G. Allais

Characteristics of Menstrual and Nonmenstrual Attacks in Women with Menstrually Related Migraine Referred to Headache Centres

Aim of this study was to determine whether menstrual attacks differ from non-menstrual attacks (NMA) as regards clinical features or response to abortive treatment in women affected by menstrually related migraine (MRM) referred to tertiary care centres. Sixty-four women with MRM were enrolled in a 2-month diary study. Perimenstrual attacks were split into three groups – premenstrual (PMA), menstrual (MA) and late menstrual (LMA) – and compared to nonmenstrual ones. Perimenstrual attacks were significantly longer than NMA. No other migraine attack features were found to differ between the various phases of the cycle. Migraine work-related disability was significantly greater in PMA and MA than in NMA. Acute attack treatment was less effective in perimenstrual attacks. Pain-free at 2 h after dosage was achieved in 13.5% of MA (OR 0.41; 95% CI 0.22, 0.76) vs. 32.9% of NMA. We concluded that, in MRM, perimenstrual attacks are longer and less responsive to acute attack treatment than NMA.

Acupuncture plus moxibustion to resolve breech presentation: a randomized controlled study

Objective: In many Western countries breech presentation is an indication for elective Cesarean section. In order to correct fetal presentation, the stimulation of the acupoint BL67 by moxibustion, acupuncture or both has been proposed. Since no studies had previously been carried out on Western populations, pregnant Italian women at 33–35 weeks gestational age carrying a fetus in breech presentation were enrolled in a randomized, controlled trial involving an active BL67 point stimulation and an observation group. Methods: A total of 240 women at 33–35 weeks of gestation carrying a fetus in breech presentation were randomized to receive active treatment (acupuncture plus moxibustion) or to be assigned to the observation group. Bilateral acupuncture plus moxibustion was applied at the BL67 acupoint (Zhiyin). The primary outcome of the study was fetal presentation at delivery. Results: Fourteen cases dropped out. The final analysis was thus made on 226 cases, 114 randomized to observation and 112 to acupuncture plus moxibustion. At delivery, the proportion of cephalic version was lower in the observation group (36.7%) than in the active-treatment group (53.6%) (p = 0.01). Hence, the proportion of Cesarean sections indicated for breech presentation was significantly lower in the treatment group than in the observation group (52.3% vs. 66.7%, p = 0.03). Conclusions: Acupuncture plus moxibustion is more effective than observation in revolving fetuses in breech presentation. Such a method appears to be a valid option for women willing to experience a natural birth.

Efficacy and tolerability of almotriptan versus zolmitriptan for the acute treatment of menstrual migraine

Menstrual migraine (MM) attacks are a challenge for the headache specialist, because they are particularly difficult to treat. Almotriptan is a second-generation triptan successfully used for the acute treatment of migraine. No data on the efficacy and safety of almotriptan in MM treatment have been published previously. The objective was to evaluate the efficacy and tolerability of almotriptan in the symptomatic treatment of MM attacks and to compare these parameters to those obtained with zolmitriptan, another second-generation triptan. Data from a multicentre, multinational, randomised, double-blind, parallel clinical trial, conducted at 118 centres in 9 European countries, to evaluate the efficacy and tolerability of almotriptan 12.5 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine were analysed retrospectively. Of the 1061 patients included, 902 were women and 255 of these treated a MM attack: 136 with almotriptan and 119 with zolmitriptan. No significant difference between the two treatments was found. Two hours after dosing, 67.9% of almotriptan-treated and 68.6% of zolmitriptan-treated patients had obtained pain relief; while 44.9% and 41.2%, respectively, were pain free. Recurrence rates 2–24 h after dosing were 32.8% for almotriptan and 34.7% for zolmitriptan. Adverse events in the 24 h after dosing were reported by 19.8% of those taking almotriptan and 23.1% of those taking zolmitriptan. In conclusion, almotriptan is effective and safe in the treatment of MM attacks.

Naratriptan in the short-term prophylaxis of pure menstrual migraine.

Menstrual migraines are particularly difficult-totreat. Few studies on the use of triptans in short-term prophylaxis of menstrually related migraine have been recently conducted, but evidences of triptans’ efficacy in the specific case of pure menstrual migraine (PMM) are lacking.The aim of this study is to explore the efficacy and tolerability of naratriptan as short-term prophylaxis of pure menstrual migraine (PMM) attacks. A multi-centre, open, non comparative, pilot six-month study was conducted in women, aged 18 years or older, with regular menstrual cycles and with a history of migraine without aura exclusively associated to the perimenstrual period. After an observation period of three months, patients took for three consecutive menstrual cycles oral naratriptan 1 mg twice daily, starting two days before the expected onset of menstruation and continuing for six days. Ninety-eight women with a history of PMM were screened for study participation, and 61 entered the study. Fifty-nine comprised the intent-to-treat population. The mean number of PMM attacks decreased from 3.5±1.4 in the 3-month observation period to 1.6±1.3 in the 3-month treatment with naratriptan. The pecentage of responders (subjects who recorded a decrease—equal or more than 50%—in the mean number of attacks) was 61.4%. A tendency towards a decrease in headache severity and in the presence of associated symptoms was observed during treatment. At least one adverse event during the treatment period was reported by 19 patients (31.1%). No serious adverse events occurred. Naratriptan may be an effective and safe treatment option in the short-prophylaxis of PMM.

Headache and anxiety–depressive disorder comorbidity: the HADAS study

Psychiatric comorbidity (prevalence and types) was tested in a naturalistic sample of adult patients with pure migraine without aura, and in two control groups of patients, one experiencing pure tension-type headache and the other combined migraine and tension-type headaches. The study population included 374 patients (158, 110 and 106) from nine Italian secondary and tertiary centres. Psychiatric comorbidity was recorded through structured interview and also screened with the Mini International Neuropsychiatry Interview (MINI). Only anxiety and depression were investigated. Psychiatric disorders were reported by 49 patients (14.6%; 10.9% of patients with migraine, 12.8% of those with tension-type headache and 21.4% of those with combined migraine and tension-type headaches). The MINI interview detected a depressive episode in 59.9% of patients with migraine, 68.3% of patients with tension-type headache and 69.6% of patients with combined migraine and tension-type headaches. Depression subtypes were significantly different across groups (p=0.03). Anxiety (mostly generalised) was reported by 18.4% of patients with migraine, 19.3% of patients with tension-type headache, and 18.4% of patients with combined migraine and tension-type headaches. The values for panic disturbance were 12.7, 5.5 and 14.2, and those for obsessive–compulsive disorders were 2.3, 1.1 and 9.4% (p=0.009). Based on these results, psychopathology of primary headache can be a reflection of the burden of the disease rather than a hallmark of a specific headache category.

Non-pharmacological approaches to chronic headaches: transcutaneous electrical nerve stimulation, lasertherapy and acupuncture in transformed migraine treatment

Abstract. In an open, randomized trial, we evaluated transcutaneous electrical nerve stimulation (TENS), infrared lasertherapy and acupuncture in the treatment of transformed migraine, over a 4-month period free of prophylactic drugs. Sixty women suffering from transformed migraine were assigned, after a one month run-in period, to three different treatments: TENS (Group T; n=20), infrared lasertherapy (Group L; n=20) or acupuncture (Group A; n=20). In each group the patients underwent ten sessions of treatment and monthly control visits. In Group T patients were treated for two weeks (5 days/week) simultaneously with three TENS units with different stimulation parameters (I: pulse rate = 80 Hz, pulse width = 120 μs; II: 120 Hz, 90 μs; III: 4 Hz, 200 μs). In Group L an infrared diode laser (27 mW, 904 nm) was applied every other day on tender scalp spots. In Group A acupuncture was carried out twice a week in the first two weeks and weekly in the next 6 weeks. A basic formula (LR3, SP6, LI4, GB20, GV20 and Ex-HN5) was always employed; additional points were selected according to each patients symptomatology. The number of days with headache per month significantly decreased during treatment in all groups. The response in the groups differed over time, probably due to the different timing of applications of the three methods. TENS, lasertherapy and acupuncture proved to be effective in reducing the frequency of headache attacks. Acupuncture showed the best effectiveness over time.

Biochemistry of neuromodulation in primary headaches: focus on anomalies of tyrosine metabolism

Recent studies have suggested that abnormalities of dopamine and trace amines (tyramine, octopamine, and synephrine), products of tyrosine metabolism, may constitute the metabolic events that predispose to the occurrence of cluster headache (CH) and migraine attacks. This hypothesis is supported by the following evidences: the discovery of trace amine associated receptors (TAARs), expressed on the olfactory epithelium, amigdala, hypothalamus, periacqueductal gray, and the biochemical anomalies of dopamine and trace amines. The possible effects of these biochemical abnormalities on TAARs and dopamine receptors, located in different areas of CNS, may explain the behaviour (restlessness, anxiety and, at times, hypersexuality) and the autonomic signs during the painful attacks of CH, and the premonitory symptoms of migraine crisis (thirst, craving, yawning, alteration of smell, depression etc.).

Pathophysiological aspects of menstrual migraine.

We review the role of several biochemical and hormonal factors in menstrual migraine pathogenesis: ovarian hormones, aldosterone circadian rhythm, nocturnal urinary melatonin excretion, sympathetic autonomic system, prolactin levels and dopaminergic function, endogenous opioid tonus, platelet activity and arachidonic acid metabolites. In particular, we focus on certain aspects of platelet function and prostaglandin metabolism, taking into consideration the different behavior of platelet sensitivity to prostacyclin, intraplatelet 5HT, peripheral plasma concentrations of 6-keto-PGF1α and PGE2 in menstrual migraine sufferers and in control subjects during the menstrual cycle. A comprehensive view of the data suggests that a complex impairment of PG and 5HT metabolism, and of platelet function, may play a significant role in the pathogenesis of menstrual migraine. However, it is not yet clear whether these alterations are primary or secondary to neuroendocrine disorders.

Naproxen sodium in short-term prophylaxis of pure menstrual migraine: pathophysiological and clinical considerations.

We investigated the biological and clinical effects of naproxen sodium (NxS) in the short-term prophylaxis of pure menstrual migraine (PMM) in 25 women suffering from migraine without aura, occurring exclusively from 2 days before to 5 days after menstruation onset. Daily oral NxS (550 mg) from 7 days before menstruation to 7 days after menstruation onset was given for 3 menstrual cycles, and 5 days before menstruation to 5 days after menstruation onset over the next 3 menstrual cycles. In the month before initiation of treatment and in the third month of treatment, 6-keto-PGF1α, TXB2 and PGE2 were measured in plasma before menstruation (day –2) and on the second day (day +2) after bleeding onset. In the 20 women analysed, 6-keto-PGF1α was 17% lower (p<0.0001) and TXB2 was 30% lower (p<0.0001) on day –2 during treatment than the same day pretreatment; TXB2 was also lower (p<0.02) on day +2 during treatment than day +2 pretreatment. The 6-keto-PGF1α/TXB2 ratio was higher (p<0.01) on day –2 treatment than day –2 pretreatment. PGE2 levels were significantly lower (p<0.002) on day +2 than pre-treatment values on the same day. The number of attacks reduced from 1.7±0.11 pretreatment to 1.2±0.10 at the 3rd month (p<0.001), to 1.1±0.06 at the 6th month (p<0.0001). The duration reduced from 25.6±4.42 h pretreatment to 15.5±4.43 h in the 3rd month (p<0.02), to 13.35±4.26 h in the 6th month (p<0.001). The intensity reduced from 2.4±0.11 pretreatment, to 1.2±0.10 in the 3rd month of treatment (p<0.0001), and 1.1±0.07 in the 6th month (p<0.0001).

Advanced strategies of short-term prophylaxis in menstrual migraine: state of the art and prospects

Patients suffering from menstrual migraine (MM) may be ideal candidates for an intermittent prophylaxis, usually termed short-term or mini-prophylaxis. It covers the whole period of vulnerability, e. g., the perimenstrual period, starting some days before the expected onset of MM attack. Theoretically MM attacks are an optimal target for drugs specifically developed for acute head pain. Unfortunately, due to their particular tendency to be longer, more intense and less responsive to analgesics, symptomatic approaches alone are not often able to completely control pain and its correlates. Many drugs have been proposed for short-term prophylaxis of MM. In this paper we analyse only non-steroidal anti-inflammatory drugs, coxibs and triptans (especially those with longer half-life, naratriptan and frovatriptan). Moreover, MM can be prevented by a variety of hormonal manipulations, including oral contraceptives, which may be administered with an extended-dosing strategy; oestrogen replacement therapy; antioestrogen agents (danazol, tamoxifen); gonadotropin-releasing hormone agonists followed by oestrogen add-back therapy. Finally, the use of some products, such as magnesium and phytoestrogens, that probably meet the requirements of those patients that appreciate a more “natural” approach, is discussed.