Psychological factors associated with failure of detoxification treatment in chronic headache associated with medication overuse.

AIM: The aim of this study was to evaluate the psychological factors associated with a negative outcome following detoxification in a 2-month follow-up in medication-overuse headache. METHODS: All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion. Psychiatric conditions and personality characteristics were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I) and the Minnesota Multiphasic Personality Inventory (MMPI)-2. χ2 tests, one-way analyses of variance, and odds ratios (ORs) were used. RESULTS: A total of 248 patients completed the follow-up: 156 stopped overuse and their headaches reverted to an episodic pattern (Group A); 23 kept overusing without any benefit on headache frequency (Group B); and 51 stopped overuse without any benefit on headache frequency (Group C). The prognostic factors for the outcome of Group B were higher scores on the correction (OR 1.128; p = 0.036), depression (OR 1.071; p = 0.05), hysteria (OR 1.106; p = 0.023), and overcontrolled hostility (OR 1.182; p = 0.04) MMPI-2 scales, whereas those for Group C were psychiatric comorbidities (OR 1.502; p = 0.021) and higher scores on the hysteria scale (OR 1.125; p = 0.004). CONCLUSIONS: The outcome of detoxification is influenced by psychological factors that should be considered when considering treatment strategies.

Variability of the characteristics of a migraine attack within patients.

BACKGROUND: Migraine attacks may present different features in different patients and also within the same patient. The percentage of patients reporting stereotyped attacks and those reporting attacks with different phenotypes has not been the object of specific investigations. OBJECTIVE: The objective of this article is to evaluate the percentage of migraine patients reporting the same characteristics, in terms of phenotype and response to symptomatic medications on three consecutive migraine attacks. METHODS: Thirty patients with migraine without aura prospectively recorded the features of three consecutive attacks in a headache diary. Characteristics recorded were: pain intensity, presence of nausea, vomiting, photophobia, phonophophia, osmophobia, allodynia, cranial autonomic symptoms (at least one), and premonitory symptoms. Patients were allowed to take frovatriptan as symptomatic medication, whose efficacy was evaluated as the two hours pain-free status. RESULTS: None of the patients presented identical characteristics on the three studied attacks. This was still the case if we reduced the number of variables evaluated from 11 to seven of the eight core features indicated by the ICHD. Considering just six variables: unilaterality and quality of pain, presence/absence of nausea, vomiting, photophobia and phonophobia, only two patients (6%) had identical features on three consecutive attacks.With respect to the response to frovatriptan, 39% of patients had the same response, either positive (i.e. pain free after two hours) or negative (i.e. not pain free after two hours) on three consecutive attacks. CONCLUSION: Migraine attacks show a high variability not just among patients, but also within the same patient. Our data indicate that stereotypy of attacks is uncommon, and reinforces the underlying logic of the current operational classification system.

Cost of Chronic and Episodic Migraine. A pilot study from a tertiary headache centre in northern Italy.

BACKGROUND: Chronic migraine (CM) has a high impact on functional performance and quality of life (QoL). CM also has a relevant burden on the National Health Service (NHS), however precise figures are lacking. In this pilot study we compared the impact in terms of costs of CM and episodic migraine (EM) on the individual and on the National Health System (NHS). Furthermore, we comparatively evaluated the impact of CM and EM on functional capability and on QoL of sufferers. METHODS: We enrolled 92 consecutive patients attending the Pavia headache centre: 51 subjects with CM and 41 with episodic migraine (EM). Patients were tested with disability scales (MIDAS, HIT-6, SF-36) and with an ad hoc semi-structured questionnaire. RESULTS: The direct mean annual cost (in euro) per patient suffering from CM was €2250.0 ± 1796.1, against €523.6 ± 825.8 per patient with EM. The cost loaded on NHS was €2110.4 ± 1756.9 for CM, €468.3 ± 801.8 for EM. The total economic load and the different sub-items were significantly different between groups (CM vs. EM p = 0.001 for each value). CM subjects had higher scores than EM for MIDAS (98.4 ± 72,3 vs 15.5 ± 17.7, p = 0.001) and for HIT-6 (66.1 ± 8.4 vs 58.7 ± 10.1, p = 0.001). The SF-36 score was 39.9 ± 14,74 for CM and 66.2 ± 18.2 for EM (p = 0.001). CONCLUSIONS: CM is a disabling condition with a huge impact on the QoL of sufferers and a significant economic impact on the NHS. The adequate management of CM, reverting it back to EM, will provide a dual benefit: on the individual and on the society.

Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of patients with medication overuse headache after withdrawal therapy.

BACKGROUND AND PURPOSE: It is currently unknown if common genetic variants influence the prognosis of patients with medication overuse headache (MOH). Here the role of two common single nucleotide polymorphisms in the COMT gene (rs4680 and rs6269), as well as the STin2 variable number tandem repeat (VNTR) polymorphism in the SLC6A4 gene, were evaluated as predictors for long-term outcomes of MOH patients after withdrawal therapy. METHODS: Genotyping was conducted by polymerase chain reaction (PCR), PCR restriction fragment length polymorphism analysis or real-time PCR allelic discrimination assay on genomic DNA extracted from peripheral blood. Gene variants association was evaluated by logistic regression analysis adjusted for clinical confounding factors, and the threshold of statistical significance for multiple testing was set at P < 0.012. RESULTS: Sixty-five MOH patients with unsuccessful detoxification and 83 MOH patients with effective drug withdrawal therapy were available for the analysis. rs4680G allele carriers or the COMT rs6269G-rs4680G haplotype were found to be associated with a lower risk of relapse within the first year after successful detoxification therapy, in comparison with homozygous rs4680A allele carriers [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.05-0.61, P = 0.007] or with the COMT rs6269A-rs4680A haplotype (OR 0.19, 95% CI 0.06-0.54, P = 0.003), respectively. In addition, carriers of the STin2 VNTR short allele were found at higher odds for the composite poor outcome including unsuccessful withdrawal therapy and relapse within 12 months of follow-up after successful detoxification (OR 2.81, 95%CI 1.26-6.25, P = 0.009). CONCLUSIONS: Our results indicate that genotyping for COMT rs4680 and SLC6A4 STin2 VNTR could be useful for the identification of MOH patients at higher risk of poor prognosis after drug withdrawal.

Risk factors in medication-overuse headache: a 1-year follow-up study (care II protocol).

To investigate factors influencing prognosis in medication-overuse headache (MOH), we conducted a 12-month follow-up of patients with probable MOH. We recruited 215 patients consecutively admitted to our headache centre for an inpatient detoxification treatment. We analysed likely predictor factors for headache resolution (sex, age, primary headache, psychiatric comorbidity, type and timing of overuse). Mann-Whitney U-test and chi-squared test were used. One year after withdrawal, we had complete data on 172 patients (80%): 38 of these patients (22%) had relapsed into overuse and 134 (78%) had not. The negative prognostic factors for relapse were: intake of more than 30 doses/month (P = 0.004), smoking (P = 0.012), alcohol consumption (P = 0.037), non-confirmation of MOH diagnosis 2 months after detoxification (P = 0.000), and return to overused drug(s) (P = 0.000). The 1-year relapse rate was 22%. The existence of sub-groups of MOH patients with such risk factors could influence treatment strategies.

Medication overuse headache and applicability of the ICHD-II diagnostic criteria: 1-year follow-up study (CARE I protocol).

Medication overuse headache (MOH) is a growing problem worldwide and a challenge for clinicians and investigators. This study aims to contribute to the ongoing debate surrounding the classification of MOH. Applying the revised diagnostic criteria for MOH contained in the updated International Classification of Headache Disorders (ICHD-II), we enrolled 140 probable MOH (p-MOH) patients. They were submitted to an in-patient detoxification protocol and re-examined 2, 6 and 12 months later to confirm, or otherwise, the diagnosis of MOH and to observe the evolution of their headache. MOH diagnosis was confirmed 2 months after detoxification in 71% of patients, who reverted to an episodic headache pattern and stopped their drug overuse The overall clinical situation at 2 months closely reflected the 1-year trend. The 2-month period after drug withdrawal should be retained as a diagnostic criterion in the ICHD-II because it is useful not only as a diagnostic parameter, but also as predictor of a good outcome of 1-year drug withdrawal. In addition, the present findings point to the need for a more objective criterion to quantify headache frequency after drug withdrawal.

The usefulness and applicability of a basic headache diary before first consultation: results of a pilot study conducted in two centres.

We tested the usefulness and applicability of a simplified headache diary in the diagnosis of migraine (M), tension-type headache (TTH) and medication overuse headache (MOH). The diary was given to headache patients before their first consultation at the headache centre. Seventy-six naive headache patients completed the study. Their understanding of the diary proved highly satisfactory. The patients' level of compliance was also good, with 71% returning the diary completely filled in. The data entered in the diary were deemed complete for the diagnostic purpose in 93% of cases. The level of agreement between headache information gathered through clinical interview and the headache diary was satisfactory. When comparing the diary with the clinical interview, sensitivity was 92% for M, 75% for TTH and MOH. Specificity was 58% for M and TTH, 87% for MOH. Combined use of a diagnostic diary and clinical interview is recommended from the first consultation for headache.

The wolframin His611Arg polymorphism influences medication overuse headache.

Homozygosis for wolframin (WFS1) mutations determines Wolfram syndrome (WS), and common polymorphisms of WFS1 are associated with psychiatric illnesses and dependence behaviour. To test the influence of WFS1 polymorphisms on medication overuse headache (MOH), a chronic headache condition related to symptomatic drugs overuse, we analyzed 82 MOH patients for the WFS1 His611Arg polymorphism, and performed a comparison between clinical features of Arg/Arg (R/R) and non-R/R individuals. Individuals harbouring the R/R genotype showed significantly higher monthly drug consumption (t=-3.504; p=0.00075) and more severe depressive symptoms on the BDI questionnaire (t=-3.048; p=0.003) than non-R/R. WFS1 polymorphism emerged as the only significant predictor of drug consumption, at the multivariate regression analysis (F=12.277; d.f.=1,80; p=0.00075, adjusted R2=0.122). These results implicate WFS1 in the clinical picture of MOH, may be through an influence on need for drugs as in other conditions of abuse behaviour.

Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval.

BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. METHODS: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. RESULTS: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P < 0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 18.9; P < 0.001) against placebo and positively affected the duration (P < 0.001), the number of hours in which pain intensity prohibits daily activity (P < 0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P < 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

Hypnic headache: PSG evidence of both REM- and NREM-related attacks.

Hypnic headache (HH) occurs exclusively during sleep. Six attacks were recorded during nocturnal polysomnographic (PSG) monitoring of 10 HH patients. The PSG data obtained indicate that the attacks arose directly from sleep: four from non-REM and two from REM sleep. In no patient were the HH attacks found to show any close temporal relationship with sleep-related breathing abnormalities.

Reliability of the nitroglycerin provocative test in the diagnosis of neurovascular headaches.

Nitroglycerin administration provokes spontaneous-like migraine attacks in migraine and cluster headache (CH) patients. Nitroglycerin-induced migraine-like headache has been used as an experimental model of migraine. In this paper, we evaluate the possibility of using the nitroglycerin provocative test (NPT) as a supportive measure in the diagnosis of primary neurovascular headaches by assessing its reliability on a large population and adopting strict criteria for rating the response as positive or negative. Our population consisted of 197 migraineurs, 42 subjects suffering from cluster headache and 53 healthy controls. In migraine without aura, the test sensitivity was 82.1%, specificity 96.2% and accuracy 85.5%, while in subjects suffering from migraine with aura, the reliability of the NPT was less satisfactory (sensitivity 13.6%, specificity 96.2% and accuracy 72%). In CH patients tested during the active phase of the disease the sensitivity was 80.6%, specificity 100% and accuracy 92.9%. NPT is an easy, low-cost and reliable method for supporting the diagnosis of migraine without aura and cluster headache.

Course of migraine during pregnancy and postpartum: a prospective study.

The aim of this study was to investigate prospectively the course of migraine during pregnancy and postpartum. Of all the pregnant women consecutively attending an obstetrics and gynaecology department for a routine first-trimester antenatal check-up, 49 migraine sufferers--two were affected by migraine with aura (MA) and 47 by migraine without aura (MO)--who had experienced at least one attack during the 3 months preceding pregnancy were identified, enrolled in the study and given a headache diary. Subsequent examinations were performed at the end of the second and third trimesters and 1 month after delivery. Migraine was seen to improve in 46.8% of the 47 MO sufferers during the first trimester, in 83.0% during the second and in 87.2% during the third, while complete remission was attained by 10.6%, 53.2%, and 78.7% of the women, respectively. Migraine recurred during the first week after childbirth in 34.0% of the women and during the first month in 55.3%. Certain risk factors for lack of improvement of migraine during pregnancy were identified: the presence of menstrually related migraine before pregnancy was associated with a lack of headache improvement in the first and third trimesters, while second-trimester hyperemesis, and a pathological pregnancy course were associated with a lack of headache improvement in the second trimester. Breast feeding seemed to protect from migraine recurrence during postpartum.

Lamotrigine in the treatment of SUNCT syndrome.

Short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is considered an intractable condition. The authors treated five patients with lamotrigine (125 to 200 mg daily), obtaining a complete remission in three patients and a substantial reduction (about 80%) of attack frequency in the other two. No adverse effects were noted.

Migraine with aura and reproductive life events: a case control study.

The course of migraine without aura (MO) is greatly influenced by the events of female reproductive life. Much less is known about migraine with aura (MA). The aim of this study was to evaluate the relationship between MA and the milestones of reproductive life. A retrospective case control study was carried out on 100 women affected by migraine with typical aura (cases) and 200 age-matched women with MO (controls). Premenstrual syndrome was found to be much more common among the patients with MA (odds ratio (OR) 6.0; confidence interval (CI) 3.1-11.6). Menstrually triggered migraine was more frequently encountered among MO than among MA patients (MA 15.0%; MO 53.5%; OR 0.1; CI 0.1-0.3). In both forms of migraine, pregnancy had a favourable effect; however, a lower percentage of MA (43.6%) than MO patients (76.8%; OR 0.2; CI 0.1-0.5) showed improvement or remission. The use of oral contraceptives worsened migraine in MA more frequently than in MO patients (MA 56.4%; MO 25.3%; OR 3.8; CI 1.6-9.3). The course of MA seems to be influenced by female reproductive life events, but in a different way with respect to MO.