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Biomedical subjects

Alan M Rapoport

Publications and source records attributed to Alan M Rapoport.

At least 19 recordsLinked to original sources

Acute treatment of headache.

Effective acute treatment of headache begins with making an accurate diagnosis and ruling out secondary causes of headache. Once a primary headache is diagnosed, it is important to choose the right combination of behavioural therapy and acute care (abortive and symptomatic) therapy for each patient. Some patients may need preventive medication on a daily basis. If patients overuse acute medications and develop medication overuse headache (previously called analgesic rebound headache), they often seek medical attention due to the chronicity and/or intensity of their pain and resultant disability. For acute care of migraine, physicians should choose a triptan they know and expect to work. They should prescribe the dose and route of administration that will provide the most rapid and complete response to all the associated symptoms of migraine, in addition to the pain. The effectiveness of the 7 available triptans in early, double-blind, controlled trials is more similar than different. How and when to give them will be discussed. Treatment of cluster headache will be presented briefly.

Administration, Oral↗

Medications associated with probable medication overuse headache reported in a tertiary care headache center over a 15-year period.

OBJECTIVES: To evaluate the substances associated with medication overuse headache (MOH) in a headache center, over the course of the past 15 years. BACKGROUND: The acute treatment of migraine has substantially changed over the past 15 years, and therefore, the substances associated with MOH may have changed as well. METHODS: We randomly reviewed charts of subjects seen during the years of 2005, 2000, 1995, and 1990, to identify substances associated with MOH. Since the criteria proposed by the second edition of the International Classification of Headache Disorders require causal attribution, demonstrated by improvement after withdrawal (and this was not assessed in this study), herein we refer to probable MOH (PMOH). We contrasted the substances associated with PMOH over the studied years. RESULTS: Our sample consists of 1200 individuals, 300 per year of interest. The proportions of subjects with a diagnosis of PMOH remained stable over the years, varying from 64% of all cases seen in the center in 1990, to 59.3% in 2005. We found a significant decrease in the relative frequency of probable ergotamine overuse headache (from 18.6% to 0%, P < .0001), and in probable combination analgesic overuse headache (from 42.2% to 13.6%, P < .0001). The differences were not significant for opioid overuse headache. The relative frequency increased significantly for the triptans (from 0% to 21.6%, P < .0001), simple analgesics (from 8.8% to 31.8%, P < .05), and for combinations of acute medications (from 9.8% to 22.7%, P = .01). CONCLUSION: While overuse of acute medications remains an important problem in the tertiary care arena, the substances associated with the overuse have dramatically changed over the past 15 years. Educational initiatives should emphasize that the newer specific acute migraine medications (triptans) may also be associated with PMOH.

Adult↗

Role of melatonin in the pathophysiology of migraine: implications for treatment.

The pineal gland and its secretory product, melatonin, have been implicated in the pathophysiology of migraine, as well as some of its comorbid disorders. Supporting this view, many migraineurs are susceptible to various environmental triggers that influence the secretion of melatonin from the pineal gland, and many prodromal symptoms are probably generated in the hypothalamus, a brain region that provides input into the pineal gland to modulate the secretion of melatonin. In addition, studies have shown abnormalities in melatonin secretion in patients who experience migraine and an improvement in migraine following administration of melatonin. However, the dysfunction in melatonin secretion in migraineurs may simply be a marker of hypothalamic dysfunction or neuronal hyperexcitability, leading to migraine susceptibility. It is also possible that abnormal melatonin secretion leads to decreased inhibitory neurotransmitter activity, decreased inhibition of the release of calcitonin gene-related peptide (CGRP) from activation of the trigeminal system, or less analgesia. Whatever its role in the pathogenesis of migraine, melatonin may prove to be a useful therapy. Future studies are necessary to further elucidate whether melatonin is a well tolerated, beneficial therapy, and to determine the optimal dose and formulation of melatonin for use in migraine therapy.

Animals↗

The Global Campaign (GC) to Reduce the Burden of Headache Worldwide. The International Team for Specialist Education (ITSE).

The social perception of headache, everywhere at low levels in industrialised countries, becomes totally absent in developing ones. Headache disorders came into the World Health Organization's strategic priorities after publication of the 2001 World Health Report. Among the leading causes of disability, migraine was ranked 19th for adults of both sexes together and 12th for females. The Global Campaign (GC) to Reduce the Burden of Headache Worldwide was planned by the major international headache organizations together with WHO in order to identify and remove those cultural, social and educational barriers recognised as responsible factors for the inadequate treatment of headache disorders worldwide. Within the GC activities, the education of the medical body will represents a central pillar. An International Team for Specialist Education (ITSE) has been created to train physicians from all over the world through the acquisition of a university level Master Degree in Headache Medicine. Once trained as headache specialists, physicians will become trainers, offering education in this field to other health care providers in their own countries. In this way they will give life to a cultural chain raising awareness locally of headache, its burden and its medical control.

Education, Medical, Graduate↗

The classification of chronic daily headache in adolescents--a comparison between the second edition of the international classification of headache disorders and alternative diagnostic criteria.

OBJECTIVES: To compare the second edition of the International Classification of Headache Disorders (ICHD-2) and the Silberstein-Lipton (S-L) criteria in the classification of adolescents with chronic daily headache (CDH). METHODS: We reviewed the clinical records and the headache diaries of 170 adolescents (13 to 17 years) seen between 1998 and 2003 at a headache center. Relevant information was transferred to a standardized form that included operational criteria for the ICHD-2. CDH subtypes were classified according the criteria proposed by S-L into transformed migraine (TM) with (TM+) and without medication overuse (TM-), chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and hemicrania continua (HC). RESULTS: From the 69 patients with TM- according the S-L criteria, most (71%) could be classified as chronic migraine (CM), while a minority of patients required a combination of diagnosis, mainly migraine and CTTH (14.4%). Of the patients with TM+, just 39.6% met the criteria for probable CM (PCM) with probable medication overuse (PMO). If instead of 15 migraine days per month, we considered 15 or more days of migraine or probable migraine, 84% of the subjects with TM- and 68.7% of those with TM+ could be classified. Of the 27 subjects classified as NDPH without medication overuse according to the S-L system, the majority (51.2%) were also classified as NDPH according the ICHD-2. Interestingly, three (11.1% of the subjects with NDPH without medication overuse) were classified as CM in the ICHD-2 because these patients had an abrupt onset of 15 or more days of migraine per month. All patients with NDPH with medication overuse according to the S-L criteria required a combination of diagnoses in the ICHD-2. All subjects with CTTH received a single diagnosis in both classification systems. CONCLUSIONS: (i) Among adolescents with TM, the majority (58.1%) could be classified as CM, according to the ICHD-2. These results were driven by TM without medication overuse. (ii) If the ICHD-2 criteria for CM are revised to require 15 days of migraine or probable migraine, the proportion of patients with TM- who meet the criteria for CM increases from 71% to 84%; for TM+, the proportion with probable chronic migraine and PMO increases from 30% to 68%. (iii) About half of the patients with NDPH according to the S-L criteria have too many migraine features to meet ICHD-2 criteria for NDPH.

Adolescent↗

Tinnitus in migraine: an allodynic symptom secondary to abnormal cortical functioning?

Tinnitus is not a common auditory symptom in migraine. Recent research suggests that central sensitization (CS) develops in most migraneurs during the course of a migraine attack. Herein we describe 3 patients with primary headache disorders and tinnitus as their chief complaint, in whom the tinnitus intensity consistently increased during headache attacks. In headache patients, tinnitus may be related to spontaneous and aberrant neural activity at any level along the auditory axis, with abnormal reorganization processes in the auditory cortex following hearing receptor damage. We hypothesize that the tinnitus intensity increase could be an allodynic symptom related to CS, or alternatively could be associated with cortical hyperexcitability.

Adult↗

Prophylactic migraine therapy: emerging treatment options.

In this paper, new treatment options for migraine prevention are reviewed. An overview about migraine pathophysiology is provided and current indications for migraine prevention and new and upcoming preventive medications are discussed briefly. Data are presented on topiramate, levetiracetam, zonisamide, botulinim toxin, tizanidine, nefazodone, lisinopril, candesartan, carabersat, petasites, and coenzyme Q.

Central Nervous System Agents↗

Botulinum neurotoxin type A in the preventive treatment of refractory headache: a review of 100 consecutive cases.

OBJECTIVES: To review the efficacy of botulinum neurotoxin type A (BoNT-A) in the preventive treatment of refractory headache. BACKGROUND: Even after receiving expert care, some patients with refractory headache continue to have high disability and persistent headaches. METHODS: Clinical records and headache calendars of 100 patients fulfilling the following inclusion criteria were reviewed: (1) age from 18 to 65 years; (2) primary headache with previous failure of at least four preventive treatments; and (3) have received BoNT-A and have been followed for at least 6 months after the BoNT-A injections. BoNT-A (100 units) was diluted in 4-cc normal saline. The muscles injected included some or all of the following: frontalis, temporalis, corrugator, procerus, occipitalis, semispinalis, splenius capitis, trapezius, cervical paraspinalis, and sternocleidomastoid. Migraine-related disability was assessed using the Migraine Disability Assessment (MIDAS) questionnaire. RESULTS: There was a statistically significant reduction of the frequency of headache days 1 month after BoNT-A was administered (14.2 vs 28.2 days at the baseline, P <.001), which was maintained through the 3 months of study; similarly, a significant reduction in the headache index (22.3 vs 40.3, P <.001) and number of severe days with headache per month (2.6 vs 7.4, P <.001) were found at 1 month and maintained through the 3 months of study. MIDAS scores were reduced from 34.5 at baseline to 15.9 at 3 months (P <.001). A similar pattern was found in those overusing versus nonoverusing acute medication, though the response was more dramatic in the nonoverusing subgroup. CONCLUSION: BoNT-A may play a role in the preventive treatment of refractory headache. A significant number of patients showed decrease in clinically important measurements of their headaches as well as reduced headache-related disability with this treatment. Prospective, controlled studies must be considered for severely disabled, refractory patients.

Adolescent↗

The effect of weather on headache.

OBJECTIVES: To assess headache patients' beliefs about how strongly weather affects their headaches; To objectively investigate the influence of multiple weather variables on headache. DESIGN AND METHODS: Our sample consisted of 77 migraineurs seen in a headache clinic, who provided headache calendars for a period ranging from 2 to 24 months. Our study was divided into two phases. First, each patient was given a questionnaire assessing their beliefs about how strongly (if so) weather affected their headaches. Second, weather data were collected from the National Weather Service, from three reporting stations central to the residences of the study participants. Analysis was performed on 43 variables to generate three meteorological factors. Linear regression was used to assess the relationship between headache and these three factors. Factor 1 represents a function of absolute temperature and humidity. Factor 2 represents a changing weather pattern. Factor 3 represents barometric pressure. RESULTS: Of the 77 subjects in the study, 39 (50.6%), were found to be sensitive to weather, but 48 (62.3%) thought they were sensitive to weather conditions (P < 0.05). Thirty (38.9%) were sensitive to one weather factor and 9 (11.7%) to two factors. Twenty-six (33.7%) were sensitive to factor 1; 11 (14.3%) to factor 2; 10 (12.9%) to factor 3. CONCLUSIONS: Our study supports the influence of weather variables on headache. We showed that patients are susceptible to multiple weather variables and that more patients thought weather was a trigger than was the case.

Attitude to Health↗

Zolmitriptan (Zomig).

New triptans are being released in rapid succession with each addition demonstrating some specific pharmacokinetic properties, which may be translated into clinical advantages. Zolmitriptan (Zomig) offers a range of alternatives to migraine sufferers. The conventional tablet is consistently effective across a wide range of migraine subtypes. The orally disintegrating tablet offers an effective option for those migraineurs who are nauseated or need to take their medication earlier in the course of their migraine. Since it can be taken without fluid, the orally disintegrating tablet may be consistently used early in the migraine attack when the pain is still mild. The nasal spray aggregates all the benefits of the oral formulations and has a faster onset of action. The 5-mg dose of all three forms of zolmitriptan offers additional benefits over the 2.5-mg dose at early time points. The physician can now choose the optimum route of delivery of zolmitriptan to stop the headache, increase the likelihood of reducing disability and restore the patient to complete functionality.

Clinical Trials as Topic↗

Sumatriptan: a decade of use and experience in the treatment of migraine.

The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Sumatriptan (Imitrex) has been available for the longest time within the class, is most flexible in form and has been given successfully to the most number of patients. It is useful for the full range of attacks experienced by a migraine suffer. The aim of this review is to provide an overview of the first 10 years of the use of sumatriptan.

Clinical Trials as Topic↗

Intranasal medications for the treatment of migraine and cluster headache.

Intranasal medications for the treatment of headache have recently received increased attention. This paper reviews intranasal formulations of a variety of available medications (dihydroergotamine mesylate [dihydroergotamine mesilate], sumatriptan, zolmitriptan, butorphanol, capsaicin and lidocaine [lignocaine]) and one experimental medication (civamide, a cis-isomer of capsaicin) for the treatment of migraine and cluster headache. Although the efficacy of intranasal agents varies with the product used, intranasal delivery may be both convenient and more effective than other modes of drug delivery for a variety of reasons: (i) intranasal administration bypasses small bowel gastrointestinal tract absorption, which is often significantly delayed during the acute phase of a migraine attack; (ii) nauseated patients may prefer non-oral formulations as they decrease the chance of vomiting and are more rapidly effective; (iii) intranasal administration causes no pain or injection site reaction and is easier and more convenient to administer than injection or suppository and so may be used earlier in a migraine attack, resulting in better efficacy; (iv) intranasal medication produces the same number or fewer adverse events than injections; and (v) intranasal formulations offer a more rapid onset of action than oral medications, for some of the above reasons and, as such, may be more useful in patients with cluster headache, although this needs to be verified. However, it is important to emphasise that a preference study showed that most patients prefer oral tablets to an intranasal formulation. Also, some nasal preparations have significant adverse effects or are not well absorbed and therefore do not work consistently; others are more challenging to administer as a result of their delivery apparatus. Nevertheless, it is our opinion that nasal preparations increase therapeutic options and may result in faster response times and better efficacy than oral formulations and better patient satisfaction than injectable preparations.

Administration, Intranasal↗

Acute treatment of migraine with zolmitriptan 5 mg orally disintegrating tablet.

OBJECTIVE: To determine the speed of onset of headache response and duration of response with zolmitriptan 5 mg orally disintegrating tablet (ODT) in the acute treatment of migraine. BACKGROUND: Rapid pain relief is important for migraine sufferers. The early efficacy (30 minutes) of the 5 mg dose of the zolmitriptan ODT formulation was evaluated. METHODS: In this double-blind, parallel-group trial, 670 patients were randomised to receive either zolmitriptan 5 mg ODT (n=329) or matching placebo (n=341) to treat two migraine headaches of moderate or severe intensity. RESULTS: Zolmitriptan 5 mg ODT was significantly more effective than placebo in achieving a headache response (reduction in migraine headache intensity from moderate or severe to mild or no pain) at 30 minutes (16.5% vs 12.5%; p=0.048; primary endpoint), 1 hour (p <0.0001), and 2 hours (p <0.0001). Significantly more patients achieved a sustained headache response for 24 hours with zolmitriptan 5 mg ODT than with placebo (42.5% vs 16.4%; p <0.0001). Zolmitriptan 5 mg ODT also produced a higher pain-free rate than placebo at all timepoints (0.5, 1 and 2 hours post-dose), with the differences becoming significant at 1 hour. Adverse events were reported by 37.7% of the patients treated with zolmitriptan 5 mg ODT and 18.1% of the patients treated with placebo. Those that occurred most often for the patients treated with zolmitriptan 5 mg ODT were tightness (7.0%), dizziness (6.7%), somnolence (6.7%) and paraesthesias (6.1%). CONCLUSIONS: A significant headache response as early as 30 minutes post-dose and good maintenance of this headache response at 24 hours makes zolmitriptan 5 mg ODT an excellent acute treatment for migraine. Together with the relatively low adverse event rate, these data demonstrate that zolmitriptan 5 mg ODT is a valuable therapy for migraine sufferers.

Acute Disease↗

New migraine preventive options: an update with pathophysiological considerations.

BACKGROUND: The pharmacological treatment of migraine may be acute or preventive. Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple threads of research over the last 15 years have led to the concept that migraine is generated from a hyperexcitable brain. A variety of causes for hyperexcitability of the brain in migraine have been suggested. These causes include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions related to increased nitric oxide or the existence of a P/Q type calcium channelopathy. The better knowledge about migraine pathophisiology led us to discuss new treatment options. OBJECTIVES: The aim of the present study is to present an evidence-based review of some new drugs or some agents that even though available for a long time, are not frequently used. METHODS/RESULTS: We present a review of anticonvulsants with various mechanisms of action such as lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We also review natural products, like riboflavin and magnesium, botulinum toxin A, a specific CGRP antagonist and the anti-asthma medication montelukast, with pathophysiological discussion. CONCLUSIONS: We aimed to present an update of newer or less frequently used preventive migraine therapies, drugs that might reduce the burden and the costs of a disease that should be considered as a public health problem all around the world.

Angiotensin-Converting Enzyme Inhibitors↗

The clinical spectrum of migraine.

The wide clinical spectrum of migraine frequently challenges the physician's diagnostic acumen. A structured approach to the patient and a better comprehension of this variability of presentation, should translate into better quality of care for migraineurs.

Adolescent↗

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.

Adult↗

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.

Adolescent↗