Oxygen Therapy: An Acute Treatment for Paroxysmal Dystonia in Alternating Hemiplegia of Childhood?

Alternating hemiplegia of childhood (AHC) is an early-onset neurodevelopmental disorder caused by pathogenic variants of ATP1A3, which encodes for a subunit of a neuronal Na+/K+ ATPase.1 Patients present various forms of paroxysmal manifestations associated with nonparoxysmal motor disorder and intellectual disability.2 Dystonic attacks are often the most disabling manifestation, and their pharmacological treatment is very disappointing. We report the case of a 25-year-old man with typical AHC attributed to a p.Glu815Lys variant in ATP1A3. He had an early psychomotor retardation. The hemiplegic episodes began at 3 months, and by 18 months he began having dystonic attacks. With aging, the dystonic attacks have become the predominant type of paroxysmal event. The dystonic attacks usually involve one or two limbs on the same side and occasionally progress toward generalized dystonia. They result in considerable pain and fatigue, with major consequences on daily activities. The patient has an intellectual disability, epilepsy, psychotic symptoms, and insomnia. His treatment comprises flunarizine, valproate, prazosin, bisoprolol, and fluoxetine. During the past 18 months, he has been experiencing up to eight dystonic attacks in a single day, which could last from 30 minutes to several hours, with an average duration of 1 hour. Acute treatment consists of a 10-mg dose of midazolam, with a maximum of two doses per day, and he used an average of 40 doses per month. Midazolam usually stops the episodes because it makes him fall asleep, but they often resume within 30 minutes after waking up. One year ago, he incidentally received a single administration of an equimolar mix of nitrous oxide/oxygen (O2) for 5 minutes during a dystonic attack, which resolved rapidly. Based on this observation, we decided to introduce high-flow oxygen inhalation (100% O2 at a flow rate of 12 L/min) as an acute treatment for the patient's dystonic events. O2 is administered as soon as the dystonic attack begins and for a duration of 15 minutes. Most attacks stop within 15 minutes after the beginning of the O2 administration. We have not changed the recommendation regarding the use of midazolam, but midazolam consumption has decreased from 40 doses per month on average to four after the introduction of O2. Oxygen therapy has not changed the frequency of the dystonic attacks, but it has led to a significant improvement in the quality of life by shortening the duration of the attacks and reducing midazolam consumption. Cortical spreading depression (CSD) may be an important mechanism for paroxysmal movement disorders in ATP1A3-related AHC3 and in ATP1A2-related hemiplegic migraine.4 CSD is associated with tissue hypoxia, and increasing O2 availability can shorten its duration.5 Therefore, high-flow oxygen inhalation could be expected to reduce the duration of paroxysmal events in AHC. We suggest that high-flow oxygen inhalation may be considered to treat dystonic attacks in AHC given the (1) safety of oxygen therapy, (2) rationale behind this therapeutical approach, (3) negative impact of dystonic attacks on quality of life, and (4) absence of an alternative pharmacological solution. The parents of the patient and the patient have given written consent for the publication. The authors declare no conflict of interest related to this research. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. Q.W.: 1C, 2A, 2B D.G.: 1C, 2B A.R.: 1C, 2B M.T.P.: 1C, 2B E.P.: 1C, 2B E.R.: 1A, 1B, 1C, 2A, 2B Q.W., D.G., and M.T.P. have no disclosure to declare. A.R. received honorarium for a speech from PTC Therapeutics. E.P. received honoraria for a speech from EISAI and for participating in an advisory board for StrideBio. She also received research support from the Association Française de l'Hémiplégie Alternante and from Fundacio La Marato de TV3 (Spain). E.R. received honoraria for speeches from Orkyn, Aguettant, and Elivie and for participating in an advisory board for Merz-Pharma. He received research support from Merz-Pharma, Orkyn, Aguettant, Elivie, Ipsen, Everpharma, Enjoysharing, Fondation Desmarest, AMADYS, ADCY5.org, Fonds de dotation Patrick Brou de Laurière, Agence Nationale de la Recherche, Societé Française de Médecine Esthétique, and the Dystonia Medical Research Foundation. Data sharing is not applicable to this article as no new data were created or analyzed in this study.