Migraine with aura and persistent foramen ovale.

The association between migraine with aura and persistent foramen ovale (PFO), as well as other right-to-left shunts, is described. A hypothesis that might explain this association is discussed. Observational studies suggested that when a PFO is closed patients who have migraine with aura are usually improved. The Migraine Intervention with STARFlex Technology (MIST) Trial was a randomised double-blind trial in patients with severe intractable migraine with aura and a moderate-large PFO that compared implantation of STARFlex devices with the intention of closing their PFO versus a sham procedure. It was hoped that the trial would demonstrate whether PFO closure would cure migraine. A series of problems in design and execution of the trial are discussed.

The persistent foramen ovale and migraine.

There is association between migraine, particularly migraine with aura, and large persistent foramen ovale (PFO) and other right-to-left shunts. Migraine is often improved by closure of a PFO in patients who have a large shunt. Inheritance of migraine is linked to the inheritance of large atrial shunts in some families. The data indicate that in some patients PFOs play a causal role in migraine with aura. These observations may also improve understanding of the etiology of migraine in patients who do not have a shunt.

Clopidogrel reduces migraine with aura after transcatheter closure of persistent foramen ovale and atrial septal defects.

OBJECTIVE: To report the clinical events leading to alteration of an anticoagulation regimen for patients undergoing transcatheter closure of an atrial shunt and how this affected migraine symptoms after the closure procedure. METHOD: Audit of a change of anticoagulant regimen. RESULTS: In the first few weeks after a closure procedure migraine frequency and severity increased despite treatment with aspirin for six months in 71 patients. Severe attacks of migraine with aura, including status migrainosus, in the first few weeks after transcatheter closure were terminated by addition of clopidogrel to aspirin treatment. Therefore, the anticoagulant regimen was changed with addition of clopidogrel for the first month after the closure procedure (90 procedures in 89 patients). Fewer patients had migraine with aura in the first month after transcatheter closure when taking the combination of clopidogrel and aspirin compared with aspirin alone (11 of 90 (12.2%) v 30 of 71 (42.3%), p < 0.001). Episodes of migraine with aura were more severe and more frequent in patients taking aspirin alone. CONCLUSION: The combination of clopidogrel for four weeks and aspirin for six months is superior to aspirin alone for six months for preventing migraine with aura after transcatheter closure of an atrial shunt. This beneficial effect of a powerful inhibitor of platelet aggregation suggests that platelets may have a role in pathogenesis of migraine. This may be because of an effect on serotonin stores. Whether clopidogrel has a role in treatment of migraine in other clinical situations requires investigation.

Inheritance of persistent foramen ovale and atrial septal defects and the relation to familial migraine with aura.

OBJECTIVE: To determine whether smaller atrial shunts (large persistent foramen ovale (PFO) and small atrial septal defect (ASD)) are inherited and whether this has a role in the inheritance of migraine with aura. METHODS: Contrast echocardiography was used to detect atrial shunts in 71 relatives of 20 probands with a significantly sized atrial shunt (large PFO or ASD). Four families with three generations, 14 families with two generations, and two sibships were studied. The contrast echocardiograms were performed blind to history of migraine. A consultant neurologist, who was blinded to cardiac findings, categorised migraine symptoms in subjects. RESULTS: The occurrence of atrial shunts was consistent with autosomal dominant inheritance. Usually shunts were large PFOs, but in some cases they were ASDs. There was also evidence that inheritance of more complex congenital heart disease may be related to the inheritance of PFOs. When the proband had migraine with aura and an atrial shunt, 15 of the 21(71.4%) first degree relatives with a significant right to left shunt also had migraine with aura compared with three of 14 (21.4%) without a significant shunt (p < 0.02). CONCLUSIONS: There is dominant inheritance of atrial shunts. This is linked to inheritance of migraine with aura in some families.

Relationship between right-to-left shunts and cutaneous decompression illness.

The presence of a large right-to-left shunt is associated with neurological decompression illness after non-provocative dives, as a result of paradoxical gas embolism. A small number of observations suggest that cutaneous decompression illness is also associated with a right-to-left shunt, although an embolic aetiology of a diffuse rash is more difficult to explain. We performed a retrospective case--control comparison of the prevalence and sizes of right-to-left shunts determined by contrast echocardiography performed blind to history in 60 divers and one caisson worker with a history of cutaneous decompression illness, and 123 historical control divers. We found that 47 (77.0%) of the 61 cases with cutaneous decompression illness had a shunt, compared with 34 (27.6%) of 123 control divers (P<0.001). The size of the shunts in the divers with cutaneous decompression illness was significantly greater than in the controls. Thus 30 (49.2%) of the 61 cases with cutaneous decompression illness had a large shunt at rest, compared with six (4.9%) of the 123 controls (P<0.001). During closure procedures in 17 divers who had cutaneous decompression illness, the mean diameter of the foramen ovale was 10.9 mm. Cutaneous decompression illness occurred after dives that were provocative or deep in subjects without shunts, but after shallower and non-provocative dives in those with shunts. The latter individuals are at increased risk of neurological decompression illness. We conclude that cutaneous decompression illness has two pathophysiological mechanisms. It is usually associated with a large right-to-left shunt, when the mechanism is likely to be paradoxical gas embolism with peripheral amplification when bubble emboli invade tissues supersaturated with nitrogen. Cutaneous decompression illness can also occur in individuals without a shunt. In these subjects, the mechanism might be bubble emboli passing through an 'overloaded' lung filter or autochthonous bubble formation.

Relationship between migraine and cardiac and pulmonary right-to-left shunts.

A relationship between migraine with aura and the presence of right-to-left shunts has been reported in two studies. Right-to-left shunts are also associated with some forms of decompression illness. While conducting research in divers with decompression illness, it was our impression that divers with a large shunt often had a history of migraine with aura in everyday life and after dives. Therefore we routinely asked all divers about migraine symptoms. The medical records of the last 200 individuals referred for investigation of decompression illness were reviewed to determine the association between right-to-left shunts and migraine aura after diving, and migraine in daily life unconnected with diving. Migraine with aura in daily life unconnected with diving occurred significantly more frequently in individuals who had a large shunt which was present at rest (38 of 80; 47.5%) compared with those who had a shunt which was smaller or only seen after a Valsalva manoeuvre (four of 40; 10%) or those with no shunt (11 of 80; 13.8%) (P<0.001). Hemiplegic migraine occurred in 10 divers, each of whom had a shunt that was present at rest; in eight of these cases the shunt was large. The prevalence of migraine without aura was similar in all groups. Post-dive migraine aura was significantly more frequent in individuals who had a large shunt present at rest (21 of 80; 26.3%) compared with those who had a shunt that was smaller or only seen after a Valsalva manoeuvre (five of 40; 12.5%) or no shunt (one of 80; 1.3%) (P<0.001). Thus individuals with a large right-to-left shunt have an increased prevalence of migraine with aura in daily life unconnected with diving, and they also have an increased incidence of migraine aura after dives, but only when the dives liberate venous bubbles. These data suggest the possibility that, in some individuals, right-to-left shunts have a role in the aetiology of migraine with aura. The observations suggest that paradoxical gas embolism may precipitate migraine with aura.

Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons.

BACKGROUND: A relation between migraine with aura and cardiac right-to-left shunts has been reported. Right-to-left shunts are also associated with stroke and certain forms of decompression illness. We investigated the effect of closure of right-to-left shunts on migraine symptoms. METHODS: A consultant neurologist, who was unaware of information about residual shunt, undertook a structured interview with individuals who had had transcatheter closure of an atrial septal defect or patent foramen ovale to assess how the procedure affected migraine symptoms. FINDINGS: 37 of 40 consecutive patients who had had a closure procedure (to permit resumption of diving after decompression illness in 29, after stroke when paradoxical thromboembolism was suspected in four, or to close a large atrial septal defect in four) could be contacted. 21 (57%) had a history of migraine before the procedure (with aura in 16, without aura in five). 11 individuals had fortification spectra in the period immediately after closure. During long-term follow-up, no migraine symptoms were reported by seven individuals who had previously had migraine with aura and three who had previously had migraine without aura. Eight others who had had migraine with aura before closure reported improvement in frequency and severity of migraines. Three (one migraine with aura, two migraine without aura) reported no alteration in migraine episodes. INTERPRETATION: These observations suggest a causal association between right-to-left shunts and migraine with aura. There may be a subgroup of patients who have severe migraine associated with a large right-to-left shunt in whom closure of the atrial defect may improve or abolish migraine.

Improving door to needle times with nurse initiated thrombolysis.

OBJECTIVE: To evaluate the effect of nurse initiated thrombolysis on door to needle time (the interval between arriving at the hospital and starting thrombolytic treatment) in patients with acute myocardial infarction. DESIGN: Comparison of door to needle times before and after the employment of nurses trained and approved to initiate thrombolysis without prescription by a doctor but with a protocol for rapid triage of patients with chest pain. SETTING: A district general hospital. SUBJECTS: All patients admitted with suspected myocardial infarction between April 1995 and March 1999. MAIN OUTCOME MEASURES: Speed (door to needle time) and appropriateness of administration of thrombolytic drugs to patients with acute myocardial infarction who gave a characteristic history and had appropriate criteria on the admission ECG. RESULTS: During seven periods (each of four months) before the introduction of nurse initiated thrombolysis and a new chest pain triage protocol, the median door to needle time varied from 50-58 minutes. In four periods (each of 4-6 months) following the introduction of the changes, the median door to needle time was 25-30 minutes. The improvement was significant (p < 0.001). Nurses trained to initiate thrombolysis currently provide cover for 66% of the time. Median door to needle time for nurses was 15 minutes. Median door to needle time for junior doctors improved to 35 minutes. The median door to needle times when nurses initiated thrombolysis was significantly shorter than when doctors did so (p < 0.001). There have been no inappropriate management decisions by nurses approved to initiate thrombolysis. CONCLUSIONS: The use of nurse initiated thrombolysis has resulted in a clinically important reduction in the time taken for thrombolysis to be started in patients with acute myocardial infarction.

Relationship between the clinical features of neurological decompression illness and its causes.

There is dispute as to whether paradoxical gas embolism is an important aetiological factor in neurological decompression illness, particularly when the spinal cord is affected. We performed a blind case-controlled study to determine the relationship between manifestations of neurological decompression illness and causes in 100 consecutive divers with neurological decompression illness and 123 unaffected historical control divers. The clinical effects of neurological decompression illness (including the sites of lesions and latency of onset) were correlated with the presence of right-to-left shunts, lung disease and a provocative dive profile. The prevalence and size of shunts determined by contrast echocardiography were compared in affected divers and controls. Right-to-left shunts, particularly those which were large and present without a Valsalva manoeuvre, were significantly more common in divers who had neurological decompression illness than in controls (P<0.001). Shunts graded as large or medium in size were present in 52% of affected divers and 12.2% of controls (P<0.001). Spinal decompression illness occurred in 26 out of 52 divers with large or medium shunts and in 12 out of 48 without (P<0.02). The distribution of latencies of symptoms differed markedly in the 52 divers with a large or medium shunt and in the 30 divers who had lung disease or a provocative dive profile. In most cases of neurological decompression illness the cause can be determined by taking a history of the dive profile and latency of onset, and by performing investigations to detect a right-to-left shunt and lung disease. Using this information it is possible to advise divers on the risk of returning to diving and on ways of reducing the risk if diving is resumed. Most cases of spinal decompression illness are associated with a right-to-left shunt.

Transcatheter closure of patent foramen ovale using the Amplatzer septal occluder to prevent recurrence of neurological decompression illness in divers.

OBJECTIVE: Large flap valve patent foramens may cause paradoxical thromboembolism and neurological decompression illness in divers. The ability of a self expanding Nitinol wire mesh device (Amplatzer septal occluder) to produce complete closure of the patent foramen ovale was assessed. PATIENTS: Seven adults, aged 18-60 years, who had experienced neurological decompression illness related to diving. Six appeared to have a normal atrial septum on transthoracic echocardiography, while one was found to have an aneurysm of the interatrial septum. METHODS: Right atrial angiography was performed to delineate the morphology of the right to left shunt. The defects were sized bidirectionally with a precalibrated balloon filled with dilute contrast. The largest balloon diameter that could be repeatedly passed across the septum was used to select the occlusion device diameter. Devices were introduced through 7 F long sheaths. All patients underwent transthoracic contrast echocardiography one month after the implant. RESULTS: Device placement was successful in all patients. Device sizes ranged from 9-14 mm. The patient with an aneurysm of the interatrial septum had three defects, which were closed with two devices. Right atrial angiography showed complete immediate closure in all patients. Median (range) fluoroscopy time was 13.7 (6-35) minutes. Follow up contrast echocardiography showed no right to left shunting in six of seven patients and the passage of a few bubbles in one patient. All patients have been allowed to return to diving. CONCLUSION: The Amplatzer septal occluder can close the large flap valve patent foramen ovale in divers who have experienced neurological decompression illness. Interatrial septal aneurysms with multiple defects may require more than one device.

Tachyarrhythmias triggered by swallowing and belching.

Three cases with supraventricular tachyarrhythmias related to oesophageal transit are reported. A 61 year old man had episodes of atrial tachycardia on each swallow of food but not liquid; this has been reported only rarely. A 55 year old man had atrial fibrillation initiated by drinking ice cold beverages; this has not been described previously although atrial tachycardia triggered by drinking ice cold beverages has been described once. A 68 year old man had supraventricular tachycardia initiated by belching; this has not been described previously. These cases illustrate the diversity of atrial tachyarrhythmias that can be precipitated by oesophageal stimulation and suggest that what is regarded as a very rare phenomenon may be found more commonly when sought.

Dysbaric osteonecrosis of the shoulder in a sport scuba diver.

The previously unreported occurrence of dysbaric osteonecrosis in an amateur sport scuba diver who had no other identified cause of avascular bone necrosis is described.