Long term decline of P100 amplitude in migraine with aura.

OBJECTIVES: To investigate visual function in migraine using visual evoked potentials. METHODS: Electroretinograms (ERGs) and visual evoked potentials (VEPs) to single flash (SF) and pattern reversal (PR) stimuli were studied in 92 migraine subjects and 62 controls. RESULTS: In subjects with migraine, ERGs to single flash were normal. Mean latencies of the P1 and P2 waves in the SFVEP were increased at the occiput by 6% and 4% respectively, but normal at the vertex. Mean latency of the P100 wave in the PRVEP was increased by 5%. These increases were not related to the presence or absence of an aura or to the duration of migraine. P100 amplitude showed a more complex abnormality. It was increased in migraine without aura by 23% compared with controls, regardless of duration of migraine. In migraine with aura it was similarly increased, by 23%, in cases of short duration, but in addition it showed a sharp decline with duration. In cases with a duration of 30 or more years it was 36% less than in cases of short duration, and 21% less than in controls. CONCLUSIONS: Subjects with migraine have constitutionally prolonged VEP latencies and increased P100 amplitude, but the latter declines to below normal in cases with a long history of migraine with aura. This decline may reflect subtle neuronal damage within the visual system from repeated transient ischaemia experienced during the aura. Future electrophysiological and other studies will need to be controlled for duration of migraine history.

Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs.

BACKGROUND: Migraine drugs can produce adverse cardiac effects. The authors have demonstrated previously that ergotamine can lead to a significant reduction of hyperemic myocardial blood flow, but little is known about the effect of the newer serotonin analogues. Coronary artery constriction caused by serotonin or its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D agonist naratriptan has no significant activity at 5HT2 receptors; however, like all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary arteries by activation of 5HT1B receptors. METHODS: The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg compared with placebo were assessed under resting and hyperemic conditions with PET using oxygen-15 labeled water during two separate visits. This study was a randomized, double-blind, placebo-controlled crossover trial in 34 migraine subjects with no evidence of ischemic heart disease, studied outside a migraine attack. RESULTS: Naratriptan did not differ significantly from placebo in its effects on resting myocardial blood flow, but did evoke a small, significant fall in hyperemic myocardial blood flow (-13% versus placebo) and an increase in hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms suggestive of myocardial ischemia. Naratriptan did not significantly affect the coronary vasodilator reserve (hyperemic/resting blood flow) compared with placebo. CONCLUSIONS: These results show that at therapeutic doses, naratriptan exerts only a minor effect on myocardial blood flow, coronary vasodilator reserve, or coronary resistance among subjects with no evidence of ischemic heart disease. These results should not be extrapolated to patients with coronary artery disease, in whom all 5HT1 agonists for migraine are contraindicated.

Comparison of rizatriptan 10 mg vs. naratriptan 2.5 mg in migraine.

Rizatriptan (MAXALT(TM), Merck & Co., Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action for the acute treatment of migraine. This randomized, double-masked, double-dummy, placebo-controlled study compared rizatriptan 10 mg to naratriptan (NARAMIG(TM), AMERGE(TM), both Glaxo Wellcome plc) 2.5 mg in 522 patients treating a single migraine attack. Rizatriptan was more effective than naratriptan. Rizatriptan provided earlier headache relief than naratriptan (hazard ratio 1.62, p < 0.001), acting as early as 30 min. More patients were pain free at 2 h on rizatriptan than on naratriptan (44.8 vs. 20.7%, p < 0.001). Rizatriptan also provided earlier relief of associated migraine symptoms within 2 h than naratriptan and more patients had normal function at 2 h (39.3 vs. 22.6%, p < 0. 001). Both active treatments were effective compared to placebo. Both active treatments were well tolerated. The most common side effects with rizatriptan were dizziness, asthenia/fatigue, nausea and somnolence, while the most common side effects with naratriptan were dizziness and asthenia/fatigue.

Effects of ergotamine on myocardial blood flow in migraineurs without evidence of atherosclerotic coronary artery disease.

The effects of intravenous ergotamine (0.25 mg) on basal and hyperemic (dipyridamole) myocardial blood flow (MBF), measured with positron emission tomography and H2(15)O, were assessed in 15 migraineurs in a double-blind, randomized, placebo controlled, crossover study. Ergotamine produced a 27% reduction in hyperemic MBF (2.62 +/- 0.11 vs 3.72 +/- 1.05 ml x min(-1) x g(-1); p <0.05), a 31% reduction in the coronary vasodilator reserve (1.81 +/- 0.50 vs 2.71 +/- 1.15; p <0.01), and a 55% increase in minimal coronary resistance (42.2 +/- 15 vs 26.7 +/- 8 mm Hg x min x ml(-1) x g(-1); p <0.001), suggesting vasoconstriction of the coronary microcirculation.

Preliminary trial of photic stimulation for premenstrual syndrome.

In an open study 17 women with confirmed, severe and long-standing premenstrual syndrome used photic stimulation with a flickering red light, every day for up to four menstrual cycles. At the end of treatment prospectively recorded median luteal symptom scores were reduced by 76% (95% confidence interval 54-93, P < 0.001), with clinically and statistically significant reductions for depression, anxiety, affective lability, irritability, poor concentration, fatigue, food cravings, bloating and breast pain. Twelve of the 17 patients (71%) no longer had the premenstrual syndrome. One patient failed to improve. One patient withdrew because of worsening premenstrual depression, but photic stimulation was otherwise well tolerated. The improvement is greater than that reported for relaxation or in open studies of fluoxetine, and much more than historical placebo rates. Photic stimulation may be a useful treatment for the premenstrual syndrome, and by its suggested action on circadian rhythms may have wider therapeutic applications.

Langerhans' cell histiocytosis and the nervous system.

We report two cases of Langerhans' cell histiocytosis with unusual central nervous system (CNS) involvement. The first patient had behavioural disturbances, memory loss and diabetes insipidus. His response to a range of treatments was poor. The second patient presented with seizures and headaches suggestive of raised intracranial pressure. Etoposide (VP16) chemotherapy led to a dramatic clinical and radiological improvement. The various CNS manifestations of Langerhans' cell histiocytosis and their management are discussed.

Regional cerebral blood flow and oxygen metabolism in dementia due to vascular disease.

Regional cerebral blood flow (CBF), oxygen utilisation (CMRO2) and fractional oxygen extraction (OER) were measured by positron emission tomography in patients with multi-infarct dementia. A matched reduction of both CBF and CMRO2 in the majority of patients indicated that in general, reduced cerebral perfusion in this condition is appropriate for the reduced metabolic demands of a damaged brain. Only in a very small minority of patients with dementia associated with bilateral carotid artery occlusion was CBF inappropriately low and OER raised. In these exceptional cases with critical cerebral perfusion, surgical measures to increase CBF could theoretically arrest or slow down the progress of dementia.

The effects of L-DOPA on regional cerebral blood flow and oxygen metabolism in patients with Parkinson's disease.

Studies performed on 18 patients with Parkinson's disease and 6 control subjects have shown that acute administration of L-DOPA in clinically effective doses gives rise to a diffuse increase in regional cerebral blood flow without accompanying stimulation of regional oxygen utilization. The data suggest that this rise in rCBF is caused by vasodilatation due to a direct action of the drug on the cerebral blood vessels. The effect of L-DOPA on rCBF did not correlate with the degree of clinical improvement seen in each patient after treatment. The therapeutic effect of L-DOPA in the brain was not reflected in any change of regional cerebral oxygen utilization as measured by our technique. We suggest that the pharmacological actions of L-DOPA in the brain take place on at least two different levels.

Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis.

Regional cerebral oxygen utilisation (rCMRO2), oxygen extraction (rOER), blood flow (rCBF), and blood volume (rCBV) have been determined for fifteen patients with multiple sclerosis in remission using positron emission tomography (PET). Cerebral oxygen utilisation and blood flow were significantly reduced in both white matter and peripheral cortical grey matter in the multiple sclerosis patients compared to a group of normal controls. No evidence of regional cerebral ischaemia in the multiple sclerosis group was found. Lowest levels of cerebral oxygen utilisation were found in patients with cerebral atrophy, and in patients in whom a significant fall in present full-scale IQ from estimated pre-morbid levels had occurred. No correlation was found between rCMRO2 values and severity of locomotor dysfunction or clinical disease duration.