suppositories (250 ? 170 mg) were inserted rectally. Anesthesia was maintained with oxygen, nitrous oxide, isoflurane, and supplemental doses of fentanyl and vecuronium. The intraoperative period was uneventful, and at the end of surgery, which lasted for 2 h, a nasogastric tube was inserted to facilitate feeding the child after the oral surgery. Neuromuscular blockade was reversed and the trachea extubated once the patient was fully awake and breathing regularly. As he was being shifted out, he sat up and started crying. He held his breath, desaturated, and became cyanosed. Saturation improved on bag-mask ventilation with 100% oxygen. Two similar episodes of desaturation occurred. After the third, a conscious effort was made to avoid any stimulation that could precipitate crying, and he was gently shifted to his mother in the post anesthesia care unit (PACU). On retrospective questioning, the parents admitted that if they force-fed the child, he would have prolonged crying with breath-holding spells; however, there was no history suggestive of cyanosis during these episodes. Worster–Drought syndrome (WDS) is a phenotypically distinct but underdiagnosed form of cerebral palsy first described in 1956 [1]. Patients share features with bilateral congenital perisylvian syndrome, a type of childhood-onset epilepsy [1]. Worster–Drought syndrome is characterized by weakness of the orofacial and bulbar muscles, leading to difficulty in feeding, swallowing, and voluntary lip, tongue, and palate movements. Attempts at feeding can cause choking and A. Chhabra D. K. Baidya Department of Anesthesiology and Intensive Care, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

Cyanotic breath‐holding spells in children respond to adenotonsillectomy for sleep‐disordered breathing

Children with breath-holding (BH) spells may demonstrate sleep-disordered breathing (SDB) during polysomnography. We studied five young children with cyanotic spells retrospectively and found both SDB and a response to adenotonsillectomy. We therefore proceeded with a prospective investigation of treatment for SDB in children with comorbid cyanotic spells. Nineteen children with cyanotic BH spells were identified and enrolled in the prospective study. Parents chose either treatment or observation. Fourteen children underwent complete SDB evaluation and treatment trials while five selected observation only (control group). Sleep and sleep-surgery specialist evaluation and polysomnography revealed the presence of a narrow upper-airway and an abnormal respiratory disturbance index in all 14 children. Nasal CPAP was not successful, but adenotonsillectomy performed near 14 months of age eliminated SDB. BH spells were eliminated 1 month after surgery, while they persisted to the end of the study (24 months of age) in the control group. In conclusion, the presence of cyanotic BH should prompt investigation and polysomnography for possible SDB. Independent treatment of SDB may hasten resolution of BH spells in these cases.

Sudden death in Lesch-Nyhan disease

To increase awareness of sudden and unexpected death in Lesch-Nyhan disease (LND) and to explore its potential causes, we report the anteceding clinical features and laboratory evaluations of five males with LND who ultimately experienced sudden and unexpected death, along with three additional males who suffered serious respiratory events during life. The ages of patients ranged from 2 to 45 years. The cause of sudden death in LND appears to have a respiratory rather than a cardiogenic basis. All cases cannot be linked readily with a single respiratory process. Instead, different respiratory processes appear to operate in different cases. These may include aspiration, laryngospasm, central apnea, cyanotic breath-holding spells, and high cervical spine damage. Better recognition of these processes will help to guide appropriate workup and management that could include chest imaging, endoscopy of the airways, polysomnography, electroencephalogram, and brain and/or spine imaging.

Anoxic-epileptic seizures: observational study of epileptic seizures induced by syncopes

Aims: To describe a large series of children with anoxic-epileptic seizures (AES)—that is, epileptic seizures induced by syncopes. Methods: Retrospective case-note review in a tertiary paediatric neurology unit. For all...

Increased QT dispersion in breath‐holding spells

Breath‐holding spells (BHS) in children can be a frightening and clinically challenging paroxysmal, non‐epileptic childhood disorder. The pathophysiology has been found to incorporate central nervous system dysregulation in addition to an underlying genetic predisposition. Akalin and colleagues found group differences (BHS versus controls) in QT dispersion and QTc dispersion. These differences, however, may have been affected mainly by normal sinus arrhythmia from the predominant cyanotic BHS cohort.Conclusion: The subtle differences measured in the current study between pallid and cyanotic breath‐holder groups, in terms of increased QTc dispersion in the pallid group, may represent an additional factor impacted upon by the resting state of underlying central autonomic dysregulation.

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 cyanotic and pallid breath-holding spells

Prospective study of cyanotic and pallid breath-holding spells

372 Is hyperventilation the reason for seizures during cyanotic breathholding spells?

372 Is hyperventilation the reason for seizures during cyanotic breathholding spells?

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.

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

In this study we sought to investigate parasympathetic activity among children with severe cyanotic breath-holding spells by examining respiratory sinus arrhythmia. The study sample was composed of two groups of patients, 16 subjects with cyanotic breath-holding spells (5 male, 11 female; mean age, 37.5 mo) and 17 controls (8 male, 9 female; mean age, 37.7 mo). 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 (0.096-0.48 Hz) corresponding to a range of respiratory rates from 6 to 30 breaths per minute. Analysis revealed after ANCOVA adjustment for age and gender with subject group and frequency bin as dependent measures, that subjects with cyanotic breath-holding spells had similar variability in their heart rates as did controls (group x frequency bin: F = 0.74, P = 0.71). This study supports the hypothesis that autonomic dysregulation in cyanotic breath-holding spells is not due to a primary disturbance in central parasympathetic control over cardiac rate and rhythm.

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.