Valproic Acid in Treating Cyanotic Breath Holding Spells

Study Overview
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Brief Summary
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Breath holding spells (BHS) are common non-epileptic paroxysmal behavioral involuntary episodes occurring in up to 5.9% of healthy children. The attacks occur in early childhood (0.5-3 years) but are self-limited by school age (4-5 years old) (90%). Classically, BHS were classified as cyanotic (blue), pallid (pale) and mixed based on the color change of the child during the spell. In general, cyanotic spells have been classically described in a toddler with excessive temper tantrums [stubborn, easily frustration or annoyed. The mechanisms of BHS are controversial. The most suggested cause of BHS is instability of the autonomic nervous system, inhibition of respiratory effort and cyanosis in cyanotic BHS and bradycardia or a brief asystole and cerebral hypoperfusion in pallid BHS. Iron deficiency anemia (IDA) has been widely regarded as a risk factor for BHS in nearly 50% of children due to reduced brain oxygenation [4]. It is generally agreed that the long-term prognosis is considered good [1]. There is no definite therapy for BHS. In children with low frequency spells, parental reassurance are just enough; however, high frequency spells may result in anxiety to the parents or fear from sudden death of the child or development of mental subnormality. Treatment of iron has been reported to result in reduction of the frequency of spells or its stoppage. Some reported improvement of BHS with piracetam [a nootropic drug known to increase brain oxygenation]. We did not find systematized published reports evaluating the effectiveness of antiepileptic drugs (AEDs) in reduction of spells frequency of cyanotic BHS or their stoppage.

Official Title
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The Effectiveness of Valproic Acid in Treating Frequent Cyanotic Breath Holding Spells

Conditions
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Breathhold

Intervention / Treatment
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* Drug: Valproic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Children with high frequency spells (≥ 4/week) of CBHS. Children with parents who were wishing to provide treatment to their children. Failure of alternatives modalities of treatment (e.g. iron supplements, piracetam, non-specific vitamins, etc) (tried for ≥ 3 months) to reduce the frequency of spells or stop them. Follow-up for 6 months after starting treatment with valproic acid. Exclusion criteria: Primary neurologic disease, history of epilepsy or febrile convulsions, abnormal neurological examination and abnormal EEG. Primary cardiac disease or presence of long QT syndrome in the ECG. Presence of a hematologic (other than IDA) or other medical disease, electrolyte disturbance, hypoglycemia, hypocalcemia, impaired kidney or liver function tests. Those with a doubtful diagnosis.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: cyanotic breath holding spells<br>drug, valproic acid: 5mg/kg/d for 6 months | Drug: Valproic Acid<br>* Treatment of children with frequent cyanotic breath holding spells (at least 4 spells per week) with 5 mg/kg/day for 6 months.<br>* Other names: sodium valproate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency of spells after starting treatment with valproic acid | The parents or legal guardians are the sources of information about the frequency of spells. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breath holding spells, cyanosis, valproic acid