Does menstruation-related headache occur exclusively in women with migraine?

To determine the relation between headache and menstruation in women with migraine and the use of estrogen by these women. This was a prospective, cross-sectional, observational study with group comparison, using non-random sample and convenience. We interviewed 79 women diagnosed with migraine or tension-type headache (TTH), according to the ICHD-3, regarding the relation between headache and menstruation. Of the 79 women with headache, 60 (76%) had migraine and 19 (24%) had episodic TTH. The most frequent subtype of migraine was without aura (54/60, 90%). The age ranged from 18 to 42 years, with an average of 22.6 ± 4.1 years. Migraine affected women aged 22.4 ± 3.6 years, whereas in TTH, the age was 23.0 ± 5.4 years. Menstruation-related headache occurred in 41.9% of women with migraine and in only 6.3% of those with TTH. These differences were significant (χ2 = 5.2; p = 0.022). Of the five women diagnosed with migraine with aura, two used estrogen. Menstruation-related headache predominates in women with migraine and often women with migraine with aura use estrogen.

BDNF and serum S100B levels according the spectrum of structural pathology in chronic pain patients.

Central sensitivity syndrome (CSS) consists of adaptive pathophysiological changes associated with neuroplasticity in some chronic pain disorders. It could be grouped in two main conceptual conditions: one includes those chronic pain patients without overt structural pathology such as fibromyalgia, and the other subgroup includes conditions with recognizable structural abnormalities, both somatic (osteoarthritis) and visceral (endometriosis). In order to understand the role of neuromodulators in CCS we aim to determine whether brain-derived neurotrophic factor (BDNF) and S100B are associated to specific chronic pain disorders. Serum BDNF and S100B were measured in chronic pain women with different diagnosis: 88 with osteoarthritis, 36 with endometriosis, 117 with fibromyalgia, 33 with chronic tension type headache and in 41 healthy controls. ANCOVA analysis followed by heteroscedasticity-consistent covariance matrix was performed to evaluate BDNF and S100B levels, adjusted for depression severity, pain levels and use of analgesics according different pathologies. Serum BDNF concentrations were higher and not different in patients with fibromyalgia and headache, the CSS group without structural pathology. In contrast, the concentrations of S100B were higher in patients with osteoarthritis and endometriosis, in comparison to controls, fibromyalgia and tensional headache patients. This study supports the hypothesis that BDNF and S100B neuromodulators present different serum levels according to the background disease associated to the chronic pain. These have the potential to be studied as markers of active disease or treatment evolution.

Distinguishing neurocysticercosis epilepsy from epilepsy of unknown etiology using a minimal serum mass profiling platform.

Neurocysticercosis is associated with epilepsy in pig-raising communities with poor sanitation. Current internationally recognized diagnostic guidelines for neurocysticercosis rely on brain imaging, a technology that is frequently not available or not accessible in areas endemic for neurocysticercosis. Minimally invasive and low-cost aids for diagnosing neurocysticercosis epilepsy could improve treatment of neurocysticercosis. The goal of this study was to test the extent to which patients with neurocysticercosis epilepsy, epilepsy of unknown etiology, idiopathic headaches and among different types of neurocysticercosis lesions could be distinguished from each other based on serum mass profiling. For this, we collected sera from patients with neurocysticercosis-associated epilepsy, epilepsy of unknown etiology, recovered neurocysticercosis, and idiopathic headaches then performed binary group comparisons among them using electrospray ionization mass spectrometry. A leave one [serum sample] out cross validation procedure was employed to analyze spectral data. Sera from neurocysticercosis patients was distinguished from epilepsy of unknown etiology patients with a p-value of 10-28. This distinction was lost when samples were randomized to either group (p-value = 0.22). Similarly, binary comparisons of patients with neurocysticercosis who has different types of lesions showed that different forms of this disease were also distinguishable from one another. These results suggest neurocysticercosis epilepsy can be distinguished from epilepsy of unknown etiology based on biomolecular differences in sera detected by mass profiling.

Vitamin D Deficiency in Patients With Chronic Tension-Type Headache: A Case-Control Study.

OBJECTIVE: To see the interrelation between chronic tension-type headache (CTTH) and serum vitamin D levels. BACKGROUND: Several studies have suggested an association between chronic pain and vitamin D deficiency. Anecdotal evidence suggests that vitamin D deficiency may be associated with tension-type headache and migraine. METHODS: This case-control study was carried out to examine the association between CTTH and serum 25-hydroxy vitamin (25(OH) D) levels. One hundred consecutive adult (>18 years) patients with CTTH and 100 matched healthy controls were enrolled. RESULTS: The serum 25(OH) D levels were significantly lower in CTTH patients than in the controls (14.7 vs 27.4 ng/mL). The prevalence of vitamin D deficiency (serum 25 (OH) D < 20 ng/mL) was greater in patients with CTTH (71% vs 25%). CTTH patients had a significantly high prevalence of musculoskeletal pain (79% vs 57%), muscle weakness (29%vs 10%), muscle tenderness score (7.5 vs 1.9), and bone tenderness score (3.0 vs 0.8) in comparison to controls. CTTH patients with vitamin D deficient group (<20 ng/mL) had a higher prevalence of musculoskeletal pain (58% vs 31%), muscle weakness (38%vs 7%), muscle and bone tenderness score, associated fatigue (44% vs 17%) and more prolonged course (15.5 months vs 11.2 months). A strong positive correlation was noted between serum vitamin D levels and total muscle tenderness score (R2 = 0. 7365) and total bone tenderness score (R2 = 0. 6293). CONCLUSION: Decreased serum 25(OHD) concentration was associated with CTTH. Intervention studies are required to find out if supplementation of vitamin D is effective in patients with CTTH.

Serum levels of adiponectin, CCL3/MIP-1α, and CCL5/RANTES discriminate migraine from tension-type headache patients / Níveis séricos de adiponectina, CCL3/MIP-1α, and CCL5/RANTES discriminam pacientes com migrânea e cefaleia do tipo tensional

ABSTRACT Objectives Inflammatory molecules and neurotrophic factors are implicated in pain modulation; however, their role in primary headaches is not yet clear. The aim of this study was to compare the levels of serum biomarkers in migraine and tension-type headache. Methods This was a cross-sectional study. We measured serum levels of adiponectin, chemokines, and neurotrophic factors in patients with migraine and tension-type headache. Depression and anxiety symptoms, headache impact and frequency, and allodynia were recorded. Results We included sixty-eight patients with migraine and forty-eight with tension-type headache. Cutaneous allodynia (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), and ADP (p = 0.017) were significantly higher in migraine than in tension-type headache. The differences occurred independently of anxiety and depressive symptoms, frequency and impact of headache, and the presence of pain. Conclusions This study showed higher CCL3/MIP-1α, CCL5/RANTES, and ADP levels in migraine in comparison with tension-type headache. Our findings suggest distinctive roles of these molecules in the pathophysiology of these primary headaches.

RESUMO Objetivos Moléculas inflamatórias e fatores neurotróficos estão implicados na modulação dolorosa, contudo, seu papel nas cefaleias primárias não é claro. O objetivo do presente estudo foi comparar níveis de biomarcadores séricos na migrânea e cefaleia do tipo tensional. Métodos Este foi um estudo transversal, no qual foram avaliados níveis de adiponectina, quimiocinas e fatores neurotróficos em pacientes com migrânea e cefaleia do tipo tensional. Sintomas depressivos e ansiosos, o impacto e a frequência da cefaleia e alodínea foram registrados. Resultados Foram incluídos 68 pacientes com migrânea e 48 pacientes com cefaleia do tipo tensional. A alodínia cutânea (p = 0.035), CCL3/MIP-1α (p = 0.041), CCL5/RANTES (p = 0.013), e adiponectina (p = 0.017) foram maiores na migrânea, independentemente de sintomas depressivos e ansiosos, frequência e impacto da cefaleia. Conclusões Níveis de CCL3/MIP-1α, CCL5/RANTES e adiponectina foram maiores na migrânea do que na cefaleia do tipo tensional, sugerindo papeis distintos destas moléculas na fisiopatologia destas duas cefaleias primárias.

Interictal plasma pituitary adenylate cyclase-activating polypeptide levels are decreased in migraineurs but remain unchanged in patients with tension-type headache.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) is associated with migraine phase; however, whether PACAP levels could be used to distinguish between migraine and tension-type headache (TTH) remains unknown. We compared interictal plasma PACAP levels among healthy controls, migraineurs, and patients with TTH. METHODS: Interictal plasma levels of PACAP were measured in 133 migraineurs, 106 patients with TTH, and 50 controls using enzyme-linked immunoassays. We further evaluated the relationships between interictal PACAP plasma concentrations and clinical parameters, such as headache severity, attack frequency, and duration. RESULTS: We found that migraineurs had significantly lower interictal plasma PACAP levels than patients with TTH and healthy controls. However, there were no significant differences between patients with TTH and healthy controls. Plasma PACAP levels were significantly lower in patients with episodic migraine (EM) than in patients with episodic tension-type headache (ETTH) and in patients with chronic migraine (CM) than in patients with chronic tension-type headache (CTTH). Interictal PACAP levels were negatively correlated with duration in the CM group. CONCLUSIONS: The results of this study demonstrated differences in interictal PACAP levels in migraine and TTH, suggesting that PACAP is involved in the pathogenesis of migraine rather than TTH.

Neurotrophic factors in tension-type headache / Fatores neurotróficos na cefaleia do tipo tensional

Neurotrophic factors (NF) are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH). We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

Os fatores neurotróficos (FN) participam da regulação da dor e podem ter um papel na fisiopatologia das cefaleias peimárias. O objetivo do presente estudo foi avaliar os níveis séricos de FN em pacientes com cefaleia do tipo tensional (CTT). Foi realizado corte transversal com 48 pacientes com CTT e 48 controles pareados por gênero e idade. Os inventários de Beck para depressão e ansiedade, bem como o inventário de impacto da cefaleia foram aplicados. Os níveis séricos de FN foram determinados por ELISA. Não houve diferenças significativas entre níveis de FN entre pacientes com TTH e controles, bem como entre pacientes com TTH episódica e crônica. Presença de cefaleia no momento da avaliação não alterou os níveis séricos de FN. Os escores de depressão, ansiedade e impacto da cefaleia não se correlacionaram com os níveis de FN. Nosso estudo sugere que não há alteração dos níveis de FN na TTH.

Clinical Value of Serum Neuroplasticity Mediators in Identifying the Central Sensitivity Syndrome in Patients With Chronic Pain With and Without Structural Pathology.

BACKGROUND AND OBJECTIVES: Central sensitivity syndrome (CSS) encompasses disorders with overlapping symptoms in a spectrum of structural pathology from persistent somatic nociception (eg, osteoarthritis) to absence of tissue injury such as in fibromyalgia, chronic tension-type headache, and myofascial pain syndrome. Likewise, the spectrum of the neuroplasticity mediators associated with CSS might present a pattern of clinical utility. METHODS: We studied the brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), and interleukins 6 (IL-6) and IL-10 in female patients with CSS absent of structural pathology (chronic tension-type headache [n=30], myofascial pain syndrome [n=29], fibromyalgia [n=22]); with CSS due to persistent somatic/visceral nociception (osteoarthritis [n=27] and endometriosis [n=32]); and in pain-free controls (n=37). RESULTS: Patients with CSS absent of structural pathology presented higher serum TNF-α (28.61±12.74 pg/mL) and BDNF (49.87±31.86 ng/mL) than those with persistent somatic/visceral nociception (TNF-α=17.35±7.38 pg/mL; BDNF=20.44±8.30 ng/mL) and controls (TNF-α=21.41±5.74 pg/mL, BDNF=14.09±11.80 ng/mL). Moreover, CSS patients absent of structural pathology presented lower IL levels. Receiver operator characteristics analysis showed the ability of BDNF to screen CSS (irrespective of the presence of structural pathology) from controls (cutoff=13.31 ng/mL, area under the curve [AUC]=0.86, sensitivity=95.06%, specificity=56.76%); and its ability to identify persistent nociception in CSS patients when experiencing moderate-severe depressive symptoms (AUC=0.81; cutoff=42.83 ng/mL, sensitivity=56.80%, specificity=100%). When the level of pain measured on the visual analog scale was <5 and moderate-severe depressive symptoms were observed TNF-α discriminated structural pathology in the chronic pain conditions (AUC=0.97; cutoff=22.11 pg/mL, sensitivity=90%, specificity=91.3%). CONCLUSION: Neuroplasticity mediators could play a role as screening tools for pain clinicians, and as validation of the complex and diffuse symptoms of these patients.

Plasma nitrite levels, total antioxidant status, total oxidant status, and oxidative stress index in patients with tension-type headache and fibromyalgia.

OBJECTIVES: Tension-type headache (TTH) and fibromyalgia syndrome (FM) are worldwide seen chronic pain syndromes of unknown etiology. Despite the growing body of data on pathophysiology and generation mechanisms of pain; our knowledge on pain mechanisms in both FM and TTH is yet to be limited. PATIENTS AND METHODS: We investigated the plasma nitrite levels, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in 35 TTH, 33 FM patients and 31 healthy controls. RESULTS: The mean plasma nitrite levels and TAS levels were significantly low and OSI was found to be significantly high in TTH and FM groups compared to the control group (p=0.001, p=0.001, p=0.001 and p=0.001, respectively). The mean serum TOS levels were also significantly higher in FM group according to the control group (p=0.034), but there was not a significant difference between TTH and control groups (p=0.066). CONCLUSION: These results indicated that; FM and TTH patients revealed higher oxidative stress index and lower total nitrite levels than healthy controls. We conclude that oxidative stress may have a role in the pathophysiological mechanisms of TTH and FM, although, whether it is the cause or the consequence, is not clear.

How to investigate and treat: headache and hyperprolactinemia.

Hyperprolactinemia is a condition characterised by an increase of prolactin blood levels (more than 100-200 ng/ml). It is the most common endocrine disorder of the hypothalamic-pituitary axis. The clinical characteristics of the headache-hyperprolactinemia-hypophyseal-adenoma association are discussed, the various diagnostic and treatment possibilities are explored and the etiology of the headache is considered in the light of several pathogenetic possibilities. We present two cases. (1) A 35-year-old woman suffering from chronic tension-type headache interspersed with occasional episodes of migraine without aura (as defined by the International Headache Society criteria). She had also suffered menstrual cycle alterations since the age of 16. At the age of 30 she developed amenorrhea with hyperprolactinemia. Computed tomography (CT) and magnetic resonance imaging (MRI) scans revealed a median-left intrasellar mass. Treatment with cabergoline resulted in complete resolution of both types of headache and the menstrual cycle and prolactin levels returned to normal. The therapy also reduced the volume of the tumour. (2) The second case relates to a 47-year-old man who had been suffering from tension-type headaches for almost 3 months. The patient had never previously suffered from headaches. CT and MRI scans showed a large sellar and suprasellar lesion with raised serum prolactin levels. Treatment with cabergoline had significantly reduced the prolactin levels and had also improved the patient's headaches. High-resolution CT, with and without contrast, or MRI is necessary to visualise microprolactinomas (and other sellar lesions) and confirm the diagnosis.

Interleukin-6 levels in tension headache patients.

OBJECTIVE: Cytokines are pain mediators in neurovascular inflammation. This study examined interleukin 6 (IL-6) levels in the serum of tension-type headache (TTH) patients, to determine if inflammation plays a role in the pathogenesis of this condition. METHODS: Serum IL-6 levels were studied in 42 patients and 37 healthy controls from the same region. Of the patients, 20 (47.6%) experiencing TTH less than 15 days per month were placed in episodic tension-type headache (ETTH) group, and 22 (52.3%) with TTH more than 15 days per month were placed in chronic tension-type headache (CTTH) group. RESULTS: The IL-6 level was significantly higher in the patients than in the controls. The IL-6 level of CTTH patients was higher than the controls (P<0.01). The IL-6 level was similar between ETTH and CTTH patients. Correlation analysis revealed a positive relationship only between age and IL-6 level in the patients. CONCLUSIONS: CTTH and ETTH patients had an elevated serum IL-6 level compared with controls. Therefore, we believe that IL-6 may be involved in pain induction or inflammatory mechanisms in TTH. Furthermore studies of the possible connection between chronicity of headaches and cytokine levels are needed.

Proinflammatory plasma cytokines in children with migraine.

Toward understanding the role of cytokines in migraine, this study focused on selected proinflammatory cytokines. The study group consisted of 21 children who had migraine with and without aura; the control group was 24 children with episodic tension-type headache. Plasma interleukin-1 alpha was undetectable in 19 control subjects with tension-type headache, but was detectable in 16 patients with migraine, which suggests that interleukin-1 alpha level might be higher in migraine. Soluble tumor necrosis factor receptor 1 in the migraine group was significantly higher than in the control group (P < 0.0005). Migraine patients tended to have increased tumor necrosis factor alpha level, compared with the control group. The interleukin-1 alpha level was significantly higher in migraine with aura than in migraine without aura (P < 0.05). Tumor necrosis factor alpha and soluble tumor necrosis factor receptor 1 levels tended to be increased in the migraine with aura subgroup. The results suggest that proinflammatory cytokines may be involved in the pathogenesis of migraine attacks, although fluctuations in cytokine levels could be different in children than in adults. Such difference could be due to long medical history of migraine in adult patients and frequent intake of analgesic drugs or prophylactic treatment.

[Tumor necrosis factor alpha (TNF-alpha) in patients with ischemic stroke]. / Czynnik martwicy nowotworu alfa (TNF-alfa) u chorych z udarem niedokrwiennym mózgu.

Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine. Stroke induces a rapid increase in TNF-alpha levels within and around the focus of damaged brain. The aim of our study was to evaluate, whether patients with stroke differ from control patients in the concentrations of TNF-alpha in cerebrospinal fluid and serum. We studied TNF-alpha levels in cerebrospinal fluid and serum in 30 patients with stroke within 24 h after onset of neurological signs and in 15 patients of control group with the diagnosis of tension headache and neurasthenia. In patients with stroke the levels of TNF-alpha in the cerebrospinal fluid and serum were significantly higher in comparison with control group. The results of our study may suggest the overproduction of TNF-alpha during first twenty-four hours of stroke.

Efficacy and effect of SI17 therapy on pancreatic polypeptide in vascular and tension-type headache.

BACKGROUND AND PURPOSE: Vascular and tension-type headache is most commonly encountered, and SI17 therapy has been tested to treat headache with good results. The efficacy of SI17 therapy for vascular and tension-type headache was compared and the effect of SI17 therapy on pancreatic polypeptide (PP) was studied. MATERIALS AND METHODS: 29 cases of vascular headache (20 cases in acute attack during the trial) and 27 cases of tension-type headache (19 cases in acute attack) were enrolled in the study. Plasma PP level before and 4th day after treatment was measured by radioimmunoassay. RESULTS: SI17 therapy is better for the treatment of vascular headache. Vascular headache with higher PP level and tension-type headache with normal PP level had good therapeutic results. CONCLUSION: The clinical efficacy is better for vascular headache with the increase of vagus tension and for tension-type headache with normal vagus tension.

Plasma levels of substance P, neuropeptide Y and vasoactive intestinal polypeptide in patients with chronic tension-type headache.

Animal and human studies have shown that substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) are involved in the pathophysiology of acute and chronic pain conditions. The primary aim of the present study was to compare plasma levels of SP, NPY and VIP in external jugular vein between patients with chronic tension-type headache and healthy controls. The secondary aim was to examine plasma levels of these neuropeptides in relation to headache state. In addition, we wanted to study the relation between cranial circulation (jugular vein) and peripheral circulation (antecubital vein). Blood from the external jugular and antecubital vein was drawn from 20 patients with chronic tension-type headache and 20 healthy controls. Plasma SP in patients, 2.0 (1.4-2.2) pmol/l, did not differ significantly from plasma SP in controls, 1.7 (1.1-2.1) pmol/l, (P=0.44). No significant differences were found between SP levels on days with headache, 1.5 (0.3-1.7) pmol/l, and SP levels on days without headache, 1.7 (1.1-1. 9) pmol/l, (P=0.06). Plasma NPY in patients, 118+/-3 pmol/l, did not differ significantly from plasma NPY in controls, 113+/-5 pmol/l, (P=0.40). There was no difference between NPY levels on days with headache, 120+/-3 pmol/l, and on days without headache, 118+/-3 pmol/l, (P=0.73). VIP levels in patients, 6 (4-7) pmol/l, did not differ significantly from VIP levels in controls, 5 (5-7) pmol/l, (P=0.50). No significant differences were found between VIP levels measured on days with headache, 5 (4-6) pmol/l, and VIP levels measured on days without headache, 6 (4-7) pmol/l, (P=0.81). Plasma levels of SP, NPY and VIP did not significantly differ between the peripheral and the cranial circulation neither in patients nor in controls (0.05). In summary, the present study indicates that plasma levels of SP, NPY and VIP are normal in chronic tension-type headache patients and largely unrelated to headache state.

Plasma levels of neuroexcitatory amino acids in patients with migraine or tension headache.

Plasma amino acids were analysed in patients with migraine with (9) and without (80) aura, in patients with tension headache (14) and in controls (62). The neuroexcitatory amino acids glutamic acid, glutamine, glycine, cysteic acid and homocysteic acid were elevated in migraine patients while total thiols (cysteine/cystine) were reduced. Patients with tension headache had values which were similar to those of controls. Tryptophan was elevated in migraine patients without aura only. Studies on two patients showed that the raised resting excitatory amino acid levels became still further elevated during a migraine attack. These results show that high concentrations of neurotransmitter amino acids occur normally in migraine patients and suggest that this profile may be a contributory factor in migraine attacks. Tension headache, however, has different biochemical parameters.

Platelet ionized magnesium, cyclic AMP, and cyclic GMP levels in migraine and tension-type headache.

Decreased serum and intracellular levels of magnesium have been reported in patients with migraine. It has been suggested that magnesium may play an important role in the attacks and pathogenesis of headaches. We measured ionized magnesium, cyclic AMP (adenosine monophosphate), and cyclic GMP (guanosine monophosphate) in platelets of patients with migraine, in patients with tension-type headache, and in healthy controls. The platelet level of ionized magnesium from patients with tension-type headache was significantly lower than the levels from the other two groups. The platelet level of cyclic AMP from patients with migraine was higher than those from the other groups. We found no significant differences in the platelet cyclic GMP levels among the three groups. It is suggested that reduced platelet ionized magnesium in patients with tension-type headache is related to abnormal platelet function, and that increased platelet cyclic AMP in patients with migraine is related to alteration of neurotransmitters in the platelet.