1110
Sumatriptan and
recurrence
of
migraine
SIR,-Dr Dahl6f (Oct 10, p 909) regards as "weak" the evidence for the effectiveness of sumatriptan in the treatment of an established migraine attack. The primary efficacy index in the worldwide clinical development programme for sumatriptan was the percentage of patients obtaining headache relief at a fixed time after an injection (11 and 2 h) or tablet (2 and 4 h). In 13 double-blind clinical trials during which 4934 migraine attacks were treated, this finding was further analysed according to whether patients were treated within 4 h of onset of headache (early) or more than 4 hours after onset of headache (late). Across all these studies the data showed reproducible and comparable efficacy for these two groups. By contrast, Dahlofs open crossover study of 24 patients uses the development of recurrent headache as an endpoint. A double-blind, parallel-group, placebo-controlled clinical trial of oral sumatriptan in more than 1200 patients was done to assess the frequency of recurrent headache during 24 h after one or two doses of oral sumatriptan. The following data show clearly that the frequency of recurrent headache in attacks treated 4-12 h after onset of headache and after attacks treated earlier did not differ: % with 7//ne from Time //o/7? onset onef of headache 0-2 h 2-4 h 4-12 h
No of attacks treated 571 110 96
recurrent
headache 24 23 23
Dahlofis correct that in clinical practice migraine attacks should be treated as early as possible. However, it is reassuring to know that if this is not possible, sumatriptan is as effective in the established attack as when treatment is taken early. Department of Cardiovascular and Metabolic Medicine, International Medical Affairs, Glaxo Group Research, Uxbridge, Middlesex UB11 1 BT, UK
D. K. LLOYD
Cardiovascular Department, Glaxo Group Research, Greenford, Middlesex
A.
J. PILGRIM
SIR,-Dr Dahlof attributes neck pain or stiffness, and tiredness adverse effects on sumatriptan therapy. I suggest that these are postdromal symptoms of the migraine attack itself and are not attributable to the drug. Neck tenderness, stiffness, or aching affected 14 and tiredness 27 in a series of 40 patients who recorded their symptoms the day after migraine attacks;’ in that study none noted paraesthesiae or chest pain. Headache recurrence recorded by Dahlof is also open to another interpretation: we could be dealing with a persistence of the underlying migraine process. If a neural hypothesis of migraine is correct,2 then sumatriptan may reverse the secondary and painful elements of attacks, leaving the neurological disturbances to recover more slowly. Further precise observations such as those made and suggested by Dahlof, could help in distinguishing various components of migraine episodes and enable deeper insights into the pathogenesis of the condition. to
National Hospital for Neurology and Neurosurgery, London WC1 N 3BG, UK
1.
J. N. BLAU
Blau JN. Migraine postdromes: symptoms after attacks. Cephalalgia 1991, 11: 229-31. JN. Migraine: theories of pathogenesis. Lancert 1992; 339; 1202-07.
2. Blau
Blindness and myocardial infarction SIR,-Dr Koudstall and colleagues (Sept 12, p 630) show how there might be an association between atypical neurological symptoms, including visual disturbances, and cardiac events. We report a patient with a very unusual presentation of ischaemic stroke in whom binocular blindness occurred 3 months after myocardial infarction. A 69-year-old woman presented with bilateral visual loss and collapse. 1 week before admission she had transient visual loss but had no ophthalmological abnormalities. She was sent home from
her local emergency department. She was eventually admitted after a syncopal episode associated with vomiting and left-sided weakness. She had had two myocardial infarctions, with the most recent being an anteroseptal infarct 3 months earlier, when she was treated with a thrombolytic agent, aspirin, and low-dose subcutaneous heparin. She was alert and orientated. She was in a regular rhythm and normotensive and there were no vascular bruits or murmurs. She could not perceive light in either eye and did not blink on being confronted with threatening gestures. Pupillary responses were symmetrical and normal. The fundi were normal, as were the cranial nerves on formal testing. There were signs of mild left-sided hemiparesis. An electrocardiogram revealed sinus rhythm and evidence of previous inferior and anteroseptal myocardial infarctions. Baseline haematological and biochemical indices were normal and a serial cardiac enzyme/electrocardiographic study showed no evidence of new infarction. She had bilateral occipital cortex infarction with some parietal extension on computed tomography. A transthoracic echocardiogram demonstrated anteroapical akinesia with a laminated echogenic mass lining the anterior endocardial wall, seen in multiple two-dimensional views, and highly suggestive of thrombus. Over the next 72 h the left-sided hemiparesis resolved. Although she intermittently experienced flashes of light, her cortical blindness persisted. She was fully anticoagulated with warfarin, registered partially sighted, and discharged after 14 days in hospital. 3 years later she remains blind. We postulate that our patient developed cortical blindness secondary to embolism of mural thrombus formed after a recent myocardial infarction. We know of only six previous reported cases, but in none was echocardiography done to demonstrate mural thrombus or ventricular wall motion abnormalities.1,2 Proving a cardiac source of cerebral embolus can be difficult, with the likelihood often being based on individual circumstances. In retrospect, echocardiography done soon after her infarct might have shown mural thrombus formation in the anterior akinetic region and might have prompted anticoagulation with full-dose heparin (25 000 U daily) initiated.3,4After detection in hospital the risk of embolism from ventricular mural thrombus is about 10% during the subsequent 6-12 months. Warfarin anticoagulation reduces this risk by two-thirds.5 Whether ventricular thrombi that form and are detected after hospital discharge have a comparable risk of embolisation is not clear. Aspirin and low-dose heparin (10 000 U daily) are thought to reduce the risk ofischaemic stroke early after an anterior myocardial infarction but do not reduce the frequency of left ventricular thrombus formation or late stroke events.6 Anticoagulation should be considered in such circumstances. Department of Cardiology, Conquest Hospital, St Leonards-on-Sea, Sussex TN37 7RD,UK
SANDEEP GUPTA
Regional Cardiac Unit, Brook General Hospital, London
JOHN FORAN
Department of Cardiology, Kings College Hospital, London and West Hill Hospital, Dartford, Kent
PAULINE CHEREK DAVID A. BRENNAND-ROPER
1. Brettle RP. A case of blindness associated with myocardial infarction. Postgrad MedJ 1980; 56: 423-24. 2. Symonds C, Mackenzie I. Bilateral loss of vision from cerebral infarction. Brain 1957; 80: 415-54. 3. Turpie AGG, Robinson JG, Doyle DJ, et al. Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. N Engl Med 1989; 320: 352-57. J 4. SCATI Group (Studio sulla Calciparina nell’ Angina e nella Trombosi Ventricolare nell’ Infarto) Randomised controlled trial of subcutaneous calcium-heparin in acute myocardial infarction. Lancet 1989; ii: 182-86. 5. Cerebral Embolism Task Force. Cardiogenic brain embolism: second report of the Cerebral Embolism Task Force. Arch Neurol 1989; 46: 727-41. 6. Vecchio C, Chiarella F, Lupi G, Belloti P, Domenicucci S. Left ventricular thrombus in antenor acute myocardial infarction after thrombolysis: a GISSI-2 connected study. Circulation 1991; 84: 512-19.
CORRECTION Maternal inheritance of atopic IgE responsiveness on chromosome 11 q.-In this article by Dr W. 0. C. M. Cookson and colleagues (Aug 15, p 381) the tenth author’s name should have been Y. Nakamuura.
Sumatriptan and
recurrence
of
migraine
SIR,-Dr Dahl6f (Oct 10, p 909) regards as "weak" the evidence for the effectiveness of sumatriptan in the treatment of an established migraine attack. The primary efficacy index in the worldwide clinical development programme for sumatriptan was the percentage of patients obtaining headache relief at a fixed time after an injection (11 and 2 h) or tablet (2 and 4 h). In 13 double-blind clinical trials during which 4934 migraine attacks were treated, this finding was further analysed according to whether patients were treated within 4 h of onset of headache (early) or more than 4 hours after onset of headache (late). Across all these studies the data showed reproducible and comparable efficacy for these two groups. By contrast, Dahlofs open crossover study of 24 patients uses the development of recurrent headache as an endpoint. A double-blind, parallel-group, placebo-controlled clinical trial of oral sumatriptan in more than 1200 patients was done to assess the frequency of recurrent headache during 24 h after one or two doses of oral sumatriptan. The following data show clearly that the frequency of recurrent headache in attacks treated 4-12 h after onset of headache and after attacks treated earlier did not differ: % with 7//ne from Time //o/7? onset onef of headache 0-2 h 2-4 h 4-12 h
No of attacks treated 571 110 96
recurrent
headache 24 23 23
Dahlofis correct that in clinical practice migraine attacks should be treated as early as possible. However, it is reassuring to know that if this is not possible, sumatriptan is as effective in the established attack as when treatment is taken early. Department of Cardiovascular and Metabolic Medicine, International Medical Affairs, Glaxo Group Research, Uxbridge, Middlesex UB11 1 BT, UK
D. K. LLOYD
Cardiovascular Department, Glaxo Group Research, Greenford, Middlesex
A.
J. PILGRIM
SIR,-Dr Dahlof attributes neck pain or stiffness, and tiredness adverse effects on sumatriptan therapy. I suggest that these are postdromal symptoms of the migraine attack itself and are not attributable to the drug. Neck tenderness, stiffness, or aching affected 14 and tiredness 27 in a series of 40 patients who recorded their symptoms the day after migraine attacks;’ in that study none noted paraesthesiae or chest pain. Headache recurrence recorded by Dahlof is also open to another interpretation: we could be dealing with a persistence of the underlying migraine process. If a neural hypothesis of migraine is correct,2 then sumatriptan may reverse the secondary and painful elements of attacks, leaving the neurological disturbances to recover more slowly. Further precise observations such as those made and suggested by Dahlof, could help in distinguishing various components of migraine episodes and enable deeper insights into the pathogenesis of the condition. to
National Hospital for Neurology and Neurosurgery, London WC1 N 3BG, UK
1.
J. N. BLAU
Blau JN. Migraine postdromes: symptoms after attacks. Cephalalgia 1991, 11: 229-31. JN. Migraine: theories of pathogenesis. Lancert 1992; 339; 1202-07.
2. Blau
Blindness and myocardial infarction SIR,-Dr Koudstall and colleagues (Sept 12, p 630) show how there might be an association between atypical neurological symptoms, including visual disturbances, and cardiac events. We report a patient with a very unusual presentation of ischaemic stroke in whom binocular blindness occurred 3 months after myocardial infarction. A 69-year-old woman presented with bilateral visual loss and collapse. 1 week before admission she had transient visual loss but had no ophthalmological abnormalities. She was sent home from
her local emergency department. She was eventually admitted after a syncopal episode associated with vomiting and left-sided weakness. She had had two myocardial infarctions, with the most recent being an anteroseptal infarct 3 months earlier, when she was treated with a thrombolytic agent, aspirin, and low-dose subcutaneous heparin. She was alert and orientated. She was in a regular rhythm and normotensive and there were no vascular bruits or murmurs. She could not perceive light in either eye and did not blink on being confronted with threatening gestures. Pupillary responses were symmetrical and normal. The fundi were normal, as were the cranial nerves on formal testing. There were signs of mild left-sided hemiparesis. An electrocardiogram revealed sinus rhythm and evidence of previous inferior and anteroseptal myocardial infarctions. Baseline haematological and biochemical indices were normal and a serial cardiac enzyme/electrocardiographic study showed no evidence of new infarction. She had bilateral occipital cortex infarction with some parietal extension on computed tomography. A transthoracic echocardiogram demonstrated anteroapical akinesia with a laminated echogenic mass lining the anterior endocardial wall, seen in multiple two-dimensional views, and highly suggestive of thrombus. Over the next 72 h the left-sided hemiparesis resolved. Although she intermittently experienced flashes of light, her cortical blindness persisted. She was fully anticoagulated with warfarin, registered partially sighted, and discharged after 14 days in hospital. 3 years later she remains blind. We postulate that our patient developed cortical blindness secondary to embolism of mural thrombus formed after a recent myocardial infarction. We know of only six previous reported cases, but in none was echocardiography done to demonstrate mural thrombus or ventricular wall motion abnormalities.1,2 Proving a cardiac source of cerebral embolus can be difficult, with the likelihood often being based on individual circumstances. In retrospect, echocardiography done soon after her infarct might have shown mural thrombus formation in the anterior akinetic region and might have prompted anticoagulation with full-dose heparin (25 000 U daily) initiated.3,4After detection in hospital the risk of embolism from ventricular mural thrombus is about 10% during the subsequent 6-12 months. Warfarin anticoagulation reduces this risk by two-thirds.5 Whether ventricular thrombi that form and are detected after hospital discharge have a comparable risk of embolisation is not clear. Aspirin and low-dose heparin (10 000 U daily) are thought to reduce the risk ofischaemic stroke early after an anterior myocardial infarction but do not reduce the frequency of left ventricular thrombus formation or late stroke events.6 Anticoagulation should be considered in such circumstances. Department of Cardiology, Conquest Hospital, St Leonards-on-Sea, Sussex TN37 7RD,UK
SANDEEP GUPTA
Regional Cardiac Unit, Brook General Hospital, London
JOHN FORAN
Department of Cardiology, Kings College Hospital, London and West Hill Hospital, Dartford, Kent
PAULINE CHEREK DAVID A. BRENNAND-ROPER
1. Brettle RP. A case of blindness associated with myocardial infarction. Postgrad MedJ 1980; 56: 423-24. 2. Symonds C, Mackenzie I. Bilateral loss of vision from cerebral infarction. Brain 1957; 80: 415-54. 3. Turpie AGG, Robinson JG, Doyle DJ, et al. Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. N Engl Med 1989; 320: 352-57. J 4. SCATI Group (Studio sulla Calciparina nell’ Angina e nella Trombosi Ventricolare nell’ Infarto) Randomised controlled trial of subcutaneous calcium-heparin in acute myocardial infarction. Lancet 1989; ii: 182-86. 5. Cerebral Embolism Task Force. Cardiogenic brain embolism: second report of the Cerebral Embolism Task Force. Arch Neurol 1989; 46: 727-41. 6. Vecchio C, Chiarella F, Lupi G, Belloti P, Domenicucci S. Left ventricular thrombus in antenor acute myocardial infarction after thrombolysis: a GISSI-2 connected study. Circulation 1991; 84: 512-19.
CORRECTION Maternal inheritance of atopic IgE responsiveness on chromosome 11 q.-In this article by Dr W. 0. C. M. Cookson and colleagues (Aug 15, p 381) the tenth author’s name should have been Y. Nakamuura.
