Katie M. Linstra, PhDKatie M. Linstra, PhD
Results from a study as part of the Leiden University Migraine Neuro-Analysis (LUMINA) program demonstrated that thermal discomfort and cold extremities (TDCE) were more often reported in women and led to a higher frequency of migraine attacks, indicating a sex-specific vascular vulnerability.

Among a population of 594 patients with migraine and 199 controls, TDCE were more often reported in women with migraine compared to controls (odds ratio [OR], 2.3; 95% CI, 1.4­–3.7; P <.001). On the other hand, there were no significant reports of TDCE in men with migraine compared to controls (OR, 2.5; 95% CI, 0.9–6.9; P = .09).

The research, conducted by Katie M. Linstra, PhD, department of neurology, Leiden University Medical Center, and colleagues, revealed that female migraineurs who reported TDCE had higher attack frequencies (4 attacks per month) compared to female migraineurs without TDCE (3 attacks per month; P = .003). Men who had TDCE reported an increased average of 6 attacks per month. 

Researchers also noted that there were no differences in TDCE when comparing migraine with or without aura (OR, 1.2; 95% CI, 0.8­–1.7; P = .43).

In this case control study, Linstra and colleagues investigated self-reported cold extremities as a marker for vascular dysfunction in migraine. Previous studies had led them to believe that migraine can act as a vascular risk factor, especially so in women with the headache condition. Additionally, the group evaluated how suffering from cold extremities can impact sleep quality and ultimately, exacerbating migraine attack frequency.

A random selection of 1084 migraine patients and 348 controls (aged 22 to 65 years) was made from the LUMINA cohort for the study. Between December 2016 and January 2017, each patient was invited to fill out questionnaires regarding TDCE and difficulties initiating sleep (DIS). Questions related to TDCE included whether and to what extent patients suffered from cold hands and/or feet over the past month, while for DIS, patients filled out questions that related to sleeping issues and/or if they had sleep onset latency of more than 30 minutes in the same timeframe.

Researchers used multiple linear regression to investigate the association of TDCE and migraine in women, correcting for age, body mass index (BMI), smoking and vasoactive medication use, followed by correction for multiple comparisons.

Upon completion of questionnaire, the cohort included the aforementioned 594 (55%) patients with migraine and 199 (57%) controls. Women accounted for 88% of migraineurs and 61% of the control population. Additionally, vasoactive medication was reported as used in 15% of migraineurs, compared with 5% of the controls.

Aside from the increased TDCE rates in women, researchers found that positive outcome of TDCE was also associated with DIS (OR, 2.4; 95% CI, 1.7–3.5; P <.001). Furthermore, DIS was reported more often in both women (OR, 5.2; 95% CI, 2.4–11.4; P <.0001) and men (OR, 3.8; 95% CI, 1.2–12.4; P = .02) suffering from migraine compared to healthy controls.

Linstra and colleagues concluded that “if cold extremities in female migraineurs are proven to be associated with development of vascular complications later in life, this may present an easily assessed marker for vascular vulnerability.”
REFERENCE
Linstra, KM, Perenboom MJL, Van Zweet EW, et al. Cold extremities in migraine: a marker for vascular dysfunction in women. Eur J Neurol. Published April 30, 2020. doi: 10.1111/ene.14289.