Serum levels of N-acetyl-aspartate in migraine and tension-type headache

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at −80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography–mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function.     

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.     

Serum and salivary magnesium levels in migraine and tension-type headache. Results in a group of adult patients

It has been suggested that magnesium plays a central role in different etiopathogenetic conditions involved in the onset of migraine. We measured, by atomic absorption spectrophotometry, serum and salivary magnesium levels in drug-free migraine patients with and without aura and in tension-type headache patients. Migraine sufferers with and without aura and tension-type headache had significantly lower levels of serum and salivary magnesium concentrations in the interical periods than a group of healthy young individuals. Serum magnesium levels tended to be further reduced during attacks in all patient groups studied. A statistically significant decrease in salivary magnesium levels was evident only for migraine patients with aura. Serum magnesium levels and to a lesser extent salivary magnesium levels might express indirectly the lowering of brain extracellular magnesium concentration which occurs in migraine patients both in the intererictal periods and ictally.     

The wavelength of light causing photophobia in migraine and tension-type headache between attacks

OBJECTIVE: To ascertain the wavelength of light that patients with migraine and tension-type headache find uncomfortable between attacks. BACKGROUND: Photophobia is an abnormal perceptual sensitivity to light experienced by most patients with headache during and, also, between attacks. METHODS: We examined the discomfort threshold to light of low, medium, and high wavelengths in a group of patients with migraine (n=21), patients with tension-type headache (n=19), and healthy controls (n=21). RESULTS: The results indicate that the migraine group had significantly lower discomfort thresholds at the low (P=.001) and high (P=.031) wavelengths compared with both the tension-type headache and control groups; the latter two groups had similar average discomfort levels at these two wavelengths. With the medium wavelength, the control group had significantly higher discomfort thresholds than the migraine (P=.002) and tension-type headache (P=.031) groups; the latter two groups had similar discomfort levels at this wavelength. With unfiltered (white) light, the migraine group had the lowest discomfort threshold and the control group the highest (P=.026), whereas the tension-type headache group had an intermediate discomfort threshold. CONCLUSIONS: There were significant differences between migraineurs, patients with tension-type headache, and healthy controls in the wavelengths that are uncomfortable between attacks.     

Plasma Lactic Acid and Pyruvic Acid Levels in Migraine and Tension-Type Headache

We examined the lactic and pyruvic acid levels in the plasma of 14 patients with migraine, 17 patients with tension-type headache, and 12 normal controls. The lactic and pyruvic acid levels in the plasma of the migraine patients were significantly higher than those of the normal controls (9.6 ± 5.0 mg/dL and 0.51 ± 0.30 mg/dL versus 3.3 ± 1.9 mg/dL and 0.26 ± 0.20 mg/dL, respectively). There were no significant differences in the levels between the patients with tension-type headache and normal controls. Our results suggest that migraine patients may have functional abnormalities in mitochondrial energy metabolism.     

Dextroamphetamine pilot crossover trials and n of 1 trials in patients with chronic tension-type and migraine headache

OBJECTIVE: To examine the preventive effects of dextroamphetamine in select small groups of patients with chronic tension-type and migraine headache. BACKGROUND: Neither amphetamine nor methylphenidate is used as a headache preventive. This study was undertaken after a chance observation led one of us to prescribe dextroamphetamine with apparent successes in specific patients with chronic tension-type or migraine headaches. METHODS: Two pilot trials were done. Trial 1 tested patients who were taking dextroamphetamine, while Trial 2 tested patients who had never taken this drug. Each trial obtained full data on eight subjects with chronic tension-type headache and eight subjects with migraine headache. A randomized, double-blinded, controlled, multiple-crossover design was used. Subjects took capsules containing dextroamphetamine or equi-stimulatory caffeine (the control) during four alternating 20-day periods. Trial 1 subjects took their pretrial dextroamphetamine dose at breakfast and lunch. Trial 2 subjects took 10 mg at these times. Subjects recorded the integer from 0 to 3 that represented their headache intensity during the previous 24 hours. The subject's data were the average daily headache grade for the two dextroamphetamine periods and for the two caffeine periods. The differential effect of amphetamine and caffeine on each group of eight subjects and on each individual was analyzed by t-tests. RESULTS: In both trials, the tension-type and migraine groups had lower mean daily headache grades in the amphetamine than in the caffeine periods. P values for these differences indicated that there were real drug effects, on the average, in the migraine groups (P<.05) and suggestive but inconclusive effects in the tension-type groups (P<.10). The individual n of 1 analyses showed that five tension-type and three migraine subjects in Trial 1 and three tension-type and three migraine subjects in Trial 2 had considerably lower mean daily headache grades on amphetamine with P values indicating, at various levels of significance (from P<.05 to P<.001), real amphetamine effects. Twelve of the remaining 18 patients had lower, albeit not significant, mean daily grades with amphetamine. No subject in either trial had a significantly lower mean daily headache grade on caffeine. CONCLUSIONS: Dextroamphetamine had real preventive effects on chronic tension-type and migraine headaches in some subjects. These results should encourage other investigators to study its effects on these headaches.     

Serum S100beta protein in children with acute recurrent headache: a potentially useful marker for migraine

Objective.—To examine the role of glia-derived S100β protein and to evaluate its use as a biochemical marker in childhood acute recurrent headache.
Methods.—Twenty-five patients with acute recurrent headache (according to International Headache Society criteria) from our department's Headache Clinic were studied. Blood samples for measurement of serum S100β were drawn: (1) ≤3-hour post pain attack from our patients and (2) from 23 healthy controls.
Results.—Of the 25 patients evaluated, 15 suffered from migraine and 10 from tension-type headache (TTH). Statistical analysis of the mean values of S100β levels demonstrated a significant elevation in children with migraine headache, with values higher than those of both children with TTH and controls ( P = .001).
Conclusions.—Our data suggest a direct relation between childhood migraine attacks and increased production of glial S100β protein. Serum S100β determination may be a useful biochemical marker for migraine in acute recurrent headache in childhood.     

Brain-derived neurotrophic factor in primary headaches

Brain derived neurotrophic factor (BDNF) is associated with pain modulation and central sensitization. Recently, a role of BDNF in migraine and cluster headache pathophysiology has been suspected due to its known interaction with calcitonin gene-related peptide. Bi-center prospective study was done enrolling four diagnostic groups: episodic migraine with and without aura, episodic cluster headache, frequent episodic tension-type headache, and healthy individuals. In migraineurs, venous blood samples were collected twice: outside and during migraine attacks prior to pain medication. In cluster headache patients serum samples were collected in and outside cluster bout. Analysis of BDNF was performed using enzyme-linked immunosorbent assay technique. Migraine patients revealed significantly higher BDNF serum levels during migraine attacks (n = 25) compared with headache-free intervals (n = 53, P < 0.01), patients with tension-type headache (n = 6, P < 0.05), and healthy controls (n = 22, P < 0.001). There was no significant difference between patients with migraine with aura compared with those without aura, neither during migraine attacks nor during headache-free periods. Cluster headache patients showed significantly higher BDNF concentrations inside (n = 42) and outside cluster bouts (n = 24) compared with healthy controls (P < 0.01, P < 0.05). BDNF is increased during migraine attacks, and in cluster headache, further supporting the involvement of BDNF in the pathophysiology of these primary headaches.     

Does Relaxation Treatment Have Differential Effects on Migraine and Tension-type Headache in Adolescents?

The present study evaluated the effects of relaxation treatment in 36 adolescents aged 13 to 18 years (mean +/- SD, 15.4 +/- 1.55 years) suffering from migraine or migraine and tension-type headache as compared with a waiting-list condition group. The subjects rated various characteristics of migraine and tension-type headache in a diary. Significant reductions were found for total headache sum (P <.05) and intensity scores of total headache activity (P <.05) as well as for migraine intensity (P <.05) for subjects treated with relaxation as compared with those in the waiting-list condition group. However, no significant differences between the two groups were found for tension-type headache. Fifty percent of the adolescents treated with relaxation training attained a clinically significant improvement, compared with 12% of those in the waiting-list condition. It is suggested that treatment goals for migraine and migraine occurring with tension-type headache might be different and that relaxation training also might benefit from focusing on specific aspects of the two headache types.     

The prevalence of headache may be related with the latitude: a possible role of Vitamin D insufficiency?

According to recent observations, there is worldwide vitamin D insufficiency (VDI) in various populations. A number of observations suggest a link between low serum levels of vitamin D and higher incidence of chronic pain. A few case reports have shown a beneficial effect of vitamin D therapy in patients with headache disorders. Serum vitamin D level shows a strong correlation with the latitude. Here, we review the literature to delineate a relation of prevalence rate of headaches with the latitude. We noted a significant relation between the prevalence of both tension-type headache and migraine with the latitude. There was a tendency for headache prevalence to increase with increasing latitude. The relation was more obvious for the lifetime prevalence for both migraine and tension-type headache. One year prevalence for migraine was also higher at higher latitude. There were limited studies on the seasonal variation of headache disorders. However, available data indicate increased frequency of headache attacks in autumn–winter and least attacks in summer. This profile of headache matches with the seasonal variations of serum vitamin D levels. The presence of vitamin D receptor, 1α-hydroxylase and vitamin D-binding protein in the hypothalamus further suggest a role of vitamin D deficiency in the generation of head pain.     

Psychosocial Functioning in Schoolchildren With Recurrent Headaches

The psychosocial functioning of 113 schoolchildren (8 to 15 years old) reporting headaches at least once a month was compared to a group of headache-free control subjects matched for sex and age. Thirteen percent of the headache sufferers had migraine headaches, 28% had episodic tension-type headaches, 30% had chronic tension-type headaches, and 29% had migraine coexisting with tension-type headaches.
Overall, the headache sufferers experienced more somatic complaints, stress, and psychological symptoms, in addition to being absent from school (due to illness), more often and reported fewer caring persons as compared to headache-free controls. Although few differences between the four headache groups emerged in the children's psychosocial functioning levels, children with migraine coexisting with tension-type headaches had significantly more frequent somatic complaints than those having episodic tension-type headaches. In addition, children with migraine or migraine coexisting with tension-type headaches were more often absent from school than those having tension-type headaches only. A significant but weak relationship between children's headache severity and their somatic complaints was noted.     

Outcome of juvenile headache in outpatients attending 23 Italian headache clinics. Italian Collaborative Study Group on Juvenile Headache (Società Italiana Neuropsichiatria Infantile [SINPI])

A multicenter 3-year follow-up study was carried out on young patients with headache referred to tertiary headache centers or pediatric clinics. Three years after the first examination in 1993, 442 (of an original sample of 719) young outpatients with headache (226 females and 216 males) were re-examined. The diagnostic criteria of the International Headache Society (IHS) and those modified for migraine without aura by Winner et al were applied at both the baseline evaluation and the 3-year re-examination. At the follow-up, 290 children still had headache, 101 were in clinical remission, and 51 had dropped out. Using the current diagnostic criteria, only 46.2% of patients having migraine without aura, 50% of those having migraine with aura, and 35.3% of those suffering from migraine disorders which do not fulfill IHS criteria for migraine received the same diagnosis at the time of follow-up. The percentage of patients receiving a diagnosis of migraine without aura rose significantly when new modified criteria were used (60.5%), whereas a drop in the frequency of migraine disorders not fulfilling IHS criteria was observed at follow-up, both in patients with the diagnosis of migraine without aura at the first examination (4.6%) and in patients with migraine not always fulfilling IHS criteria at the first examination (6.2%). Among all patients who received this latter diagnosis at the first examination, it was possible to make a diagnosis of migraine with aura at the follow-up in 8.8% of cases and that of migraine without aura in 26.5%. No significant variations in the frequency of either episodic tension-type headache or chronic tension-type headache were found, with the exception of a slight decrease in the percentage of tension-type headache which did not fulfill IHS criteria, but the difference between the first examination and the follow-up values does not reach the level of statistical significance (5% versus 12%). As far as the evolution of migraine is concerned, 17.4% of patients with migraine were headache-free at the 3-year follow-up. In tension-type headache, the percentage of patients who were headache-free was particularly high in those with the episodic form (32.9%) and in those suffering from tension-type headache not fulfilling IHS criteria (29.1%). The majority of patients who had been diagnosed as having unclassifiable headache at the first examination received a correct diagnosis at the follow-up with the exception of one patient. As observed in adult patients, variations in the headache characteristics were also observed in children and adolescents (that is, migraine with aura can change to migraine without aura, or the latter can transform into episodic tension-type headache or chronic tension-type headache can change into the episodic form). This follow-up study was aimed at reaching a better understanding of headache disturbances in children and adolescents, examining, in particular, variations of headache with time in this stage of life.     

Electromyographical Ischemic Test and Intracellular and Extracellular Magnesium Concentration in Migraine and Tension-Type Headache Patients

Headache has often been described in the hyperexcitability syndrome which recognizes an alteration of calcium and magnesium status in its etiopathogenesis. Moreover, in migraine patients magnesium has been shown to play an important role as a regulator of neuronal excitability and, therefore hypothetically, of headache. The present research involves a neurophysiological evaluation and magnesium status assessment of a group of headache patients. Nineteen patients (15 women and 4 men) with episodic tension-type headache and 30 patients (27 women and 3 men) with migraine without aura were examined. An ischemic test was carried out on the right arm with electromyographic (EMG) recording of motor unit potential activity during the interictal period. The determination of extracellular (serum and saliva) and intracellular (red and mononuclear blood cells) magnesium was also performed. The EMG test was positive in 25 of 30 migraine patients and in 2 of 19 tension-type headache patients. Between the two patient groups, there were no significant variations in the concentration of extracellular and white blood cell magnesium, while the red blood cell concentration of this mineral in the group of migraineurs was significantly reduced with respect to that in the group of tension-type headache patients (P<0.05). The positive EMG test was significantly associated with a low concentration of red blood cell magnesium (P<0.0001). These results confirm previous findings by demonstrating different etiopathogenic mechanisms as the basis of migraine and tension-type headache. Migraine seems to be related to an altered magnesium status, which manifests itself by a neuromuscular hyperexcitability and a reduced concentration in red blood cells.     

Screening for genetic and acquired thrombophilia in a cohort of young migrainous patients

Abstract Growing evidence suggests a possible relationship between migraine and thrombotic risk factors. The aim of this study was to analyze the possible relationship between migraine and acquired and genetic thrombophilia in a young population. We compared 16 migrainous adolescents, 12 children with tension-type headache, and controls in terms of frequencies of prothrombotic polymorphisms (factor V Leiden, C677T mutation of 5,10 methylenetetrahydrofolate reductase, G20210A mutation of prothrombin), platelet aggregability, anticoagulant antibodies, blood lipid pattern, serum folate and vitamin B12 levels, homocysteinemia, coagulation parameters, and family history for migraine and precocious thrombotic events. This study confirms the link between migraine and increased platelet responsiveness. Overall, 62.5% of migrainous patients carried at least three thrombophilic factors. Our preliminary data suggest that, in order to assess prevention strategies, it could be appropriate to perform a complete thrombophilia screening in young patients suffering from migraine and with a family history of thrombosis.     

Headache, anxiety and depressive disorders: the HADAS study

The objective of this paper was to assess prevalence and characteristics of anxiety and depression in migraine without aura and tension-type headache, either isolated or in combination. Although the association between headache and psychiatric disorders is undisputed, patients with migraine and/or tension-type headache have been frequently investigated in different settings and using different tests, which prevents meaningful comparisons. Psychiatric comorbidity was tested through structured interview and the MINI inventory in 158 adults with migraine without aura and in 216 persons with tension-type headache or migraine plus tension-type headache. 49 patients reported psychiatric disorders: migraine 10.9%, tension-type headache 12.8%, and migraine plus tension-type headache 21.4%. The MINI detected a depressive episode in 59.9, 67.0, and 69.6% of cases. Values were 18.4, 19.3, and 18.4% for anxiety, 12.7, 5.5, and 14.2%, for panic disorder and 2.3, 1.1 and 9.4% (p = 0.009) for obsessive–compulsive disorder. Multivariate analysis showed panic disorder prevailing in migraine compared with the other groups (OR 2.9; 95% CI 1.2–7.0). The association was higher (OR 6.3; 95% CI 1.4–28.5) when migraine (with or without tension-type headache) was compared to pure tension-type headache. This also applied to obsessive–compulsive disorder (OR 4.8; 95% CI 1.1–20.9) in migraine plus tension-type headache. Psychopathology of primary headache can reflect shared risk factors, pathophysiologic mechanisms, and disease burden.     

Increased plasma transforming growth factor-beta1 in migraine

BACKGROUND AND OBJECTIVES: Migraine is characterized by the peripheral and central sensitization of pain perceptive neural systems, and neurogenic inflammation is a key step in the development of migraine headache. We focused on transforming growth factor-beta1 (TGF-beta1), which is a multifunctional proinflammatory cytokine. To address the possibility of TGF-beta1 involvement in migraine, we investigated the plasma level of TGF-beta1 in patients with migraine headache during headache-free periods. Subjects and METHODS: Sixty-eight subjects with migraine participated: 23 with migraine with aura (MWA) and 45 without aura (MWoA). We recruited 58 healthy subjects without headache as controls. In addition, we examined 12 subjects with episodic tension-type headache. Platelet poor plasma (PPP) was obtained from subjects during headache free-periods. TGF-beta1 levels in PPP were determined by enzyme-linked immunosorbent assay. RESULTS: The TGF-beta1 level in PPP was 2.62*+/- 0.23 (mean +/- SE) ng/mL in migraine, 2.08 +/- 0.20 ng/mL in tension-type headache, and 1.80 +/- 0.09 ng/mL in controls (P= .007, ANOVA; *P < .01, post hoc tests vs. the controls). CONCLUSION: TGF-beta1 in PPP was significantly increased in patients with migraine during headache-free periods. TGF-beta1 may play some role in the development of migraine headache.     

Association between blood pressure measures and recurrent headache in adolescents: cross-sectional data from the HUNT-Youth study

The relationship between blood pressure and headache in youth has not been explored and the objective of the present study was to provide data on this association in an adolescent population. Cross-sectional data from a large population-based survey, the Young-HUNT study, on 5,847 adolescents were used to evaluate the association between blood pressure (systolic, diastolic, mean arterial and pulse pressure) and recurrent headache, including migraine and tension-type headache. Increasing pulse pressure was inversely related to recurrent headache prevalence, and both tension-type headache and migraine. For systolic blood pressure such an inverse relationship was present for recurrent headache and tension-type headache prevalence. For migraine, the results were not significant, although there was a tendency in the same direction (p = 0.05). High-pulse pressure has previously been found to be inversely related to the prevalence of migraine and tension-type headache in an adult population. This inverse relationship has now been demonstrated to be present among adolescents also, supporting the results from a previous study in adults, that blood pressure regulation may be linked to the pathophysiology of headache.     

Psychopathology and quality of life burden in chronic daily headache: influence of migraine symptoms

The aim of this study is to compare the psychopathology and the quality of life of chronic daily headache patients between those with migraine headache and those with tension-type headache. We enrolled 106 adults with chronic daily headache (CDH) who consulted for the first time in specialised centres. The patients were classified according to the IHS 2004 criteria and the propositions of the Headache Classification Committee (2006) with a computed algorithm: 8 had chronic migraine (without medication overuse), 18 had chronic tension-type headache (without medication overuse), 80 had medication overuse headache and among them, 43 fulfilled the criteria for the sub-group of migraine (m) MOH, and 37 the subgroup for tension-type (tt) MOH. We tested five variables: MADRS global score, HAMA psychic and somatic sub-scales, SF-36 psychic, and somatic summary components. We compared patients with migraine symptoms (CM and mMOH) to those with tension-type symptoms (CTTH and ttMOH) and neutralised pain intensity with an ANCOVA which is a priori higher in the migraine group. We failed to find any difference between migraine and tension-type groups in the MADRS global score, the HAMA psychological sub-score and the SF36 physical component summary. The HAMA somatic anxiety subscale was higher in the migraine group than in the tension-type group (F(1,103) = 10.10, p = 0.001). The SF36 mental component summary was significantly worse in the migraine as compared with the tension-type subgroup (F(1,103) = 5.758, p = 0.018). In the four CDH subgroups, all the SF36 dimension scores except one (Physical Functioning) showed a more than 20 point difference from those seen in the adjusted historical controls. Furthermore, two sub-scores were significantly more affected in the migraine group as compared to the tension-type group, the physical health bodily pain (F(1,103) = 4.51, p = 0.036) and the mental health (F(1,103) = 8.17, p = 0.005). Considering that the statistic procedure neutralises the pain intensity factor, our data suggest a particular vulnerability to somatic symptoms and a special predisposition to develop negative pain affect in migraine patients in comparison to tension-type patients.     

Photophobia and phonophobia in tension-type and cervicogenic headache

Light and sound-induced discomfort and pain thresholds were measured in 26 patients with cervicogenic headache, in 40 patients with tension-type headache, and in 100 headache-free controls. Neither headache group was significantly different as to photophobia and phonophobia, but both were significantly more sensitive to light and sound than controls ( p <0.0001), even when patients were tested in the headache-tree period ( p <0.05). Episodic and chronic tension-type headache had similar photo- and phonophobia thresholds ( p ≥0.7). Tension-type headache patients were more photo- and phonophobic during headache than outside attack ( p <0.05), but this was not true for cervicogenic headache ( p ≥0.56). In cervicogenic headache patients, photophobia ( p <0.05) but not phonophohia ( p =0.28) was greater on the symptomatic side than on the non-symptomatic side.