Emerging behavioral treatments for migraine.

Although the efficacy of behavioral interventions for migraine (e.g., relaxation training, stress management, cognitive-behavioral therapy, biofeedback) is well established, other behavioral interventions that have shown efficacy for other conditions are being adapted to treat migraine. This paper reviews the literature to date on acceptance and commitment therapy (ACT), mindfulness-based interventions, and behavioral interventions for common migraine comorbidities. ACT and mindfulness interventions prioritize the outcome of improved functioning above headache reduction and have demonstrated efficacy for chronic pain broadly. These emerging behavioral therapies show considerable promise for improving outcomes of migraine patients, particularly in reducing headache-related disability and affective distress, but efficacy to date is limited by small trials, short follow-up periods, and a need for comparison or integration with established pharmacologic and behavioral migraine treatments.

Double-blind, placebo-controlled, crossover study of early-intervention with sumatriptan 85/naproxen sodium 500 in (truly) episodic migraine: what's neck pain got to do with it?

OBJECTIVE: Published studies of triptans in acute migraine have shown relatively disappointing 2-hour pain-free rates, ranging from 18% to 58%, with 2- to 24-hour sustained pain-free rates from 17% to 25%. A major flaw in the design of previous studies may have contributed to disappointing results: many subjects are not truly episodic in the nature of their headaches-they discount days with mild headache and ignore days with migraine-related neck pain. Believing that neck pain is integrally related to migraine, we sought to ascertain whether early treatment with sumatriptan 85/naproxen sodium 500 (sumatriptan/naproxen) in truly episodic migraineurs is more robust than results when neck pain has not been considered. METHODS: Successfully screened adult migraineurs who returned baseline diaries showing 2 to 7 migraine attacks monthly and < 15 headache and/or neck pain days/month received blister packs containing 3 sumatriptan/naproxen/1 placebo for treatment of 4 migraines. Instructions were to treat within the first 30 minutes of mild headache or neck discomfort-but only if the preceding day was completely free of both headache and neck pain. RESULTS: In our study, 63.9% of patient attacks treated with sumatriptan/naproxen achieved 2-hour pain freedom compared with 33.3% of those with placebo (P < 0.001). Sustained pain freedom (2-24 hours) was achieved in 69.1% of sumatriptan/naproxen-treated attacks, compared with 23.3% with placebo (P < 0.01). More subjects using sumatriptan/naproxen achieved sustained pain freedom (than 2-hour pain freedom), due to 6 time points when the subject was sleeping/napping 2-hours post dose (5 sumatriptan/naproxen, 1 placebo), yet attested to no discomfort between 2 and 24 hours post dose. Had the attacks been scored as pain-free at 2 hours, the 2-hour pain-free and sustained pain-free rates with sumatriptan/naproxen would have been identical at 69.1% (vs 36.7% with placebo). With truly episodic migraineurs, pain freedom was significant as soon as 15 minutes following treatment with sumatriptan/naproxen (5.2% vs 0% with placebo; P < 0.01). CONCLUSION: Our study results support a fundamental re-evaluation of the role of neck pain in migraine.

The impact of extended-cycle vaginal ring contraception on migraine aura: a retrospective case series.

OBJECTIVE: To determine whether extended-cycle dosing of an ultralow dose vaginal ring contraceptive decreases frequency of migraine aura and prevents menstrual related migraine (MRM). BACKGROUND: Many women are denied therapy with combined hormonal contraceptives due to published guidelines that recommend against their use in migraine with aura (MwA). The concern is that these products might further elevate the risk of ischemic stroke that accompanies aura. Stroke risk has been reported to vary directly with aura frequency, and aura frequency in turn has been shown to have a direct relationship to estrogen concentration. With the evolution of increasingly lower dosed combined hormonal contraceptives, we now have formulations that--provided that ovulation is inhibited--result in lower peak levels of estrogen than the concentrations attained during the native menstrual cycle. These formulations would thus be expected to result in a lower frequency of migraine aura. Furthermore, as extended-cycle therapy eliminates monthly estrogen withdrawals, this therapy would likewise be expected to prevent MRM. METHODS: This pilot study is an institutional review board-approved retrospective database review. We queried our database of 830 women seen in a subspecialty menstrual migraine clinic to identify women who met all inclusion criteria: (1) current history of MwA; (2) confirmed diagnosis of MRM; and (3) treatment with extended-cycle dosing of a transvaginal ring contraceptive containing 0.120 mg etonogestrel/15 µg ethinyl estradiol. Standardized calendars that specifically document bleeding patterns, headache details, and occurrence of aura are required of all patients in this clinic. RESULTS: Twenty-eight women met study criteria, none of whom were smokers. Of these, 5 discontinued use of etonogestrel/ethinyl estradiol within the first month, leaving 23 evaluable subjects. At baseline, subjects averaged 3.23 migraine auras/month (range: 0.1-12). With extended dosing of the vaginal ring contraceptive, median frequency was reduced to 0.23 auras per month following treatment after a mean observation of 7.8 months (P < .0005). No subject reported an increase in aura frequency. On this regimen, MRM was eliminated in 91.3% of the evaluable subjects. CONCLUSION: In this sample of women with both MwA and MRM, use of an extended-cycle vaginal ring contraceptive was associated with a reduced frequency of migraine aura and with resolution of MRM. This cannot be extrapolated to suggest that stroke risk in MwA will be similarly reduced. Studies to evaluate this relationship are warranted.

The point prevalence of dizziness or vertigo in migraine--and factors that influence presentation.

OBJECTIVE: To ascertain and characterize the point prevalence of dizziness or vertigo in migraineurs presenting for routine appointments at a specialty headache clinic. BACKGROUND: Migraine, dizziness, and vertigo are all common in the general population, affecting 13%, 20-30%, and 5-10% respectively. Thereby, chance concurrence of migraine with either dizziness or vertigo would be expected in roughly 4% of the general population. It is the authors' clinical impression that severe attacks of migraine are far more commonly associated with these complaints than chance would predict. METHODS: This is a prospective, cross-sectional study of 462 consecutive patients who presented for consultation at a specialty headache clinic over a 4-month period of time. During routine check-in procedures, patients were asked to report their headache pain on a 1-10 Likert scale. Patients were also asked to report if they were currently experiencing dizziness or vertigo. Responses to these questions were recorded along with vital signs. Diagnosis of migraine with or without aura was made by headache medicine specialists in accordance with International Classification of Headache Disorders--second edition criteria. Chi-square analysis was used to examine the prevalence of vertigo or dizziness in subjects with varying intensity of headache, and by history of aura. RESULTS: Of the 425 evaluable subjects, 28% experienced aura. Subjects' average age was 43.8 years (range 15 to 76 years); 89.5% were female. At the time of evaluation, 72.4% of subjects reported some degree of ongoing headache pain and 15.7% reported concurrent dizziness or vertigo. The prevalence of dizziness or vertigo was twice as high (24.5% vs 12.1%) in migraine with aura compared to migraine without aura (P < .01), and prevalence increased with age (P < .05). There was a strong correlation between migraine pain and subjective complaint of vertigo (P < .001). When migraine pain was present at an intensity of 7 or greater (on a scale of 1-10), almost half of the subjects (47.5%) reported concomitant dizziness or vertigo. CONCLUSIONS: Subjective complaints of dizziness or vertigo appear to be relatively common accompaniments of migraine, particularly migraine with aura, and prevalence increases with age. Disequilibrium symptoms have a strong and positive association with the severity of migraine pain. With co-occurrence higher than expected by chance, the relationship either reflects comorbidity or these symptoms may be part of the migraine presentation. With a point prevalence of 15.7%, and factors that link expression both to the intensity of migraine pain and to migraine aura, the authors believe that the true relationship may prove to be the latter.

Patient characteristics associated with frequent calls to a headache specialty clinic.

OBJECTIVE: To identify characteristics of patients who frequently initiate contact with a headache specialty clinic outside of scheduled appointments. MATERIALS AND METHODS: We scanned records of all telephone calls received during 1 calendar year at an academic headache clinic to identify frequent callers. High-frequency (HF) callers were defined as established patients who initiated calls on ≥20 days during the year. We compared these patients with a cohort of established low-frequency (LF) callers who initiated no telephone calls during the same year. Clinic records were analyzed for demographic characteristics, diagnoses, and medication use. Additionally, we administered a questionnaire to clinic physicians and administrative staff querying their perception of each patient's demands on clinic resources. RESULTS: High-frequency (n=26) and LF (n=18) callers did not differ significantly in marital status, ethnicity, diagnosis, or age. There was a trend toward female gender among HF callers and toward being outside of a body mass index range of 19 to 30 kg/m2. The groups were similar in their use of triptans and botulinum toxin treatments, but HF callers were more likely to be opioid users (96% vs 11.1%) and more likely to be taking multiple opioids in substantially higher potency, dosage, and quantity (154.4 mg vs 1.4 mg morphine equivalents/day). More than 80% of each group were migraineurs, but HF callers were more likely to have comorbid psychiatric disorders (P<0.05). High-frequency callers were also more likely to be rated by administrative staff and physicians as demanding and time-consuming. CONCLUSIONS: In this university-based headache specialty clinic, HF callers were more likely to be opioid users on high morphine-equivalent doses. Compared with LF callers, HF callers placed a greater burden on health care resources as perceived by staff and physicians.

Presence of neck pain may delay migraine treatment.

OBJECTIVE: To determine whether the presence of neck pain (NP) is associated with a delay in migraine treatment. BACKGROUND: We have previously shown that 1) NP is exceedingly common in migraine; 2) its presence on the day preceding migraine is associated with impaired treatment response; and 3) NP is predictive of migraine-related disability independent of headache frequency and severity. MATERIALS AND METHODS: This was a prospective, observational, cross-sectional study of 113 patients with migraine, ranging in attack frequency from episodic to chronic migraine. Subjects were examined by headache specialists to confirm the diagnosis of migraine and exclude both cervicogenic headache and fibromyalgia. Details of all headaches were recorded over the course of at least 1 month and until 6 qualifying migraines had been treated. Subjects were permitted to treat at the stage they customarily treated. A chi-square test of independence was performed to examine the relationship between the presence of NP and treatment within 30 minutes of headache onset. Analysis of variance was used to test the relationship of NP intensity with headache intensity at the time of migraine treatment. RESULTS: Subjects recorded 2411 headache days, 786 of which were migraines, the majority of which were treated in the moderate pain stage. Presence of NP in the hour preceding initial migraine treatment was associated with delay in treatment beyond 30 minutes of headache onset (P < 0.01) and initiation of treatment at a greater headache pain intensity (P < 0.001). When NP accompanied migraine, those with moderate or severe NP were more likely to treat within 30 minutes of headache onset than those with mild NP (P < 0.05). CONCLUSION: Presence of NP was associated with delayed treatment of migraine, as indicated not only by higher pain burden at time of treatment but also by delay beyond 30 minutes.

The prevalence of neck pain in migraine.

OBJECTIVE: To determine the prevalence of neck pain at the time of migraine treatment relative to the prevalence of nausea, a defining associated symptom of migraine. METHODS: This is a prospective, observational cross-sectional study of 113 migraineurs, ranging in attack frequency from episodic to chronic migraine. Subjects were examined by headache medicine specialists to confirm the diagnosis of migraine and exclude both cervicogenic headache and fibromyalgia. Details of all migraines were recorded over the course of at least 1 month and until 6 qualifying migraines had been treated. For each attack, subjects recorded the presence or absence of nausea as well as the intensity of headache and neck pain (graded as none, mild, moderate, or severe). RESULTS: Subjects recorded 2411 headache days, 786 of which were migraines. The majority of migraines were treated in the moderate pain stage. Regardless of the intensity of headache pain at time of treatment, neck pain was a more frequent accompaniment of migraine than was nausea (P< .0001). Prevalence of neck pain correlated with chronicity of headache as attacks moved from episodic to chronic daily headache. CONCLUSIONS: In this representative cross-section of migraineurs, neck pain was more commonly associated with migraine than was nausea, a defining characteristic of the disorder. Awareness of neck pain as a common associated feature of migraine may improve diagnostic accuracy and have a beneficial impact on time to treatment.

Elimination of menstrual-related migraine beneficially impacts chronification and medication overuse.

OBJECTIVES: This study seeks to determine whether menstrual-related migraine (MRM) has a discrete, attributable impact on migraine chronicity and medication overuse. BACKGROUND: Menstrual-related migraine can be a disabling headache on its own; but when seen in headache clinics, it is often enmeshed in the setting of chronic migraine (CM) and medication overuse headache (MOH). Whereas nonspecific migraine preventives bestow their benefit uniformly, hormonal preventives (HPs)--when they are successful--address a discrete hormonal mechanism. They confer no known benefit to migraines that are not hormonally triggered. This selective property of HPs could potentially isolate MRM and segregate its effect on the overall clinical picture. METHODS: This is a retrospective review of 229 consecutive women seen in follow-up for hormonal prevention of MRM at an academic headache center. Patients kept standardized diaries from which separate menstrual-week (MW) and nonmenstrual week (nonMW) headache indices were calculated and compared. Resolution of MRM was defined by reduction of the MW headache index to a score not exceeding the nonMW headache indices. Consumption of all acute and preventive agents used in the preceding month was tallied. We performed post-treatment comparisons of medication usage and headache characteristics among subjects in whom MRM was resolved and those in whom it was not resolved. RESULTS: At baseline, CM was present in 92% of subjects, 72% of whom also met criteria for MOH. Resolution of MRM was achieved in 81% of subjects who were compliant with HP and was associated with reversion to episodic migraine (59% vs 18%, P < .001) and resolution of medication overuse (54% vs 20%, P < .001). Resolution of MRM was associated with significant decreases in per capita consumption of triptans, opioids, all acute agents, and migraine preventive medications. CONCLUSIONS: Resolution of MRM correlated not only with conversion of CM to an episodic pattern, but also with a significant reduction in medication usage. It offers preliminary evidence that hormonal regimens may have a beneficial role in prevention of MRM.

Predictors of disability in migraineurs referred to a tertiary clinic: neck pain, headache characteristics, and coping behaviors.

OBJECTIVE: The aim of this retrospective study was to determine if neck pain, select headache characteristics, and migraine-related coping response predicted disability in migraineurs referred to a tertiary headache clinic. METHODS: Patients seeking treatment at a neurology-based headache clinic were included if they met diagnostic criteria for migraine with or without aura according to the International Headache Society (1.1, 1.2). Subjects completed a self-report headache history form and a detailed headache and neurologic examination. The headache history form assessed: 1)weekly headache frequency; 2) number of weekly severe headaches; 3) presence of migraine-related neck pain; 4) photophobia; 5) phonophobia; 6) headache duration; 7) vomiting; 8) monthly headache-free days; and 9) behavioral coping style. Disability was assessed using a self-report inventory (HIT-6). RESULTS: Self-reported headache severity, frequency, and headache-free days were strongly associated with disability. The presence of neck pain during migraine and one's coping response to migraine significantly predicted disability independent of headache characteristics. CONCLUSIONS: These data suggest the need for prospective research exploring the causal mechanisms by which neck pain and coping response influence disability and underscores the importance of multidisciplinary approaches to headache management.

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.

Asymmetrical ventricular enlargement in Parkinson's disease.

Parkinson's disease (PD) typically manifests with asymmetric motor symptom onset. Ventricular enlargement, a nonspecific measure of brain atrophy, has been associated with cognitive decline in PD, but not with motor symptom asymmetry. Asymmetrical ventricular enlargement on magnetic resonance images was explored in a monozygotic twin pair discordant for PD and in nine healthy monozygotic twin pairs. The left-right lateral ventricular volumetric difference of the PD-twin was greater than that of his twin and all other healthy twins, with the larger ventricle observed contralateral to the more symptomatic side. Moreover, the lateral ventricle asymmetry difference between twin pairs was significantly higher for the discordant PD-twin pair than for the healthy twin pairs. This is the first report to suggest the presence of asymmetrical ventricular enlargement in PD, findings that may be worthy of further study.

The prevalence and spectrum of sleep problems in women with transformed migraine.

OBJECTIVES: It is our clinical observation that patients with transformed migraine (TM) almost invariably report nonrestorative sleep. In this study we sought first to validate that clinical observation, then to describe the prevalence and spectrum of factors that might contribute to nonrestorative sleep in a TM population. BACKGROUND: Although headaches have been linked with sleep problems for over a century, there is little information about the spectrum or prevalence of specific sleep problems associated with TM in adults. METHODS: We conducted a detailed sleep interview on 147 consecutive women with TM. Subjective sleep quality was assessed by asking patients to describe their state upon awakening as "refreshed" or "tired." RESULTS: None of the 147 patients reported awakening "refreshed," and 83.7% stated that they awakened "tired." Sleep complaints were prevalent and varied in this population. CONCLUSIONS: Although the relationship between pain and sleep is complex and ill understood, we found a very high prevalence of nonrestorative sleep and a similarly high prevalence of modifiable poor sleep habits in patients with TM. Since behavioral approaches have been found effective in improving sleep quality in patients with poor sleep hygiene, we propose that studies be undertaken to assess the impact of such treatment on TM.

No gender differences in the progression of nervous system disease in HIV infection.

The past decade has seen a marked increase in the number of HIV-infected women in the United States. There has been recent concern that HIV disease in general may progress more rapidly in women than men, and some studies, primarily retrospective reviews, have suggested higher rates of neurologic disease among females. The objective of this study was to assess gender differences in HIV-related central and peripheral nervous system disease over time. Participants were enrolled in a longitudinal cohort study at the University of North Carolina and had annual follow-up evaluations. At baseline, 42 HIV-negative females, 52 HIV-positive females, and 52 HIV-positive males were compared for age, education, mode of infection, absolute CD4 cell count, and plasma/cerebrospinal fluid HIV RNA load. Subjects were evaluated by standardized clinical neurologic, neuropsychological, and laboratory examinations every year. The results indicated that both HIV-positive males and HIV-positive females had poorer neurologic functioning than the control group. However, there was no evidence from the parameters measured that the rate of decline differed between HIV-positive males and HIV-positive females.

Highly active antiretroviral therapy improves neurocognitive functioning.

Although the effects of highly active antiretroviral therapy (HAART) have resulted in substantial improvements in the systemic health of patients with HIV infection, concerns remain that these medications, which cross the blood-brain barrier poorly, may have a less beneficial effect on nervous system function. This raises the possibility that there may be a progressive long-term decline in neurologic function in patients with adequate systemic response. In a prospective longitudinal study, subjects were evaluated immediately before instituting HAART. Forty-eight subjects underwent ultrasensitive HIV RNA quantitative evaluation of both plasma and cerebrospinal fluid as well as neurologic and neuropsychological examinations. They were reevaluated 6 months after treatment initiation while receiving stable HAART. Both plasma and cerebrospinal fluid viral levels significantly declined after treatment. There was significant improvement in neurologic and neuropsychological functioning after HAART. These results indicate that despite the poor central nervous system penetration of most of these agents, there is satisfactory short-term improvement in both central nervous system viral burden and nervous system function with HAART. However, because treatment failure is increasingly likely over time, continued longitudinal evaluation of this group of subjects is required.