Domenico D’Amico

Disability and quality of life in different primary headaches: results from Italian studies

Abstract.Headaches may have a wide range of impact on patients’ lives. We report the results of Italian studies in which disability and health-related quality of life (HRQOL) in patients with different primary headaches were evaluated. The Short Form 36 (SF-36) was used to assess HRQOL; the Migraine Disability Assessment Score questionnaire (MIDAS) was used to assess disability in patients with migraine without aura or with chronic migraine. Mean MIDAS total scores were evaluated in migraine without aura and chronic migraine patients. The scores at the eight SF-36 scales were calculated in patients with the three studied headaches, and were compared with Italian normative data (Student’s t-test with Bonferroni correction). Primary headaches had a considerable negative impact on patients’ lives, with poor quality of life and decreased ability to function in daily duties. The mean MIDAS total score was 23.4 in 264 patients with migraine without aura, and 79.2 in 150 patients with chronic migraine. Mean SF-36 scores in migraine without aura (68 subjects), chronic migraine (84) and cluster headache (56) were lower than those from the Italian general population, with significant differences for 3 scales in migraine without aura, for 6 in chronic migraine, and for all scales in cluster headache. Our results confirmed a marked personal and social burden in patients with migraine without aura, and also in the less well-studied forms of primary headaches, cluster headache and chronic migraine.

A systematic review of the psychosocial difficulties relevant to patients with migraine

Migraine is a common disease which causes significant burden to individuals, in terms of personal suffering and activity reduction, and to societies, in terms of disease cost. The purpose of this study is to identify the most relevant psychosocial difficulties related to migraine, the variables associated with them and the most relevant determinants of their evolution over time. MEDLINE and PsychINFO were searched for studies published in English between 2000 and 2010 that examined psychosocial difficulties in persons with migraine with and without aura, from clinical trials and observational studies. Information on the description of each difficulty, its determinants of onset and change over time and associated variables were extracted and categorized at a higher level. In total, 34 difficulties have been collected from 51 papers: the most frequent were reduced vitality and fatigue, emotional problems, pain, difficulties at work, general physical and mental health, social functioning and global disability. Evidence exists that pharmacological treatments have an impact toward improvement in patients’ difficulties, in particular emotional problems, physical and mental health, difficulties with employment and global disability. Migraine treatments and decreased headaches frequency are the major determinants of improvements in psychosocial difficulties, while no information is available for determinants of worsening; understanding the role of such factors is of primary public health relevance, given the high prevalence and the relevant personal and societal costs of migraine.

The role of tyrosine metabolism in the pathogenesis of chronic migraine

Objective: The pathogenesis of chronic migraine (CM) remains largely unknown. We hypothesized that anomalies of tyrosine metabolism, found in migraine without aura (MwwA) patients, play an important role in the transformation of MwwA into CM, since the increase in the number of MwwA attacks is the most predisposing factor for the occurrence of CM. Methods: To test our hypothesis we measured the plasma levels of dopamine (DA), noradrenaline (NE) and trace amines, including tyramine (TYR) and octopamine (OCT), in a group of 73 patients with CM, 13 patients with chronic tension-type headache (CTTH) and 37 controls followed in the Headache Centers of the Neurology Departments of Asti, Milan and Vicenza hospitals in Italy. Results: The plasma levels of DA and NE were several-fold higher in CM patients compared with control subjects (p > 0.001). The plasma levels of TYR were also extremely elevated (p > 0.001); furthermore, these levels progressively increased with the duration of the CM. Conclusions: Our data support the hypothesis that altered tyrosine metabolism plays an important role in the pathogenesis of CM. The high plasma levels of TYR, a potent agonist of the trace amine associated receptors type 1 (TAAR1), may ultimately down-regulate this receptor because of loss of inhibitory presynaptic regulation, therein resulting in uncontrolled neurotransmitter release. This may produce functional metabolic consequences in the synaptic clefts of the pain matrix implicated in CM.

Disability in chronic daily headache: state of the art and future directions

Aim of this literature review is to summarize the most relevant research findings on disability in subjects with chronic daily headache (CDH) and chronic migraine (CM) measured with the MIDAS and the HIT-6, and to address issues for further research in the field. Research strategy aimed to find papers published after 2001 that focused on disability in patients with CDH, CM and transformed migraine. Both, general population surveys or clinical series were included if they reported total scores, or distribution of the different disability levels, derived from the MIDAS and/or from the HIT-6. Fifteen papers were selected. Studies demonstrated that these subjects report a remarkable impact on functioning, with high disability scores, and reduced ability in work and non-work activities. Modern definitions of disability conceptualize it as the result of the interaction between a health condition and environmental factors. Research strategies should therefore recognize that disability may represent a global evaluation which should be added to more specific endpoints, using instruments that measure disability in a multi-dimensional way, such as the WHO-DAS II.

Coagulation abnormalities in migraine and ischaemic cerebrovascular disease: a link between migraine and ischaemic stroke?

Abstract.Migraine, particularly migraine with aura, is a risk factor for ischaemic stroke. The mechanisms underlying this association are obscure. One hypothesis is that shared risk factors may be the cause of this association. Over the last decade, studies have suggested an association between migraine and genetic abnormalities in coagulation factors which play an important role in stroke pathogenesis. Although the results of studies on various prothrombotic conditions are conflicting, findings suggest a higher frequency of some genetic abnormalities in migraine with aura patients. Thus, persistent hypercoagulability may explain the tendency for these patients to develop thromboembolic cerebrovascular events, especially when they are exposed to additional procoagulant stresses. Further studies on larger samples are required to test this hypothesis.

Pharmacological prophylaxis of chronic migraine: a review of double-blind placebo-controlled trials

Chronic migraine is an important public health problem. The aim of treatment should be to reduce migraine frequency and its negative impact on functioning, as well as to limit the use of acute medications. These goals may be accomplished by introducing effective prophylaxis. The aim of the present article is to critically review the published evidence on the pharmacological prophylaxis of chronic migraine, analysing published double-blind, placebo-controlled studies on adult patients. The results of the review indicate that tizanidine, gabapentin, valproic acid, and particularly topiramate are effective prophylactics against chronic migraine, with improvements in several endpoints that were significantly superior to those achieved by placebo. However, the different results found by different trials, as well as several methodological problems inherent in the trials, suggest the need for further research to provide clear indications from large, multicentre, controlled trials with homogeneous inclusion criteria and adequate endpoints.

Correlation between presence of allodynia and sleep quality in migraineurs

Cutaneous allodynia is a frequent complaint in migraine patients, possibly induced by central sensitisation of trigeminal nucleus. The objective of this study is to investigate if sleep quality is related to the presence of migraine-associated allodynia. A total of 175 consecutive migraineurs were included, 124 with episodic and 51 with chronic forms. As control group, 73 subjects free from any kind of headache were included (HC). The presence of allodynia and sleep disturbances was assessed by a set of semi-structured questions. Chi-square test was applied to compare frequencies among groups. Sleep quality was worse among migraineurs with respect to controls for each sleep item analysed. This difference was significant for all items but one (i.e. frequency in drug use to induce sleep). The frequency of sleep disturbances was higher than in controls in both allodynic and non-allodynic migraineurs, although statistical analysis showed that all these differences were still significant in allodynic migraineurs (also in this case for all the sleep items but one, i.e. frequency in drug use to induce sleep), whilst non-allodynic migraineurs were significantly different from controls only for one item (frequency of initial insomnia). These results suggest that allodynia is strongly related to sleep quality, in a bi-directional way: sleep disturbances may favour central sensitisation, and, in turn, allodynia may impair sleep.

Disability and quality of life in headache: where we are now and where we are heading

Headache disorders determine relevant personal and societal burden, and thus the use of patient-reported outcome measures (PROMs) investigating the level of disability and health-related quality of life (HRQoL) have been increasingly used in headache research. The aim of this review was to address the status of research on disability and HRQoL, by addressing results from recently published clinical trials as well as in longitudinal observational studies on headache patients. PubMed has been searched for papers in which measures of HRQoL and/or disability were used as primary or secondary outcome on adult subjects with primary headache, and published in 2010–2012. Among the 70 records retrieved, 12 papers were selected for narrative synthesis. They included data on 2,621 patients with episodic migraine with and without aura, chronic daily headache, and/or chronic migraine with and without medication overuse. The selected trials investigated the efficacy of different pharmacological prophylaxis, of some surgical approaches, of education programmes and osteopathic manipulative treatment; two studies reported longitudinal observations of patients currently under treatment. Overall, the results of our review showed that headache frequency as well as HRQoL and disability were positively impacted by treatment interventions; positive outcomes were less evident in two studies, and similar results were found in the two observational studies. Our findings confirmed that the most commonly used PROMs, including disease-specific tools to assess disability and HRQoL and SF-36, are sensitive to the beneficial effects occurring over time in functioning and quality of life domains in headache patients. They also suggest that the personal and societal costs of headache disorders are likely to be reduced when headache patients receive appropriate treatments and when continuity of care is offered. In terms of future directions, we note that the systematic use of appropriate PROMs should be encouraged both in the clinical practice and in the research field, as they offer a valid option to assess the global effect of treatments on patient-perceived sense of well-being and quality of performance.

Psychological variables in chronic migraine with medication overuse before and after inpatient withdrawal: results at 1-year follow-up

Investigations on psychological variables and migraine have confirmed a strong association between migraine and depression or migraine and anxiety disorders. In particular patients suffering from chronic migraine with medication overuse have an elevated risk of mood and anxiety disorders, which may compromise treatment efforts. The aim of this study was to investigate a group of patients suffering from CM with medication overuse before and after inpatient withdrawal program after a long-term follow-up to examine clinical indexes and psychological variables changes in particular anxiety and depression by using Spielberger State-Trait Anxiety Inventory (STAI) 1, 2 and Zung Self-rating Depression Scale (Zung) tests, in order to verify if a specific psychological pattern in these patients is present, and if changes in psychological variables correspond with clinical improvement. The changes of clinical indexes and of psychological parameters are discussed and analyzed in order to address the most adequate therapeutic strategy for this kind of patients.

Topiramate in migraine prophylaxis

This paper reviews results of placebo-controlled trials on topiramate (TPM) prophylaxis in migraine patients, and discusses issues regarding the use of this medication in clinical practice. Data from well conducted double-blind controlled trials and from a comparative trial show that TPM is effective against migraine, confirming the experience of physicians in various countries. Lack of major contraindications, high responder rate, good tolerability at the target dose (100 mg/day) following slow titration, and lack of weight gain make TPM one of the most effective and well accepted drugs for migraine prophylaxis.