Behavioral sleep modification may revert transformed migraine to episodic migraine

BACKGROUND: Sleep problems have been linked with headaches for more than a century, but whether the headaches are the cause or the result of the disrupted sleep is unknown. OBJECTIVES: We previously reported that nonrestorative sleep and poor sleep habits are almost universal in a referral population of women with transformed migraine (TM). Since cognitive behavioral therapy is effective in improving sleep quality in individuals with poor sleep hygiene, we designed a randomized, placebo-controlled study to assess the impact of such treatment on TM. We hypothesized that behavioral sleep modification (BSM) would be associated with improvement in headache frequency and intensity and with reversion to episodic migraine. METHODS: Subjects were 43 women with TM referred to an academic headache center. After obtaining informed consent, patients were randomized to receive either behavioral sleep instructions or placebo behavioral instructions in addition to usual medical care. Subjects recorded headaches in standardized diaries. The first postintervention visit was scheduled at 6 weeks. At that visit, the blind was broken and all subjects received BSM instructions. A final visit was scheduled 6 weeks later. RESULTS: Compared to the placebo behavioral group, the BSM group reported statistically significant reduction in headache frequency [F (1, 33 = 12.42, P=.001)] and headache intensity [F(1, 33 = 14.39, P= .01)]. They were more likely to revert to episodic migraine chi2 (2, n = 43) = 7.06, P= .029. No member of the control group reverted to episodic migraine by the first postintervention visit. By the final visit, 48.5% of those who had received BSM instructions had reverted to episodic migraine. CONCLUSIONS: In this pilot study of women with TM, we found that a targeted behavioral sleep invention was associated with improvement in headache frequency, headache index, and with reversion to episodic migraine.     

Naratriptan in the prophylaxis of transformed migraine

We report three patients with transformed migraine, previously refractory to a wide variety of traditional preventive pharmacologic and nonpharmacologic interventions. Naratriptan 2.5 mg given each morning, with a second tablet allowed for breakthrough headache, at least 4 hours later, demonstrated a remarkable reduction in frequency and intensity of daily headache. In addition, a subjective improvement in quality of life and restoration of functioning including a decrease in missed workdays was noted. All three patients had previously experienced good responses to sumatriptan or zolmitriptan, but were limited in frequency of use by the authors. The patients were not experiencing rebound phenomena at the onset of treatment with naratriptan. Clinical responses were noted within 3 to 7 days of initiation of treatment. Traditional risk factor analysis and screening were performed. Naratriptan was extremely well tolerated, with no cardiovascular adverse events reported or observed. Possible mechanisms of action are discussed.     

Naratriptan in the preventive treatment of refractory transformed migraine: a prospective pilot study

OBJECTIVE: To assess the efficacy, safety, and tolerability of daily naratriptan in the preventive treatment of transformed migraine (TM) refractory to previous first line therapies. BACKGROUND: Limited evidence suggests that the triptans can be used in the preventive treatment of refractory headaches. DESIGN/METHODS: We included subjects from 18 to 65 years old, with TM, with or without medication overuse (Silberstein and Lipton, 1996). All participants had previously failed at least two preventive medications. Concomitant, preventive medications were allowed if on a stable dose. After the baseline period, all patients received naratriptan 2.5 mg bid. The treatment phase lasted 3 months. The primary endpoint was change in headache frequency per month. Safety assessment included monthly ECGs, complete ophthalmologic exam, and monthly blood tests. Statistical analyses were performed using the intent-to-treat (ITT) population. We also conducted per-protocol (PP) analyses. RESULTS: Our ITT population consisted of 30 subjects (79% female, mean age of 46.5 years). Mean headache frequency per month at baseline was 27.1 days and a significant reduction of headache frequency was obtained in 1 month (20.4, P < .001), 2 months (18.9, P < .001), and 3 months (19.0, P < .001). HIT scores were 64.3 at baseline, 57.4 after 1 month (P < .001), 55.7 after 2 months (P < .01), and 60 at 3 months (P < .05). The mean number of days using rescue medication was reduced from 17.7 at baseline, to 9.7 at 3 months (P < .001). Our PP population consisted of 22 subjects, and 54% had fewer than 15 headaches per month at the end of the study (converted to an episodic pattern). No serious adverse events were reported. No significant changes were observed in blood pressure or in heart rate. ECGs and ophthalmologic exam were unchanged from baseline. CONCLUSIONS: (1) Daily use of naratriptan provided good preventive efficacy in an important subset of subjects with TM refractory to other preventive treatments. (2) The tolerability of this treatment was excellent. (3) Over a short period of time (3 months), no serious adverse events were reported, nor significant changes were found in the ECG or ophthalmologic evaluation.     

Levetiracetam in the preventive treatmentof transformed migraine: A prospective, open-label, pilot study

Background:

Most preventive agents used for transformed migraine (TM)have not been studied specifically for the treatment of this syndrome. Open-label trials have demonstrated the effectiveness of levetiracetam in the treatment of refractory headaches.

Objective:

The aim of this study was to assess the effectiveness and tolerabilityof levetiracetam in the preventive treatment of refractory TM.

Methods:

This prospective, open-label, pilot study was conducted at TheNew England Center for Headache, Stamford, Connecticut. We included patients aged ≥ 18 years with refractory TM according to the criteria proposed by Silberstein et al. All participants had failed on at least 1 but not more than 3 preventive drugs. Other preventive drugs were allowed if they had been received at a stable dose for > 30 days. The dosage of the levetiracetam tablets ranged from 1000 to 3000 mg/d in 2 divided doses. The treatment phase lasted 3 months. The primary end point was headache frequency (expressed as the number of headache days per month), and the secondary end point was the frequency of moderate or severe headache (d/mo). Other end points were headache score, Migraine Disability Assessment (MIDAS) Questionnaire score, and Headache Impact Test (HIT-6) score. Statistical analyses were performed in the intent-to-treat (ITT) population (patients who received at least 1 dose of study medication) using data subjected to the last-observation-carried-forward algorithm. We also conducted per-protocol (PP) analyses in patients who completed the study.

Results:

The ITT population consisted of 36 patients (26 women, 10 men;mean [SD] age, 46.5 [17.4] years). The mean headache frequency at baseline was 24.9 d/mo, and a significant reduction in headache frequency was obtained at l, 2, and 3 months of treatment (19.4, 18.4, and 16.2 d/mo, respectively; all, P < 0.001 Reproduction in whole or part is not permitted. vs baseline). At baseline, the mean number of moderate or severe headache days was 16.8 d/mo compared with 13.2, 11.9, and 9.7 d/mo at 1, 2, and 3 months, respectively (P=NS, <0.01, and <0.01, respectively). The mean MIDAS score was significantly reduced at 3 months compared with baseline (40.8 vs 62.8 d/mo; P = 0.01). The mean HIT-6 score was 59.4 at 3 months versus 63.4 at baseline (P < 0.01). In the PP population, the mean (SD) headache frequency was reduced from 26.1 (4.1) d/mo at baseline to 14.3 (4.8) d/mo at the end of the study (P < 0.001). The mean (SD) headache score was reduced from 51.3 (17.1) at baseline to 34.0 (22.0) at 3 months (P < 0.016).

Conclusion:

The results of this study in patients with TM support the role of levetiracetam in the preventive treatment of refractory TM.     

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.     

Pain thresholds in daily transformed migraine versus episodic migraine headache patients

OBJECTIVE: The objective of this study was to test whether pain thresholds of patients with episodic migraine (EM) are significantly different from transformed migraine (TM) patients as measured by Quantitative Sensory Testing (QST) and Semmes-Weinstein Monofilaments (SW). BACKGROUND: Although there are many theories, none have undeniably proven why many TM patients are refractory to triptans and other gold standard medications. The hypothesis was that baseline pain thresholds of TM patients are lower than EM patients. METHODS: Episodic (n = 40) and Transformed (n = 41) migraineurs with and without aura were examined with QST and SW over eight locations (bilateral ophthalmic, maxillary, C4/posterior neck, and forearm). All patients completed two visits, baseline and severe migraine. RESULTS: TM patients have lower pain thresholds, than EM patients, as measured on QST and SW testing. A total of 81 out of 129 patients completed both parts of the study at baseline and severe migraine. There were significant differences (P < .05) between EM and TM groups at baseline on maxillary, neck (EM = 45.91 degrees C and TM = 42.94 degrees C), and arm. CONCLUSIONS: TM patients, clinically known to report skin hypersensitivity during migraine, were found to have lower pain thresholds than EM patients, both with severe migraine, and at baseline, measured by QST and SW mechanical testing. As with Burstein's work in EM patients with lowered pain thresholds during their acute migraine, central sensitization may be the explanation for non-responsiveness to triptans in a high proportion of TM patients. The difference in pain threshold at the neck location was such a strikingly frequent difference between EM and TM patients, that this indicates the need for future research to clarify the directional relationship and the relative importance of muscular versus peripheral versus central hypersensitivity in the determination of allodynia.     

Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes

Studies suggest that a substantial proportion of headache sufferers presenting to headache clinics may overuse acute medications. In some cases, overuse may be responsible for the development or maintenance of a chronic daily headache (CDH) syndrome. The objectives of this study are to evaluate patterns of analgesic overuse in patients consulting a headache centre and to compare the outcomes in a group of patients who discontinued medication overuse to those of a group who continued the overuse, in patients with similar age, sex and psychological profile. We reviewed charts of 456 patients with transformed migraine (TM) and acute medication overuse defined by one of the following criteria: 1. Simple analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically considered overuse > 1 tablet per day for > 5 days per week. Patients who were able to undergo detoxification and did not overuse medication (based on the above definition) after one year of follow-up were considered to have successful detoxification (Group 1). Patients who were not able to discontinue offending agents, or returned to a pattern of medication overuse within one year were considered to have unsuccessful detoxification (Group 2). We compared the following outcomes after one year of follow-up: Number of days with headache per month; Intensity of headache; Duration of headache; Headache score (frequency x intensity). The majority of patients overused more than one type of medication. Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight (10.5%) subjects took >10 tablets per day. Considering patients seen in the last 5 years, we found the following overused substances: Butalbital containing combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%; Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%; Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%) were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The comparison between groups 1 and 2 after one year of follow-up showed a decrease in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P < 0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and 14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully detoxified subjects in Group 1 returned to an episodic pattern of migraine, compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing guidelines for patients with frequent headaches are urgently needed. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications.     

Similarities and differences between chronic migraine and episodic migraine

OBJECTIVE: To quantify and characterize the similarities and the differences between chronic migraine (CM) patients with medication overuse and episodic migraine (EM) patients with only occasional analgesic use. BACKGROUND: Population-level epidemiology, characteristics, mechanisms of chronic daily headache, and medication-overuse headache have been widely studied but patient characteristics have received less attention. Methods.-We compared sociodemographic data, family history, physiological and medical history, health services utilized, drugs taken/prescribed, and outcome of 2 groups of subjects: 150 patients, suffering from CM, complicated by probable medication-overuse headache (CM group), consecutively admitted during 2005 to the inpatients' ward of the Headache Centre of the University Hospital of Modena and Reggio Emilia, Italy, to undergo withdrawal from their overused medications; 100 patients suffering from EM, uncomplicated by medication overuse (EM group), consecutively referred to the outpatients' ward of the Headache Centre during November and December 2005. RESULTS: All sociodemographic characteristics were significantly different between the 2 groups. As a whole, the CM group began to suffer from migraine earlier than the EM group. Drug and/or alcohol abuse was significantly higher among first-degree relatives of CM (19%) than of EM (6%) patients. The most frequent comorbid disorders were psychiatric (67%) and gastrointestinal diseases (43%) in the CM group, and allergies in the EM group (31%). Seventy percent of CM patients and 42% of EM patients were taking daily at least another drug, besides those for headache treatment. Most overused medications in the CM group were triptans (43%); the EM group used above all single NSAIDs (56%). At 3-month follow-up, prophylactic treatments reduced, by at least 50%, the frequency of headache in about three-fourths of patients of both the groups; however, headache remained significantly more frequent in the CM than in EM group: only a minority (15%) of CM patients reverted to a headache frequency comparable to that of the EM group. CONCLUSIONS: CM patients present more multiple comorbid disorders, polypharmacy, and social impediments than EM patients. These associated conditions complicate CM clinical management. Even after withdrawal from medication overuse, CM could not be completely reverted by current prophylactic treatments.     

From migraine to chronic daily headache: the biological basis of headache transformation

Migraine headache carries the potential of transforming into chronic daily headache (CDH) over a period of time. Although several risk factors for migraine progression to CDH have been identified, the biological basis of this transformation is unknown. In this review, the consequences of stressful life events and medication overuse, 2 risk factors associated with the development of CDH, on brain processes involved in headache are examined. The extensive overlap in both neural circuitry and cellular events that occur with stress, medication overuse, and migraine provide insight into potential mechanisms that may lead to CDH. Particular attention is devoted to the effect of stress and medication overuse on peripheral and central neuroimmune interactions that can facilitate pain signaling. These interactions include the degranulation of mast cells in the dura, causing the sensitization of primary afferent neurons, as well as the activation of glial cells in the brain that can lead to central sensitization. It is hypothesized that the biological processes involved in migraine headache are directly impacted by stress, medication overuse, and other risk factors, resulting in a reduced threshold for induction of headache and transformation of episodic migraine to CDH.     

Naratriptan in the preventive treatment of refractory chronic migraine: a review of 27 cases

OBJECTIVE: To review the efficacy of naratriptan as preventive treatment in 27 patients with chronic migraine refractory to other commonly used preventive therapies. BACKGROUND: The treatment of chronic migraine often poses a major challenge to the clinician. Even when given expert care, patients with chronic migraine may continue to have daily or near-daily headaches. METHODS: Clinical records and headache calendars were reviewed of 27 patients fulfilling the following inclusion criteria: (1) aged 18 to 65 years; (2) diagnosis of chronic migraine (formerly transformed migraine), according to the criteria proposed by Silberstein et al; (3) previous failure of at least 4 preventive medications prescribed as part of a management program that included nonpharmacological measures, preventive medication, acute care medication, and detoxification from overused medication; and (4) have used daily naratriptan for no less than 2 consecutive months. The dose of naratriptan prescribed was 2.5 mg twice daily. We considered the following outcomes: (1) frequency of headache, (2) intensity of pain, (3) number of days per month with severe headache, (4) headache index (frequency times intensity), and (5) proportion of patients who reverted to an episodic pattern of pain after 6 months of treatment. RESULTS: There was a statistically significant reduction in the frequency of headache days 2 months (15.3 days versus 24.1 days at baseline, P<.001), 6 months (9.1 days, P<.001), and 1 year (7.3 days, P<.001) after daily treatment with naratriptan was initiated. There was also a statistically significant reduction in the number of days per month of severe pain at 1 month (5.6 days versus 12.5 days at baseline, P<.01), 2 months (5.7 days, P<.01), 6 months (2.8 days, P<.01), and 1 year (2.6 days, P<.01). Similarly, there was a statistically significant reduction in the headache index at 2 months (33 versus 56.4 at baseline, P<.001), 6 months (19.5, P<.001), and 1 year (17.2, P<.001). Of the 20 patients who continued to use naratriptan daily for at least 6 months, 13 (65%) reverted to an episodic pattern of pain (migraine). At 1 year, 11 (55%) still continued to experience episodic headache, 1 (5%) relapsed to chronic migraine, and 2 (10%) were lost to follow-up. No patients had intolerability to naratriptan during the treatment period, and no one stopped treatment due to adverse events. CONCLUSIONS: Naratriptan may have a role in the preventive treatment of intractable chronic migraine. Prospective, controlled studies should be considered.     

A comparison of disability and psychological factors in migraine and transformed migraine

The classification of patients with migraine who develop chronic daily headache is controversial, with some classifying such patients as 'transformed migraine'. We compared patients with intermittent migraine attacks and patients with transformed migraine in terms of mean headache intensity on days with headache, depression, pain-related anxiety and headache-related disability. Patients classified clinically as also having tension-type headache were excluded. Aside from the number of days with headache per month, patients with intermittent migraine attacks and patients with transformed migraine were very similar in terms of all parameters studied. Our results support the concept that these two headache groups are closely related.     

Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study

Background.— Though symptomatic medication overuse is believed to play a major role in progression from episodic to chronic or transformed migraine (TM), population‐based longitudinal data on these agents are limited. Objectives.— To assess the role of specific classes of acute medications in the development of TM in episodic migraine (EM) sufferers after adjusting for other risk factors for headache progression. Methods.— As a part of the American Migraine Prevalence and Prevention study (AMPP), we initially surveyed a population sample of 120,000 individuals to identify a sample of migraineurs to be followed annually over 5 years. Using logistic and linear regression, we modeled the probability of transition from EM in 2005 to TM in 2006 in relation to medication use status at baseline. Adjustments were made for gender, headache frequency and severity, and prevention medication use. Results.— Of 8219 individuals with EM in 2005, 209 (2.5%) had developed TM by 2006. Baseline headache frequency was a risk factor for TM. Using acetaminophen user as the reference group, individuals who used medications containing barbiturates (OR = 2.06, 95%CI = 1.3‐3.1) or opiates (OR = 1.98, 95%CI = 1.4‐2.2) were at increased risk of TM. A dose–response relationship was found for use of barbiturates. Use of triptans (OR = 1.25, 95%CI = 0.9‐1.7) at baseline was not associated with prospective risk of TM. Overall, NSAIDs (OR = 0.85, 95%CI = 0.63‐1.17) were not associated with TM. Indeed, NSAIDs were protective against transition to TM at low to moderate monthly headache days, but were associated with increased risk of transition to TM at high levels of monthly headache days. Conclusion.— EM sufferers develop TM at the rate of 2.5% per year. Any use of barbiturates and opiates was associated with increased risk of TM after adjusting for covariates, while triptans were not. NSAIDs were protective or inducers depending on the headache frequency.     

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   

Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: To evaluate the efficacy and safety of topiramate (100 mg/day) compared with placebo for the treatment of chronic migraine. METHODS: This was a randomized, placebo-controlled, parallel-group, multicenter study consisting of 16 weeks of double-blind treatment. Subjects aged 18 to 65 years with 15 or more headache days per month, at least half of which were migraine/migrainous headaches, were randomized 1:1 to either topiramate 100 mg/day or placebo. An initial dose of topiramate 25 mg/day (or placebo) was titrated upward in weekly increments of 25 mg/day to a maximum of 100 mg/day (or to the maximum tolerated dose). Concomitant preventive migraine treatment was not allowed, and acute headache medication use was not to exceed 4 days per week during the double-blind maintenance period. The primary efficacy endpoint was the change from baseline in the mean monthly number of migraine/migrainous days; the change in the mean monthly number of migraine days also was analyzed. A fixed sequence approach (ie, gatekeeper approach) using analysis of covariance was used to analyze the efficacy endpoints. Assessments of safety and tolerability included physical and neurologic examinations, clinical laboratory parameters, and spontaneous reports of clinical adverse events. RESULTS: The intent-to-treat population included 306 (topiramate, n = 153; placebo, n = 153) of 328 randomized subjects who provided at least 1 efficacy assessment; 55.8% of the topiramate group and 55.2% on placebo were trial completers. The mean final topiramate maintenance dose was 86.0 mg/day. The mean duration of therapy was 91.7 days for the topiramate group and 90.6 days for the placebo group. Topiramate treatment resulted in a statistically significant mean reduction of migraine/migrainous headache days (topiramate -6.4 vs placebo -4.7, P= .010) and migraine headache days relative to baseline (topiramate -5.6 vs placebo -4.1, P= .032). Treatment-emergent adverse events occurred in 132 (82.5%) and 113 (70.2%) of topiramate-treated and placebo-treated subjects, respectively, and were generally of mild or moderate severity. Most commonly reported adverse events in the topiramate group were paresthesia (n = 46, 28.8%), upper respiratory tract infection (n = 22, 13.8%), and fatigue (n = 19, 11.9%). The most common adverse events in the placebo group were upper respiratory tract infection (n = 20, 12.4%), fatigue (n = 16, 9.9%), and nausea (n = 13, 8.1%). Discontinuations due to adverse events occurred in 18 (10.9%) topiramate subjects and 10 (6.1%) placebo subjects. There were no serious adverse events or deaths. CONCLUSIONS: Topiramate treatment at daily doses of approximately 100 mg resulted in statistically significant improvements compared with placebo in mean monthly migraine/migrainous and migraine headache days. Topiramate is safe and generally well tolerated in this group of subjects with chronic migraine, a burdensome condition with important unmet treatment needs. Safety and tolerability of topiramate were consistent with experience in previous clinical trials involving the drug.     

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.     

Cutaneous allodynia in transformed migraine patients

BACKGROUND: There is growing evidence that central sensitization plays a role in migraine pathogenesis, and that cutaneous allodynia is its clinical correlate. In headache research, allodynia has largely been studied in episodic migraine. The purpose of this investigation was to determine whether cutaneous allodynia occurs in transformed migraine, using individuals without headaches as controls. METHODS: Fifteen patients with a diagnosis of transformed migraine and 15 control subjects with no history of headaches were included. All subjects were females between 18 and 50. Similar to the methods of Burstein et al, Von Frey hairs (VFH) were sequentially applied to territories supplied by divisions of the trigeminal nerve, cervical paraspinal muscles, trapezius muscles, ventral forearm, and lower leg to determine a pain threshold. As a milder stimulus, a cotton swab was stroked in the same locations. Each trial was repeated 3 times on 2 occasions. Group comparisons were made using the Student's t-test. RESULTS: Mean pain thresholds were lower among migraine patients than control subjects across all test areas. The thresholds were statistically significantly lower in migraine patients than in control subjects for the 1st division of the trigeminal nerve (34.0 g versus 115.8 g, P= .035) and for the 2nd division (23.5 g versus 97.6 g, P= .039). Six patients found a cotton swab-stroke painful, compared to zero control subjects. Using a quantitative definition of allodynia, 75% of patients had allodynia to mechanical stimuli. CONCLUSIONS: This study is the first to demonstrate allodynia in transformed migraine patients using a headache-free control population and supports the hypothesis that central sensitization plays a role in the evolution of transformed migraine.     

Kaplan Award 1998. Epidemiology of chronic daily headache in the general population

Background and Objectives.—Although chronic daily headache, mainly transformed migraine, is an important reason for consultation in headache clinics, its actual prevalence is unknown. This study analyzes the prevalence of the different types of chronic daily headache in an unselected population.
Methods.—A questionnaire exploring headache frequency was distributed to 2252 unselected subjects. Those having headache 10 or more days per month were given a headache diary and were seen by a neurologist who classified their headaches. The varieties of chronic daily headache were classified according to the second revision of IHS criteria proposed by Silberstein et al published in Neurology 1996;47:871.
Results.—The questionnaire was returned by 1883 subjects (83.5%). One hundred thirty-five admitted to headache 10 or more days per month. Chronic daily headache criteria were fulfilled by 89 individuals (4.7%). Eighty were women. Forty-two (47.2% of subjects with chronic daily headache and 2.2% of all subjects) had chronic tension-type headache. Analgesic overuse was found in 8 (17%). Transformed migraine was diagnosed in 45 (50.6% of subjects with chronic daily headache and 2.4% of all subjects). Fourteen (31.1%) individuals with this form of chronic daily headache overused ergots or analgesics. The remaining 2 cases in this series met the criteria of new daily persistent headache. No one was diagnosed as having hemicrania continua.
Conclusions.—Almost 5% of the general population (9% of women) suffers from chronic daily headache, the proportion of chronic tension-type headache and transformed migraine being quite similar. Less than one third overuse analgesics. The prevalence of chronic daily headache subtypes shown here differs from data obtained from headache clinics, emphasizing that caution is needed in extrapolating data from specialized units to the general population.     

Understanding the patient with migraine: the evolution from episodic headache to chronic neurologic disease. A proposed classification of patients with headache

Traditionally, episodic primary headache disorders are characterized by a return of preheadache (normal) neurologic function between episodes of headache. In contrast, patients with chronic headache often do not return to normal neurologic function between headache attacks. This article proposes that the evolution from episodic migraine to chronic headache may parallel the neurologic disruption observed during the progression of an acute migraine attack and that changes in baseline neurologic function between episodes of headache may be a more sensitive indicator of headache transformation than headache frequency alone. Early recognition of nonheadache changes in nervous system function may offer a more sensitive and specific approach to migraine prevention.     

Safety,tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractory chronic migraine with cardiovascular risk factors: A retrospective study

Background

Dihydroergotamine (DHE), like triptans, is contraindicated in patients with ischemic heart disease or coronary vasospasm. Its true safety, tolerability, and efficacy in patients with cardiovascular risk without ischemic heart disease or coronary vasospasm remain unclear.

Objectives

To assess the safety, tolerability, and effectiveness of repetitive intravenous DHE in patients with cardiovascular risk factors.

Methods

A single-center, retrospective cohort study was conducted at the Jefferson Headache Center inpatient unit for refractory chronic migraine patients treated with our intravenous DHE protocol between January 1, 2019, and October 15, 2019. We evaluated tolerability and effectiveness outcomes based on atherosclerotic cardiovascular disease 10-year calculated risk scores, stratified into low (<5.0%) and elevated (≥5.0%) risk. Data were presented in mean ± standard deviation or median (25th percentile, 75th percentile) if non-normally distributed.

Results

Among 347 patients (median age of 46 [36, 57], female n = 278 [80.1%]), who received inpatient intravenous DHE, 227 patients (age 53 [45, 60], female 81.1%) had calculable risk scores, 64 (28.2%) had elevated risk, and 38 (16.7%) had cardiology consultations. There were no clinically significant electrocardiogram abnormalities or cardiovascular adverse events. The median hospital length of stay was 6 (5, 7) days. Compared to the low-risk group, those with elevated risk had higher nausea (31.3% vs. 14.1%, p = 0.008), but similar initial DHE dose (0.5 [0.25, 0.5] vs. 0.5 [0.25, 0.5], p = 0.009), lower final DHE dose (0.75 [0.5, 1] vs. 1 [0.75, 1] p < 0.001), and lower pain reduction after admission (−3.8 [2.1, 6] vs. −5 [3, 7] p = 0.037).

Conclusion

Patients receiving intravenous DHE by the Jefferson Headache Center inpatient headache protocol had significantly reduced pain severity at discharge. No clinically significant cardiac or electrocardiogram abnormalities were detected in patients with elevated (or low) atherosclerotic cardiovascular disease risk. Repetitive intravenous DHE used by our protocol was safe in refractory chronic migraine patients.