Migraine/Headache

Reliable population-based data on the prevalence and characteristics of primary headache across the lifespan are essential. However, robust data are lacking. We utilized questionnaire data from a random general population sample in Germany, that comprised 2,478 participants aged ≥14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. The 6-month prevalence of self-reported headache in the total sample amounted to 39.0% (known diagnosis of migraine 7.2%; tension-type headache 12.4%; another diagnosis or unknown diagnosis 23.4%). Age-specific prevalence rates were 37.9% (14-34 years), 44.6% (35-54 years), 38.5% (55-74 years), and 26.9% (≥75 years). Compared to age group 14-34, participants aged 35-54 were more ( = 1.29, 95%- 1.05-1.60, = 0.018) and those aged ≥75 were less ( = 0.55, 95%- 0.40-0.76, < 0.001) likely to have any headache. Of the participants with headache, 79.5% reported headache on <4 days per month, 15.6% on 4-14 days per month and 4.9% on >14 days per month. The frequency of headache did not differ significantly between age groups in men [ = 1.45, > 0.05], but in women [ = 21.57, < 0.001]: women aged ≥75 years were over-represented in the group reporting 4-14 headache days per month. The analgesic use (days per month) differed significantly between age groups among participants with headache on <4 days per month and on >14 days per month: 1.8 (14-34 years), 2.5 (35-54 years), 3.2 (55-74 years), and 3.4 (≥75 years), respectively 7.9 (14-34 years), 11.4 (35-54 years), 18.4 (55-74 years), and 22.8 (≥75 years). In general, the prevalence of headache decreases with age. However, older women suffer from more frequent attacks and older participants take analgesics on more days per month than younger participants. This might put them at risk of medication overuse which may lead to medication overuse headache. More research is needed to understand these specifics in headache frequency and treatment behavior in older people.

There is strong evidence that neuronal hyper-excitability underlies migraine, and may or may not be preceded by cortical spreading depression. However, the mechanisms for cortical spreading depression and/or migraine are not established. Previous studies reported that cerebrospinal fluid (CSF) [Na+] is higher during migraine, and that higher extracellular [Na+] leads to hyper-excitability. We raise the hypothesis that altered choroid plexus Na+, K+-ATPase activity can cause both migraine phenomena: inhibition raises CSF [K+] and initiates cortical spreading depression, while activation raises CSF [Na+] and causes migraine. In this study, we examined levels of specific Na+, K+-ATPase inhibitors, endogenous ouabain-like compounds (EOLC), in CSF from migraineurs and controls. CSF EOLC levels were significantly lower during ictal migraine (0.4 nM +/- 0.09) than from either controls (1.8 nM +/- 0.4) or interictal migraineurs (3.1 nM +/- 1.9). Blood plasma EOLC levels were higher in migraineurs than controls, but did not differ between ictal and interictal states. In a Sprague-Dawley rat model of nitroglycerin-triggered central sensitization, we changed the concentrations of EOLC and CSF sodium, and measured aversive mechanical threshold (von Frey hairs), trigeminal nucleus caudalis activation (cFos), and CSF [Na+] (ultra-high field 23Na MRI). Animals were sensitized by three independent treatments: intraperitoneal nitroglycerin, immunodepleting EOLC from cerebral ventricles, or cerebroventricular infusion of higher CSF [Na+]. Conversely, nitroglycerin-triggered sensitization was prevented by either vascular or cerebroventricular delivery of the specific Na+, K+-ATPase inhibitor, ouabain. These results affirm our hypothesis that higher CSF [Na+] is linked to human migraine and to a rodent migraine model, and demonstrate that EOLC regulates them both. Our data suggest that altered choroid plexus Na+, K+-ATPase activity is a common source of these changes, and may be the initiating mechanism in migraine.

Migraine is a neurological disorder characterized by paroxysms of head pain accompanied by trigeminovascular system activation and autonomic dysfunction. Diagnosis is currently based on clinical diagnostic criteria. Though physiological differences exist between migraineurs and non-headache controls, true physiological biomarkers have been elusive, especially for the full clinical spectrum of migraine, inclusive of chronic, episodic, and probable migraine. We used edge-light pupil cycle time (PCT) as a probe of the pupillary light circuit in migraine, paired with clinical assessment of migraine characteristics, and compared these to non-headache controls. We found significantly increased PCT in probable, episodic, and chronic migraine, compared to controls. Additionally, increased PCT correlated with the presence of craniofacial autonomic symptoms, linking pupillary circuit dysfunction to peripheral trigeminal sensitization. The sensitivity of PCT, especially for all severities of disease, distinguishes it from other physiological phenotypes, which may make it useful as a potential biomarker.

Children with migraine headaches appear to have a range of sleep disturbances. The aim of the present study was to assess the NREM sleep instability in a population of school-aged individuals affected by migraine without aura (MoA). Thirty-three children with MoA (20 males, 13 females, mean age 10.45 ± 2.06 years) underwent to overnight Polysomnographic (PSG) recordings and Cyclic Alternating Pattern (CAP) analyses accordingly with international criteria. MoA group showed a reduction in sleep duration parameters (TIB, SPT, TST; ≤ 0.001 for all) and in arousal index during REM sleep and an increase in awakenings per hour (AWK/h) vs. Controls (C) ( = 0.008). In particular, MoA children showed a reduced CAP rate% ( ≤ 0.001), CAP rate% in S1 ( ≤ 0.001) and CAP rate% in SWS ( = 0.004) vs. C. Moreover, A phases distribution were characterized by a reduction in slow wave components (total number CAP A1%, CAP A1 index) ( ≤ 0.001) and an increase of fast components representation (total number of CAP A2% and CAP A3%) ( < 0.001) in MoA vs. C. Moreover, MoA children showed an increased A1 and A2 mean duration ( ≤ 0.001). Our findings show a reduction of arousability in MoA group and lower NREM lower sleep instability associated with MoA in children.