Altered metabolites in the periaqueductal gray of COVID-19 patients experiencing headaches: a longitudinal MRS study

Abstract

Background: Headache is one of the most common symptoms of acute COVID-19 infection. However, its mechanisms remain poorly understood, and there is a lack of studies investigating changes in the periaqueductal gray (PAG) in COVID-19 patients exhibiting headaches. Purpose: The study aimed to explore the alterations in metabolites of the PAG pre- and post-COVID-19 infection in individuals who suffered from headaches during the acute phase of the disease using proton magnetic resonance spectroscopy (1H-MRS). Methods: Fifteen participants who experienced headaches during the acute phase of COVID-19 were recruited. All subjects underwent two proton magnetic resonance spectroscopy (1H-MRS) examinations focusing on the PAG before and after they were infected. Metabolite changes were assessed between the pre- and post-infection groups. Results: The combined glutamine and glutamate/total creatine ratio (Glx/tCr) was increased in the PAG following COVID-19 infection. The total choline/total creatine ratio (tCho/tCr) in the pre-infection group was negatively correlated with the duration of headache during the COVID-19 acute phase. Conclusion: The present study indicates that PAG plays a pivotal role in COVID-19 headaches, thereby supporting the involvement of trigeminovascular system activation in the pathophysiology of COVID-19 headaches.