Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: The treatment of a migraine attack can be difficult when first-line medication is unsuccessful and options for parenteral "rescue" therapy are limited. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging, multicenter study was conducted to assess the efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults. RESULTS: A total of 331 patients were enrolled; 305 were treated. Headache response at 2 hours was better (p < 0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of patients achieving a pain-free response at 2 hours after treatment was significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for patients initially responding by 2 hours was lower in patients treated with droperidol than placebo, but differences failed to reach significance. A significantly greater percentage of patients receiving droperidol 2.75 mg reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo. Although most adverse events were of mild or moderate intensity, anxiety, akathisia, and somnolence were rated as severe in 30% of patients who experienced those symptoms. Hypotension was uncommon. No patient had QT prolongation.

What's in a name? tension-type headache versus migraine.

For years clinicians and researchers have debated the nosology of headache generally and of "migraine" versus "tension-type headache" in particular, an exhaustive process that arguably has done little to improve patient management and clinical outcome. New research data now indicate that the migraine versus tension-type distinction indeed may possess some clinical use, because patients with migraine or "mixed" headache syndromes may respond differently to a specific therapeutic intervention than patients with "pure" tension-type headache. This variable response to treatment intervention would seem to imply that similarly distinctive biologies are generating the respective headache syndromes, but to date we have insufficient evidence to support that conclusion.

An analysis of the "carry-over effect" following successful short-term treatment of transformed migraine with divalproex sodium.

OBJECTIVE: To determine whether successful short-term prophylactic treatment of transformed migraine may be followed by a continued respite from headaches once the treatment has been discontinued ("carry-over effect"). BACKGROUND: The optimal duration of prophylactic treatment for pervasive headache and for migraine, in particular, is unknown. METHODS: We prospectively evaluated a series of patients with transformed migraine, all of whom were managed according to a uniform treatment protocol involving prophylactic therapy with divalproex sodium for a period not exceeding 12 weeks. All patients reporting a positive treatment response were followed for at least 2 months after the discontinuation of divalproex sodium, and the incidence of the carry-over effect in that group was assessed. RESULTS: A short-term carry-over effect occurred in 12 (60%) of 20 patients, but more sustained relief occurred in only 8 (40%). CONCLUSIONS: The successful short-term treatment of transformed migraine with divalproex sodium will often produce a short-term carry-over effect, but this response will be sustained only in a minority of patients.

Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies.

BACKGROUND: While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic. OBJECTIVES: To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies. METHODS: On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I-III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy. RESULTS: Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05). CONCLUSIONS: Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin.

Management of chronic daily headache utilizing a uniform treatment pathway.

OBJECTIVE: To determine if the use of a uniform treatment pathway might be effective in treating patients with primary chronic daily headache. METHODS: Thirty-three consecutive patients with primary chronic daily headache were managed according to a treatment pathway which involved sequential administration of divalproex sodium, amitriptyline, amitriptyline plus phenelzine, or methadone. RESULTS: Twenty-two patients (67%) reported a 50% or greater reduction in headache days per month following initiation of treatment. Most positive treatment responses (17 [77%] of 22) were attributed to divalproex sodium. CONCLUSION: Implementation of a uniform treatment pathway may result in significant clinical improvement in a sizable proportion of patients with chronic daily headache.

An interregional comparative study of headache clinic populations.

We present a comparative study between headache clinic populations from 2 inherently different regions of the United States. Using standardized methods, 1 of us (JFR) prospectively evaluated 578 new patients attending the headache clinic at the University of California in San Diego. In a similar manner, we subsequently evaluated 115 new patients presenting to the headache clinic at the University of South Alabama in Mobile, Alabama. We found few differences between the 2 populations. These differences more likely reflect regional variations in healthcare delivery or methodologic artifact than intrinsic dissimilarities.

Intravenous t-PA for acute ischemic stroke: therapeutic yield of a stroke code system.

Subsequent to publication of the NINDS t-PA Stroke Study results, we sought to determine the proportion of patients eligible for and receiving intravenous tissue plasminogen activator (t-PA) at an active acute stroke treatment center. Over a 12-month period there were 185 stroke code activations. Of these, 134 involved patients with ischemic stroke, and 48 of these (36%) were potentially eligible for treatment with t-PA by the time criterion (i.e., interval from stroke onset to hospital presentation < 3 hours). Nine of the 48 potentially eligible patients (19%) and 9 of 134 ischemic stroke patients (7%) overall received t-PA. In our patient population only a small proportion of all patients with acute ischemic stroke presently are eligible for treatment with t-PA.

Accuracy of paramedic diagnosis of stroke.

BACKGROUND AND PURPOSE: Accurate prehospital diagnosis of acute stroke may lead to fewer delays in hospital presentation. In addition, prehospital personnel soon may be administering therapies to patients with presumed stroke. We sought to determine the sensitivity and positive predictive value (PPV) of paramedic diagnosis of stroke in Mobile, Alabama, and to evaluate the impact of an educational program on paramedic diagnostic capability. METHODS: We collected data from all paramedic-diagnosed stroke patients transported to a University of South Alabama hospital by Mobile Fire Medics. Final diagnosis was determined by a neurologist and classified as stroke or nonstroke (i.e., PPV). Paramedic diagnoses for all hospitalized stroke patients transported by Mobile Fire Medics were also reviewed (i.e., sensitivity). Sensitivity and PPV were calculated for the period 6/13/95 to 3/13/97. In addition, both indices were calculated for the period before (6/13/95 to 5/5/96) and after (6/25/96 to 3/13/97) an 8-week intensive educational program. RESULTS: Seventy-one hospitalized stroke patients were transported by Mobile Fire Medics during the study period. Paramedics correctly identified 67 patients in total (94% sensitivity), 29 during the pre-education period (91% sensitivity), and 29 during the posteducation period (97% sensitivity; P=.33). Twenty-five patients were incorrectly diagnosed with stroke (73% PPV), 15 during the pre-education period (66% PPV), and 9 during the posteducation period (76% PPV; P=.30). CONCLUSION: Although paramedics in Mobile misdiagnose few patients with acute stroke, there is a tendency toward overdiagnosis. An educational intervention resulted in a trend toward improved accuracy of diagnosis, but this did not reach statistical significance.

Migrainous stroke causing thalamic infarction and amnesia during treatment with propranolol.

We report a case of migraine-associated ischemic stroke causing amnesia, wherein treatment with propranolol may have been contributory. The possible mechanisms involved in migrainous stroke occurring in association with use of propranolol are discussed.

Implementation of a stroke code system in Mobile, Alabama. Diagnostic and therapeutic yield.

BACKGROUND AND PURPOSE: There is now therapy of proven benefit for acute ischemic stroke. Successful interventional therapy for stroke patients requires implementation of a system that facilitates rapid triage and diagnostic evaluation. METHODS: We initiated a 24-hour, 7-day-per-week stroke code system at the University of South Alabama Hospitals and prospectively collected data from the first 100 patients whose clinical presentations triggered this system. RESULTS: Seventy-eight patients (78%) had acute ischemic stroke. Of the remaining 22, 9 had evidence of intracerebral hemorrhage. The most common nonstroke diagnosis was seizure (n = 5). Forty-eight of the 87 stroke patients (55%) presented within 6 hours of stroke onset (40/78 = 51% of the ischemic stroke patients), and 35 of the 87 (40%) presented within 3 hours of onset (28/78 = 36% of the ischemic stroke patients). Thirty-one (31% of the group overall; 40% of the ischemic stroke patients) were eligible for acute therapy. Twenty-five of these eligible patients were entered into a treatment study, 4 declined participation, and 2 were treated with open-label tissue plasminogen activator. CONCLUSIONS: Implementation of a stroke code system may result in a high yield of patients with acute stroke and relatively few "stroke mimickers." A significant proportion of all cases generated will be eligible for acute treatment under current experimental protocols or with tissue plasminogen activator, but the majority will not.

Clinical studies of valproate for migraine prophylaxis.

Within the last decade our understanding of the pathophysiologic mechanisms which generate migraine has expanded considerably. Accompanying these advances in basic science, new agents designed to treat migraine acutely have exhibited unprecedented pharmacologic selectivity and clinical efficacy. While these abortive agents clearly can provide many migraine patients with a degree of headache control they previously have not enjoyed, such treatment typically will not provide lasting benefit to individuals whose headaches are more pervasive and may require stabilization through effective prophylactic therapy. Unfortunately, our arsenal of agents for migraine prophylaxis has not grown as rapidly as that of the abortive medications, and for the most part clinicians and patients are left to rely upon a small handful of "traditional" drugs for that purpose. One notable exception to this is divalproex sodium; the safety and efficacy of this new agent for migraine prevention have been documented consistently in a series of recent clinical trials.

Chronic daily headache with migrainous features due to papilledema-negative idiopathic intracranial hypertension.

Patients with the syndrome of chronic daily headache often report migrainous symptoms and consequently are diagnosed as having a primary headache syndrome. We report two cases of idiopathic intracranial hypertension causing chronic daily headache with migrainous features in the absence of associated papilledema.

Migraine: definitions, mechanisms, and treatment.

Although ubiquitous, migraine remains incompletely understood and thus often ineffectively managed. Fortunately, new advances in our understanding of migraine's origins have led to identification and application of therapeutic intervention that is unparalleled in its specificity and clinical efficacy. We present a unified model of migraine genesis and explain how application of the model to clinical practice may improve therapeutic management of this common disorder.

Differential effect of aspirin versus warfarin on clinical stroke types in patients with atrial fibrillation. Stroke Prevention in Atrial Fibrillation Investigators.

The Stroke Prevention in Atrial Fibrillation II study compared the efficacy and safety of aspirin and warfarin in patients with atrial fibrillation. Three neurologists, blinded to patient therapy, categorized the pathophysiology of ischemic strokes that occurred in the trial based on predetermined clinical criteria. Upon analyzing the patients being treated with these two drugs, warfarin proved significantly more effective than aspirin in preventing cardioembolic strokes (p = 0.005) and strokes of uncertain pathophysiology (p = 0.01). There was no significant difference in the efficacy for prevention of noncardioembolic strokes.