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Biomedical subjects

A M Rapoport

Publications and source records attributed to A M Rapoport.

At least 19 recordsLinked to original sources
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

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

Tolosa-Hunt syndrome: critical literature review based on IHS 2004 criteria.

In 2004, the International Headache Society (IHS) re-defined the diagnostic criteria of Tolosa-Hunt syndrome (THS) specifying that granuloma, demonstrated by magnetic resonance imaging (MRI) or biopsy, is required for diagnosis. We reviewed the literature on THS published from 1988 (year of publication of first IHS criteria) to 2002, analysing individual cases in relation to the new IHS criteria. One hundred and twenty-four cases were identified. As far as it was possible to discern, clinical presentation was similar in all, but 44 (35%) were reported to have inflammation on MRI or bioptic evidence of granuloma, 41/124 (33%) had normal neuroimaging findings and 39 (31%) had a specific lesion, so the THS was secondary. These data confirm that clinical criteria for THS are common to several conditions and their application alone does not guarantee a correct diagnosis. The requirement for inflammation on MRI will result in better classification of painful ophthalmoplegias; nevertheless, an MRI protocol that best defines inflammation should be specified. The status of cases which fulfil the clinical criteria but have normal MRI remains to be clarified.

Clinical Trials as Topic↗
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↗
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 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↗
PubMed2004

Primary chronic daily headache and its subtypes in adolescents and adults.

OBJECTIVES: To determine the relative frequency of chronic daily headache (CDH) subtypes in adolescents and to compare the distribution of CDH subtypes in adolescents and adults of various ages. METHODS: Adolescents (13 to 17 years, n = 170) and adults (18 or older, n = 638) were recruited during the same time frame. CDH subtypes were classified according the criteria proposed by Silberstein and Lipton (1996) as transformed migraine (TM), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). RESULTS: Among adolescents and adults there were substantial differences in the distribution of CDH subtypes. The relative frequency of TM was lower in adolescents (68.8% vs 87.4%, p < 0.001), while NDPH (21.1% vs 10.8%, p < 0.001) and CTTH (10.1% vs 0.9%, p < 0.0001) were more common. HC (0 vs 0.9%, NS) was equally rare. The lower relative frequency of TM in adolescents was accounted for by TM with medication overuse (TM+), much more common in adults (28.2% vs 62.5%, p < 0.001). In fact, TM without medication overuse (TM-) was more common in adolescents (40.5% vs 24.9%, p < 0.001). The relative frequency of TM+ increased until the age of 50 years (p < 0.001). CONCLUSIONS: In adolescents with CDH, TM usually develops without medication overuse. Adolescents with the early onset form of TM may develop the disorder in the absence of medication overuse because they are at increased biologic risk.

Adolescent↗
PubMed2004

Preventive migraine therapy: what is new.

In this paper we review new treatment options for migraine prevention. Because we focus on new drugs, some of the data we present herein were acquired in well design double blind, controlled studies, while the efficacy of other medication is supported only by open, uncontrolled trials (noted in the text wherever appropriate).

Analgesics↗
PubMed2004

ID-migraine.

Migraine is a highly prevalent and disabling illness that remains substantially undiagnosed in primary care. Validated migraine screening tools are of potential value in addressing this important barrier for migraine treatment. Herein we briefly discuss reasons for screening migraine in the primary care setting, and focus on the ID-migraine, a validated migraine screening tool.

Humans↗
PubMed2004

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.

Adolescent↗
PubMed2003

MMPI personality profiles in patients with primary chronic daily headache: a case-control study.

We assessed the psychological profile of a large sample of patients with chronic daily headache (CDH) seen in tertiary care. We used a case-control design to study 791 patients who fell into the following categories: ARH group, chronic migraine with analgesic overuse (analgesic rebound headache, ARH), n=399; CM group, chronic migraine (CM) without analgesic overuse, n=158; and new daily persistent headache (NDPH) group, n=69. These groups were compared to two control groups: 1, migraine, n=100; 2, chronic posttraumatic headache (CPTH), n=65. We assessed personality and psychopathology with the Minnesota multiphasic personality inventory (MMPI)-2. The number of patients with Tscores > or =65 and < or =40 were analyzed by the two-sided Fischer's exact test. The ARH and CM groups had a higher number of subjects with T-scores > or =65, when compared to the migraine group, on the following scales: 1 (hypochondrias), 2 (depression), 8 (schizophrenia) and 0 (social introversion). No differences were observed between the NDPH and migraine groups. Considering CPTH as the control group, the pattern we found was quite the opposite of that described above: NDPH group presented a higher number of subjects with T-scores > or =65 on the following scales: 1, 2, 7 (psychasthenia) and 8. ARH and CM groups had significantly higher T-scores for scale 7 alone. NDPH showed T-scores < or =40 in scale 9 when compared to both control groups. We conclude that: (1) psychopathological factors are common in CDH patients, and appear to be a consequence of the chronification process; (2) low scores on scale 9 (hypomania) may relate to the development of NDPH; (3) psychopathological profiles differ among the subgroups of CDH and the MMPI-2 is reliable in identifying such patterns; and (4) psychological assessment is an essential step in the evaluation and treatment of patients with CDH.

Adult↗