Promising new treatment for rare childhood disease

Cortical neurons. Credit: National Center for the Development of Translational Sciences, NIH.

Alternating hemiplegia is a debilitating neurodevelopmental disorder that is associated with a mutation in the ATP1A3 gene. This condition affects children at an early age and has a serious impact on their quality of life. During episodes of paralysis, which can last from a few minutes to several days, one or more sides of the body may become paralyzed. In addition, patients may experience repetitive muscle contractions, known as dystonia, which can last for hours and cause severe pain.

Currently, the treatment of this condition is focused on the use of sedatives, since the symptoms tend to subside during sleep. Avoidance of precipitating factors such as stress or exercise may help reduce the incidence of hemiplegic and dystonic episodes.

“We don’t know how to help these patients. Therefore, we remain especially attentive to the sometimes unexpected factors that can alleviate them,” explains Emmanuel Flament-Rose, neurologist and expert on abnormal movements. “Recently, a 25-year-old man told us that after being injected with laughing gas during an episode of dystonia, his symptoms disappeared within minutes. We tried to determine the cause, knowing that this gas – nitrous oxide – is usually injected with 50% oxygen. Since it is not possible to give nitrous oxide daily, we wanted to test whether oxygen was responsible for stopping the attack.”

The researchers then installed an oxygen therapy device in the patient’s home. “We observed that the dystonic attacks stopped 15 minutes after the introduction of oxygen,” says the researcher. This is a significant advantage as this young man may have experienced up to 8 episodes per day, some of which may have lasted several hours. His quality of life has improved. Oxygen therapy is a safe and affordable treatment that can significantly reduce the use of potent sedatives such as midazolam, which the patient was taking at a rate of 40 doses per month.”

Team member Quentin Velniartz proposed a hypothesis to explain the effects of oxygen. According to him, a phenomenon called cortical spreading depression (CSD), which corresponds to a wave of electrical disturbances in the brain, plays a significant role in causing the symptoms of alternating hemiplegia. This wave consists of a fast phase of neuronal hyperactivity and a slower phase of electrical silence in cortical cells. It is also associated with hypoxia, i.e. reduced oxygen availability. Thus, the rapid administration of oxygen during attacks can interrupt or mitigate this phenomenon.

To ensure that the association between oxygen delivery and mitigation of dystonic attacks is not coincidental, investigators should verify that the same effect is observed in other patients under comparable conditions. Similarly, it remains to be seen how to optimize the use of oxygen therapy, especially at home, so that it is as unrestrictive as possible.

Reference: “Oxygen therapy: emergency treatment of paroxysmal dystonia in children with alternating hemiplegia?” Quentin Velniartz, PhD, Domitil Gras, MD, Agatha Ruberty, MD, PhD, Maria T. Papadopoulou, MD, Eleni Panagiotakaki, MD, PhD. and Emmanuel Rose, MD, 16 February 2023, Movement Disorders.
DOI: 10.1002/mds.29357