Background-Patent foramen ovale (PFO) is prevalent in patients with migraine with aura. Observational studies show that PFO closure resulted in migraine cessation or improvement in Ϸ80% of such patients. We investigated the effects of PFO closure for migraine in a randomized, double-blind, sham-controlled trial. Methods and Results-Patients who suffered from migraine with aura, experienced frequent migraine attacks, had previously failed Ն2 classes of prophylactic treatments, and had moderate or large right-to-left shunts consistent with the presence of a PFO were randomized to transcatheter PFO closure with the STARFlex implant or to a sham procedure. Patients were followed up for 6 months. The primary efficacy end point was cessation of migraine headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) had right-to-left shunts consistent with a moderate or large PFO. One hundred forty-seven patients were randomized. No significant difference was observed in the primary end point of migraine headache cessation between implant and sham groups (3 of 74 versus 3 of 73, respectively; Pϭ0.51). Secondary end points also were not achieved. On exploratory analysis, excluding 2 outliers, the implant group demonstrated a greater reduction in total migraine headache days (Pϭ0.027). As expected, the implant arm experienced more procedural serious adverse events. All events were transient. Conclusions-This trial confirmed the high prevalence of right-to-left shunts in patients with migraine with aura. Although no significant effect was found for primary or secondary end points, the exploratory analysis supports further investigation. The robust design of this study has served as the model for larger trials that are currently underway in the

One hundred and fifty patients presenting with small cell lung cancer (SCLC)

The number of referrals by primary care practitioners to secondary care neurology services, particularly for headache, may be difficult to justify. Access to imaging by primary care practitioners could avoid referral without compromising patient outcomes, but the decision to refer is based on a number of complex factors. Due to the paucity of rigorous evidence in this area, available data are combined with expert opinion to offer support for GPs. The study suggests management for three levels of risk of tumour: red flags >1%; orange flags 0.1-1%; and yellow flags <0.1% but above the background population rate of 0.01%. Clinical presentations are stratified into these three groups. Important secondary causes of headache where imaging is normal should not be overlooked, and normal investigation does not eliminate the need for follow-up or appropriate management of headache.

Two multi-centre studies - one double-blind, placebo-controlled (study 1) and one open (study 2) - were set up to assess if pizotifen prophylaxis improved migraine beyond the benefit offered by acute sumatriptan therapy alone. Eighty-eight patients completed the blinded study and 63 patients completed the open study. Both studies were of crossover design with patients undertaking a 4 week run-in period prior to a 12-week treatment period. Following a 4-week washout period patients commenced a second 12-week treatment period on the alternative treatment regimen. All breakthrough attacks were treated with 100 mg oral sumatriptan with an optional 2 doses available to treat any recurrence within 24 h of taking dose 1. Pizotifen was built up to a final daily dose of 1.5 mg over a 2-week period and patients remained on this dose for a further 10 weeks. Patients in the blinded study were given matching placebo tablets for one of the two treatment periods. The efficacy of sumatriptan was not affected by pizotifen. The median of the monthly attack rate experienced by patients was slightly lower whilst patients were on pizotifen and sumatriptan than while on placebo prophylaxis and sumatriptan or sumatriptan alone; study 1, 3.5 vs. 3.9 attacks per month (p = 0.008); study 2, 2.9 vs. 3.2 attacks per month (p = 0.23). Also, while on pizotifen and sumatriptan more patients had a greater proportion of their time in the study migraine-free. From the results of these studies it does not appear that pizotifen reduces migraine severity; regardless of the treatment regimen the initial headache severity of most attacks was moderate. Weight gains experienced by patients while on pizotifen and sumatriptan were greater than the weight gains experienced while on placebo prophylaxis and sumatriptan or sumatriptan alone (period 1); study 1, 2.6 vs. 1.0 kg (p = 0.002); study 2, 1.6 vs. -0.8 kg (p < 0.0001). The combination of pizotifen and sumatriptan did not result in any additional adverse events other than those usually seen with each medication alone. In these studies, where the average number of migraine attacks was around 4 per month, the benefits conferred by pizotifen were at the expense of the adverse events associated with the drug, particularly weight gain. Therefore the clinical benefit of treatment with pizotifen for patients who have less than 4 attacks per month should be carefully reviewed as acute treatment with sumatriptan may be the most appropriate treatment. Pizotifen may be better reserved for those patients who have 4 of more attacks per month.

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