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BACKGROUND: Tanacetum parthenium (feverfew) has been used traditionally to treat migraine, and although its mechanism of action is not fully understood, serotonin 5-HT receptor blocking effects have been suggested. T. parthenium and Salix alba (white willow) either alone or in combination (Mig-RL) were recently shown to inhibit binding to 5-HT(2A/2C) receptors; T. parthenium failed to recognise 5-HT(1D) receptors, whereas S. alba or the combination did. It was hypothesised that S. alba in combination with T. parthenium may provide superior migraine prophylactic activity compared with T. parthenium alone. METHODS: A prospective, open-label study was performed in 12 patients diagnosed with migraine without aura. Twelve weeks' treatment with T. parthenium 300 mg plus S. alba 300 mg (Mig-RL) twice daily was administered to determine the effects of therapy on migraine attack frequency (primary efficacy criterion), intensity and duration (secondary efficacy criteria), and quality of life, together with tolerability for patients. RESULTS: Attack frequency was reduced by 57.2% at 6 weeks (p < 0.029) and by 61.7% at 12 weeks (p < 0.025) in nine of ten patients, with 70% patients having a reduction of at least 50%. Attack intensity was reduced by 38.7% at 6 weeks (p < 0.005) and by 62.6% at 12 weeks (p < 0.004) in ten of ten patients, with 70% of patients having a reduction of at least 50%. Attack duration decreased by 67.2% at 6 weeks (p < 0.001) and by 76.2% at 12 weeks (p < 0.001) in ten of ten patients. Two patients were excluded for reasons unrelated to treatment. Self-assessed general health, physical performance, memory and anxiety also improved by the end of the study. Mig-RL treatment was well tolerated and no adverse events occurred. CONCLUSION: The remarkable efficacy of Mig-RL in not only reducing the frequency of migraine attacks but also their pain intensity and duration in this trial warrants further investigation of this therapy in a double-blind, randomised, placebo-controlled investigation involving a larger patient population.

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Although frequently investigated in the general population, the epidemiology of insomnia complaints and their treatment have received little attention in general practice. This study recruited patients > or =15 years of age, consecutively, from 127 general practitioners in France. The physicians collected data from 11,810 of their patients, of whom 55.5% were women. Insomnia complaints were reported by 26.2% (25.4% to 27%) of the sample and use of sleep-promoting medication by 10.1% (9.7% to 10.7%). About 47% of the prescribed drugs used were anxiolytics and 45% hypnotics. Most consumers took sleep-enhancing drugs on a daily and long-term basis and most reported that the medication improved their quality of sleep. However, few distinctions emerged between elderly drug-taking insomniacs and elderly nontreated insomniacs with respect to the various dimensions of sleep. Results underscore the persistent general tendency among French general practitioners to overprescribe anxiolytics for the treatment of insomnia complaints and that they do so on a long-term basis, despite the findings of numerous studies showing that benzodiazepines are ineffective in the treatment of sleep complaints over the long term.

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A double-blind, randomized controlled trial using an electroencephalograph computerized analysis and cartography was carried out to investigate the spectral modifications induced by diazepam and hydroxyzine. Without monitoring response to stimulation, the spectra found for diazepam and for hydroxyzine were qualitatively very similar, showing increase of the slow waves, reduction of the alpha rhythm and accentuation of the beta 1 rhythms. These traces suggested strongly that both drugs had produced a sedative, anti-anxiety effect. The intensity of the effect produced by 50 mg of hydroxyzine appeared to be less than that produced by 10 mg diazepam. After monitoring response to stimulation, the spectra were modified and the reactivity of the two drugs differed with regard to the slow delta, theta and alpha 1 frequency bands. It was possible to distinguish between the sedative and anti-anxiety effects of both diazepam and hydroxyzine. Even if the two drugs had some similar effects, the mode of action in the central nervous system was certainly different, as can be seen from the characteristics of distribution of the slow waves, their reactivity and, with regard to frequency, the fluctuation of the dominant frequency of rapid rhythms.

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In a double-blind, crossover, randomized clinical pharmacological study performed on 10 healthy volunteers, peripheral and central effects of 10 mg cetirizine and 10 and 40 mg loratadine were compared. Cetirizine (10 mg) significantly (P less than 0.001) inhibited 10 or 100 mg/ml histamine-induced weals 2 and 6 h after drug intake. Cetirizine was more potent than 10 mg loratadine after 2 and 6 h, and was even more potent than 40 mg loratadine after 6 h. Neither drug affected subjective evaluation of central effects and cetirizine was completely devoid of electro-encephalographic (EEG) changes, whereas 10 and 40 mg loratadine induced only slight and limited EEG changes.

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The high incidence rate and the invalidating nature of post-traumatic epilepsy after severe brain injury have encouraged the authors to review the prophylactic treatment of this type of epilepsy. Thirty-four out of 86 randomised patients with brain injuries admitted into a neurotraumatology intensive care unit were treated prophylactically, immediately after the injury, with an intravenous hydantoin injection in a dose sufficient to provide stable and effective blood levels. This was followed by dose-adjusted oral administration maintained for a minimum period of 3 months. After a 2 years' follow-up, there was a significant difference between treated and untreated patients, since only 6 per cent of the patients treated suffered from post-traumatic epilepsy, as against 42 percent in the untreated group.

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The effects of five beta blockers on the central nervous system of healthy subjects was studied by computerized EEG analysis. All subjects underwent continuous recording with a Holter magnetic type recorder during the experimental period. For 10 consecutive days, five groups of subjects received alternately placebo and the beta blockers acebutolol 600 mg, carteolol 20 mg, metoprolol 200 mg, pindolol 30 mg and sotalol 320 mg. EEG recordings (C4/P4, P4/02 and C3/P3, P3/01) lasting 5 min were made between 8.30 and 9.30 a.m. Subjects were at rest with eyes closed and there was no vigilance control. The signal was recorded on a magnetic tape recorder and then processed by Nicolet MED 80 system. Comparisons of absolute and relative powers and of average frequencies were then made between the different sequences and groups. The possible correlations between the changes observed in the power spectrum and the clinical, pharmacological and pharmacokinetic specific properties of each beta blocker are discussed.

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The peripheral and central effects of 10 mg cetirizine 2 HCl and 60 mg terfenadine have been compared with placebo in 9 healthy male volunteers. The peripheral effect, in terms of cutaneous reactivity to 1 microgram histamine i.d., was measured by planimetry of the wheal and erythemas. Central effects were assessed with a self-evaluation visual scale and from the results of electroencephalographic spectrum analysis. Peripheral inhibition of histamine reactivity was more intense and quicker for cetirizine than for terfenadine. On the self-evaluation scale, no significant difference between terfenadine, cetirizine and placebo was noted. The quantified EEG did not show any variation in spectral parameters at any time after cetirizine. By contrast, at 6 h terfenadine had increased slow waves and had inhibited the alpha band. Thus, 10 mg cetirizine 2 HCl had less effect on the central nervous system than terfenadine 60 mg, whilst its peripheral action appeared more quickly and was more intense.

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Topographic electroencephalography was carried out to study reaction to photic stimulation in 29 normal volunteers, and 12 patients who had presented frequent clinically confirmed migraines for at least 3 years. In the group of migraineurs photic stimulation resulted in an increase in the alpha band power. The difference between the two groups was statistically significant. This reaction to photic stimulation is of help in diagnosis and suggests that a diagnosis and therapeutic orientation might be possible in patients for whom clinical diagnosis is not clear. The specificity of the migraineur's reaction to photic stimulation and its possible origin are discussed.

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The effects of sotalol dosing, 160, 240, and 320 mg/day, for 10 days in seven healthy volunteers were studied. Twenty-four-hour ECG was recorded continuously under placebo and on days 2, 4, 6, 8, 10, 11, 13, and 14. Sotalol at the three doses significantly lowered mean heart rate, reducing mean diurnal heart rate significantly between noon and 6:00 PM and decreasing mean nocturnal heart rate between midnight and 6:00 AM at 320 mg/day. Although there was no change in plasma sotalol between days 4 and 10, at high doses a significant decrease in bradycardiac effect occurred. PR intervals and QTc intervals were lengthened at all doses during the daytime. At the highest dose, the PR interval was lengthened during the nighttime.

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The value of prophylactic anti-epileptic treatment in surgery of osteomeningeal breaches has been studied. This surgery exposes to a high risk of seizures, 20 to 25 of our cases after conventional surgery. 74 operated cases of osteomeningeal breaches, among then 38 under preventive anti-epileptic therapy are reviewed. The pre and postoperative epileptic fits up to 24 hours after the operation were taken in consideration.

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Various clinical and experimental reports indicate that antidepressant drugs can have analgesic properties. The authors tested successively the anti-nociceptive activity of desipramine, clomipramine, maprotiline, viloxazine and nomifensine on the acute experimental pain model designed by Charpentier. At 25 mg/kg, desipramine showed a marked antalgic action. Clomipramine and maprotiline had a similar though much weaker action. On the other hand, nomifensine and viloxazine did not reduce pain perception; their effects on the parameters studied were variable. The usefulness of the test itself is discussed and suggestions are made regarding the relations between the analgesic potency of the drugs and the main neurotransmitter system they are assumed to act on.

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The effects of the tricyclic antidepressant clomipramine were studied in two analgesic tests in rats: (1) vocalization threshold response; and (2) scored behavioral response to electric shock to the tail. Clomipramine (20-50 mg/kg i.p.) produced analgesia, decreasing behavioral response scores and increasing vocalization threshold. Morphine also reduced the response scores in the second test. Naloxone (0.8 mg/kg i.p) or methysergide (20 mg/kg i.p.) (no effect when given alone) abolished the analgesic effect of clomipramine as evaluated by vocalization threshold response. Naloxone alone (0.6 or 2 mg/kg i.p.) increased the behavioral response at 20 and 30 V but did not modify the score at 40 V. Naloxone reduced the analgesic effect of clomipramine or morphine in the behavioral test. These results suggest that the analgesic effect of clomipramine could involve both serotonergic and endorphin central systems.

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A study of the effect of gamma-globulins on sleep was conducted in 8 patients aged 1 to 35 years with epilepsy not responding to any of the conventional treatments. Two polygraphic recordings were carried out during the 4th and 5th nights following a placebo injection and then an injection of gamma-globulin 16 Merieux (1 ml/kg). The short-term effects of the gamma-globulins were : --reduction in percentage of paroxysms, --an acceleration in the electroencephalographic tracings of the different stages of sleep and those of the waking period, --a statistically significant increase in the percentage of paradoxical sleep, though the general organization of sleep remained unchanged.

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A 16 year old boy with Bruton type agammaglobulinaemia developed acute encephalitis. Echo virus type 3 was isolated on two occasions from the same sample of CSF. Clinical improvement occured after treatment with gammaglobulin with high anti-Echo virus titers given intramuscularly and intrathecally. However the C.S.F. protein is still raised so that it is not certain he has been completely cured.

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The influence of chronic hemicerebellectomy on cortical epileptiform after-discharge (AD) induced by focal electrical stimulation was studied in the baboon. These preliminary results include 22 ADs elicited from motor cortex and 22 ADs elicited from premotor cortex before and after hemicerebellectomy. Only full-developed, generalized seizures with postictal silence were considered. EEG morphology, average duration and average current threshold were compared for each set of ictal events. No significant differences were found before and after hemicerebellectomy.

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PRELIMINARY RESULTS: The authors have treated 10 children presenting with severe epilepsy with repeated large doses of gamma-globulin. They noted a marked improvement in 7 of the children with respect to behaviour and a disappearance of seizures in 8 with comparable EEG improvement. Four children have been able to reduce their conventional anticonvulsant therapy considerably and 2 others havers received no other medication at all for 8 months. The possibility of an immune disturbance in some childhood epilepsies is thus suggested.

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