Zonisamide prophylaxis in refractory pediatric headache

INTRODUCTION: Currently, no medications are approved for pediatric headache prophylaxis in the United States. Zonisamide is an antiepileptic drug with preliminary studies suggesting some efficacy in the adult headache population. METHODS: A retrospective chart review was conducted on refractory headache patients in our multidisciplinary Headache Clinic who were treated with zonisamide, an antiepileptic drug, for headache prophylaxis. Records were reviewed for pertinent data including patient history, diagnosis, prior treatment regimens, and zonisamide response, along with headache frequency. RESULTS: Twelve patients were identified (8 girls); mean age was 13.5 years. Eight of the 12 patients had a positive response to zonisamide with greater than 50% reduction in headaches from pretreatment values. CONCLUSION: Zonisamide had some efficacy in headache reduction. It was well tolerated with only minor side effects. Further prospective studies with zonisamide are warranted in refractory pediatric headache patients.     

Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study

The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, placebo-controlled trial demonstrates that topiramate is effective and reasonably well tolerated when used for the preventive treatment of chronic migraine, even in the presence of medication overuse.     

Nefazodone for chronic daily headache prophylaxis: an open-label study

OBJECTIVE: To assess effectiveness, tolerability, and safety of nefazodone as a prophylactic agent for chronic daily headache. BACKGROUND: Nefazodone is a potent, selective 5-HT2 antagonist with a distinct and atypical mechanism of action. The evolution of intermittent migraine to chronic daily headache has been linked to up-regulation of 5-HT2 receptors as well as other factors. Other effective migraine prophylactic medications are also 5-HT2 antagonists. Although research has shown nefazodone to be an effective antidepressant with a good tolerability and safety profile, its potential role in headache prophylaxis has not been tested. DESIGN: This was a two-center, open-label study with a 4-week baseline, followed by 12 weeks of treatment with nefazodone at a median dose of 300 mg (mean, 303.66 +/- 65.57 mg; range, 100 to 450 mg depending on tolerability). Potential patients were required to report more than 15 days of headache per month for at least 3 months prior to screening. Only patients with at least 15 days of recorded headache during baseline were included in the final sample (N=52). Most patients (n=48) had a history of migraine based on International Headache Society criteria; 4 had primarily chronic tension-type headache, but with more migrainous features than permitted by International Headache Society criteria for a primary chronic tension-type headache diagnosis. RESULTS: Significant improvement was demonstrated for all headache diary measures, with significance levels ranging from P<.00001 for average intensity, duration, headache index (intensity x duration), peak intensity, headache days per week, and peak impairment, to P<.0033 for severe headache days per week, and P<.0051 for rescue medication days. During the last month of treatment, 71% of the patients completing the study showed at least a 50% reduction in headache index compared to baseline, and 59% had at least a 75% improvement. Visual analog scales completed at 4-week intervals showed significant improvement in patient ratings of overall headache status, quality of life, sleep, mood (P<.00001), and sexual function (P<.00053). Significant improvements were also observed in the Pain Disability Index (P<.00007), Beck Depression Inventory-II (P<.00001), Hamilton Rating Scale for Depression (P<.0008), and Hamilton Psychiatric Rating Scale for Anxiety (P<.00007). Headache indices for patients in the top quartile on the depression and anxiety scales (clinical depression/anxiety) did not differ from the other patients during baseline. However, patients who were depressed or anxious showed significantly more improvement over the course of 12 weeks of treatment (P<.0006 or less for the depression scales, P<.026 for anxiety). Common mild to moderate adverse events reported by 10% or more of the patients included fatigue, nausea, dry mouth, dizziness, sleep disturbance, blurred vision, irritability/nervousness, and sedation. Only 5 of the 52 patients discontinued the study due to adverse events: headache (2 patients), and nausea, sleep disturbance, and a drugged feeling (1 patient each). CONCLUSIONS: These results provide preliminary support for the efficacy of nefazodone in the prophylaxis of chronic daily headache. In this sample, nefazodone was safe and generally well tolerated. Patient ratings of sexual function improved over the course of treatment, in contrast to what is generally observed with most antidepressants. Nefazodone may be particularly beneficial for patients with chronic daily headache and comorbid depression. Further research is indicated.     

Migraine days decline with duration of illness in adolescents with transformed migraine

The aim of this study was to assess the proportion of subjects with transformed migraine (TM) who have 15 or more migraine days per month as a function of duration of chronic daily headache (CDH) in an adolescent sample. CDH is a syndrome characterized by 15 or more headache days per month. In specialty care, TM is the most common type of CDH. Most adults who meet criteria for TM do not meet the International Headache Society (IHS) criteria for chronic migraine (CM). TM criteria require 15 or more headache days per month (not necessarily migraine), with a current or past history of migraine. CM requires 15 or more migraine days per month. As TM develops, attack frequency increases and the number of migraine features diminishes. If this observation is correct, individuals who meet criteria for TM but not CM may be at a later stage in the evolution of the disease, compared with those who meet criteria for CM. We reviewed charts of 267 adolescents (13-17 years) seen in a headache centre, to identify 117 with TM. We divide subjects with TM into those with recent onset (1 year) and examined the number of migraine days per month and demographic features. We modelled predictors of CM (>15 migraine days per month) using logistic regression. Of 117 adolescents with TM, 55 (47%) had recent-onset (<1 year) and 62 (53%) had long-duration TM. Those with recent-onset TM were much more likely also to meet criteria for CM (74.5% vs. 25.8%, P < 0.001). This was verified in the TM with medication overuse subgroup (recent onset 66.7%, vs. long duration 37%, P = 0.01) and in the TM without medication overuse subgroup (62.2% vs. 19.2%, P = 0.001). Modelling the dichotomous outcome of CM (>15 days of migraine/month) in logistic regression, CM was predicted by recent onset of CDH, recent onset of migraine (<36 months), and younger ages (相似文献   

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.     

A prospective, open-label, long-term study of the efficacy and tolerability of topiramate in the prophylaxis of chronic tension-type headache

This open study evaluates the effectiveness and safety of topiramate for the prophylaxis of chronic tension-type headache. Fifty-one patients were enrolled, of whom 46 completed 24 weeks of treatment with topiramate. Daily dosing was titrated from 25 mg to 100 mg by treatment week 4. The primary efficacy parameter was headache frequency at weeks 13-24 compared with baseline. Headache frequency declined from 23.50 +/- 5.32 days (baseline, mean, SD) to 12.58 +/- 6.28 days at weeks 13-24 (P < 0.0001), with frequency of severe headaches dropping from 8.18 to 3.14 days (P < 0.0001). The average headache intensity dropped from 6.13 to 2.07 on the visual analogue scale (P < 0.0001). These parameters were not significantly reduced at weeks 5-12. A 50% reduction in headache frequency was achieved in 73% of patients at weeks 13-24. Also improved were mood, sleep, quality of life (all parameters, P < 0.0001) as well as the Beck Depression Inventory-II (P < 0.0001). In addition, a highly significant weight loss of 2.14 kg (mean) was observed between baseline (71.64 +/- 10.65 kg) and week 24 [69.50 +/- 10.04 kg (SD)] (P < 0.0001). There were only few side-effects, none of these rated severe. The results provide preliminary confirmation of the efficacy and tolerability of topiramate in the prophylaxis of chronic tension-type headache.     

Field testing alternative criteria for chronic migraine

The criteria for chronic migraine (CM), as proposed by the Second Edition of the International Classification of Headache Disorders (ICHD-2) is very restrictive, excluding most patients that evolve from episodic migraine. In this study we empirically tested three recent proposals for revised criteria for CM. We included individuals with transformed migraine (TM) with or without medication overuse, according to the criteria proposed by Silberstein and Lipton. All individuals had headache calendars for at least three consecutive months. We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+). We also tested three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM + would require at least 15 days of migraine or probable migraine per month. Proposal 2 suggests that CM/CM + would be classified in those with >or= 15 days of headache per month, where at least 50% of these days are migraine or probable migraine. Proposal 3 suggests that CM/CM + would be classified in those with chronic daily headache and at least 8 days of migraine or probable migraine per month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just 10.2% were classified as CM+ 158 (37.5%) had TM without medication overuse; just nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria, proposal 1 included 48.7% of patients with TM without medication overuse; proposal 2 captured 88%, and proposal 3 classified 94.9% of these patients. For TM with medication overuse, the proportions for proposals 1-3 were, respectively, 37%, 81% and 91%. The differences were statistically significant, favouring proposal 3. Consistently, criteria for CM and CM+ should be revised to require at least 8 days of migraine or probable migraine per month, in individuals with 15 or more days of headache per month.     

Defining Refractory Migraine: Results of the RHSIS Survey of American Headache Society Members

Objectives.— To gauge consensus regarding a proposed definition for refractory migraine proposed by Refractory Headache Special Interest Section, and where its use would be most appropriate. Background.— Headache experts have long recognized that a subgroup of headache sufferers remains refractory to treatment. Although different groups have proposed criteria to define refractory migraine, the definition remains controversial. The Refractory Headache Special Interest Section of the American Headache Society developed a definition through a consensus process, assisted by a literature review and initial membership survey. Design.— A 12‐item questionnaire was distributed at the American Headache Society meeting in 2007 during a platform session and at the Refractory Headache Special Interest Section symposium. The same questionnaire was subsequently sent to all American Headache Society members via e‐mail. A total of 151 responses from AHS members form the basis of this report. The survey instrument was designed using Survey Monkey. Frequencies and percentages of the survey were used to describe survey responses. Results.— American Headache Society members agreed that a definition for refractory migraine is needed (91%) that it should be added to the International Classification of Headache Disorders‐2 (86%), and that refractory forms of non‐migraine headache disorders should be defined (87%). Responders believed a refractory migraine definition would be of greatest value in selecting patients for clinical drug trials. The current refractory migraine definition requires a diagnosis of migraine, interference with function or quality of life despite modification of lifestyle factors, and adequate trials of acute and preventive medicines with established efficacy. The proposed criteria for the refractory migraine definition require failing 2 preventive medications to meet the threshold for failure. Although 42% of respondents agreed with the working definition of refractory migraine, 43% favored increasing the number to 3 (50%) or 4 (26%) preventive treatment failures. When respondents were asked if they felt that the proposed definition was appropriate to select patients for invasive procedures (patent foramen ovale repair or stimulators) only 44% agreed. Conclusions.— There is a consensus for a need for a definition for refractory migraine and that it should be added to the International Classification of Headache Disorder‐2. There was also general agreement by the responders that refractory forms of non‐migraine headache disorders should be defined.     

A prospective study of migraine with aura attacks in a headache clinic population

In order to investigate the prevalence of migraine with aura (MA) attacks according to the criteria set by the International Headache Society (IHS) for diagnosis down to the three-digit level of classification, and to determine the recurrence and possible variability of MA attacks over time, we conducted a 6-15-month-long prospective study on 64 MA patients (42 women and 22 men) consecutively referred for the first time to the University of Parma Headache Centre. At the end of the follow-up period, diagnosis was the same as at the first visit for 80.0% of patients, while it was changed for 20.0%. Throughout the duration of the study, the average number of attacks for each patient was 5.3 +/- 6.2 (range 0-30). Attacks of migraine with typical aura were the most frequent (69.1% of patients), but migraine aura without headache (29.1%) and migraine with prolonged aura (20.0%) were also common; by contrast, basilar migraine and migraine with acute onset aura were reported only by one patient in either case. Migraine aura without headache was statistically significantly more frequent in males than in females. Our study results suggest that in most cases the frequency of recurrent MA attacks is relatively low and provide interesting indications about the prevalence of the different MA subtypes listed in the IHS classification, albeit in a headache clinic population.     

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.     

The International Classification of Headache Disorders revised criteria for chronic migraine—field testing in a headache specialty clinic

In the absence of a biological marker and expert consensus on the best approach to classify chronic migraine (CM), recent revised criteria for this disease has been proposed by the Headache Classification Committee of the International Headache Society. This revised criteria for CM is now presented in the Appendix. Herein we field test the revised criteria for CM. We included individuals with transformed migraine with or without medication overuse (TM+ and TM–), according to the criteria proposed by Silberstein and Lipton, since this criterion has been largely used before the Second Edition of the International Classification of the Headache Disorders (ICHD-2). We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+), as well as the revised ICHD-2 (ICHD-2R) criteria for CM (15 days of headache, 8 days of migraine or migraine-specific acute medication use—ergotamine or triptans). We also tested the ICHD-2R vs. three proposals. In proposal 1, CM/CM+ would require at least 15 days of migraine or probable migraine per month. Proposal 2 required 15 days of headache per month and at least 50% of these days were migraine or probable migraine. Proposal 3 required 15 days of headache and at least 8 days of migraine or probable migraine per month. Of the 158 patients with TM–, just 5.6% met ICHD-2 criteria for CM. According to the ICHD-2R, a total of 92.4% met criteria for CM (P < 0.001 vs. ICHD-2). The ICHD-2R criterion performed better than proposal 1 (47.8% of agreement, P < 0.01) and was not statistically different from proposals 2 (87.9%) and 3 (94.9%). Subjects with TM+ should be classified as medication overuse headache (MOH), and not CM+, according to the ICHD-2R. Nonetheless, we assessed the proportion of them who had 8 days of migraine per month. Of the 399 individuals with TM+, just 10.2% could be classified as CM+ in the ICHD-2. However, most (349, 86.9%) had 8 days of migraine per month and could be classified as MOH and probable CM in the ICHD-2R(P < 0.001 vs. ICHD-2). We conclude that the ICHD-2R addresses most of the criticism towards the ICHD-2 and should be adopted in clinical practice and research. In the population where use of specific acute migraine medications is less common, the agreement between ICHD-2R CM and TM may be less robust.     

Results of screening with the brief headache screen compared with a modified IDMigraine.

BACKGROUND: Patients with chronic migraine and chronic daily headache syndromes have greater morbidity than patients with episodic migraine, and are less frequently diagnosed. A screening tool which identifies daily headache syndromes as well as migraine would promote more patients receiving appropriate treatment, including prophylaxis. METHODS: A post-hoc analysis of data obtained to evaluate the prevalence of somatic symptoms in primary care patients was conducted on a convenience sample of primary care patients who completed the Patient Health Questionnaire portion of the PRIME-MD (Primary Care Evaluation of Mental Disorders). Patients who endorsed the symptom of headache were asked to complete the Brief Headache Screen (BHS), a 4-item screening tool, supplemented by 3 clinical questions (nausea, light sensitivity, and noise sensitivity). The data obtained allowed a post-hoc comparison of the BHS with a modified version of the screening tool, IDMigraine(TM) (IDM(TM)). Diagnostic interviews were performed on patients whose diagnoses differed by the 2 screening methods, and on patients who screened positive for daily headache on BHS. RESULTS: Of the 1000 patients who completed the PRIME-MD, 302 (30.2%) indicated headache as a concern, and there were sufficient data for both the BHS and IDM(TM) for 259. There was substantial concordance between the 2 instruments with 82.6% agreement in identified migraine (95% confidence interval: 77.8%-87.4%). The BHS screened positive for migraine in an additional 15.1% of patients who were not identified by IDM(TM), whereas the IDM(TM) identified an additional 2.3% of patients. Of the 173 which both tools recognized as migraine, the BHS identified 42.8% as having a daily headache syndrome (chronic migraine: 23.1%; episodic migraine + chronic tension-type headache [CTTH]: 19.7%). BHS also identified 7 non-migraine patients as having CTTH alone. Diagnostic interviews confirmed that 6/18 (33%) of BHS+ but IDM-, and one of 2 (50%) patients BHS-/IDM+ met full criteria for migraine. Additionally, interviews confirmed the diagnoses of 85.4% of those patients who the BHS identified with daily headache and 67% of those who were identified as medication overuse headache. CONCLUSION: The BHS and a modified IDM(TM) are concordant in screening for migraine in 82.6% of a primary care population who endorsed the symptom of headache. However, the BHS screens effectively not only for migraine but also for chronic daily headache and medication overuse. A screening paradigm based on headache frequency and the frequency of medication use can rapidly and sensitively identify migraine, daily headache syndromes, and medication overuse. This paradigm may improve clinical care by identifying patients who merit preventive as well as acute therapy for migraine.     

The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind,multicentre, randomized placebo-controlled dose-response study

Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.     

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.     

Peripheral neurostimulation for the treatment of chronic,disabling transformed migraine

BACKGROUND: Up to 5% of the general population suffers from transformed migraine. This study analyzes clinical responses of transformed migraine to cervical peripheral nerve stimulation. METHODS: Headache frequency, severity, and disability (Migraine Disability Assessment [MIDAS] scores) were independently measured in an uncontrolled consecutive case series of 25 patients with transformed migraine implanted with C1 through C3 peripheral nerve stimulation. All patients met International Headache Society (IHS) criteria for episodic migraine, as well as suggested criteria for transformed migraine, and had been refractory to conventional treatment for at least 6 months. Responses to C1 through C3 peripheral nerve stimulation were recorded. RESULTS: Prior to stimulation, all patients experienced severe disability (grade IV on the MIDAS) with 75.56 headache days (average severity, 9.32; average MIDAS score, 121) over a 3-month period. Following stimulation, 15 patients reported little or no disability (grade I), 1 reported mild disability (grade II), 4 reported moderate disability (grade III), and 5 continued with severe disability (grade IV), with 37.45 headache days (average severity, 5.72; average MIDAS score, 15). The average improvement in the MIDAS score was 88.7%, with all patients reporting their headaches well controlled after stimulation. CONCLUSIONS: These results raise the possibility that C1 through C3 peripheral nerve stimulation can help improve transformed migraine symptoms and disability. A controlled study is required to confirm these results.     

Refractory headache: historical perspective, need, and purposes for an operational definition

The study of migraine has yielded many benefits for headache patients. Little research, however, has been performed on refractory migraine (RM) headache, a term often used interchangeably with intractable migraine. This may be a consequence of a lack of a well-accepted definition. In a survey performed by the Refractory Headache Special Interest Section (RHSIS) on the American Headache Society (AHS) in 2006, 58% of the members agreed that a definition for refractory headache should be added to the International Classification of Headache Disorders-2. A PubMed search identified 21 articles that defined refractory or intractable headache/migraine. Sixteen (76%) defined the term "refractory" and 5 (24%) defined the term "intractable." Many of these definitions did not address the need for an adequate trial of a preventive medicine, disability, and medication overuse. An operational definition will allow us to better characterize the disorder, address unmet medical needs, and identify the most effective treatments. RHSIS of the AHS has proposed a definition of RM. It is our hope that this definition will spur interest in this entity and will lead to further research in the area.     

Zonisamide for migraine prophylaxis in topiramate-intolerant patients: an observational study

(Headache 2011;51:287‐291) Background.— Zonisamide, a sulfonamide analog, is an antiepileptic drug with mechanisms of action similar to topiramate. Because of its pharmacodynamic and pharmacokinetics profiles, zonisamide is also potentially suitable for migraine prevention. Methods.— Tolerability and effectiveness of zonisamide for migraine prophylaxis in patients with a good response to topiramate, but interrupting it for intolerable side effects, were evaluated in 34 patients. After a 1‐month period of wash‐out, patients were treated with zonisamide (up to a 100 mg/day dosage) for 6 consecutive months. Results.— Zonisamide was well tolerated, only 4 (12%) patients reported transient and tolerable side effects. Mean number of days with headache per month was reduced from 14.9 ± 5.3 during the wash‐out period to 2.5 ± 0.6 after 6 months of zonisamide (P < .001). We observed a significant reduction in headache severity and disability, as assessed by visual analog scale and migraine disability assessment scale. Finally, when compared with the 1‐month period prior to starting zonisamide, a reduced use of analgesics was recorded at the end of the follow‐up. Conclusion.— Our findings support the use of zonisamide as an alternative therapy for migraine prevention in patients with good response, but poor tolerance to topiramate.     

Surgical treatment of patients with refractory migraine headaches and intranasal contact points

Contact point headaches have been attributed to intranasal contact between opposing mucosal surfaces, resulting in referred pain in the distribution of the trigeminal nerve. In subjects with primary headaches, contact points may be associated with treatment refractoriness. We aimed to assess the benefits of surgical correction in patients with refractory migraine or transformed migraine, and radiographic evidence of contact points in the sinonasal area. We reviewed charts of patients who underwent endoscopic sinus surgery and septoplasty for contact point in the same surgical facility, from October 1998 through August 2003. Subjects eligible for surgery had: (i) refractory migraine (failed to standard pharmacological headache treatments) or refractory transformed migraine; (ii) contact points demonstrated by computed tomography scan; (iii) reported significant headache improvement after topical anaesthesia to the contact area. Headache characteristics were assessed preoperatively and at follow-up (6-62 months after surgery) using a standardized questionnaire. A total of 21 subjects (72.5% women) were assessed. Mean headache frequency was reduced from 17.7 to 7.7 headache days per month (P = 0.003). Mean headache severity was reduced from 7.8 to 3.6 on a 0-10 scale (P = 0.0001). Headache-related disability was reduced from 5.6 (10-point scale) to 1.8 (P < 0.0001). A total of 16 subjects (76.2%) had their headache scores improved by 50% or more; nine (42.9%) were pain free at the last follow-up. A total of 18 (95.8%) had at least a 25% reduction in their headache scores. Two patients (9.5%) had increase in their headache score by less than 25%. For selected patients with refractory headaches, demonstrable contact points, and positive response after topical anaesthesia, surgical approach toward the triggering factor may be useful. Prospective studies are necessary to confirm our results.