Migraines associated with increased iron deposition in various brain structures

1. Patients with migraines had increased iron deposition in the putamen, caudate, and nucleus accumbens as compared to healthy controls.

2. Higher volumes of iron deposition were significantly associated with disease progression and disease burden.  

Evidence Rating Level: 2 (Good)    

Study Rundown:

Migraine is a widespread condition that has significant socioeconomic impact. Patients with chronic migraines (CM) experience lower health-related quality of life and higher levels of disability than those with episodic migraine (EM), of which 3% develop CM annually. The exact neural mechanism that leads to the development of chronic migraine is not yet fully understood. This cross-sectional study employs magnetic resonance imaging and a novel post-processing technique to analyze the brain iron concentration in subcortical nuclei among CM and EM individual relative to healthy controls. Migraineurs had increased iron deposition in the putamen (Pu), caudate (Ca) and nucleus accumbens (NAC) as compared to healthy controls. Patients with CM had significantly higher iron deposition in multiple subcortical brain nuclei compared to patients with EM. Furthermore, higher iron concentration in NAC was associated with longer disease duration, higher frequency of attacks, and higher scores on the Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI). Overall, the study confirms and expands on previous literature that have demonstrated increased iron deposition of subcortical nuclei in migraine patients.It also found that higher concentrations were associated with disease progression and burden. These results underscore the potential utility of neuroimaging to track patient disability and monitor their treatment regimes.

Click to read the study in BMC Medicine

In-Depth [cross-sectional study]:

A total of 200 patients with migraine (mean age 40.6± 12.3) and 41 healthy age- and sex-matched controls (mean age 43.6 ± 12.3) underwent MRI scans. These scans were processed using quantitative susceptibility mapping (QSM), a novel post-processing technique that was used to quantify iron deposition in different subcortical brain nuclei. Data on disease duration, frequency of migraine attacks, and peak headache pain intensity was also collected. The degree of migraine-related functional disability and sleep quality of migraineurs was assessed using the HIT-6, MIDAS and PSQI. Significantly higher QSM values were observed in Pu (P=0.001), Ca (P=0.002), and NAC (P<0.001)  in patients with CM comared to controls. Patients with EM had significantly higher QSM values in NAC (P<0.001) compared to controls. Additionally, when compared to patients with EM, patients with CM had significantly higher QSM values in Pu (p = 0.002), NAC (p < 0.001), substantia nigra pars compacta (p = 0.018), pallidum (p = 0.003), and hypothalamus (p = 0.017). The study also found that the volume of iron in NAC can be used to distinguish migraineurs from controls with a sensitivity of 72.9% and specificity of 86.8, and CM from EM with a sensitivity of 85.45% and specificity of 71.53%. Finally, higher QSM values in NAC were significantly associated with longer disease duration (r = 0.160, p = 0.045), higher frequency of attacks (r = 0.405, p < 0.001), more migraine days per month (r = 0.403, p < 0.001), and higher scores in HIT-6 (r = 0.423, p < 0.001), MIDAS (r = 0.605, p < 0.001), and PSQI (r = 0.428, p < 0.001). The study’s cross-sectional design and broad age range of participants restricted the ability to draw longitudinal associations and examine age-related effects and comorbidities. As such, further investigation is required to determine the causal link between migraines, iron deposition, and subsequent disease burden. 

Image: PD

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