Top PDF Genetic factors in migraine and chronic tension-type headache

Mitochondrial proteins function in the oxidative pathways and are encoded by both the mitochondrial and the nuclear genomes. Diseases caused by alterations of the mitochondr- ial genome have a maternal inheritance, because mitochon- drial DNA is transmitted from mothers to children. Migraine has been associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and less frequently with MERRF (mitochondrial disease, myoclonic epilepsy with ragged-red fibers). MELAS is caused by a point mutation at base pair 3243 and MERRF is caused by a point mutation at base pair 8344. However, neither of the two base pair point mutations nor large scale deletions were found in 23 Germans with MA [52], excluding a significant role of this mutation in Caucasians. A point mutation in mitochondrial nucleotide pair 11 084 was reported in Japanese migraineurs [53]. Twenty-five percent (13 of 53) of Japanese migraineurs had this mutation, while none of 39 normal and 60 tension-type headache sufferers did [53]. The mutation was not detected in Danes [54]. Thus, mitochondrial mutations might explain some cases of migraine in Japanese, but confirmation of the result is necessary.

In this study we aimed to identify specific risk factors for the development of chronic migraine and chronic tension-type headache in order to support the clinical distinction between these two most common primary headache disorders on the basis of their respective epi- demiological risk factor profile. The prevalence of mi- graine in our study was 17.7% (1.1% CM + 16.6% EM). This is comparable to previous studies from Europe and the USA [6-10] which reported a prevalence of 13.2% to 21.3%. Previous data on the prevalence of TTH are more heterogeneous and differ from 20.7% to more than 63% [10-13]. In our study the prevalence of TTH was lower with 13% (0.5% CTTH + 12.5% ETTH). The wide vari- ation of estimated prevalence in TTH might be due to different questionnaires used, the improper distinction between life-time and one-year prevalence and different age profiles.

Methods: A total of 50 patients (35 female, 15 male) were evaluated during a headache-free episode: 30 migraine patients without aura (mean age: 32 ± 8 years), 10 migraine patients with aura (mean age: 34±4 years), and 10 patients with chronic tension-type headache (mean age: 34±5 years). Results: No significant difference was present between anterior, middle, and posterior cerebral and vertebral arteries’ blood flow velocities between migraine patients, with and without aura, or in patients with a tension-type headache, and normal controls (p> 0.05). However, a signifi- cant increase in basilar artery cerebral blood flow velocities relative to controls was present in patients with a tension-type headache (p> 0.001).

tinued during the main study. The preliminary data sug- gest, however, that our questionnaire is comparable in quality with others reported in the international literature. The sensitivity and specificity values are quite similar to those of the German version [3]. Several other validated headache questionnaires exist, most of them constructed as screening instruments for migraine and consisting of 3–8 items based on the IHS criteria [11–18]. Lipton et al. pre- sented a very short screening questionnaire for migraine with only three items and were able to achieve a sensitivi- ty of 0.81 and specificity of 0.75, with a kappa of 0.68 [14]. More detailed migraine questionnaires have been pre- sented by Kallela et al. [19] and Hagen et al. [20]. The for- mer, for migraine only, obtained a sensitivity of 0.99 and a specificity of 0.96, whilst the kappa value for the compar- ison between telephone interview and clinical examination was 0.85. Questionnaires seeking more than one diagnosis result in considerably lower agreement levels. The ques- tionnaire of Hagen et al. differentiated between migraine, non-migraine headache and chronic daily headache with kappa values of 0.59, 0.43 and 0.44 respectively [20]. The questionnaire suggested by Rasmussen et al. for migraine, episodic tension-type headache and chronic tension-type headache achieved relatively low kappa values of 0.43, 0.30 and 0.24 respectively [10].

headache, previous studies reported allodynia during cluster episodes, in accord with present results [39], while this is the first study suggesting the presence of allodynia in other TACs, as paroxysmal migraine and hemicranias continua. Actually we cannot advance conclusions on reduced expression of allodynia in the mixed headaches group, which was a very heterogeneous group and worthy of further case series enlargement, considering the importance of a better knowledge of these rare disorders. Unfortunately, cases of hyping headache were also few, deserving further consideration in a larger group. Pericranial tenderness was also more expressed in chronic migraine compared to other head- ache groups, excluding chronic tension type headache. This confirmed the relation between pericranial pain and chronic tension type headache and migraine [15] but suggested the scarce presence of this symptom in TACs and other primary headache forms. Quantity more than other sleep problems seemed to be critical for central sensitization symptoms severity in our headache series, with a strong correlation with both allodynia and pericranial tenderness. Gender was a critical factor for both allodynia and pericranial tenderness, but not for

Table 1 shows the prevalence and temporal presentation of CDH. Mixed headache was the most prevalent (62.9%): in 70.6% of the cases it occured at onset. Comorbid pattern (migraine and tension-type headache) was never displayed at onset, but developed exclusively from other types of headache. We found no difference between onset or trans- formed chronic tension-type. CDH at onset outnumbered the transformed types (58.2% vs. 41.8%). Of the patients with transformed headache, 9 (26.5%) presented a basis of tension-type headache (in 80% chronic tension-type) plus episodic migraine crises (67% without aura and 33% with aura). Chronic tension-type headache was characterized by de novo onset of daily crises in half of the cases.

The literature provides information on several twin studies on migraine. The majority is based on questionnaires and lay interview [2]. The most precise survey was based on a pop- ulation-based twin registry where the twin pairs were blind- ly interviewed by physicians [18, 19]. The probandwise con- cordance rate was significantly higher in monozygotic (MZ) than same gender dizygotic (DZ) twin pairs in both migraine without aura and migraine with aura (Table 2). The concor- dance rates in MZ twin pairs were less than 100%. The results support the importance of both genetic and environ- mental factors. Cluster headache has been reported in five concordant monozygotic twin pairs [16]. This indicates the importance of genetic factors, although publication itself introduces selection bias [20]. In a single large twin survey based on the Swedish Twin Registry and the Swedish Inpatient Registry, the two monozygotic and nine dizygotic twin pairs were all discordant for cluster headache and had been discordant for 10–31 years [21]. The twin data on clus- ter headache support the importance of both genetic and environmental factors. Tension-type headache, with excep- tion of its chronic form, is not suited for a genetic epidemio- logical survey due to its high prevalence, but a twin study can be helpful. As migraine is a confounding factor, it is important to exclude twin pairs with co-occurrence of migraine in such a study. Table 2 shows the results of a pop-

recent studies suggested that patients with chronic daily headache have a significant impairment of serotonin metabolism [32, 33]. So the dysfunction of cerebral sero- tonergic system seems to be one of the key features in the mechanism of transformation of an episodic to a chronic form of headache and it may play a role in the abnormali- ties in anger experience and control observed in our patients. The results obtained by the administration of the CBA 2.0 and the BDI evidence a lack of psychopathologi- cal impairment in the migraine group compared to con- trols. On the contrary, the chronic tension-type headache and migraine associated with tension-type headache patients experienced higher levels of depressive symp- toms, state and trait anxiety, phobias (especially social refusal and departures), emotion liability, psychophysio- logical disorders and obsessive-compulsive symptoms in comparison with controls. Episodic headaches differed from controls only on trait anxiety, emotion liability and obsessive-compulsive symptoms. Our results provided evi- dence that patients with chronic tension-type headache and migraine associated with tension-type headache experi- ence more emotional distress in comparison to both migraine and tension-type headache with an episodic occurrence. However, it is important to highlight the self- report nature of the tests used and the consequent method- ological limitations of the interpretation of the data.

The placebo response in the management of headache is approximately 30% in both pharmacological and non- pharmacological clinical trials [18,19]. The self-reported efficacy of CAM in our study is only slightly higher than the placebo effect. The efficacy of acupuncture was bet- ter in those with chronic tension-type headache (CTTH) and co-occurrence of migraine than in CTTH without co-occurrence of migraine. Otherwise we found no significant differences in the CAM efficacy. A recent Cochrane review of acupuncture for migraine prophy- laxis [20] and a meta-analysis of manual therapies for migraine and cervicogenic headache shows it is likely to be as effective as prophylactic medication for migraine [21,22]. Thus, CAM might have an effect in some types of headaches.

Unremitting head and neck pain (UHNP) is a commonly encountered phenomenon in Headache Medicine and may be seen in the setting of many well-defined headache types. The prevalence of UHNP is not clear, and establishing the presence of UHNP may require careful questioning at repeated patient visits. The cause of UHNP in some patients may be compression of the lesser and greater occipital nerves by the posterior cervical muscles and their fascial attachments at the occipital ridge with subsequent local perineural inflammation. The resulting pain is typically in the sub-occipital and occipital location, and, via anatomic connections between extracranial and intracranial nerves, may radiate frontally to trigeminal- innervated areas of the head. Migraine-like features of photophobia and nausea may occur with frontal radiation. Occipital allodynia is common, as is spasm of the cervical muscles. Patients with UHNP may comprise a subgroup of Chronic Migraine, as well as of Chronic Tension-Type Headache, New Daily Persistent Headache and Cervicogenic Headache. Centrally acting membrane-stabilizing agents, which are often ineffective for CM, are similarly generally ineffective for UHNP. Extracranially-directed treatments such as occipital nerve blocks, cervical trigger point injections, botulinum toxin and monoclonal antibodies directed at calcitonin gene related peptide, which act primarily in the periphery, may provide more substantial relief for UHNP; additionally, decompression of the occipital nerves from muscular and fascial compression is effective for some patients, and may result in enduring pain relief. Further study is needed to determine the prevalence of UHNP, and to understand the role of occipital nerve compression in UHNP and of occipital nerve decompression surgery in chronic head and neck pain.

Abstract The objective of this study was to investigate the impor- tance of genetics in tension-type headache. A MEDLINE search from 1966 to December 2006 was performed for “tension-type headache and prevalence” and “tension-type headache and genet- ics”. The prevalence of tension- type headache varies from 11 to 93%, with a slight female prepon- derance. Co-occurrence of migraine increases the frequency of tension-type headache. A family study of chronic tension-type headache suggests that genetic fac- tors are important. A twin study analysing tension-type headache in migraineurs found that genetic fac- tors play a minor role in episodic tension-type headache. Another twin study analysing twin pairs without co-occurrence of migraine

different clinical entities with specific definitions. Patients with TM/CM typically have a past history of migraine. It is more frequent in women with a past history of migraine without aura. Subjects usually report a process of transformation over months or years, and as headache increases in frequency, associated symptoms become less severe and frequent. The process of transformation fre- quently ends in a pattern of daily or nearly daily headache that resembles chronic tension-type headache, with some attacks of full-migraine superimposed [1–3, 34, 35]. In the clinical setting, migraine transformation most often is related to acute medication overuse, but transformation may occur without overuse. In the more general popula- tion, most cases of TM are not related to medication overuse [36]. Multiple risk factors may be involved in these cases.

Case presentations: Four women with long histories of migraine or frequent tension-type headache that meet the International Classification of Headache Disorders criteria for Chronic Migraine or Tension-type Headaches were given a systemic treatment(s) of autologous stromal vascular fraction or autologous ‘ StroMed ’ isolated from lipoaspirate. StroMed is stromal vascular fraction cells prepared by ultrasonic cavitation. Two of the four patients, both of whom are Arab women aged 40 and 36 years, ceased having migraines after 1 month, for a period of 12 to 18 months. The third patient, a Slavic woman aged 43 years, had a significant decrease in the frequency and severity of migraines with only seven migraines over 18 months. The fourth patient, an Asian woman aged 44 years, obtained a temporary decrease for a period of a month and was retreated 18 months later and has been free of migraines to date for 1 month. Pain medication was typically reduced from prescribed opioid analgesia to non-steroidal anti-inflammatory drugs and paracetamol.

Migraine often co-exists with TTH [35]. TTH in migraineurs may be different from episodic tension-type headache [35] [36] [37] and has been reported to be similar in people with migraine and in non migraineurs [38]. The rate of mi- graine co-existing with TTH in this study is 5.8% higher than 0.8% reported by Schramm et al. [38]. The reason for this is not known. Whether migraine and TTH are separate entities or a continuum remains controversial. As headache frequency increases, the phenotypic spectrum of individual headache episodes broadens, and the clinical distinction between migraine and TTH may become less obvious. Migraine and TTH may also aggravate and precipitate each other possibly due to overlapping trigger factors. Furthermore, both disorders may share common pain characteristics hence making misdiagnosis very likely [32] [39].

The general level of information did not differ in the three study groups, even though patients from the popu- lation had significantly less severe headaches with sig- nificantly less impact on working capability and quality of life. Comparable to the findings regarding the patients’ personal experience, weather was best known, followed by stress and menstruation. The level of knowl- edge about specific trigger factors differed most marked- ly in the “classical” nutritional triggers of migraine attacks, i.e., red wine, chocolate and cheese, which were best known in the MIG-C group. However, there is only evidence supporting the role of red wine, whereas choco- late and cheese have not been proven to trigger migraine attacks [22, 23, 26].

Other NSAIDs with proven efficacy in acute migraine treatment are naproxen, ketoprofen, tolfenamic acid and diclofenac potassium [3]. The NSAID indomethacin plus prochlorperazine plus caffeine suppositories (49% pain free) was more effective than sumatriptan suppositories (34% pain free) in one randomised clinical trial (RCT) [4]. Frequent intake of analgesics, 15 days or more per month, leads to chronic headache and medication overuse headaches, and this can also happen with over-the-counter drugs [5].

The co-morbidity of sleep disorders and migraine in childhood has led to the suggestion that they may have a common genetic or pathophysiological mechanism [26]. The serotonergic system is likely to be involved, as it has been implicated in the physiology of migraine and plays an important role in the initiation and maintenance of sleep activity [26]. Serotonin also plays an important role in emotional disorders such as depression, which has also been implicated in the physiology of migraine [31] and studies with adults have found that depression precedes migraine onset [55]. Although we did not find depression was related to childhood migraine or TTH, analyses with larger samples are needed to confirm this and to determine whether serotonin links the underlying pathophysiology between migraine, sleep problems and emotional disorders. Though we didn’t find an association between head- ache and depression, our results indicate that many other areas of psychological functioning were signifi- cantly associated with childhood headache. This is con- sistent with a growing body of literature suggesting a link between childhood headache disorders and emo- tional and behavioural difficulties [27-31]. In our study, psychological functioning was assessed by parent report at ages 3.5, 7, and 11 (and self-report at 11) using the SDQ. This questionnaire assesses emotional symptoms, conduct problems, hyperactivity/impulsivity, and peer problems. Scores from these subgroups are summed to provide a total difficulty score.

influence of gender or headache type on primary out- come (≥ 50% reduction of headache frequency). In a population-based longitudinal study Bigal et al. assessed the influence of baseline body mass index on the response to headache preventive treatment. Patients suf- fering from episodic, chronic or transformed migraine who sought care in a headache clinic were included. Baseline information included headache frequency, number of days with severe headache and headache- related disability. The same information was obtained after three months of preventive treatment. After treat- ment, headache frequency declined in the entire popula- tion but no significant differences were found among BMI groups. Furthermore, BMI did not account for changes in disability, headache frequency, or in the number of days with severe headache per month [12]. These results are in line with our data in showing no significant difference in BMI groups and reduction of headache days with categorization of BMI into only two subgroups (< 25 vs. ≥ 25) and a longer follow-up (twelve months). High BMI was a risk factor for increasing headache frequency in some studies [13,14] but not others [15,16]. Moreover, we could not find an associa- tion between smoking and reduction of headache days. These findings are supported by a metanalysis of three studies focusing on the association of lifestyle factors (BMI, alcohol, smoking and physical activity) and head- ache prevalence in Germany which also found no asso- ciation between migraine and obesity or smoking [17].

Abstract Headache aetiology and presentation are con- siderably different in elderly individuals. However, litera- ture on headache characteristics among Asians is limited. The objective of this study was to evaluate the headache characteristics among elderly in an outpatient clinic setting in Malaysia, a South-East Asian country with diverse ethnicity. In this prospective cross-sectional study, patients presenting with headache to Neurology and Primary Care Clinics of University Malaya Medical Centre between February 2010 and July 2010 were included. Data for con- secutive eligible adult patients were entered in a prospective headache registry. International Headache Criteria II (ICHD-II) were used to classify various headache subtypes. Patients with headache due to intracranial space occupying lesions were excluded. Patient were divided into two age groups—elderly (55 years and above) and younger (less than 55 years of age). Of the 175 screened patients, 165 were included in the study—70 in elderly age group and 95 in younger group. Tension-type headache was the com- monest subtype (45.7 %) among the elderly while Migraine without aura (54.7 %) was more common in young adults. More elderly patients suffered from chronic daily head- ache as compared to younger patients (47.1 vs. 28.4 %; p = 0.015). Headache subtypes and frequency differ con- siderably among elderly South East Asian patients.

After giving written informed consent the patients completed the Eurolight questionnaire once. The Euro- light questionnaire was developed to gather data on the personal, social and economic impact of migraine, TTH and MOH in 15 countries in the European Union (EU) [10, 15]. It is a 103-item self-reporting questionnaire, validated in five languages, with good construct validity, good test-retest reliability and good internal consistency [15]. The questionnaire covers biographic data, headache symptoms, use of acute and prophylactic medications during the previous month, former examinations due to headache, quality of life as well as symptoms of anxiety and depression. The Eurolight questionnaire differenti- ates EH, i.e. headache on <15 days/month, and CH, i.e. headache on ≥15 days/month, and it is validated for diagnosing migraine, probable migraine, tension -type headache (TTH), probable tension-type headache (pTTH) and probable medication overuse headache (pMOH) according to ICHD-2 [15, 16]. Other headaches than mentioned above are classified as “other headache”. It does not allow diagnosing the underlying headache in patients with CH and pMOH. Therefore we diagnosed these patients based on their questionnaire entries con- cerning their most bothersome headache.