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Biomedical subjects

M E Bigal

Publications and source records attributed to M E Bigal.

At least 19 recordsLinked to original sources
PubMed2006

Familial risk of migraine: variation by proband age at onset and headache severity.

BACKGROUND: It is well established that migraine aggregates within families. Less is known about the influence of proband characteristics (e.g., age at onset, headache severity) on familial aggregation. OBJECTIVE: To examine the association between the proband's migraine severity and age at migraine onset and familial aggregation of migraine. METHODS: The authors investigated the migraine prevalence in first-degree relatives of 532 persons with migraine and control subjects in a population study. Familial aggregation was expressed as the risk of migraine in family members of probands divided by risk in control family members. RESULTS: The relative risk (RR) of migraine in first-degree relatives of migraine probands was elevated compared with family members of controls (RR = 1.88; 95% CI: 1.30 to 2.72). The RR was also significantly higher for relatives of probands reporting onset of migraine before age 16 (2.50; 95% CI: 1.65 to 3.79) compared with those with onset at age 16 or older (1.44; 95% CI: 0.93 to 2.23). Among probands with very severe average pain scores (i.e., 9 to 10 on a 0 to 10 scale), the RR of migraine in family members was 2.38 (95% CI: 1.56 to 3.62) compared with 1.52 (0.99 to 2.34) for less severe pain (p < 0.05). CONCLUSION: Early onset of migraine in the proband as well as the severity of migraines are associated with higher levels of family aggregation.

Adult↗
PubMed2006

Which triptan for which patient?

The triptans were developed for the acute treatment of a migraine attack and have revolutionised the treatment of this disorder since their introduction in the early 1990s. Although their mechanisms of actions are similar and based on the stimulation of specific serotonin (5-hydroxytryptamine) receptors including peripheral 1B and central and peripheral 1D subtypes, each triptan has its own distinctive pK properties that result in different profiles of efficacy and tolerability. Triptans work by decreasing neurogenic inflammation peripherally in the meninges, vasoconstriction of meningeal vessels and by modulating secondary-order neurons in the brain stem. Studies of patient attitudes towards their acute care regimens reveal that they are often unhappy with some aspect of their treatment-usually the speed of action, degree of efficacy, presence of adverse events and the need for additional doses due to frequent and/or rapid recurrence. The majority of patients, when asked in a clinical trial performed at tertiary care headache centres, are willing to try another triptan. The aim of this article is to review the pK and clinical characteristics of these acute care, migraine-specific triptan medications and discuss how their individual characteristics lead to their preferred choice in various clinical scenarios. The pK and clinical efficacy data presented are taken from older published studies in which triptans were compared to placebo or each other, but the patients were asked to wait till the headache reached moderate or severe intensity prior to taking study medication. New studies have looked at early treatment paradigms and result in better efficacy data, but are difficult to compare due to different endpoints.

Humans↗
PubMed2006

Patterns of medical diagnosis and treatment of migraine and probable migraine in a health plan.

The objectives of this study were to assess the proportion of subjects with strict migraine (SM, migraine with and without aura), probable migraine (PM), and all migraine (AM, SM and PM pooled together), who receive a medical diagnosis or a specific treatment within a health plan. Eligible participants were 18-55-year participants of a non-profit health maintenance organization (HMO) who had received out-patient, emergency department, or in-patient care from a physician within the past year. We used a validated computer-assisted telephone interview (CATI) survey to identify SM, PM and controls (received out-patient, emergency department, or in-patient care from a physician for any reason within the past year, but did not have SM or PM). Medical and prescription drug claims for the 24-month period were linked to participant files. Among 8579 respondents, we identified 1265 SM sufferers and 1252 PM sufferers, which were compared with 960 randomly selected controls. Just 194 (15.3%) SM, 21 (1.7%) PM, and 215 (8.5%) AM sufferers received an in-patient or out-patient primary migraine claim in the previous 24 months, compared with six (0.5%) controls; 240 (18.9%) SM, 39 (3.1%) PM, 279 (11.1%) AM sufferers, and eight controls (0.6%) received any migraine claim. There were claims for migraine drugs (ICD-9 code for triptans or ergot compounds) for just 140 (11.1%) SM and 34 (2.7%) PM sufferers, and migraine analgesics (butalbital and isomethepthene compounds), for 6.3% SM and 2.2% PM sufferers (0.7% of the controls). Migraine preventives were used for a larger number of SM and PM sufferers (19.6% and 13.1%), but also for controls (10.5%), indicating that they were probably used for other medical reasons. Both SM and PM are underdiagnosed and undertreated within a health plan. Educational strategies should focus on physician education addressing diagnosing the full spectrum of migraine and physician management of migraine with specific migraine therapy in appropriate patients.

Adolescent↗
PubMed2006

Headache prevention outcome and body mass index.

A population-based longitudinal study suggests that obesity is a strong risk factor for the development of headaches on 15 or more days per month. Little is know about the influence of weight on the response to headache preventive treatment. Herein we prospectively assessed the influence of the baseline body mass index (BMI) on the response to headache preventive treatment. We included adults with episodic or chronic migraine (ICHD-2), or transformed migraine (Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was assessed in the first visit. Baseline information included headache frequency, number of days with severe headache (prospectively obtained over 1 month), and headache-related disability (HIT-6). The same information was obtained after 3 months of preventive treatment. Subjects were categorized based on BMI in: normal weight (</=24.9), overweight (25-29.9), or obese (>/=30). We contrasted the headache end-points using anova with post-test and Kruskal-Wallis with post-test. We used logistic regression to model BMI and headache parameters adjusting for covariates. Our sample consisted of 176 subjects (79.5% women, mean of 44.4 years). At baseline 40.9% had normal weight, 29.5% were overweight and 27.3% were obese. No significant differences were observed in the number of headache days at baseline. After treatment, frequency declined in the entire population, but no significant differences were found by BMI group. Regarding the number of days with severe pain per month, there were also no significant differences at baseline (normal = 6.1, overweight = 6.5, obese = 6.7), and improvement overall (P = 0.01). However, changes were greater in the obese (reduction in 2.7 days with treatment) and overweight (3.9) vs. normal (1.5, P < 0.01). Finally, HIT scores at baseline did not differ by BMI group (normal weight = 63.8, overweight = 64.1, obese = 63.6). However, compared with the normal weighted group, change in HIT scores (follow-up baseline) were greater in the obese (6.4 vs. 3.5, P < 0.05) and overweight groups (6.8 vs. 3.5, P < 0.05). In the logistic regression model, BMI did not account for changes in disability, headache frequency, or in the number of days with severe headache per month, after adjusting for covariates. Contrary to what we hypothesized, obesity at baseline does not seem to be related to follow-up refractoriness to preventive treatment.

Adolescent↗
PubMed2006

Mitochondrial dysfunction and migraine: evidence and hypotheses.

The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ((31)P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals.

Animals↗
PubMed2006

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.

Adolescent↗
PubMed2006

Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine: a double-blind, randomized, cross-over, placebo-controlled study.

Gastroparesis frequently happens during migraine attacks, postponing the onset of action of orally administered drugs. Furthermore, triptans seem to work better in the earlier phases of the migraine attacks. Therefore, associating a gastrokinetic drug with a triptan may translate into better efficacy and higher consistency of response. Trimebutine is an opioid derivative with exclusive action on receptors of the Meissner and Auerbach plexus throughout the digestive tube. It has no absorption or central penetration. Herein we contrast the combination of rizatriptan plus trimebutine with rizatriptan alone in the acute treatment of migraine. Forty patients with migraine consecutively seen in our clinic were randomized to treat two consecutive moderate or severe attacks with one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two attacks with the same triptan and placebo, in counterbalanced order. We collected information on the severity of the attack, as well as presence of nausea and photophobia at the time of drug intake, and after 1, 2 and 4 h. Recurrence and adverse events were also contrasted. Sixty-four attacks were treated with each drug regimen. At 1 h postdose, 30 (46.8%) of 64 attacks treated with the combination resolved completely, vs. eight (12.5%) of the rizatriptan-treated attacks, a difference of 34% (P < 0.01). At 2 h postdose, 47 (73.4%) attacks treated with the combination vs. 20 (31.2%) of those treated with rizatriptan alone resolved completely, a difference of 42% (95% confidence interval 26, 58, P < 0.001). Regarding nausea and photophobia, the combination was also associated with significantly better response. Recurrence was similar among the two drug regimens, as well as adverse events. The combination rizatriptan and trimebutine is more effective than rizatriptan alone. The combination does not increase adverse events or recurrence of pain.

Acute Disease↗
PubMed2005

Clinical trials of acute treatments for migraine including multiple attack studies of pain, disability, and health-related quality of life.

Because migraine has features in common with episodic monophasic pain disorders (such as postoperative or posttraumatic pain) and with chronic pain disorders (such as osteoarthritis or painful neuropathy), it is often considered an episodic-chronic disorder. In clinical practice, the chronic aspects of migraine are addressed using preventive treatment strategies, while the episodic attacks are addressed by acute treatment strategies. Acute treatment strategies have generally been supported by clinical trial designs that focus on single attacks, whereas preventive treatment strategies evaluate multiple attacks over a period of time. Recently, long-term acute treatment clinical designs have emerged that may inform the design of clinical trials for other episodic-chronic disorders. After reviewing traditional acute treatment clinical trials, we focus here on study methods designed to evaluate treatment and management strategies for migraine over multiple attacks, including outcomes that assess the chronic-episodic nature of migraine (such as headache recurrence and consistency of relief), rather than relief from single attacks. We also discuss end points that reflect the treatment needs of patients, such as disability and health-related quality of life. The traditional randomized controlled trial designed to assess treatment efficacy for a single attack is insufficient to address the broader set of issues that arise in clinical practice. We consider clinical trials strategies designed to address the more complex clinical and policy requirements for meeting the needs of those with migraine.

Chronic Disease↗
PubMed2005

Chronic migraine is an earlier stage of transformed migraine in adults.

BACKGROUND: Chronic migraine (CM) is characterized by 15 or more migraine days per month. Most adults with chronic daily headache (CDH) that evolved from migraine have < 15 days of migraine/month. They are often classified as transformed migraine (TM), a disorder not addressed in the International Headache Society classification. OBJECTIVE: To test the hypothesis that early in the course of migraine chronification, the frequency of migraine attacks is high and that as illness progresses the frequency of nonmigraine headaches increases. METHODS: Information was collected on 402 adults with TM and was divided into two groups. Group 1 TM had > or = 15 days of migraine/month, whereas Group 2 TM had < 15 days of migraine/month. Risk factors were modeled for number of migraine days per month using logistic regression. RESULTS: Of 402 subjects with TM, 121 (30.1%) were in Group 1. The proportion of Group 1 subjects decreased with age, from 71% below age 30 to 22% age 60 or above. The correspondent proportion of Group 2 increased from 29 to 78%. More than 15 days of migraine per month was independently predicted by younger ages (< 40 years; p = 0.002), shorter interval from episodic to CDH (< 5 years; p = 0.003), and shorter time since the development of CDH (< 6 years; p < 0.0001). CONCLUSION: Chronic migraine is an earlier stage of transformed migraine.

Adolescent↗
PubMed2005

Migraine: barriers for care.

Migraine headaches affect 12% of the adult population in occidental countries and cause a significant economic loss due to decreased workplace productivity. However only a minority of migraine sufferers worldwide ever receive a correct diagnosis or appropriate treatment. Several barriers for adequate care contribute to this situation. In this article we discuss some strategies to bypass these barriers, summarised herein as: (1) identifying migraine sufferers in need of care; (2) improving medical recognition; (3) supporting the differential diagnosis; (4) improving medical confidence; (5) improving medical treatment; and (6) assessing treatment outcomes.

Diagnosis, Differential↗
PubMed2005

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.

Adult↗
PubMed2005

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) vs. longer duration (>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 (</=15 years), but not gender or use of migraine preventive drugs or medication overuse. Among adolescents with TM, CM is more likely in individuals who are young, whose episodic headache began recently, and with CDH of recent onset. These findings suggest that early in the process of transformation, migraine is more frequent, and that as CDH evolves, fewer typical attacks of IHS migraine occur.

Adolescent↗