Tolerability of acute migraine medications: influence of methods of assessment and relationship with headache attributes.

Tolerability is an important attribute of patient satisfaction with, and consequence adherence to, migraine acute treatment. Nevertheless, the determinants of tolerability are poorly explored. Accordingly, our objectives were: (i) in subjects receiving triptans, to contrast two methods of assessing adverse events (AEs); and (ii) to explore the relationship between migraine features and treatment attributes with tolerability. We surveyed 365 migraineurs who had been using the same triptan for at least 3 months. After prospectively treating an attack, headache characteristics and treatment response were assessed using headache calendars. Subjects also completed a standardized questionnaire, first asking about any AE and then prompting patients with a list of possible AEs. We contrasted both sets of answers and conducted logistic regression to assess if headache attributes or response to therapy influenced tolerability. Using the unprompted method, AEs occurred in 11.5-36.4% of patients, depending on the triptan used. Using the prompted method, they ranged from 26.9 to 64.3%. Chest and neck tightness were spontaneously reported by 3.5% of the sample, vs. 7.4% when prompted (P < 0.05). Chest pain was not spontaneously reported and was elicited in nine patients (2.5%, P = 0.002). Feeling groggy occurred in 5.7 and 17.5% (P < 0.001). AEs were not a function of headache severity, disability, efficacy of the drug, time to meaningful relief with the drug or recurrence of pain. The report of AEs varies dramatically with the methods of assessment. However, tolerability is not influenced by the severity of the attacks or by medication efficacy.

Mitochondrial dysfunction and migraine: evidence and hypotheses.

The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals.

Headache prevention outcome and body mass index.

A population-based longitudinal study suggests that obesity is a strong risk factor for the development of headaches on 15 or more days per month. Little is know about the influence of weight on the response to headache preventive treatment. Herein we prospectively assessed the influence of the baseline body mass index (BMI) on the response to headache preventive treatment. We included adults with episodic or chronic migraine (ICHD-2), or transformed migraine (Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was assessed in the first visit. Baseline information included headache frequency, number of days with severe headache (prospectively obtained over 1 month), and headache-related disability (HIT-6). The same information was obtained after 3 months of preventive treatment. Subjects were categorized based on BMI in: normal weight (/=30). We contrasted the headache end-points using anova with post-test and Kruskal-Wallis with post-test. We used logistic regression to model BMI and headache parameters adjusting for covariates. Our sample consisted of 176 subjects (79.5% women, mean of 44.4 years). At baseline 40.9% had normal weight, 29.5% were overweight and 27.3% were obese. No significant differences were observed in the number of headache days at baseline. After treatment, frequency declined in the entire population, but no significant differences were found by BMI group. Regarding the number of days with severe pain per month, there were also no significant differences at baseline (normal = 6.1, overweight = 6.5, obese = 6.7), and improvement overall (P = 0.01). However, changes were greater in the obese (reduction in 2.7 days with treatment) and overweight (3.9) vs. normal (1.5, P < 0.01). Finally, HIT scores at baseline did not differ by BMI group (normal weight = 63.8, overweight = 64.1, obese = 63.6). However, compared with the normal weighted group, change in HIT scores (follow-up baseline) were greater in the obese (6.4 vs. 3.5, P < 0.05) and overweight groups (6.8 vs. 3.5, P < 0.05). In the logistic regression model, BMI did not account for changes in disability, headache frequency, or in the number of days with severe headache per month, after adjusting for covariates. Contrary to what we hypothesized, obesity at baseline does not seem to be related to follow-up refractoriness to preventive treatment.

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.

Variations in the platelet arginine/nitric oxide pathway during the ovarian cycle in females affected by menstrual migraine.

Previous studies have reported the existence of an arginine/nitric oxide (NO) pathway and the involvement of a Ca2+, NADPH-dependent nitric oxide synthase enzyme (NOS) in the generation of NO in human platelets. In the present research, we determined the rate of production of NO and cGMP in the cytosol of platelets stimulated by collagen in 20 females with menstrual migraine (MM), (age range 24-40 years), assessed in the follicular and luteal phases, interictally and ictally in the latter period. The same patients were also assessed at mid-cycle. At the same time, the variations in the collagen response of platelets were evaluated. Moreover, these parameters were determined in the same periods in 20 age-matched control females and in 20 females affected by non-menstrually related migraine (nMM). The collagen-stimulated production of NO in the cytosol of the platelet cytosol was significantly higher in migraine patients with MM than in the control subjects. In MM patients, the increase was greater in the luteal phase of the cycle than during the follicular phase (p < 0.005). A rise in NO production in platelets was also present, although to a lesser extent, in females affected by nMM compared to the healthy females, but this rise was most evident at ovulation (p < 0.001). A slight but significant increase was also observed at mid-cycle in control women, but this increase did not reach the values determined in the migraine groups (p < 0.02). NO production in platelets stimulated by collagen was significantly increased during attacks with respect to the interictal period in both patient groups. Similar variations were observed in the production of cGMP in MM and nMM patients. The increase in NO production was accompanied by a decrease in platelet aggregation in the migraine groups compared with the control group; this decrease was most evident at mid-cycle in nMM patients and in the luteal phase in MM patients. These data suggest an activation of the L-arginine/ NO pathway in MM and nMM patients which could explain the modifications in the platelet response to collagen evidenced in migraine-free periods and during attacks. The activation of this pathway is more accentuated in the luteal phase in MM patients, and this could be the cause of the increased susceptibility to migraine attacks in perimenstrual and menstrual periods in these patients.