Mitochondrial Impairment in Healthy Controls With Recent Headache and Multiple Symptoms

Persistent headache and multiple symptoms have each been tied to mitochondrial dysfunction. We assess whether reported recent headache and multiple symptoms (last two weeks) relate to bioenergetics in individuals who do not meet criteria for chronic multisymptom illness (CMI).

Twenty participants screening negative for CMI rated the presence/absence and severity (0-10) of recent (last two weeks) headache and multiple symptoms and underwent ³¹P-MRS (phosphorus-31 magnetic resonance spectroscopy) to assess the post-exercise phosphocreatine (PCr) recovery time constant (PCr-R). Phosphocreatine is depleted with exercise, and the post-exercise PCr recovery rate depends on the ATP production rate.

Eighteen of 20 participants successfully depressed PCr (on ³¹P-MRS) with exercise, enabling PCr-R assessment. Five participants (28%) reported recent headache. Headache presence was related to PCr-R (seconds): PCr-R mean±SD without headache: 34.6±11.5; PCr-R mean±SD with headache 62.3±22.6, p=0.003. Headache severity (0-10) was correlated with PCr-R (seconds): r=0.79, p=0.0001. Headache presence and severity were related to greater multiplicity of recent nonheadache symptoms: headache severity vs summed nonheadache symptom severity, r=0.68, p=0.001 (correlation to summed symptom ratings without excluding headache, r=0.72, p=0.0004). Longer PCr-R predicted greater summed symptom severity: regression β=0.47 (SE=0.15), p=0.007.

Recent headache and multiple symptoms were related to prolonged post-exercise PCr-recovery in persons screening negative for CMI. Future studies should distinguish among potential foundations for these associations.