Male and female sex hormones in primary headaches.

BACKGROUND: The three primary headaches, tension-type headache, migraine and cluster headache, occur in both genders, but all seem to have a sex-specific prevalence. These gender differences suggest that both male and female sex hormones could have an influence on the course of primary headaches. This review aims to summarise the most relevant and recent literature on this topic. METHODS: Two independent reviewers searched PUBMED in a systematic manner. Search strings were composed using the terms LH, FSH, progesteron*, estrogen*, DHEA*, prolactin, testosterone, androgen*, headach*, migrain*, "tension type" or cluster. A timeframe was set limiting the search to articles published in the last 20 years, after January 1st 1997. RESULTS: Migraine tends to follow a classic temporal pattern throughout a woman's life corresponding to the fluctuation of estrogen in the different reproductive stages. The estrogen withdrawal hypothesis forms the basis for most of the assumptions made on this behalf. The role of other hormones as well as the importance of sex hormones in other primary headaches is far less studied. CONCLUSION: The available literature mainly covers the role of sex hormones in migraine in women. Detailed studies especially in the elderly of both sexes and in cluster headache and tension-type headache are warranted to fully elucidate the role of these hormones in all primary headaches.

Reversible cerebral vasoconstriction syndrome secondary to caffeine withdrawal.

We describe a 39-year-old man who developed thunderclap headaches during a hospital admission for accidental superficial burns. His magnetic resonance brain imaging was normal expect for diffuse segmental vasoconstriction. Prior to admission, he was consuming excessive amounts of caffeine which was restarted and slowly tapered and stopped over weeks. Repeat magnetic resonance angiogram showed resolution of segmental vasoconstriction. The implications of prescribed and non-prescribed drugs on cerebral vasculature have been discussed.

No Pattern Alteration in Single Nocturnal Melatonin Secretion in Patients With Hypnic Headache: A Case-Control Study.

OBJECTIVE: To investigate headache-related serum melatonin levels and melatonin excretion rhythmicity in patients with hypnic headache (HH). BACKGROUND: Strict sleep dependency of headache attacks is a pathognomonic feature of HH. Changes in melatonin levels, a marker for circadian rhythm, are assumed to play a pivotal role in the pathophysiology of HH. METHODS: Serum melatonin levels were acquired in nine patients with HH and nine age- and gender-matched healthy controls over a 20-hour time period (12 pm, 4 pm, 7 pm, 10 pm, time of headache, and 8 am). RESULTS: No significant changes of melatonin levels could be detected comparing HH patients and healthy controls. Melatonin excretion rhythmicity was not significantly altered in patients with HH (Mean melatonin level in ng/mL ± SD, patients vs controls at 12 pm: 21.5 ± 9.5 vs 13.6 ± 6.3 [P = .077], 4 pm: 18.4 ± 8.4 vs 14.0 ± 4.7 [P = .222], 7 pm: 19.4 ± 5.1 vs 15.1 ± 4.5 [P = .094], 10 pm: 59.5 ± 45.0 vs 29.4 ± 12.7 [P =.136], headache time: 96.9 ± 68.3 vs 49.1 ± 22.8 [P = .94], and 8 am: 31.6 ± 18.3 vs 26.7 ± 15.6 [P = .489]). CONCLUSION: This study is not able to confirm a significant role of melatonin concentration changes in the pathophysiology of HH and vetoes that melatonin deficiency plays a major role in the pathophysiology of the disorder.

Reduced circulating endothelial progenitor cells in reversible cerebral vasoconstriction syndrome.

BACKGROUND: The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) remains elusive. Endothelial dysfunction might play a role, but direct evidence is lacking. This study aimed to explore whether patients with RCVS have a reduced level of circulating circulating endothelial progenitor cells (EPCs) to repair the dysfunctional endothelial vasomotor control. METHODS: We prospectively recruited 24 patients with RCVS within one month of disease onset and 24 healthy age- and sex-matched controls. Flow cytometry was used to quantify the numbers of circulating EPCs, defined as KDR+CD133+, CD34+CD133+, and CD34+KDR+ double-positive mononuclear cells. The Lindegaard index, an index of vasoconstriction, was calculated by measuring the mean flow velocity of middle cerebral arteries and distal extracranial internal carotid arteries via color-coded sonography on the same day as blood drawing. A Lindegaard index of 2 was chosen as the cutoff value for significant vasoconstriction of middle cerebral arteries based on our previous study. RESULTS: Patients with RCVS had a reduced number of CD34+KDR+ cells (0.009 ± 0.006% vs. 0.014 ± 0.010%, p = 0.031) but not KDR+CD133+ cells or CD34+CD133+ EPCs, in comparison with controls. The number of CD34+KDR+ cells was inversely correlated with the Lindegaard index (rs = -0.418, p = 0.047). Of note, compared to controls, patients with a Lindegaard index > 2 (n = 13) had a reduced number of CD34+KDR+ cells (0.007 ± 0.005% vs. 0.014 ± 0.010%, p = 0.010), but those with a Lindegaard index ≤ 2 did not. CONCLUSIONS: Patients with RCVS had reduced circulating CD34+KDR+ EPCs, which were correlated with the severity of vasoconstriction. Endothelial dysfunction might contribute to the pathogenesis of RCVS.

Peripheral levels of BDNF and NGF in primary headaches.

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), have been implicated in the generation and modulation of pain. To investigate whether alterations in neurotrophin levels can be detected in subjects suffering from nociceptive disorders, such as primary headaches, we determined the peripheral (platelet and plasma) levels of BDNF and NGF in patients suffering from migraine, with or without aura, or cluster headache (CH), in the interictal phase, and in healthy volunteers. All primary headaches patients studied showed significantly decreased platelet levels of BDNF (migraine vs. controls P<0.001; CH vs. controls P<0.01), while a selective reduction of platelet NGF was observed in migraine sufferers and not in CH patients compared with control subjects (migraine vs. controls P<0.001). These changes were not accompanied by significant modifications of neurotrophin plasma levels. Our findings show for the first time that changes in peripheral levels of neurotrophines (BDNF and NGF) occur in patients suffering from different types of primary headaches, suggesting a potential involvement of BDNF and NGF in the pathophysiology of these disorders, and raising the possibility that differences in peripheral neurotrophins may help to distinguish migraine biologically from CH.