Cortical neurons. Credit: National Center for Advancing Translational Sciences, NIH.
Alternating Hemiplegia is a debilitating neurodevelopmental disorder that stems from a mutation in the ATP1A3 gene. This condition affects children at an early age and has a major impact on their quality of life. During episodes of paralysis, which can range from a few minutes to several days, one or alternating sides of the body may become paralyzed. Additionally, patients may experience repetitive muscle contractions, known as dystonia, which can last for hours and cause significant pain.
Currently, the management of the condition focuses on the use of sedatives, as symptoms tend to subside during sleep. Avoiding triggers, such as stress or physical exertion, may help to reduce the frequency of hemiplegic and dystonic episodes.
“We don’t know how to help these patients. Therefore, we remain particularly attentive to the sometimes-unexpected factors that could relieve them,” explains Emmanuel Flamand-Roze, neurologist and expert in abnormal movements. “Recently, a 25-year-old man told us that after receiving laughing gas during an episode of dystonia, his symptoms subsided within minutes. We tried to identify the reason, knowing that this gas – nitrous oxide – is usually administered with 50% oxygen. As it is impossible to give nitrous oxide in daily treatment, 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 dystonic attacks stopped 15 minutes after the oxygen was administered,” says the researcher. This is a significant benefit, as this young man could experience up to 8 episodes a day, some of which could last several hours. His quality of life was improved. Oxygen therapy is a safe, highly accessible 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 Welniarz proposed a hypothesis to explain the effect of oxygen. According to him, a phenomenon called cortical spreading depression (CSD), which corresponds to a wave of electrical disturbance in the brain, plays an essential role in triggering the symptoms of alternating hemiplegia. This wave consists of a rapid phase of neuronal hyperactivity and a slower phase of electrical silence in the cortex cells. It’s also associated with hypoxia – i.e., reduced oxygen availability. Rapid administration of oxygen at the time of attacks could therefore interrupt or mitigate this phenomenon.
To ensure that the association between oxygen delivery and mitigation of dystonia attacks is not coincidental, researchers must ensure that the same effect occurs in other patients under comparable conditions. Similarly, it remains to be clarified how to optimize the use of oxygen therapy, especially at home, so that it is as little restrictive as possible.
Reference: “Oxygen Therapy: An Acute Treatment for Paroxysmal Dystonia in Alternating Hemiplegia of Childhood?” by Quentin Welniarz, Ph.D., Domitille Gras, MD, Agathe Roubertie, MD, Ph.D., Maria T. Papadopoulou, MD, Eleni Panagiotakaki, MD, Ph.D. and Emmanuel Roze, MD, Ph.D., 16 February 2023, Movement Disorders.
DOI: 10.1002/mds.29357