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.

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.

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.

A case-control investigation of the relation between hyperlipidaemia and calcific aortic valve stenosis.

OBJECTIVE: To investigate the relation of hyperlipidaemia to calcific aortic valve stenosis. DESIGN: A case-control study designed to detect a clinically relevant difference in the fasting plasma concentrations of total cholesterol between the groups at the 5% level with a power of 90%. Predefined subgroup analyses were based on presence of significant coronary disease and valve morphology (that is, bicuspid or tricuspid). SETTING: A district general hospital. SUBJECTS: 20 patients with severe calcific aortic stenosis and 20 controls. RESULTS: Mean (SD) fasting plasma total cholesterol in patients with aortic stenosis was 0.79 (1.50) mmol/l greater than in the controls (p = 0.029). The magnitude of differences between patients with aortic stenosis and controls was similar whether the patients had coronary artery disease (0.78 (1.73) mmol/l) or not (0.80 (1.37) mmol/l). The presence of a stenosed tricuspid aortic valve was associated with a significant increase in plasma cholesterol (1.70 (0.87) mmol/l, p = 0.012). For bicuspid valves the degree of elevation of plasma cholesterol was less and not statistically significant. CONCLUSIONS: Calcific aortic stenosis is associated with hypercholesterolaemia, especially when the valve is tricuspid. Further studies are necessary to confirm that the relation is causal. This finding may have implications for measures to prevent the most common cause of cardiac valve replacement in the developed world.

Restrictive and hypertrophic cardiomyopathies in Noonan syndrome: the overlap syndromes.

A woman with Noonan syndrome had clinical and haemodynamic features of restrictive cardiomyopathy. There was no ventricular hypertrophy on echocardiography but myocardial biopsies showed myocyte hypertrophy without pathological disarray. This case illustrates the overlap of the cardiac phenotypes of Noonan syndrome, restrictive cardiomyopathy, and hypertrophic cardiomyopathy.

Critical illness poly-neuropathy following severe hyperpyrexia.

Two patients developed critical illness polyneuropathy after severe hyperpyrexia. Fever was secondary to a phaeochromocytoma in one patient and sepsis in the other. These observations suggest that high fever may be one possible aetiology of critical illness polyneuropathy.

Effects of a patent foramen ovale on arterial saturation during exercise and on cardiovascular responses to deep breathing, Valsalva manoeuvre, and passive tilt: relation to history of decompression illness in divers.

OBJECTIVE: To determine whether the presence of a patent foramen ovale could result in significant arterial desaturation and affect the responses of heart rate and blood pressure to physiological manoeuvres and to determine whether responses differed between those with and those without prior clinical events associated with a patent foramen ovale. DESIGN: Blind controlled study. SETTING: Teaching hospital. PATIENTS: Divers with a large patent foramen ovale shown by contrast echocardiography and divided into those who had neurological decompression illness that started within 30 minutes of surfacing (group 1), those who had no history of decompression illness (group 2), and age and sex matched control divers who had no evidence of intracardiac shunts (group 3). MAIN OUTCOME MEASURES: The change in percentage haemoglobin oxygen saturation during treadmill exercise and the response of heart rate and blood pressure to physiological manoeuvres. RESULTS: There were no significant differences between the three groups but two divers in group 1 showed clinically important desaturation during exercise and unusual blood pressure and heart rate responses to passive tilt. These divers were notable for having the greatest number of episodes and the most severe single episode of spinal cord decompression illness. CONCLUSION: A large patent foramen ovale may be associated with clinically significant arterial desaturation and unusual responses of heart rate and blood pressure in some healthy subjects.

Effect of aortic valve replacement on syncope in patients with aortic stenosis.

OBJECTIVE: To determine the role of exertion as a precipitating factor in syncope in patients with aortic stenosis. DESIGN: Follow up for at least one year after aortic valve replacement. SETTING: Regional cardiac centre. PATIENTS: Consecutive patients who underwent aortic valve replacement for aortic stenosis and who had a history of syncope and no other clinically significant cardiac lesion were recruited during a five year period. METHODS: Patients were interviewed to determine the characteristics of syncope and were divided into those in whom syncope was consistently related to exertion (group 1, 26 patients) and those in whom it was not (group 2, 13 patients). Recurrence of syncope after valve replacement was determined at visits to the clinic. RESULTS: Groups 1 and 2 did not differ significantly with respect to valve area, age, or sex. In 13 of the 26 patients in group 1 syncope was preceded by angina despite the absence of coronary artery disease, but none of the 13 patients in group 2 had angina. After valve replacement none of group 1 and eight of the 13 patients in group 2 had recurrence of syncope (p < 0.01). CONCLUSION: When patients with aortic stenosis experience syncope unrelated to exertion, the symptom is usually unrelated to the valve disease and another cause should be sought.

Histoplasma endocarditis on a stenosed aortic valve presenting as dysphagia and weight loss.

A 40-year-old man with aortic stenosis and disseminated histoplasmosis did not respond to treatment with itraconazole. Though there was no haemodynamic deterioration, valvar regurgitation, or embolic phenomena a presumptive diagnosis of infective endocarditis was made. This was confirmed at aortic valve replacement. Antifungal treatment was continued for 18 months after valve replacement and serological tests for Histoplasma became progressively more negative during a three year follow up.