Neurochemical metabolite alterations of the occipital lobe in migraine without aura by proton magnetic resonance spectroscopy.

BACKGROUND: Migraine without aura is the most common type of migraine headache, accounting for about 80% of all migraines. The aim of the present investigation was to determine the neurochemical metabolite alterations in the occipital lobe of patients suffering from migraine without aura using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Fifteen patients suffering from migraine without aura with an occipital plaque and 16 healthy controls were included in this study. Changes in the neurochemical metabolites in the occipital lobe were assessed using 1H-MRS. The ratios of N-acetylaspartate (NAA) to creatine (Cr), choline (Cho) to Cr and myo-inositol (MI) to NAA were measured by voxel volume at 8 cm3. RESULTS: The mean NAA/Cr ratio decreased significantly in patients compared to controls. Cho/Cr and MI/NAA ratios increased significantly in patients. In addition, the duration of the disease and the frequency of headache attacks were significantly associated with a decrease in the NAA/Cr ratio and an increase in the Cho/Cr ratio. CONCLUSIONS: Migraine without aura shows a significant association with changes in neurochemical metabolites detectable by 1H-MRS in the occipital lobe of patients. In addition, changes in metabolic ratios showed a significant relationship with the duration of the disease and the frequency of headache attacks.

The Posterior Insula Shows Disrupted Brain Functional Connectivity in Female Migraineurs Without Aura Based on Brainnetome Atlas.

Long-term headache attacks may cause human brain network reorganization in patients with migraine. In the current study, we calculated the topologic properties of functional networks based on the Brainnetome atlas using graph theory analysis in 29 female migraineurs without aura (MWoA) and in 29 female age-matched healthy controls. Compared with controls, female MWoA exhibited that the network properties altered, and the nodal centralities decreased/increased in some brain areas. In particular, the right posterior insula and the left medial superior occipital gyrus of patients exhibited significantly decreased nodal centrality compared with healthy controls. Furthermore, female MWoA exhibited a disrupted functional network, and notably, the two sub-regions of the right posterior insula exhibited decreased functional connectivity with many other brain regions. The topological metrics of functional networks in female MWoA included alterations in the nodal centrality of brain regions and disrupted connections between pair regions primarily involved in the discrimination of sensory features of pain, pain modulation or processing and sensory integration processing. In addition, the posterior insula decreased the nodal centrality, and exhibited disrupted connectivity with many other brain areas in female migraineurs, which suggests that the posterior insula plays an important role in female migraine pathology.

Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo.

OBJECTIVE: To evaluate in vivo the dynamics of endogenous dopamine (DA) neurotransmission during migraine ictus with allodynia. METHODS: We examined 8 episodic migraineurs and 8 healthy controls (HC) using PET with [11C]raclopride. The uptake measure of [11C]raclopride, nondisplaceable binding potential (BPND), would increase when there was a reduction in endogenous DA release. The opposite is true for a decrease in [11C]raclopride BPND. Patients were scanned twice: one PET session was during a spontaneous migraine ictus at rest, followed by a sustained thermal pain threshold (STPT) challenge on the trigeminal region, eliciting an allodynia experience; another was during interictal phase. RESULTS: Striatal BPND of [11C]raclopride in migraineurs did not differ from HC. We found a significant increase in [11C]raclopride BPND in the striatum region of migraineurs during both headache attack and allodynia relative to interictal phase. However, when compared to the migraine attack at rest, migraineurs during the STPT challenge had a significant sudden reduction in [11C]raclopride BPND in the insula. Such directional change was also observed in the caudate of HC relative to the interictal phase during challenge. Furthermore, ictal changes in [11C]raclopride BPND in migraineurs at rest were positively correlated with the chronicity of migraine attacks, and negatively correlated with the frequency during challenge. CONCLUSIONS: Our findings demonstrate that there is an imbalanced uptake of [11C]raclopride during the headache attack and ictal allodynia, which indicates reduction and fluctuation in ictal endogenous DA release in migraineurs. Moreover, the longer the history and recurrence of migraine attacks, the lower the ictal endogenous DA release.

Decreased functional connectivity density in pain-related brain regions of female migraine patients without aura.

Migraine is one of the most prevalent neurological disorders which is suggested to be associated with dysfunctions of the central nervous system. The purpose of the present study was to detect the altered functional connectivity architecture in the large-scale network of the whole brain in migraine without aura (MWoA). Meanwhile, the brain functional hubs which are targeted by MWoA could be identified. A new voxel-based method named functional connectivity density (FCD) mapping was applied to resting-state functional magnetic resonance imaging data of 55 female MWoA patients and 44 age-matched female healthy controls (HC). Comparing to HC, MWoA patients showed abnormal short-range FCD values in bilateral hippocampus, bilateral insula, right amygdale, right anterior cingulate cortex, bilateral putamen, bilateral caudate nucleus and the prefrontal cortex. The results suggested decreased intraregional connectivity of these pain-related brain regions in female MWoA. In addition, short-range FCD values in left prefrontal cortex, putamen and caudate nucleus were significantly negatively correlated with duration of disease in MWoA group, implying the repeated migraine attacks over time may consistently affect the resting-state functional connectivity architecture of these brain hubs. Our findings revealed the dysfunction of brain hubs in female MWoA, and suggested the left prefrontal cortex, putamen and caudate nucleus served as sensitive neuroimaging markers for reflecting the disease duration of female MWoA. This may provide us new insights into the changes in the organization of the large-scale brain network in MWoA.

MicroRNA profiling in migraine without aura: pilot study.

BACKGROUND AND PURPOSE: MicroRNAs (miRNAs) are short, non-coding RNAs whose deregulation has been shown in several human diseases, including pain states and diseases associated with increased cardiovascular (CV) risk. This study aimed at identifying differentially expressed circulating miRNAs in patients with 'migraine without aura' (MO), a pain condition whose link with CV risk remains debated. METHODS: Fifteen female MO patients and 13 matching healthy controls underwent a circulating microRNA expression profiling. MiR-22, miR-26a, miR-26b, miR-27b, miR-29b, let-7b, miR-181a, miR-221, miR-30b, and miR-30e were selected for validation by quantitative real-time polymerase chain reaction. RESULTS: In migraineurs versus controls, four miRNAs were differentially expressed: miR-27b was significantly up-regulated (q < 0.004), while miR-181a, let-7b, and miR-22 were significantly down-regulated (q ≤ 0.01). MiR-22 and let-7b down-regulation was also confirmed in circulating blood monocytes. A logistic regression model based on microRNA expression profile showed a high accuracy for identifying migraine (AUC of ROC curve: 0.956; P < 0.001). CONCLUSION: A specific circulating miRNAs profile is associated with migraine without aura. Remarkably, the same miRNAs are known to be modulated in the setting of atherosclerosis and stroke in humans. This study represents a first step towards further characterization of MO diagnosis/pathophysiology, also in relation to its link with cardiovascular risk.

Abnormal Connectivity Within Executive Resting-State Network in Migraine With Aura.

OBJECTIVE: To evaluate the executive control network connectivity integrity in patients with migraine with aura, in the interictal period, in comparison to patients with migraine without aura and healthy controls. METHODS: Using resting-state functional magnetic resonance imaging, we compared executive control network functional connectivity in 20 patients with migraine with aura vs 20 sex and age-matched patients with migraine without aura and 20 healthy controls, and assessed the correlation between executive control network functional connectivity and clinical features of patients with migraine. We used voxel-based morphometry and diffusion tensor imaging to investigate potential structural or microstructural changes. RESULTS: Neuropsychological data revealed no significant executive dysfunction in patients with migraine. Resting-state functional magnetic resonance imaging showed significant group differences in right middle frontal gyrus (Talairach coordinates x, y, z: +26, +2, +48) and dorsal anterior cingulate cortex (Talairach coordinates x, y, z: +6, +13, +49), indicating that these areas had a decreased component activity in both patients with migraine with and without aura when compared with healthy controls. Conversely, there were no significant differences in the executive control network functional connectivity between patients with migraine with and without aura (P < .05, cluster-level corrected). These functional abnormalities are independent of structural and microstructural changes and did not significantly correlate with clinical parameters. CONCLUSIONS: Our data demonstrate a disrupted executive control network functional connectivity in patients with migraine with and without aura, in the interictal period. Although this functional phenomenon is present in the absence of clinically relevant executive deficits, it may reflect a vulnerability to executive high-demanding conditions of daily living activities in patients with migraine.

Midriasis benigna episódica. Experiencia en una consulta monográfica de neuro-oftalmología de un hospital terciario / Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic of a tertiary hospital

Introducción: Las anisocorias son un motivo de consulta relativamente frecuente en unidades de neuro-oftalmología (UNO). Suponen un reto diagnóstico por la variedad de procesos que pueden ocasionarla. En ausencia de síntomas acompañantes, suelen estar ocasionadas por procesos benignos. La midriasis benigna episódica (MBE) es una causa aislada de asimetría pupilar intermitente, de fisiopatología no esclarecida y predominio en mujeres jóvenes migrañosas. Sujetos, material y métodos: Describimos las características epidemiológicas y clínicas de los pacientes con MBE valorados en una UNO de un hospital terciario. Resultados: Un total de 7 pacientes fueron diagnosticadas de MBE. Todas eran mujeres, con edad media de 33 ± 10 años. Los motivos de consulta fueron asimetría pupilar (n = 5) y visión borrosa (n = 2) de presentación fundamentalmente unilateral (n = 6). La duración fue variable, desde minutos hasta 48 h. Cuatro pacientes (57%) presentaban como antecedente migraña sin aura. En estas, los episodios eran recidivantes (75%), de minutos de duración (75%) y asociaban visión borrosa (50%). Los estudios de neuroimagen (resonancia magnética cerebral) fueron normales. Discusión: La midriasis benigna episódica se presenta predominantemente en mujeres jóvenes. Se asocia al antecedente de migraña y hace plantear si se trata de un síntoma acompañante de la migraña, un aura migrañosa o de migraña oftalmopléjica. De predominio unilateral, puede sin embargo existir alternancia del ojo afectado o ser bilateral de forma simultánea, lo que nos hace cuestionarnos la idoneidad del término. En ausencia de síntomas acompañantes y en episodios de corta duración, no consideramos necesaria la realización de pruebas de imagen

Introduction: Anisocorias are a relatively frequent reason for consultation in neuro-ophthalmology units. They remain a diagnostic challenge for specialists as they may be due to several etiological factors. In the absence of other accompanying symptoms, anisocorias are usually due to benign processes. Benign episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in which the pathophysiology is still not fully understood, and is predominant in young women with migraine. Subjects, material and methods: We describe the epidemiological and clinical characteristics of patients with BEM, assessed in a neuro-ophthalmology unit in a tertiary hospital. Results: A total of 7 patients were diagnosed with BEM, all of them females, with a mean age of 33 ± 10 yrs. The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2), and 6 of the 7 patients had unilateral involvement. The duration of impairment varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history of migraine without aura. The episodes in these 4 patients were recurrent (75%), often lasted for a few minutes (75%), and had associated blurred vision (50%). The neuroimaging studies were normal. Discussion: BEM appears predominantly in young women. It is frequently related to a previous history of migraine, and the specialist must consider if it is a concomitant symptom of common migraine, migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral predominance, there may be alternation of the affected eye or even bilateral impairment during the same episode, which makes us question the adequacy of the term to describe the process. Imaging tests are not recommended in the absence of other accompanying symptoms, or in short-term episodes

Measurement of visual sensitivity in migraine: Validation of two scales and correlation with visual cortex activation.

OBJECTIVE: The objectives of this article are to compare interictal and ictal visual sensitivity between migraine and controls using two published questionnaires, and to correlate responses with a physiologic measure of visual cortex activation. METHODS: Migraine with (MWA, n = 51) and without (MwoA, n = 45) aura and control individuals (n = 45) were enrolled and underwent BOLD fMRI with a visual stimulus. The visual discomfort score (VDS) assessed interictal and the migraine photophobia score (MPS) assessed ictal visual sensitivity. RESULT: VDS was significantly higher both in MWA and MwoA vs controls (both p = 0.0001). MPS was greater in MWA vs MwoA (p = 0.008). Ictal and interictal visual sensitivity strongly correlated in MWA (p = 0.004) but not MwoA patients (p = 0.12). BOLD activation in visual cortex was greater in MWA vs controls (2.7% vs 2.3%, p = 0.003) but similar between MwoA and controls. Increasing VDS was associated with greater BOLD signal change in MWA (p = 0.03) but not MwoA (p = 0.65) or controls (p = 0.53). MPS did not correlate with BOLD activation in either group. CONCLUSION: Increased interictal visual sensitivity is present both in MWA and MwoA. However, the correlation with ictal visual sensitivity and with cortical hyper-responsivity varies between MWA and MwoA, suggesting underlying differences between groups.

α-[11C] methyl-L tryptophan-PET as a surrogate for interictal cerebral serotonin synthesis in migraine without aura.

BACKGROUND: Alteration in central serotonin biology has been implicated in migraine, and serotonin (5-HT) agonists have been available for more than a decade in the treatment of that condition. OBJECTIVES: To test this hypothesis, we studied in vivo using positron-emission tomography (PET) and α-[(11)C] methyl-L-tryptophan (α-[(11)C]MTrp) as a surrogate marker of cerebral 5-HT synthetic rate before and after administration of eletriptan in migraine and control subjects. METHODS: Six nonmenopausal female migraine subjects with migraine without aura (MoA) and six nonmenopausal age-matched female control subjects were scanned at baseline and after oral administration of 40 mg of eletriptan. Migraine subjects at the time of PET had to have been headache free for a minimum of three days. Images of (α-[(11)C]MTrp) brain trapping were colocalized with individual MRI images in three dimensions and analyzed. RESULTS: There was no difference in baseline cerebral global 5-HT synthesis between migraine and control subjects. After administration of eletriptan, there was a striking global reduction in cerebral 5-HT synthesis (K*) in the migraine group and in 22 regions of interest (ROIs). In control subjects, no significant changes were found in global cerebral 5-HT synthesis (K*) or in any of the ROIs. CONCLUSIONS: These findings suggest in migraine an interictal alteration in the regulation mechanisms of cerebral 5-HT synthesis.

[Evaluation of platelet serotonin levels in migraine without aura]. / Aurasiz migrende trombosit serotonin düzeylerinin degerlendirilmesi.

OBJECTIVES: The relation between migraine and serotonin levels is not clear. Plasma serotonin levels in migraineurs were investigated in previous studies. However, in the current literature, it is stated that measurement of serotonin level in platelets is more reliable. METHODS: Thirty female migraine without aura patients who were diagnosed according to the criteria of the International Headache Society and 20 healthy controls were enrolled in the study. The Hamilton depression scale (HAM-D) was applied to all subjects and those scoring 10 and above were not considered. Fasting venous blood samples were taken from subjects in the morning. Platelet rich and poor plasma were prepared. The samples were measured with high performance liquid chromatography and platelet serotonin concentration was calculated. RESULTS: Our results suggest that migraineurs have significantly low platelet serotonin concentration compared to controls. The ratio of family history of migraine in the patient group was clearly higher than in controls. HAM-D scores were significantly higher in migraineurs than in the control group. Although there was a weak correlation between low serotonin levels and attack duration and number, there was no statistical significance. CONCLUSION: Our results suggest the role of heredity and low serotonin levels in the migraine pathogenesis. Even though all subjects enrolled in the study had scores under the depression level, HAM-D scores were higher in migraineurs than controls. This may indicate the presence of subclinical depression associated with low serotonin levels in migraineurs. Extensive studies including both serotonin and other markers during pain and pain-free periods are needed.

Associations between lipid levels and migraine: cross-sectional analysis in the epidemiology of vascular ageing study.

BACKGROUND: Migraine with aura has been associated with increased prevalence of cardiovascular risk factors, including elevated levels of some vascular biomarkers. However, little research has been done on this association among the elderly. We examined the associations of lipid levels with headache and migraine in a cohort of elderly individuals. METHODS: Cross-sectional study among 1155 participants enrolled in the Epidemiology of Vascular Ageing Study with available information on headache and blood biomarkers. We used multinomial logistic regression to evaluate the association between biomarker tertiles and headache categories. RESULTS: 925 people had no severe headache, 64 people had non-migraine headache and 166 people had migraine, of whom 23 had aura. Compared with participants without headache, we observed strong associations between increasing tertiles of total cholesterol and migraine with aura. The odds ratio (95% confidence interval) was 4.67 (0.99-21.97) for the 2nd tertile and 5.97 (1.29-27.61) for the 3rd tertile. We also found strong associations between triglycerides and migraine with aura (odds ratio for 3rd tertile: 4.42 (1.32-14.77)). We did not see significant associations between increased biomarker levels and any other headache group. CONCLUSIONS: Elevated levels of total cholesterol and triglycerides are associated with migraine with aura but not other headache forms in the elderly.

Almotriptan for menstrually related migraine.

INTRODUCTION: Approximately 50% of migrainous women associate their headache temporally to menses. Menstrually related migraine (MRM) is a disabling form of migraine characterized by attacks that are generally longer, more severe and less drug-responsive than nonmenstrual ones. Since MRM may be difficult to treat, it is important to find an appropriate treatment option for women suffering from this condition. AREAS COVERED: This paper provides an overview of the clinical features of MRM, with special attention on the use of almotriptan for its treatment. Four studies on almotriptan in the treatment of MRM are present in the medical literature. Two report post hoc analyses of data derived from larger studies on the use of almotriptan for migraine treatment. One reports the results from a study specifically dedicated to MRM and one illustrates a subanalysis on the accompanying symptomatology. EXPERT OPINION: Evidence demonstrates that almotriptan is a molecule with a high efficacy in the treatment of MRM and with an excellent tolerability profile when compared with other triptans. Moreover, it shows a proven ability to control migraine-associated symptoms. All these qualities play a decidedly positive role in making almotriptan a product of choice for the treatment of MRM.

Does visual cortex lactate increase following photic stimulation in migraine without aura patients? A functional (1)H-MRS study.

Proton magnetic resonance spectroscopy ((1)H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS ((31)P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional (1)H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1-0.2 µmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients.

31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients.

BACKGROUND: Differences in brain energy metabolism have been found between migraine patients and controls in previous phosphorus magnetic resonance spectroscopy ((31)P-MRS) studies, most of them emphasizing migraine with aura (MwA). The aim of this study was to verify potential changes in resting-state brain energy metabolism in patients with migraine without aura (MwoA) compared to control subjects by (31)P-MRS at 3 tesla. METHODS: Quantification was performed using the phantom replacement technique. MRS measurements were performed interictally and in the medial occipital lobe of 19 MwoA patients and 26 age-matched controls. RESULTS: A significantly decreased phosphocreatine concentration ([PCr]) was found as in previous studies. While adenosine triphosphate concentration ([ATP]) was considered to be constant in previously published work, this study found a significant decrease in the measured [ATP] in MwoA patients. The inorganic phosphate ([P(i)]) and magnesium ([Mg(2+)]) concentrations were not significantly different between MwoA patients and controls. CONCLUSIONS: The altered metabolic concentrations indicate that the energy metabolism in MwoA patients is impaired, certainly in a subgroup of patients. The actual decrease in [ATP] adds further strength to the theory of the presence of a mitochondrial component in the pathophysiology of migraine.

Monitoring cortical hemodynamic changes after sumatriptan injection during migraine attack by near-infrared spectroscopy.

The aim of the present study is to provide effective tools for monitoring hemodynamic changes in the cortical and scalp surface during migraine attack and treatment. Using near-infrared spectroscopy system (NIRS) and laser Doppler skin blood flow (SkBF) devices in combination, we monitored changes in extra- and intra-cranial vasculature states upon sumatriptan injection during spontaneous migraine attack. We examined 4 control subjects and 4 migraine patients. Multi-channel NIRS probes were placed over the temporoparietal area bilaterally and oxygenated hemoglobin (oxy-Hb) was analyzed. Laser Doppler SkBF was simultaneously recorded to measure scalp surface blood flow changes. All patients were treated with a sumatriptan injection (3 mg), and all control subjects received a saline injection as a control for oxy-Hb/SkBF signals caused by injection pain over the monitoring period. There was a marked reduction of oxy-Hb/SkBF in all patients after sumatriptan injection, consistent with pain relief. Moreover, the changes in oxy-Hb/SkBF were significantly correlated. By contrast, saline injection did not cause any significant changes. These data suggest that sumatriptan induces blood vessel contraction at both cortical and scalp surfaces. Simultaneous oxy-Hb/SkBF recording enables real-time continuous monitoring of the effects of sumatriptan treatment in clinical situations.

(1)H-MRS of brain metabolites in migraine without aura: absolute quantification using the phantom replacement technique.

OBJECTIVE: Several studies have demonstrated differences in migraine patients when performing (1)H-MRS; however, no studies have performed (1)H-MRS in migraine without aura (MwoA), the most common migraine subtype. The aim of this (1)H-MRS study was to elucidate whether any differences could be found between MwoA patients and controls by performing absolute quantification. MATERIALS AND METHODS: (1)H-MRS was performed in 22 MwoA patients and 25 control subjects. Absolute quantification was based on the phantom replacement technique. Corrections were made for T (1) and T (2) relaxation effects, CSF content, coil loading and temperature. The method was validated by phantom measurements and in vivo measurements in the occipital visual cortex. RESULTS: After calibration of the quantification procedure and the implementation of the required correction factors, measured absolute concentrations in the visual cortex of MwoA patients showed no significant differences compared to controls, in contrast to relative results obtained in earlier studies. CONCLUSION: In this study, we demonstrate the implementation of quantitative in vivo (1)H-MRS spectroscopy in migraine patients. Despite rigorous quantification, no spectroscopic abnormalities could be found in patients with migraine without aura.

Intact neurovascular coupling during executive function in migraine without aura: interictal near-infrared spectroscopy study.

An altered neurovascular coupling has been proposed in migraine. We aimed to investigate neurovascular coupling during a mental task interictally in patients with migraine without aura (MO) by near-infrared spectroscopy (NIRS). Twelve migraineurs and 12 healthy controls were included. Using NIRS, we recorded the magnitude and latency of cortical changes in oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (Hb) during the colour-word matching Stroop test via 16 channels covering the forehead. We found no differences in the magnitude of responses between migraineurs and healthy subjects in the incongruent Stroop task subtracted by the neutral Stroop task on either side of the frontal cortex for HbO(2) (left, P = 0.984; right, P = 0.406) or Hb (left, P = 0.689; right, P = 0.406) values. No differences in error rate (P = 0.611) or reaction time (P = 0.936) were found between healthy subjects and MO patients for incongruent tasks. The present study suggests that vascular reactivity and oxygen supply during a mental task in patients with MO are intact interictally.

Matrix metalloproteinases during and outside of migraine attacks without aura.

To test the hypothesis that permeability of the blood-brain barrier (BBB) is altered during migraine attack due to enhanced activation of matrix metalloproteinases (MMPs), we investigated MMP-3, MMP-9 and tissue inhibitor of metalloproteases (TIMP)-1 in the external jugular vein during and outside of migraine attacks in 21 patients with migraine without aura. In addition, we measured plasma levels of several other proteins including MMP-7, -8, -10 and TIMP-2. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study plasma concentration of MMPs. There was no difference in MMP-9 and TIMP-1 levels between ictal and interictal periods. We found significantly decreased plasma levels of MMP-3 in the external jugular (P = 0.002) and cubital (P = 0.008) vein during attacks compared with outside of attacks. We found no correlation of ictal or interictal MMP-3, MMP-9 and TIMP-1 to migraine duration and frequency analysed in 21 patients (P > 0.05). There was no difference between ictal and interictal plasma levels of MMP-7, -8, -10 and TIMP-2 (P > 0.05). Our data suggest that plasma MMP-9 cannot be used as a biomarker of BBB disruption in migraine without aura. Decreased MMP-3 levels are an interesting and unexpected finding warranting further investigation.

Interictal brain 5-HT1A receptors binding in migraine without aura: a 18F-MPPF-PET study.

In this study we aimed to assess the brain distribution of 5-HT(1A) receptors in migraine patients without aura. Ten female migraine patients and 24 female healthy volunteers underwent magnetic resonance imaging and positron emission tomography using a radioligand antagonist of 5-HT(1A) receptors [4-(2'-methoxyphenyl)-1-[2'-(N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine ((18)F-MPPF)]. A simplified reference tissue model was used to generate parametric images of 5-HT(1A) receptor binding potential (BP) values. Statistical Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior cortical areas and hippocampi bilaterally in patients compared with controls. Region of interest (ROI) analysis showed a non-significant trend in favour of a BP increase patients in cortical regions identified by the SPM analysis except in hippocampi, left parietal areas and raphe nuclei. During the interictal period of migraine patients without aura, the increase of MPPF BP in posterior cortical and limbic areas could reflect an increase in receptor density or a decrease of endogenous serotonin, which could explain their altered cortical excitability.