Platelet Activity in Migraine

SYNOPSIS
Migraine is a disease associated with increased platelet activity.
The aim of this paper was to study "in vivo" platelet activation by assessing platelet serotonin (5HT) content and beta-thromboglobulin (B-TG) and platelet factor four (PF4) plasma levels, in headache-free-periods and during migraine attacks.
In headache-free-periods, there was no differences in platelet 5HT values between migraine patients and control subjects. On the other hand, there were significant differences in B-TG and PF4 plasma levels. Furthermore, two groups of migraine patients were observed, one with normal B-TG plasma levels and the other with high B-TG plasma levels. PF4 plasma levels behave similarly.
During migraine attacks, platelet 5-HT fell, while B-TG and PF4 plasma levels rose, if compared to the values recorded immediately before attacks.
We suggest that migraine patients, particularly those ones with high basal values of B-TG and PF4 plasma levels, form a high risk group to cerebrovascular ischaemic diseases. For these patients a prophylaxis with antiplatelet drugs is indicated.     

Painful Temporomandibular Disorder Is Associated With Migraine in Adolescents: A Case-Control Study

Some types of primary headaches and temporomandibular disorders (TMD) are comorbid in adults and highly prevalent in adolescents. Herein, we investigated the association of painful TMD with specific headache diagnoses (migraine, tension-type headache) and with headache frequency in adolescents. We also explored the association of headache diagnosis with the number of painful sites in the trigeminal area. Painful TMD was assessed using the Research Diagnostic Criteria for TMD. We conducted a case-control study of adolescents from 13 to 15 years old who were recruited among participants in a previous epidemiologic study conducted in Araraquara, SP, Brazil. Headaches were classified according to the second edition of the International Classification for Headache Disorders. Logistic, multinomial logistic and linear regression models were used to test associations. Of 149 individuals, 55.7% presented painful TMD. Adolescents with painful TMD (cases) were more likely to have migraine compared with those without TMD (controls; odds ratio = 3.0, 95% confidence interval = 1.47–6.19, P = .033). Significant differences were not observed for probable tension-type headache (P = .307) or tension-type headache (P = .834). Painful TMD was also associated with an increase in headache frequency (linear-by-linear association = 8.051; P = .005). Only migraine was associated with a greater number of painful sites on palpation in the trigeminal area (P = .001). Migraine and frequency of headache were associated with painful TMD in adolescents.PerspectiveMigraine and headache frequency were strongly associated with painful TMD in adolescents, and causality must be determined. For now, the presence of 1 condition should raise suspicion of the other and warrants collaboration between orofacial pain specialists and neurologists.     

Migraine: A Psychosomatic Disorder

SYNOPSIS
Migraine has no single cause. It can be seen as a reaction of the organism, probably determined by the hypothalamus and released by a variety of extrinsic and intrinsic factors. Several factors may determine attacks at different times within a patient's lifetime. Vascular reactions are secondary to the primary cerebral mechanism, and account for many of the symptoms, notably the headache. The prodrome, aura, and the incubation during sleep are part of the attack.
Emotional disturbance is the commonest single trigger mechanism, and is the most important cause of frequent and severe attacks. There is, however, nothing specific about the emotional stimulus, nor is there a consistent personality type in migraine subjects. Certain personality reactions and patterns of behavior recur in migraine subjects; a tendency to anxiety reactions, sensitivity to stress and difficulty in handling aggressive and hostile drives. In this respect, migraine is similar to many other "psychosomatic diseases" without demonstrable pathology but characterized by disorders of homeostasis. In some patients extrinsic physical and biochemical precipitants are prominent and the "psychosomatic element" is slight. In most migraine patients, however, psychologic factors are important but are secondary rather than precipitating etiologic agents.     

Posttraumatic Stress Disorder in Migraine

Objective.— To evaluate the relative frequency of posttraumatic stress disorder (PTSD) in episodic migraine (EM) and chronic daily headache (CDH) sufferers and the impact on headache-related disability.
Background.— Approximately 8% of the population is estimated to have PTSD. Recent studies suggest a higher frequency of PTSD in headache disorders. The association of PTSD and headache-related disability has not been examined.
Methods.— A prospective study was conducted at 6 headache centers. PTSD was assessed using the life events checklist and PTSD checklist, civilian version (PCL-C). We compared data from EM to CDH, and migraine with PTSD to migraine without PTSD. The PHQ-9 was used to assess depression, and headache impact test (HIT-6) to assess disability.
Results.— Of 767 participants, 593 fulfilled criteria for EM or CDH and were used in this analysis. The mean age was 42.2 years and 92% were women. The frequency of PTSD was greater in CDH than in EM (30.3% vs 22.4%, P  = .043), but not after adjusting for demographics and depression ( P  = .87). However, participants with major depression and PTSD were more likely to have CDH than EM (24.6% vs 15.79%, P  < .002). Disability was greater in migraineurs with PTSD, even after adjustments (65.2 vs 61.7, P  = .002).
Conclusion.— The frequency of PTSD in migraineurs, whether episodic or chronic, is higher than the historically reported prevalence of PTSD in the general population. In addition, in the subset of migraineurs with depression, PTSD frequency is greater in CDH sufferers than in episodic migraineurs. Finally, the presence of PTSD is independently associated with greater headache-related disability in migraineurs.     

Platelet Fibrinogen Receptors in Migraine Patients

SYNOPSIS
In order to determine the platelet characteristics responsible for aggregation, the number and apparent dissociation constant (K D aPP ) of fibrinogen receptors were determined in 12 women with common migraine. The studies were performed by the use of 125 -fibrinogen. The patients were assessed in headache-fee intervals. The mean number of platelet fibrinogen receptors exposed in migraine patients was significantly higher than those obtained in healthy controls (p<0.05). The (K D aPP ) in migraineurs was about three times lower than in the controls (p<0.02). The results indicate that both the number and affinity of fibrinogen receptors or platelets are increased in migraine patients. The authors conclude that this phenomenon may be responsible for the increased number of circulating platelet aggregates in migraine patients and for the prevalence of various kinds of strokes during migraine attacks.     

Platelet Lipid Composition in Human Migraine

SYNOPSIS
Fatty acid profiles were determined in platelets of 21 patients suffering from Classical Migraine and these results were compared with those obtained in a control group of 24 healthy individuals. Cholesterol levels and the cholesterol/phospholipid ratios of 4 of the migraine patients were investigated and compared with values obtained from 4 age-matched control persons.
No significant differences could be detected between the fatty acid profiles of the migraine and control groups, Analysis of the cholesterol content and the cholesterol/phospholipid ratio of the platelets revealed no significant differences between the two groups.
Freeze-fracture electron microscopy of the platelet membranes of the two groups revealed no striking differences in the protein distribution and environment in the migraine condition.
We conclude that the membranes of platelets of migraine-suffering and control individuals have a similar composition, the symptoms of this disorder thus being mediated by other differences between the platelets.     

Platelet Antibodies in Patients With Migraine

The reported decrease of platelet serotonin receptors in patients with migraine could be due to an autoimmune reaction. We, therefore, examined sera from 42 migraineurs without aura, 26 migraineurs with aura, and 107 headache-free blood donors for platelet-reactive antibodies using the platelet adhesion immunofluorescence test, the NIH-lymphocytotoxicity test, and the monoclonal antibody-specific immobilization of platelet antigens test. IgG antibodies against non-HLA class I platelet antigens were found in 9.5% of patients with migraine without aura, 7.6% of patients with migraine with aura, and in 7.5% of controls; IgM antibodies were found in 11.9% of patients with migraine without aura, in 30.8% of patients with migraine with aura, and in 13.1% of controls. Most antibodies ware directed against glycoprotein complexes IIb-IIIa (fibrinogen receptor) or IB-IX (thrombin receptor). Two patients with migraine without aura but no patient with migraine with aura nor any control subject had IgG antibodies of unknown specificity. One patient (2.4%) with migraine without aura and two patients (7.7%) with migraine with aura, as well as 2 controls (1.9%) had IgM antibodies not further specified. The differences in frequency of platelet antibodies of known or unknown specificity in patients with migraine without aura and migraine with aura and controls were not statistically significant. Therefore, our data do not support the hypothesis of a pathophysiologically relevant autoimmune reaction against platelet serotonin receptors in the majority of patients with migraine. We can not exclude the occurrence of antibodies against neuron-specific serotonin receptors.     

Migraine Patients Show Increased Platelet Vasopressin Receptors

This study was designed to investigate vasopressin receptor status (B_max and K_d) on platelets, vasopressin plasma levels, and vasopressin-induced platelet aggregation in migraine patients (21 females and 6 males) during a headache-free interval and in a matched control group. In the migraine group, B max was significantly higher ( P = 0.02) at 53.9 ± 20.6 fmol/mg than in the control group (36.8 + 21.0 fmol/mg). A correlation between B_max and high or low sensitivity to vasopressin as an aggregator was evident in the control group, but not in the migraine group. No differences in K_d or in plasma levels of vasopressin between the migraine and control group were apparent. Men in both groups were much less sensitive to vasopressin as a platelet aggregator than were women ( P < 0.01). Whether the higher B_max in the migraine group is a reflection of temporarily higher vasopressin levels during headache or reflects a primary increase in sensitivity to vasopressin, remains to be clarified. The higher sensitivity of platelets (as a model for vessel wall receptors) from women may indicate why many more women than men suffer from migraine. Since the B_max of the vasopressin receptor on platelets from migraine patients is increased compared to controls, treating migraine headache with vasopressin may deserve more attention.     

The Platelet Release Reaction During Migraine Attacks

SYNOPSIS
An investigation is reported of serum levels of Beta Thromboglobulin (BTG), a platelet release reaction specific protein, and the stable metabolites of thromboxane B2 and prostacyclin during and between migraine attacks, and in age and sex matched controls.
The level of BTG in plasma from controls was 61.3 ngml (± 26.15), in patients during migraine attacks 127.69 ngml (± 82.8) whilst between attacks the level was 69.06 ngml.
No changes were observed in the levels of the stable metabolite of thromboxane B2 and prostacyclin.
The significant rise in BTG (p = < .02) during migraine attacks indicates that the platelet release reaction occurs during the headache phase.     

Platelet Norepinephrine and Serotonin Balance in Migraine

Platelet serotonin (5 hydroxytryptamine, 5-HT) and norepinephrine (NE) were measured in common and classic migraine patients and healthy controls. Common migraine sufferers had high NE levels and a low 5-HT/NE ratio. Classic migraine patients had a high 5-HT level and a high 5-HT/NE ratio. The data suggest disparate NE and 5-HT metabolism between common and classic migraine.     

Obsessive-Compulsive Disorder and Migraine With Medication-Overuse Headache

Objective.— A strong association has been demonstrated between migraine, particularly in the chronic form and with medication overuse, and either major depression or various anxiety disorders. However, there has been less systematic research on the links between migraine with medication-overuse headache (MOH) and obsessive-compulsive disorder (OCD). A drug-seeking behavior shares with OCD the compulsive quality of the behavior. We investigated the relationship between OCD and MOH in migraineurs.
Methods.— A structured questionnaire was administered to subjects with: episodic migraine (EM) (n = 30), chronic migraine (CM) (n = 24), and MOH with a previous history of EM (n = 33) and 29 control subjects. Psychiatric diagnoses were made by a senior psychiatrist blinded to the diagnosis of migraine. Psychiatric assessment of OCD illness was evaluated by means of The Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Results.— In the subgroup of patients with MOH, psychiatric comorbidity (anxiety and mood disorders) was prevalent compared with CM, EM, and controls ( P  < .0001). Subclinical OCD was significantly prevalent in MOH patients with respect to other groups ( P  < .0002). Higher scores in Y-BOCS, as a measure of severity of obsessive-compulsive symptoms, were found in both MOH and CM compared with controls and EM.
Conclusions.— The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and undertreated.     

Platelet Monoamine Oxidase Activity in Female Migraine Patients

Platelet monoamine oxidase activity (MAO) in a group (n = 17) of white, female migraineurs during an acute migraine attack was similar to both the values obtained for the same group of patients two to three weeks after the headache episode (pain-free period) and to the results obtained for a group (n = 18) of sex and race-matched, age-comparable, drug-free healthy volunteers (blind study; substrate p-tyramine, 38.7 +/- 5.7, 41.9 +/- 8.8 and 43.0 +/- 3.4 or p-methoxybenzylamine, 178.9 +/- 11.3, 177.2 +/- 6.9 and 181.0 +/- 9.7 nmole/hr/10(9) platelets +/- SD respectively). With each patient serving as its own control, MAO activity during the migraine episode and when pain-free failed to show a significant trend. Neither a number of other medical conditions nor the use of several medications appeared to significantly influence our results. The present work, while dealing only with a small but well defined patient population, argues against the possible usefulness of platelet MAO activity as a biological marker for migraine headaches.