Valproic Acid in Treating Cyanotic Breath Holding Spells

Assiut University

Status and phase: Completed; Phase 1

Conditions: Breathhold

Treatments: Drug: Valproic Acid

Study type: Interventional

Funder types: Other

Identifiers

NCT04482764

BHS-VPA-SH-2017

Details and patient eligibility

About

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.

Enrollment: 150 patients

Sex: All

Ages: 6 months to 5 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

1. Children with high frequency spells (≥ 4/week) of CBHS.
2. Children with parents who were wishing to provide treatment to their children.
3. 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.
4. Follow-up for 6 months after starting treatment with valproic acid.

Exclusion criteria:

1. Primary neurologic disease, history of epilepsy or febrile convulsions, abnormal neurological examination and abnormal EEG.
2. Primary cardiac disease or presence of long QT syndrome in the ECG.
3. Presence of a hematologic (other than IDA) or other medical disease, electrolyte disturbance, hypoglycemia, hypocalcemia, impaired kidney or liver function tests.
4. Those with a doubtful diagnosis.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 1 patient group

cyanotic breath holding spells

Other group

Description:

drug, valproic acid: 5mg/kg/d for 6 months

Treatment:

Drug: Valproic Acid