Valproic acid is effective in migraine prophylaxis at low serum levels: a prospective open-label study

OBJECTIVE: We evaluated the efficacy of prophylactic valproic acid treatment (6 months) on the frequency of migraine attacks and the number of migraine headache days with respect to serum levels. BACKGROUND: Valproic acid, a GABAergic drug, has been shown to be effective for migraine prophylaxis. Results from several dose- and serum level-adjusted studies have recommended valproic acid doses within a range of 500 to 1500 mg per day for migraine prophylaxis. Design and METHODS: In this prospective open-label study, 52 patients received valproic acid doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic acid serum levels increased linearly in relation to the valproic acid dose and were between 21 and 107 microg/mL at the end of the treatment period. Patients were divided into two groups: those with valproic acid serum levels less than 50 microg/mL (group 1) and those with serum levels greater than 50 microg/mL (group 2). RESULTS: The frequency of migraine attacks was significantly reduced in group 1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache days also decreased (6.4 +/- 3.5 to 4.6 +/- 2.9 days per month). In the high serum level group, a reduction of migraine attacks from 3.5 +/- 0.9 to 2.8 +/- 1.0 attacks per month and only a slight decrease in headache days (6.4 +/- 3.5 to 6.1 +/- 2.4 days per month) was observed. The outcome of group 1 (low serum level) was significantly better than that of group 2 with respect to both parameters (P<.05). Side effects were generally mild and temporary. CONCLUSIONS: Due to the lack of additional benefit from higher valproic acid doses (more than 600 mg per day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum level less than 50 microg/mL for the prophylactic treatment of migraine.     

Increased plasma transforming growth factor-beta1 in migraine

BACKGROUND AND OBJECTIVES: Migraine is characterized by the peripheral and central sensitization of pain perceptive neural systems, and neurogenic inflammation is a key step in the development of migraine headache. We focused on transforming growth factor-beta1 (TGF-beta1), which is a multifunctional proinflammatory cytokine. To address the possibility of TGF-beta1 involvement in migraine, we investigated the plasma level of TGF-beta1 in patients with migraine headache during headache-free periods. Subjects and METHODS: Sixty-eight subjects with migraine participated: 23 with migraine with aura (MWA) and 45 without aura (MWoA). We recruited 58 healthy subjects without headache as controls. In addition, we examined 12 subjects with episodic tension-type headache. Platelet poor plasma (PPP) was obtained from subjects during headache free-periods. TGF-beta1 levels in PPP were determined by enzyme-linked immunosorbent assay. RESULTS: The TGF-beta1 level in PPP was 2.62*+/- 0.23 (mean +/- SE) ng/mL in migraine, 2.08 +/- 0.20 ng/mL in tension-type headache, and 1.80 +/- 0.09 ng/mL in controls (P= .007, ANOVA; *P < .01, post hoc tests vs. the controls). CONCLUSION: TGF-beta1 in PPP was significantly increased in patients with migraine during headache-free periods. TGF-beta1 may play some role in the development of migraine headache.     

Mmp-9 immunoreactivity in acute migraine

OBJECTIVE: To examine the role of matrix metalloproteinase 9 (MMP-9) in migraine during headache and asymptomatic periods. METHODS: Thirty-four patients with migraine with and without aura (according to International Headache Society criteria) were studied. Clinical characteristic of headache were recorded. Blood samples for measurement of MMP-9 were drawn during headache attacks and during asymptomatic periods in all patients and in 10 healthy controls. RESULTS: We found higher plasma MMP-9 levels in migraine patients than in control group (129.3 [78.0-258.9] vs. 49.6 [39.1-64.3] ng/mL; P < .001). Migrainous patients showed higher MMP-9 plasma levels during headache attacks than in asymptomatic periods, both in migraine without aura (338.4 [275.1-396.2] vs. 118.2 [75.3-137.5] ng/mL; P < .0001), and migraine with aura (389.3 [273.4-487.1] vs. 139.3 [107.3-191.4] ng/mL; P < .0001). CONCLUSIONS: Our study showed an increased production of MMP-9 during migraine attacks. These data suggest a possible role of inflammation or blood-brain barrier disruption during the migraine attack.     

Effectiveness of topiramate in the prevention of childhood headaches

BACKGROUND: Migraine is a significant problem for many children. Topiramate has been suggested to be effective for the prophylaxis of migraine in adults, but has not yet been examined in children. The drug has been demonstrated to be safe and effective for childhood seizure disorders. The objective of this study was to demonstrate the safety and efficacy of topiramate for the prevention of pediatric migraine. METHODS: Children with frequent migraine were prescribed topiramate for headache prevention. Dosages, serum levels, and Serum Glutamic Oxalacetic Transaminase (SGOT) levels were monitored. Changes in frequency, severity, and duration of headaches were recorded and changes in headache-related disability using PedMIDAS also were measured. RESULTS: Ninety-seven children were treated with topiramate, and 75 were reevaluated 88.7 +/- 35.7 days later, 41 were seen at a second follow-up, and 17 were seen at a third follow-up evaluation. The daily dose reached at second evaluation was 84.0 +/- 38.6 mg/day or 1.42 +/- 0.74 mg/kg/day. This corresponded to a mean serum level of 2.8 +/- 1.6 micro g/mL. The mean headache frequency was reduced from 16.5 +/- 10.0 to 11.6 +/- 10.2 days per month (P<0.001) with a further reduction to 9.4 +/- 8.4 days by the second follow-up (P<0.001). Severity and duration of headache also were reduced. Headache disability improved, with a reduction of Pediatric Migraine Disability Assessment score from 36.0 +/- 42.3 to 20.8 +/- 34.0 at the first follow-up (P<0.05), 19.1 +/- 22.0 at the second follow-up (P<0.005), and 10.9 +/- 16.9 at the third follow-up (P<0.001). Most patients tolerated topiramate well. The most common side effects reported were cognitive (12.5%), weight loss (5.6%), and sensory (2.8%). CONCLUSIONS: Topiramate is potentially an effective prophylactic medication for children with frequent migraine.     

Assessment of migraine disability using the migraine disability assessment (MIDAS) questionnaire: a comparison of chronic migraine with episodic migraine

BACKGROUND: Chronic migraine is the most common type of chronic daily headache seen in headache tertiary care centers. Most patients with chronic migraine report their ability to function and feeling of well-being as severely impaired. OBJECTIVE: To measure the headache-related disability of patients with chronic migraine using the Migraine Disability Assessment (MIDAS) Questionnaire, comparing it with that obtained in a control group of patients with episodic migraine. METHODS: The clinical records of 703 patients with chronic daily headache treated in a headache specialty clinic were reviewed to identify 182 with chronic migraine who were evaluated using the MIDAS at their initial visit. Our control group consisted of 86 patients with episodic migraine. RESULTS: Of the 182 patients with chronic migraine, 127 (69.8%) were overusing acute-care medication. Patients were predominantly women (72.5%), with a mean age of 38.3 years. The group with episodic migraine consisted of 59 women (68.6%), with a mean age of 36.1 years. No statistically significant demographic differences were observed between the two groups. The group with chronic migraine had more total headache days over 3 months (66.7 versus 15.5, P<.001), missed more days of work or school (5.3 versus 2.3, P =.0007), had more reduced effectiveness days at work or school (11.9 versus 4.6, P =.0001), missed more days of housework (16.5 versus 3.3, P<.0001), and missed more days of family, social, or leisure activities (7.0 versus 5.5, P =.03). The group with chronic migraine was more likely to be in MIDAS grade IV (64.3% versus 43.2%, P =.001), reflecting the great likelihood of severe disability in this group. The average total MIDAS score was 34.9 in the group with chronic migraine versus 19.3 in the group with episodic migraine (P<.001). CONCLUSION: In subspecialty centers, patients with chronic migraine demonstrate remarkable impairment of their daily activities and are severely burdened by their headache syndrome, reflected by their high MIDAS scores. The chronicity and pervasiveness of migraine thus is associated with increased functional impairment as well as increase in headache frequency.     

Sodium valproate prophylaxis in childhood migraine

Migraine is a cause of recurrent headache in childhood. The efficacy of sodium valproate is well known in the prophylactic treatment of adult migraine, but there are few studies involving the drug's effect in pediatric migraine. OBJECTIVE: To determine the efficacy of sodium valproate in the prophylactic treatment of childhood migraine. METHODS: Fifteen children with migraine according to International Headache Society criteria were included in the study. Headache severity was measured and assessed by Algology unit by a using visual analog scale and a numerical rating scale. All of the subjects were asked to keep a headache diary for 8 weeks. Three subjects who had no headache attacks during the baseline period and two cases who were lost to follow up were excluded. Thus, sodium valproate was initiated in 10 subjects (six boys, four girls), 500 mg/night, and the daily dose was increased up to 1000 mg according to blood levels. Their ages ranged from 9 to 17 (mean age 13.6 +/- 3.2 years). Therapy continued for at least 12 weeks. RESULTS: Headache severity as measured via the mean visual analog score was 6.8 +/- 1.8 at baseline and was 0.7 +/- 1.2 at the end of the treatment period (P = 0.000). Mean headache attacks per month were 6 +/- 4.2 at baseline and were 0.8 +/- 1.9 at the end of the treatment period (P = 0.002). The duration of headache was significantly decreased from a mean of 5.5 +/- 3.9 hours to 1.1 +/- 2.5 hours with treatment (P = 0.001). The observed side effects were dizziness, drowsiness, and increase in appetite; none required drug withdrawal. In two cases, headache attacks recurred after the cessation of valproate, and therapy was restarted. Headache control lasted for six months following cessation of the drug in the remainder of the subjects. CONCLUSION: Sodium valproate appears to be effective and safe in selected patients with childhood migraine.     

Duration of migraine is a predictor for response to botulinum toxin type A

OBJECTIVE: To identify the clinical characteristics and/or injection parameters that predict a favorable response to botulinum toxin type A in patients with episodic and chronic migraine. BACKGROUND: There is emerging scientific and clinical evidence to support the utility of botulinum toxin type A (BoNT-A) in the prophylaxis of episodic and chronic migraine headache. However, the patient characteristics and injection strategies that predict a favorable treatment response are unknown. METHODS: We conducted a prospective, open-label study on 74 patients from our clinic receiving BoNT-A for episodic or chronic migraine. For all patients, migraine-related disability (Migraine Disability Assesment [MIDAS]), headache frequency, and average headache intensity were obtained at baseline and at 3 months post-BoNT-A. Information regarding demographic characteristics and injection parameters was also collected. RESULTS: Sixty-one patients met the study criteria and were available for 3-month follow-up. At the 3-month follow-up visit, the mean MIDAS scores of the 61 qualified study patients had decreased from 102 at baseline to 49 (52% decrease, P<.001). The mean number of headache days was reduced from 60 to 39 (P<.001), and the mean headache intensity decreased from 7.6 at baseline to 5.9 (P<.001). Frequency of migraine attacks, presence of analgesic overuse, total BoNT-A dose, and presence of underlying muscle tenderness were not predictive of treatment response. Age and duration of migraine were the only clinical factors significantly predictive of treatment response. Age likely was a predictor only as a consequence of duration of illness as subjects with migraine duration greater than 30 years were significantly less likely to respond to treatment with BoNT-A. CONCLUSION: BoNT-A may be effective in decreasing headache frequency, headache intensity, and headache-related disability in episodic and chronic migraine patients. Duration of illness emerged as a predictor of treatment response. Randomized controlled studies should evaluate headache-related disability as a primary endpoint in patients with episodic and chronic headache.     

Visual cortex excitability in migraine evaluated by single and paired magnetic stimuli

OBJECTIVE: To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single- and paired-pulses. METHODS: Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti-migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS with an interstimulus interval of 50 ms. RESULTS: The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%) (P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired-pulse stimulation than with single pulses (P < .001). CONCLUSIONS: PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single-pulse TMS, paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.     

Blood flow velocity and pulsatility index differences in patients with unilateral migraine

OBJECTIVE: To evaluate blood flow velocity and pulsatility in unilateral migraine without aura during the headache-free period using transcranial Doppler (TCD) sonography. METHODS: Patients with unilateral headache were recruited during the headache-free period. Maximum mean flow velocity (MFV) and pulsatility index (PI) were measured in the middle cerebral (MCA) and basilar arteries. Controls were headache-free individuals without cerebrovascular disease. RESULTS: Twenty-five patients with right-sided migraine, 25 patients with left-sided migraine, and 19 controls were studied. The MCA PI was higher on the right headache side versus the left headache side (0.97 +/- 0.2 versus 0.86 +/- 0.1 cm/s, P =.02) and versus controls (0.9 +/- 0.2 cm/s, NS). The basilar artery MFV was higher in patients with right-sided headache versus left-sided headache (39.5 +/- 5.6 versus 34.7 +/- 8.2 cm/s, P =.02) and versus controls (38.2 +/- 8 cm/s, NS). No decrease in MFV with age was observed in patients with migraine. CONCLUSIONS: Middle cerebral artery flow pulsatility and basilar artery velocity are higher in patients with right-sided migraine compared with left-sided migraineurs, during the headache-free period. Although these parameters were similar to controls, the differences found during the headache-free period in migraineurs may indicate vascular involvement predisposing to the unilateral headache recurrence.     

Outcome of a multidisciplinary approach to pediatric migraine at 1, 2, and 5 years

OBJECTIVE: To assess the long-term effectiveness and outcome of multidisciplinary treatment of childhood headaches 1, 2, and 5 years after initial treatment. BACKGROUND: Headaches are a common problem for children and adolescents and for many patients continue into adulthood. Outcome research for pediatric migraine headaches is limited, thus restricting knowledge of the effectiveness of long-term management and outcome. METHODS: Headache characteristics were assessed at the initial visit and were reevaluated 1, 2, and 5 years later in independent sub-groups of consecutive patients. These characteristics included headache frequency, severity, average duration, school absences, and overall perceived response to treatment. RESULTS: At 1 year, 96 patients were evaluated (mean age = 11.0 +/- 3.4, 59% females), 69 patients at 2 years (mean age = 10.6 +/- 3.4, 48% females), and 32 at 5 years (mean age = 10.5 +/- 3.9, 66% females). The headaches were reported as better in 94% at 1 year, 85% at 2 years, and 94% at 5 years. The initial frequency was at 13.4 +/- 10.8 headaches per month, 4.9 +/- 7.0 at 1 year (P < .001), 4.7 +/- 7.6 at 2 years (P < .001), and 4.5 +/- 7.5 at 5 years (P < .001). The severity decreased from 6.8 +/- 1.8 to 5.1 +/- 2.3 at 1 year (P < .001), to 5.0 +/- 2.4 at 2 years (P < .001), and to 4.6 +/- 2.5 at 5 years (P < .01). The school days missed per month showed a marked decrease from 4.5 +/- 9.5 at initial visit to 1.55 +/- 2.8 at 5 years (P < .001). Patients that were only seen at their initial visit and did not choose to return for follow-up had less frequent and shorter duration headaches on initial visit when compared with the rest of the sample and continued to be doing well at the 1-, 2-, and 5-year assessments. CONCLUSIONS: Multidisciplinary treatment was found to be effective for children and adolescents with improvement of multiple outcome variants of pediatric migraine care, including frequency, severity, and school days missed. Patients who did not return to follow-up evaluation were more likely to have less frequent and shorter duration headaches at initial presentation. Regular follow-up care is needed for those children with more severe initial headache presentation.     

Topiramate in patients with episodic migraine: reducing the risk for chronic forms of headache

OBJECTIVE: The aim was to evaluate whether preventive treatment with topiramate in patients with episodic migraine reduces the risk of developing chronic forms of headache. BACKGROUND: Chronic forms of headache, including chronic migraine or medication overuse headache (MOH), are characterized by 15 or more headache days per month. Acute medication overuse has been shown to be a risk factor for developing chronic headache, but it is not known whether preventive treatment can reduce the risk of developing chronic forms of headache or the development of MOH. METHODS: Pooled data from 3 trials in patients with episodic migraine randomized either to treatment with 100 mg topiramate per day (n = 384) or with placebo (n = 372) were analyzed with regard to the number of headache days during a prospective 4-week baseline period and the individual final 4 weeks of each patient's treatment during the planned 26-week double-blind treatment period. RESULTS: The number of headache days per month in the topiramate versus the placebo-treated groups was 7.3 +/- 3.0 versus 7.3 +/- 3.1 during baseline and 4.1 +/- 4.2 versus 5.6 +/- 4.9 during the final 4 weeks, respectively (P < .001). At the end of the study, 8 versus 16 patients fulfilled International Headache Society criteria of chronic headache (odds ratio: 2.11, P= .082). Moreover, a significantly lower number of patients receiving topiramate treatment reported an increase in headache days per month by the end of the study when compared to placebo (66 vs 88 patients, respectively; odds ratio: 1.49, P < .05). Finally, the number of days with usage of acute medication was significantly lower in the topiramate arm compared with placebo (3.3 +/- 3.7 vs 4.3 +/- 3.6, respectively; P < .001). CONCLUSION: Preventive treatment with topiramate in patients with episodic migraine may reduce the risk of developing chronic forms of headache.     

Hormone supplementation differently affects migraine in postmenopausal women

OBJECTIVE: To evaluate the effects of three schemes of oral hormone replacement therapy (HRT) on migraine course in postmenopausal women. METHODS: Thirty-eight patients presenting for clinical evaluation of menopausal status and suffering from migraine were enrolled. The observational period lasted 7 months, during which women filled in a daily diary with the clinical features of headache attacks and analgesic use. We evaluated climacteric symptoms, anxiety and depression. After a 1-month run-in period, women were assigned to one of three regimens of HRT: estradiol hemihydrate 1 mg/day plus norethisterone 0.5 mg/day for 28 days, in a continuous combined scheme; oral conjugated estrogens 0.625 mg/day for 28 days plus medroxyprogesterone acetate 10 mg/day in the last 14 days, in a sequential continuous scheme; and estradiol valerate 2 mg/day for 21 days plus cyproterone acetate 1 mg/day from day 12 to 21 in a sequential cyclical scheme. Follow-up evaluations were performed at 3 and 6 months. RESULTS: During the run-in period, the three subgroups of patients were similar as far as the features of migraine are concerned. Overall, a progressive increase in attack frequency (from 2.2 +/- 1.0 to 3.8 +/- 1.3, P<.001), days with headache (from 3.4 +/- 1.3 to 4.9 +/- 1.9, P<.001), and analgesic consumption (from 3.4 +/- 1.3 to 5.6 +/- 2.2, P<.001) was observed after 6 months. Duration of attacks decreased (from 18.1 +/- 7.4 to 13.6 +/- 4.2 hours, P =.005), whereas severity worsened (from 1.9 +/- 0.2 to 2.1 +/- 0.2, P<.001). The increase in number of days with headache and number of analgesics used was smaller in the group receiving the continuous combined regimen than in the other two groups. CONCLUSION: Although HRT typically will lead to some worsening of headache syndrome, estradiol hemihydrate plus norethisterone given in a combined continuous scheme was the regimen best tolerated by our patients.     

Zonisamide for migraine prophylaxis in refractory patients

Zonisamide is a new antiepileptic drug with multiple mechanisms of action and a favourable pharmacokinetic profile. Preliminary data suggest that zonisamide may be effective in migraine prophylaxis. We evaluated the efficacy and tolerability of zonisamide for migraine prophylaxis in refractory patients. We reviewed the charts of adult patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) according to the Silberstein-Lipton criteria, who had been treated with zonisamide at our out-patient clinic for at least 60 days. Demographic data, zonisamide dosage and duration of treatment were collected and analysed. Headache frequency, attack duration, headache severity and headache-related disability before and after treatment initiation with zonisamide were compared. Thirty-three patients were included in the study (average age 43.9 +/- 8.4 years; 23 (70%) with TM and 10 (30%) with EM). The patients had failed an average of 6.2 migraine prophylactic drugs prior to zonisamide. The average zonisamide daily dose was 337.9 +/- 146.3 mg and the average duration of treatment was 186.4 +/- 174.0 days. The average number of days with headache per month was reduced in the entire study population from 20.7 +/- 9.5 before zonisamide treatment to 18.0 +/- 11.3 after its initiation (P = 0.06) [in TM from 24.7 +/- 7.3 to 21.0 +/- 10.7 (P = 0.06); in EM from 11.6 +/- 7.6 to 11.0 +/- 9.7 (P = NS)]. No significant changes in other headache parameters were found. Fourteen patients (42.4%) reported adverse events (AEs), the most common of which was fatigue. Most patients (12/14, 85.7%) rated AEs as mild or moderate. In this group of refractory migraine patients, zonisamide therapy did not result in a statistically significant beneficial effect on headache or on associated symptoms.     

Enteral feeding with a solution enriched with antioxidant vitamins A, C, and E enhances the resistance to oxidative stress

OBJECTIVE: To assess whether dietary supplementation with the antioxidant vitamins A, C, and E enhances parameters of oxidative stress and influences the course of critically ill patients. DESIGN: Prospective, randomized, double-blinded, placebo-controlled study. SETTING: Department of medicosurgical intensive care of an academic hospital. PATIENTS: Fifty-one patients expected to require at least 7 days of enteral feeding. Thirty-seven of these patients (age, 57 +/- 7 yrs; Simplified Acute Physiology Score II, 33 +/- 6 points) completed the study. INTERVENTIONS: Twenty patients were randomized to receive the formula supplemented with vitamins A (67 microg/dL), C (13.3 mg/ dL), and E (4.94 mg/dL), and 17 patients received an isocaloric and isonitrogenous control solution. MEASUREMENTS AND MAIN RESULTS: Plasma levels of antioxidant vitamins, lipid peroxidation (estimated by the malonyldialdehyde assay), and low-density lipoprotein (LDL), and erythrocyte resistance to experimental oxidative stress were determined on samples drawn two consecutive days before the initiation of feeding and at the end of the 7-day period. Clinical outcome measures included documented infection and intensive care unit and 28-day survival. Administration of the supplemented solution increased significantly the concentration of plasma beta-carotene (from 0.2 +/- 0.0 microg/mL to 0.6 +/- 0.1 microg/mL; p < 0.01) and plasma and LDL-bound alpha-tocopherol (from 6.0 +/- 0.4 microg/mL and 2.9 +/- 0.9 microg/mL to 9.7 +/- 0.5 microg/mL and 4.3 +/- 1.2 microg/mL, respectively; p < 0.05), and improved LDL resistance to oxidative stress by 21 +/- 4% (p < 0.05). No such change was observed in the control group. There was no significant difference in clinical outcome between the two groups. CONCLUSIONS: Supplemental antioxidant vitamins added to enteral feeding solutions are well absorbed. Dietary supplementation with vitamins A, C, and E is associated with an improvement in antioxidant defenses, as assessed by ex vivo tests.     

Recognition and management of migraine in primary care: influence of functional impact measured by the headache impact test (HIT)

The objective of the present study was to investigate the influence of headache-related disability on the recognition and management of migraine by French general practitioners (GPs). Forty-nine teaching GPs at the Faculty of Medicine in the Nice-Sophia-Antipolis University were involved in this study. On one day, each patient who presented during the surgery hours of these GPs was invited to complete a questionnaire aimed at identifying if he/she was a headache sufferer and, if so, whether the headache corresponded to migraine and had an impact on his/her functional ability. Functional disability was measured by the short-form of the Headache Impact Test (HIT-6). Being blind to the patients' responses, the GPs completed a questionnaire for each patient aimed at identifying if he/she considered the patient to suffer from migraine and, if so, whether he/she managed the patient for migraine. A total of 696 patients were included in this study and 289 (41.52%) of them had episodic headache. According to the new International Headache Society (IHS) criteria, 113 (16.24%) patients suffered from headache without migrainous features and 176 (25.29%) patients were migraine sufferers (migraine according to IHS categories 1.1 and 1.2.1: 11.21%, and probable migraine according to IHS categories 1.6.1 and 1.6.2: 14.08%). The mean HIT score of these migraine sufferers was 59.1+/-8.8 and 50% of them presented with a very severe impact score (HIT score>60). Among the 176 migraine sufferers, 105 (59.7%) were not recognized as having migraine, 21 (11.9%) were recognized as having migraine but without migraine management and 50 (28.4%) were recognized as having migraine with migraine management. Recognition of migraine by GPs was statistically associated with the HIT score (OR=1.105, 95% CI: 1.056-1.157, P<0.001) and with the 1.1 and 1.2.1 IHS diagnostic categories (OR=2.942, 95% CI: 1.286-5.025, P=0.0107) whereas management of patients recognized as having migraine was only associated with the patient's age (OR=1.051, 95% CI: 1.000-1.104, P=0.0486). These results indicate that the continuing medical education of GPs should focus on the diagnosis of migraine and its impact on the lifestyle of the patient.     

Open-label trial of cinnarizine in migraine prophylaxis

OBJECTIVE: To assess the effectiveness and safety of cinnarizine as a migraine-preventive therapy. METHODS: Sixty patients with more than 2 migraine headache attacks during a 4-week baseline entered the study and received a 25-mg tablet cinnarizine twice daily for the first 3 days and then 3 times daily. They were assessed on weeks 2, 6, 10, and 14. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Reduction in migraine attacks duration and severity was also evaluated. RESULTS: The mean reduction in 4-week migraine headache rate was 4.6 +/- 2.2 from the baseline of 6.2 +/- 2.2 after 14 weeks of treatment, which was statistically significant (P < 0.001). Percent reduction in 4-week migraine frequency was 35% after 2 weeks, 74% after 6 weeks, 74% after 10 weeks, and 75% after 14 weeks of treatment. Significant reduction in attack duration (P < 0.001) and severity (P < 0.001) was also noted. No serious adverse events were observed in this series of patient. CONCLUSION: Cinnarizine is an efficacious and well-tolerated prophylactic antimigraine medication, which has early onset effectiveness.     

Prophylaxis of migraine,transformed migraine,and cluster headache with topiramate

OBJECTIVE: To assess the efficacy and tolerability of topiramate for prophylaxis of migraine and cluster headache via a retrospective chart analysis. BACKGROUND: Topiramate has multiple mechanisms of action that could potentially contribute to migraine prophylaxis. We conducted a retrospective chart review to assess the efficacy of topiramate as add-on therapy in patients with transformed migraine or cluster headache, and as first-line therapy in patients with episodic migraine. METHODS: Patients diagnosed with transformed migraine, episodic migraine, or cluster headache, who received topiramate either as add-on therapy or monotherapy were selected via retrospective chart review. Patients had begun topiramate therapy at 25 mg/day for the first week and increased their dosage by 25 mg/week to a maximum of 200 mg/day. Topiramate was used as add-on therapy for patients with transformed migraine and cluster headache, and as a first-line monotherapy in patients with episodic migraine who had no previous prophylactic therapy. The outcome parameters examined included a mean 28-day migraine frequency, migraine severity, number of headache days/month, number of abortive medication tablets/month, patient global evaluation, and the MIDAS scale. RESULTS: One hundred seventy-eight patients (transformed migraine: n = 96; episodic migraine: n = 70; and cluster headache: n = 12) were included in the retrospective analysis. The mean dose of topiramate for all patients was 87.5 mg/day. For patients with transformed migraine, mean migraine frequency decreased from 6.3/28 days to 3.7 (P = 0.005). Mean severity decreased from 7.1 to 3.8 on a 10-point scale, with 10 representing the most severe pain (P = 0.003). The mean number of headache days/month decreased from 22.1 to 9.6 (P = 0.001), and the mean number of abortive medication tablets decreased from 28.7/month to 10.6 (P = 0.001). Patient global evaluation indicated substantial or moderate improvement in 53% of patients with transformed migraine who used topiramate as add-on therapy. Mean MIDAS scale values decreased from 90.2 to 24.9 (P< 0.0001). The 70 episodic migraine patients who were administered topiramate as first-line therapy exhibited a decrease in mean migraine frequency (5.8/28 days to 1.9, P = 0.001), while mean migraine severity decreased from 8.1 to 2.0 (P = 0.003). Sixty-one percent of patients reported marked improvement. Nine of the 12 cluster headache patients exhibited substantial or moderate improvement in symptoms, whereas three had no improvement. The most common adverse effects were paresthesias (12%), cognitive effects (11%), and dizziness (6%). Eight patients discontinued topiramate due to adverse effects; cognitive effects were the most common reason. No patient discontinued topiramate treatment due to lack of efficacy. Twelve percent of patients lost more than 5 lbs during treatment (a range of 5-120 lbs). CONCLUSION: For both patients with transformed migraine (add-on therapy) and patients with episodic migraine (first-line monotherapy), topiramate yielded significant reductions in migraine frequency, migraine severity, number of headache days/month, and use of abortive medications. Topiramate also appears to be well tolerated and useful in the adjunctive treatment of cluster headache. Prospective double-blind, placebo-controlled trials will be required to confirm our results.     

Health resource utilization of the emergency department headache "repeater"

OBJECTIVE: To document the health resource utilization of patients who repeatedly use emergency department services for headache care. BACKGROUND: Patients with headache who frequently use emergency department services may differ from patients with more typical, episodic migraine. Previous studies of health resource utilization have often failed to distinguish the high utilizer as a specific subset of the migraine population. DESIGN: Retrospective review of urgent care/emergency department charts, clinic charts, and pharmacy rosters. PATIENTS AND METHODS: Patients who made three or more visits for headache to an urgent care/emergency department (UC/ED) facility for headache over a 6-month study period were identified and designated as "repeaters" for this study. Pharmacy profiles and appointment histories of 52 of the 54 repeaters whose records were available were reviewed for the 12 months prior to the study period. RESULTS: Over the 6-month study period, 518 patients visited the UC/ED 1004 times for primary headache complaints. Fifty-four (10%) repeaters made 502 visits (50% of total visits; mean 9.3, range 3-50). In the 12 months prior to the study period, 52 of these repeaters made 1832 visits to the UC/ED or clinic (mean 35.2, range 0-178): 1458 (79.6%) were headache related, and 1271 (69.4%) of all visits were to the UC/ED. An estimated 12-month cost for all visits was $183,760. Pharmacy rosters showed use of narcotics in 41 of the 52 patients (annual mean +/- SD, 613 +/- 670 tablets), benzodiazepines in 30 patients (500 +/- 486 tablets), and butalbital products in 27 patients (395 +/- 590 tablets). Mean daily use of all symptomatic medications combined was 3.9 +/- 3.2 doses/day. CONCLUSION: Health resource utilization of emergency department headache repeaters is predominantly headache-related acute care. Associated medication overuse is frequently present. Efforts to improve care for patients with headache will benefit from distinguishing the high utilizer as a subset of the migraine population.     

Coenzyme Q10 in plasma and erythrocytes: comparison of antioxidant levels in healthy probands after oral supplementation and in patients suffering from sickle cell anemia

BACKGROUND: The membrane-associated antioxidant coenzyme Q10 (CoQ10) or ubiquinone-10 is frequently measured in serum or plasma. However, little is known about the total contents or redox status of CoQ10 in blood cells. METHODS: We have developed a method for determination of CoQ10 in erythrocytes. Total CoQ10 in erythrocytes was compared to the amounts of ubiquinone-10 and ubihydroquinone-10 in plasma using high-pressure liquid chromatography (HPLC) with electrochemical detection and internal standardisation (ubiquinone-9, ubihydroquinone-9). RESULTS: Investigations in 10 healthy probands showed that oral intake of CoQ10 (3 mg/kg/day) led to a short-term (after 5 h, 1.57+/-0.55 pmol/microl plasma) and long-term (after 14 days, 4.00+/-1.88 pmol/microl plasma, p<0.05 vs. -1 h, 1.11+/-0.24 pmol/microl plasma) increase in plasma concentrations while decreasing the redox status of CoQ10 (after 14 days, 5.37+/-1.31% in plasma, p<0.05 vs. -1 h, 6.74+/-0.86% in plasma). However, in these healthy probands, CoQ10 content in red blood cells remained unchanged despite excessive supplementation. In addition, plasma and erythrocyte concentrations of CoQ10 were measured in five patients suffering from sickle cell anemia, a genetic anemia characterised by an overall accelerated production of reactive oxygen species. While these patients showed normal or decreased plasma levels of CoQ10 with a shifting of the redox state in favour of the oxidised part (10.8-27.2% in plasma), the erythrocyte concentrations of CoQ10 were dramatically elevated (280-1,093 pmol/10(9) ERY vs. 22.20+/-6.17 pmol/10(9) ERY). CONCLUSIONS: We conclude that normal red blood cells may regulate their CoQ10 content independently from environmental supplementation, but dramatic changes may be expected under pathological conditions.     

Increased plasma matrix metalloproteinase-9 levels in migraineurs

BACKGROUND AND OBJECTIVE: Cortical spreading depression and neurogenic inflammation have been hypothesized to be key steps in the development of migraine headache. Recent studies have highlighted matrix metalloproteinase-9 (MMP-9) in cortical spreading depression, neurogenic inflammation, and cerebral ischemia. To seek their possible association, we investigated plasma MMP-9 levels in migraineurs during headache-free periods. METHODS: Plasma MMP-9 levels in 84 migraine subjects and 61 controls were determined by enzyme-linked immunosorbent assay. In addition, 23 patients with tension type headache were included in the study as comparative subjects. RESULTS: The MMP-9 levels in migraineurs (42.5+/-4.6 ng/mL, mean+/-SE) were significantly higher than those in controls (25.4+/-2.7 ng/mL, P< .005). Those levels in tension type headache subjects (24.6+/-4.8 ng/mL) did not differ from those in controls. There was no significant difference between subjects having migraine with aura and those without aura. The MMP-9 levels did not correlate with age, duration of illness, frequency of migraine attack, duration of headache attack, or medication for headache. Mean plasma MMP-9 levels were the highest in subjects from whom blood samples were taken 2-4 days after their latest attack. CONCLUSIONS: The degradation of extracellular matrix showing the increase of MMP-9 in migraineurs may be associated with an abnormality in their blood vessel permeability. MPP-9 plays some role in migraine pathophysiology. Further studies of MMPs are necessary to elucidate their role.