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Biomedical subjects

A M Rapoport

Publications and source records attributed to A M Rapoport.

At least 37 records · Page 2Linked to original sources

Hemicrania continua: clinical and nosographic update.

Hemicrania continua (HC) is an uncommon primary headache syndrome. The main features of HC are: (i) strict unilaterality of the pain (moderate, fluctuating, relatively long-lasting); and (ii) absolute response to indomethacin. These two features may reflect the most reliable characteristics of the syndrome. Autonomic symptoms are not as prominent in HC as they are in cluster headache and chronic paroxysmal hemicrania, although they may exist. HC will be addressed in the 2003 revision of the International Headache Society (IHS). In this paper we review the clinical features, classification and treatment of HC.

Anti-Inflammatory Agents, Non-Steroidal↗

Cluster headache as a manifestation of intracranial inflammatory myofibroblastic tumour: a case report with pathophysiological considerations.

We report a patient with a secondary form of chronic cluster headache, caused by an intracranial presentation of inflammatory myofibroblastic pseudotumour located in the posterior fossa, with total remission of the pain after resection. The headaches were resistant to many of the usual treatments for cluster headache. The patient had two normal computed tomography scans and one normal magnetic resonance imaging of the head before the additional diagnosis of brain tumour was made. This is an unusual cause of cluster headache with intracranial mass, with an unexpected clinical presentation, a rare triggering manoeuvre, unusual pathology and successful treatment. This patient probably had the hypothalamic biological predisposition to cluster headache and, when a small mass disturbed pain-sensitive structures in the posterior fossa, it excited the trigeminovascular system via posterior fossa trigeminal and upper cervical afferents, and triggered the pathophysiological processes that resulted in a secondary form of chronic cluster headache.

Adult↗

Hemicrania continua: comparison between two different classification systems.

Hemicrania continua is an uncommon primary headache disorder. This study of nine patients compares two different classification systems, proposed by Pareja et al. and Goadsby and Lipton. Although it seems logical to position the nosologic status of hemicrania continua under group 3 of the International Headache Society Classification, as proposed by Pareja et al., the Goadsby and Lipton classification is more clinically useful and should be included in future International Headache Society reclassification.

Adult↗

Chronic daily headache in a tertiary care population: correlation between the International Headache Society diagnostic criteria and proposed revisions of criteria for chronic daily headache.

The International Headache Society (IHS) has been criticized for its approach to classification of chronic daily headache (CDH); Silberstein and Lipton criteria provide an alternative to this approach. The aim of this study is to apply the alternative diagnostic approaches to a sample of CDH patients consulting in specialty care. Our sample consisted of 638 patients with CDH. Patients were classified according to both classification systems. Patients were predominantly female (65.0%), with ages ranging from 11 to 88 years. According to the Silberstein and Lipton classification, we found eight different diagnoses. The most common diagnosis was chronic migraine (87.4%), followed by new daily persistent headache (10.8%). Just six patients had chronic tension-type headache (CTTH). Applying the IHS criteria we found 14 different diagnoses. Migraine was found in 576 (90.2%) patients. CTTH occurred in 621 (97.3%), with only 10 (1.57%) having this as the sole diagnosis. We conclude that both systems allow for the classification of most patients with CDH when daily headache diaries are available. The main difference is that the IHS classification is cumbersome and requires multiple diagnoses. The Silberstein and Lipton system is easier to apply, and more parsimonious. These findings support revision of the IHS classification system to include chronic migraine.

Adolescent↗

The clinical spectrum of migraine.

The variable clinical features of migraine and some relationships of migraine with other headache disorders have been reviewed. Although these views generally are shared by most headache specialists, some respected headache investigators reject the concept of a spectrum of migraine and conclude that the continuum model is an artifact.

Diagnosis, Differential↗

Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine.

OBJECTIVE: To compare the safety and efficacy of isometheptene mucate, dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment of mild-to-moderate migraine, with or without aura, when taken at the first sign of an attack. BACKGROUND: The Food and Drug Administration approved sumatriptan succinate and the combination of isometheptene mucate, dichloralphenazone with acetaminophen for the treatment of migraine. As part of the stratified treatment of migraine, those patients whose headaches are mild or moderate may benefit from nontriptan medications. Additionally, early treatment of acute migraine before the headache has become moderate or severe may improve response to treatment. METHODS: This was a multicenter, double-blind, randomized, parallel-group study to assess the safety and efficacy of the combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the early stages of a single migraine attack. Patients diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria were enrolled. RESULTS: One hundred thirty-seven patients were enrolled in the study. Data for efficacy were available for 126 patients; safety data were available for 128 patients. No statistically significant difference between the two active agents in the patient's response to treatment was demonstrated. Headache recurrence was not significantly different over the 24-hour evaluation period for those patients responding in the first 4 hours. In those with headache recurrence, it was statistically significantly more severe in those patients treated with sumatriptan succinate. Improvement in functional disability was, in general, better among those treated with isometheptene mucate, dichloralphenazone with acetaminophen. Global analysis of efficacy was similar in the two active groups. Patients treated with sumatriptan succinate were somewhat more likely to have adverse effects than the isometheptene mucate, dichloralphenazone with acetaminophen group. CONCLUSIONS: Both isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate are safe and effective when used early in the treatment of an acute migraine. Several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild-to-moderate migraine.

Acetaminophen↗

Frovatriptan: pharmacological differences and clinical results.

Frovatriptan is a 5-HT(1B/1D) agonist demonstrating consistently effective headache relief at a low dose of 2.5 mg. A striking pharmacokinetic characteristic is its long half-life of 25 h. This is balanced by an average Tmax of 2-3 h, a low degree of lipophilicity and a low oral bioavailability of 24-30%. Fifty per cent of the drug is renally excreted and the rest is partially metabolized by P450 CYP 1A2. In three short-term multicentre, double-blind, placebo-controlled phase III trials, the 2 h headache response for 2.5 mg frovatriptan varied from 36 to 46% (placebo 21-27%). The 4 h headache responses were considerably higher--up to 65%. Thirty-five per cent of patients were consistent rapid responders. The recurrence rate was 10-25%. In addition to effective and prolonged relief of head pain, frovatriptan reduced associated migraine symptoms such as nausea, photophobia and phonophobia. There was an excellent tolerability profile with the incidence of adverse events for frovatriptan only slightly higher than placebo. The most commonly reported adverse events for both frovatriptan and placebo were dizziness, nausea, headache and fatigue.

Carbazoles↗

The cost effectiveness of stratified care in the management of migraine.

OBJECTIVE: To examine the cost effectivess of a stratified-care regimen for patients with migraine--in which patients are stratified by severity of illness, and then prescribed differing treatments according to level of severity--compared with a conventional stepped-care approach. DESIGN AND METHODS: A decision analytic model was constructed to simulate a controlled clinical trial in which patients with migraine receiving primary medical care were randomly assigned to treatment under a stepped-care or a stratified-care regimen. A health service payer perspective was adopted and the time horizon was 1 year. Data inputs were: (i) the frequency and disability of migraine, derived from population-based studies; (ii) disability level-specific treatment response rates for over-the-counter analgesics,aspirin/metoclopramide and zolmitriptan as the representative of high-end therapy obtained from an international consensus opinion enquiry; and (iii) unit costs of healthcare obtained from UK health service sources. MAIN OUTCOME MEASURES AND RESULTS: The estimated 1-year direct healthcare costs per primary care patient with migraine were pound sterling 156.82 for stepped care and sterling pound 151.57 for stratified care. Estimates of treatment response rates were 40 and 71% for stepped and stratified care, respectively. The cost per successfully treated attack was sterling pound 23.43 for stepped care and sterling pound 12.60 for stratified care. Stratified care remained cost effective when tested in a wide range of one-way sensitivity analyses, and probabilistic sensitivity analysis showed the cost effectiveness of stratified care to be significant at the 3% level. Conditional confidence analysis showed that the level of confidence in the cost effectiveness of stratified care varied positively with the case mix, i.e. in populations where the proportion of moderate and severely disabled patients with migraine was greater than 25%, the cost effectiveness of stratified care remained statistically significant. CONCLUSION: A stratified-care treatment strategy (including zolmitriptan as the representative of high-end therapy) is a highly cost-effective method of managing migraine in the primary care setting compared with stepped care, delivering improved clinical outcomes at no additional cost.

Anti-Inflammatory Agents, Non-Steroidal↗

Migraine pharmacotherapy with oral triptans: a rational approach to clinical management.

The recent clinical development of a number of migraine specific 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs), relative to the first drug of this class sumatriptan, and with a range of different metabolic, pharmacokinetic and receptor affinity profiles, provides the potential for critically different clinical profiles. Eletriptan, naratriptan, rizatriptan and zolmitriptan display both increased stability to first pass metabolic inactivation by monoamine oxidase (MAO-A) and enhanced lipophilicity (4- to > 120-fold more than sumatriptan), leading to increased oral bioavailability (2- to 5-fold more than the 14% reported for oral sumatriptan). Central penetration and increased receptor affinity and selectivity for the neuronal (5-HT1D) receptor also combine to allow for lower total oral dosing (i.e., unit doses of 15 mg or less compared with 50-300 mg doses of sumatriptan) and reduced peripheral exposure to the coronary vasoconstrictor (5-HT1B) receptor. The notable exception being eletriptan, where an active P-glycoprotein blood-brain barrier efflux system effectively negates these benefits and requires an 80 mg oral dose. Differences in the metabolic balance between hepatic P450 (especially CYP 1A2) and MAO-A inactivation lead to potential drug interactions for all TELs with the oral contraceptive pill (OCP), fluvoxamine and the quinilone antibiotics (with increased triptan levels). An important but complex MAO-A interaction between a metabolite of propranolol and rizatriptan mandates dosage reduction (to 5 mg) for rizatriptan in the presence of propranolol treatment. There is also an absolute contraindication for the concurrent administration of the MAO-A inhibitor moclobemide and rizatriptan. All the new-marketed TELs have potential clinical benefits and were well-tolerated relative to sumatriptan. Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5 mg) demonstrate at least equivalent efficacy to sumatriptan 25, 50 and 100 mg, respectively, making them suitable first line agents for moderate or severe migraine headaches. Rizatriptan has the fastest onset of effect of the TELs. Naratriptan would appear to have lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. Therefore, for headaches of long duration and with a tendency to recur naratriptan may be the most appropriate treatment. Thus, knowledge of the metabolic, pharmacokinetic and clinical profiles of the TELs facilitates the selection of a triptan which allows optimisation of the clinical benefits for individual patients, minimising the risk of drug interactions and a minimally effective dose to reduce potential adverse events (AEs).

Clinical Trials as Topic↗

Rizatriptan in the treatment of migraine.

Rizatriptan is a selective 5-hydroxytriptamine1B/1D receptor agonist that was launched in 1998 for the acute treatment of migraine in adults. Based on data from 6 large clinical trials in patients > or =18 years of age in whom migraine was diagnosed according to International Headache Society criteria, the marketed 10-mg and 5-mg oral doses of rizatriptan are effective in relieving headache pain and associated migraine symptoms. The 10-mg dose is more effective than the 5-mg dose. At 2 hours after dosing, up to 77% of patients taking rizatriptan 10 mg had pain relief compared with 37% of those taking placebo, up to 44% were completely pain free compared with 7% of those taking placebo, and up to 77% were free of nausea compared with 58% of those taking placebo (P < 0.05 for all 3 comparisons). Both doses of rizatriptan are generally well tolerated. In placebo-controlled studies involving treatment of a single migraine attack, the most common side effects (incidence > or =2%) occurred in <10% of patients, typically were transitory (2 to 3 hours), and were mild or moderate. Rizatriptan is an effective and well-tolerated acute treatment for migraine.

Administration, Oral↗

Migraine preventive medications: a reappraisal.

Newer acute care migraine medications demonstrate improved rapidity of action, consistent effectiveness, excellent safety profiles, and rarely cause rebound headaches. Their use could decrease the need for migraine-preventive medication. The present analysis derives a formula that can be used by practitioners to determine the cost-effectiveness of various migraine-preventive medications relative to selected acute-care medications. We propose a measure called the cost-equivalent number (CEN), the number of headaches per month at which the cost of the preventive medication equals the cost savings in acute-care treatment realized by using the preventive medication. The use of the CEN individualizes the decision of whether to use a migraine-preventive medication, weighing both the efficacy and cost of the preventive medication against the cost of the acute-care medication. A CEN lower than the migraine frequency suggests that use of a preventive medication will be cost-effective.

Cost-Benefit Analysis↗

[Clinical characteristics of migraine without aura].

A detailed study of the clinical characteristics of migraine without aura (MOA) reveals some interesting data. A questionnaire was returned by 200 patients who met the International Headache Society criteria for MOA. The peak of onset of migraine was between 10 and 19 years of age. The headache was side-locked in 19%. It was exclusively bilateral in 9%. The majority (86.2%) of the patients who described headaches in only one site located them in the fronto-temporal area. Neck pain was associated with migraine attacks in 70.5% and face pain in 73.5%. A pounding quality was noted by 81%. Every patient described the headache as moderate to severe. Only 55% stated that it was aggravated by routine physical activity. Nausea occurred in 91%, photo and phonophobia in 77%, and vomiting in 50%. This close look at MOA uncovers a great complexity of symptoms.

Adult↗

Cost of migraine management: a pharmacoeconomic overview.

Migraine is a chronic, sometimes debilitating, condition that tends to afflict young people who are otherwise healthy and productive. Because diagnostic criteria and effective treatment modalities have not been well taught to physicians, the condition is often undiagnosed, misdiagnosed, and mismanaged, causing unnecessary pain, hardship to the individual, disability, loss of productivity, and increased expense to the healthcare system. This paper discusses a rational approach to the behavioral and pharmacologic treatment of migraine, highlighting the relative costs of preventive and acute care therapies. Several cases are presented to illustrate how the costs of inefficiently managed migraine therapy can be decreased even by using medications that have a higher per-dose cost, as they decrease the pain and disability and actually lower the total cost of managing the patient with migraine.

Acute Disease↗

Pharmacological prevention of migraine.

Although abortive treatment and nonpharmacologic interventions are effective for many if not most patients' occasional migraine attacks, patients who have frequent and/or severe attacks may benefit from preventive pharmacotherapy. This is particularly critical for those patients whose migraines are not treated effectively by acute-care medications because lack of pain control may lead to overuse syndromes that complicate further treatment. Inappropriate use of acute-care medication may contribute to chronic daily headache, tolerance to symptomatic medication, and headache refractory to all treatment. In addition, patients who increase use of acute-care medication due to lack of effect may suffer ergotism, GI problems, liver toxicity, analgesic nephropathy, drug induced-headache, and withdrawal symptoms when overused agents are withdrawn. Finally, overuse of acute-care medication may interfere with the effectiveness of preventive medication. The remainder of this article will focus on when to treat with preventive medication and which medications are currently available for prevention of migraine.

Adrenergic beta-Antagonists↗

Characteristics of migraine visual aura.

Visual auras (VAs) of 100 patients with migraine with aura were studied by questionnaire. Visual auras accompanied the patients' first headache (HA) in 39% of patients. Only 19% had VAs with every attack. Patients with VAs over the entire HA history had a high frequency (greater than 50%) of attacks with VA; patients with VA during only part of the HA history had a low frequency (less than 50%) of attacks with VA. The auras occurred exclusively prior to the HA in 57%. The free interval between the end of the VA and the start of the HA was usually (75%) shorter than 30 minutes. Most (59%) patients had VAs that lasted from 1 to 30 minutes. They started in the periphery of the visual fields in 56%. The most common phenomena described were: small bright dots (42%), flashes of light (39%), "blind spots" (32%), and "foggy vision" (27%). Fortification spectra was reported by only 20%. Although most (65%) patients had a combination of phenomena, the majority (72%) had only one uniform constellation of manifestations. There was no clear-cut relationship between side of VA and side of HA. Migraine VA is a pleomorphic and complex symptom. Many patients not qualifying for the diagnostic criteria of migraine with aura, as proposed by the International Headache Society (IHS), unequivocally present with visual phenomena that strongly suggest this diagnosis.

Adolescent↗