837
markers
were
available, by direct DNA sequencing.
Therefore, our current strategy for prenatal diagnosis is screen the parents first to identify the mutations, and
to to
confirm the diagnosis by RFLP linkage analysis whenever
possible. Occasionally, novel mutations will be encountered, and RFLP linkage or, if time permits, direct DNA sequencing provide an alternative approach. This strategy can be adopted for other ethnic groups at risk for &bgr;-thalassaernia, as indeed we have done for the UK Cypriot population. Seven ARMS primers were sufficient to detect the mutation in every case of 73 at-risk couples. In couples where both partners carried the IVSIntl 10 mutation, it was possible to screen for the mutation in the parents first and then carry out a prenatal diagnosis on chorionic villus DNA later the same day. The approach has proved as reliable as haplotype analysis, and in one case more so with the identification of mislabelled samples. We wish to thank Alison Fitches and Debra Valler for their technical assistance in haplotype analysis and direct DNA sequencing. We also thank all clinicians who referred samples for prenatal diagnosis.
REFERENCES 1. Saiki RK, Bugawan TL, Horn
GT, Mullis KB, Erlich HA. Analysis of enzymatically amplified &bgr;-globin and HLA-DQ &agr; DNA with allelicspecific oligonucleotide probes. Nature 1986; 324: 163-66.
Arterial responses
CR, Graham A, Heptinstall LE, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucl Acids Res 1989; 17: 2503-16. 3. Newton CR, Heptinstall LE, Summers C, et al. Amplification refractory mutation system for prenatal diagnosis and carrier assessment in cystic fibrosis. Lancet 1989; ii: 1481-82. 4. Old JM, Higgs DR. Gene analysis. In: Weatherall DJ, ed. Methods in haematology, vol 6. The thalassaemias. Edinburgh: Churchill Livingstone, 1982: 74-102. 5. Thein SL, Hesketh C, Wallace RB, Weatherall DJ. The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis. Br J Haematol 1988; 70: 225-31. 6. Kulozik AE, Lyons J, Kohne E, Geliger H, Bartram CR, Kleihauer E. Rapid and non-radioactive prenatal diagnosis of &bgr;-thalassaemia and sickle cell disease: application of the polymerase chain reaction (PCR). Br J Haematol 1988; 70: 455-58. 7. Semenza GL, Dowling CE, Kazazian HH Jr. Hinf I polymorphism 3’ to the human &bgr;-globin gene detected by the polymerase chain reaction (PCR). Nucl Acids Res 1989; 17: 2376. 8. Thein SL, Hesketh C, Brown JM, Anstey AV, Weatherall DJ. Molecular characterisation of a high A2 &bgr;-thalassaemia by direct sequencing of single strand enriched amplification genomic DNA. Blood 1989; 73: 924-30. 9. Kretz KA, Carson GS, O’Brien JS. Direct sequencing from low-melt agarose with Sequenase. Nucl Acids Res 1989; 17: 5864. 10. Saiki RK, Chang CA, Levenson CH, et al. Diagnosis of sickle cell anaemia and &bgr;-thalassaemia with enzymatically amplified DNA and non-reactive allele-specific oligonucleotide probes. N Engl J Med 1988; 319: 537-41. 11. Chehab FF, Kan YW. Detection of specific DNA sequences by fluorescent amplification: A colour cocomplementation assay. Proc Natl Acad Sci USA 1989; 86: 9178-82. 2. Newton
during migraine headache
The superficial temporal artery has been thought to be the main focus of pain during migraine attacks, but its diameter has never been measured directly. The use of a new, high-resolution ultrasound machine to measure arterial size in 25 migraine patients with unilateral head pain showed that the lumen was wider on the painful than on the non-painful side during a migraine attack. The diameters of both radial arteries and the temporal artery on the non-painful side were smaller during than between attacks. The generalised vasoconstriction was not shared by the temporal artery on the affected side, which suggests a local vasodilatory response. The findings suggest that cephalic arteries may play a role in migraine pathogenesis.
Introduction Studies on the mechanism of migraine have focused on the dilatation and increased pulsations of the external carotid artery and its branches.1-3 So far the diameter of the temporal artery has been measured by indirect methods. A new, high-resolution ultrasound machine has now made it possible to measure directly, yet non-invasively, the luminal diameter of superficial small arteries such as the temporal arteryThe purpose of our investigation was to examine whether the temporal artery dilates on the symptomatic side during a migraine headache.
Patients and methods women with migraine who had unilateral pain-3 with aura (classic migraine) and 22 without aura (common migraine) - entered the study. Their median age was 49 years (range 24-84). The diagnosis was made according to the criteria of the International Headache Society.s Patients were asked to go to the hospital during a spontaneous, unilateral migraine attack. Patients with daily headache were not included. The median monthly frequency of migrainous attacks was 3 (range 1-8) and of tension-type headaches 2 (range 0-20). The study was approved by the local ethical committee and patients gave their informed consent. The luminal diameter of the temporal artery was measured with a high-resolution ultrasound unit (’Dermascan C’, Cortex technology, 20 MHz centre frequency and 15 MHz bandwidth).
25
When the sound beam is directed perpendicular to the skin superficially located arteries such as the temporal artery can be located, since the high amplitudes reflect the interfaces between blood and vessel wall that are seen pulsating (fig 1).The mean of four measurements randomly distributed within the shortest possible interval (within 1 minute) was used to augment precision. The measurements were taken at sound velocity 1605 m/s, reported to be the sound velocity in human blood.4 Patients arrived at the clinic as soon as possible after onset of a migraine attack. No ergotamine or morphine-like agent was allowed for 48 h, and no analgesics for 6 h, before the study. Patients were carefully instructed not to reveal laterality of migraine headache to the investigator. With the patient supine the right and left frontal
Neurology, Gentofte Hospital Olesen) and Bispebjerg Hospital (P. Tfelt-Hansen), University of Copenhagen, Denmark. Correspondence to Dr H. K Iversen, Department of Neurology, Gentofte Hospital, 2900 Hellerup, Denmark
ADDRESSES Department of (H. K Iversen, T H. Nielsen, Prof J
838
TABLE II-LUMINAL DIAMETER OF THE FRONTAL BRANCH OF THE TEMPORAL AN D RADIAL ARTERIES DURING AND BETWEEN MIGRAINE ATTACKS
*p < 0 01 fordifference from non-symptomatic temporal artery
Fig 1-Ultrasound B-mode presentation of the frontal branch of the temporal artery (lower part) and luminal diameter as the peak to peak distance on A-mode (upper part). The peaks represent the tissue interfaces.
branches of the superfical temporal arteries were gently palpated without being compressed. Any palpable difference in size between the sides was noted. The sites at which measurements were made were defmed in terms of the angle and distance relative to the orbitomeatal line to ensure that repeat measurements were made at exactly the same position. After the patient had rested for 30 min, the luminal diameters of both temporal arteries were measured. The two radial arteries were measured at a point 2 cm proximal to the distal volar crest of the wrist. After the measurements had been made, the patients were asked to palpate the frontal branch of their temporal arteries and report any difference in size. When patients had been free from migraine for at least a week, the measurements were repeated at the same positions. The room temperature was
keptat21-23°C. Statistics Wilcoxon’s rank
sum test
for
paired
data
was
used
to
evaluate
differences in diameters of temporal and radial arteries. The sign test was
used for palpation and pain data.
diameter of the temporal artery on the symptomatic side during an attack did not differ from that between attacks (p = 0-75), but on the other side the diameter decreased by 9-4% during attacks (median value) (p < 0-003) (fig 2). The diameter of the radial arteries was measured in 20 of the 25 patients. There was no difference between sides during or between attacks (p =0-4) (table n), but on both sides the diameters were smaller during than between attacks by 4-3% on the symptomatic side and by 4-6% on the non-symptomatic side. Clinically the investigator judged the temporal artery to be larger on the symptomatic side in 15, and on the non-symptomatic side in 3 of 22 patients. In 4 patients no difference was found (p < 0-01) (table III). Palpation reflects the outer diameter of the artery, as opposed to the luminal diameter measured by ultrasound. Of 21 patients, 14 reported the symptomatic side and 1 the non-symptomatic side to be greater, and 6 patients found no difference between the two sides (p < 001). Neither the investigator nor the patients found any significant difference between sides in the attack-free intervals (table III). After the investigation, 23 patients were asked if the gentle palpation caused local pain-15 did not, 7 did, and 1 could not tell (p>0 05). Furthermore, they were asked if the migraine headache changed during palpation-20 patients reported no change, 2 worsening, and 1 relief.
Results Clinical characteristics of migraine patients and of the attacks studied are given in table I. The investigations were done at a median of 5 h (range 2-58) after onset of attacks. Headache was right sided in 14 and left sided in 11patients. During a migraine headache the median luminal diameter of the frontal branch of the temporal artery of the affected side was greater than that on the other side, but during intervals between attacks the diameters were similar (table n). The TABLE I-CHARACTERISTICS OF MIGRAINE ATTACKS
.
Non-symptomatic side
Symptomatic side
Fig 2-Luminal diameter of the frontal branch of the temporal artery during migraine attack. The box
covers
the middle 50% of the values between the lower and
upper quartiles ; the central line is at the median, the "whiskers" extend out to the extremes, but only to those points that are within 1 5 times the interquartiles range.
839
TABLE III-SIZE OF FRONTAL BRANCH OF THE TEMPORAL ARTERY BY PALPATION
migraine pain originates from extracranial perivascular neurogenic inflammation one would expect palpation to aggravate or elicit pain, but this was not observed. A slight but widespread irritation of perivascular nerves could, because of spatial summation, explain pain. There is also the possibility that the extracranial artery dilatation is paralleled by intracranial arterial dilatation which might be an equally or even more important souce of pain. Our findings are important, not because they fully explain migraine pain, but because they show abnormal reactions of the arterial system in migraine. REFERENCES
Discussion Pulse amplitude measurements have been used to evaluate the temporal artery in migraine studies.1-3 The recently developed Korotkov sound microphone displacement transducer and photoplethysmograph systems improve the accuracy of pulse amplitude measurements of the temporal artery and were used in a study3 of 62 patients with unilateral migraine headaches. In a subgroup of 22 patients with "extracranial headache" (headache relieved partly or completely by compression of the superficial temporal artery) the mean pulse amplitude of the frontal branch of the temporal artery was greatest on the symptomatic side. The conclusion was that in only a minority of patients did dilatation of the superficial temporal artery and its branches contribute substantially to migraine headache. These methods of estimating diameters are, however, based on the pulse amplitude measurements and therefore only indirectly reflect the arterial diameter. With the ultrasound technique that we used diameters can be measured accurately and reproducibly.4 The patients were investigated during unilateral migraine attacks. The luminal diameter of the frontal branch of the temporal artery was significantly larger on the symptomatic than on the non-symptomatic side during but not between attacks. The attack was associated with generalised arterial constriction, as indicated by constriction of both radial arteries and the non-symptomatic temporal artery. Raised plasma and noradrenaline concentrations unloading of to induce constriction of seem mainly baroreceptors stimulation of the median nerve arterioles, whereas electrical or of sympathetic fibres and local infusion of serotonin constrict mainly large arteries.6-8 Recently, it has been shown in man that the cold pressor test induces direct neurogenic sympathetic constriction of the brachial arteries, whereas infusion of adrenaline does not.9 The widespread peripheral constriction during migraine attacks could thus be due to generally increased sympathetic activity or to changes in serotonin release from platelets, which have been reported earlier.10-12 The general arterial constriction was not shared by the temporal artery on the symptomatic side, which suggests a local dilatation. Decreased local sympathetic activation and structural changes in the artery are unlikely to account for our fmdings, since migraine changed side from attack to attack in 16 patients. The adventitia of extracranial and intracranial arteries are richly supplied with sympathetic, parasympathetic, and trigeminal nerve fibres. These are near the media and contain monoamines and peptide transmitters with vasoactive and inflammatory properties.13,14 Activity in dilatory nerves is therefore likely to sensitise perivascular nociceptors. Thus our fmdings of local vasodilator effects may also contribute towards understanding of migraine pain mechanisms. If
1. Tunis
MM, Wolfe HG. Studies of headache. Arch Neurol Psychiatry
1953; 70: 551-57. 2. Brazil P, Friedman AP. Craniovascular studies in headache. A report and analysis of pulse volume tracings. Neurology 1956; 6: 96-102. 3. Drummond PD, Lance JW. Extracranial vascular changes and the source of pain in migraine headache. Ann Neurol 1983; 13: 32-37. 4. Nielsen TH, Iversen HK, Tfelt-Hansen P. Determination of the luminal diameter of the radial artery in man by the high frequency unltrasound. A methodological study. Ultrasound Med Biol (in press). 5. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988; 8 (suppl): 19-28. 6. Abboud FM, Eckstein JW. Comparative changes in segmental vascular resistance in response to nerve stimulation and to norepinephrine. Circulation Res 1966; 18: 263-77.
7. Abboud FM. Vascular responses to norepinephrine, angiotensin, vasopressin and serotonin. Fed Proc 1968; 27: 1391-95. 8. Grega GJ, Adamski SW. Patterns of constriction produced by vasoactive agents. Fed Proc 1987; 46: 270-75. 9. Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation 1989; 79: 93-100. 10. Sicuteri F, Testi H, Ansalmi A. Biochemical investigations in headache: increase in hydroxyindolacetic acid excretion during migraine. Int Arch Allergy 1961; 19: 55-58. 11. Fog-Møller F, Genefke IK, Bryndum B. Changes in concentration of catecholamines in blood during spontaneous migraine attacks and reserpine-induced attacks. In: Greene R (ed). Current concepts in migraine research. New York: Raven, 1978: 115-19. 12. Anthony M. Biochemical indices of sympathetic activity in migraine. Cephalalgia 1981; 1: 83-89. 13. Moskowitz MA. The neurobiology of vascular head pain. Ann Neurol 1984; 16: 157-68. 14. Edvinsson L, MacKenzie ET, McCulloch, Uddman R. Nerve supply and receptor mechanisms in intra- and extracerebral blood vessels. In: Olesen J, Edvinsen L, eds. Basic mechanisms of headache. Amsterdam: Elsevier 1988: 129-44.
From The Lancet Dangers of
London street crossings
It is hardly necessary to recall the fact that street accidents are of frequent occurrence in London in order to assure ourselves that the traffic in public thoroughfares is in dangerous excess of its natural limits. The evil, moreover, shows no sign of abatement, but rather of annual increase. It is time, therefore, to consider how we may best secure the safety of pedestrians, and we shall in this connexion direct attention especially to the useful suggestion of a contemporary, which proposes the formation of subways or bridges at the more frequented crossings. Of these two alternatives, the bridge has this in its favour, that it would form a conspicuous, and sometimes even an ornamental, object, and would by its evident convenience invite the passer-by. On the other hand, it would also assuredly present an obstacle in the course of the busy stream rushing beneath its arches and eddying round its pillars.... In any case, many foot-passengers would use neither, but continue to travel, as now, among the wheels and quadrupeds. A certain number, however, including most of the old, infirm, or timid-those, in a word, more liable to accidentwould observe caution and go by the new and special routes. All conclusions on the subject are doubtless premature, but the practical value of this suggestion might as well be experimentally tested by its application at one or two chosen spots in the metropolis.
(Sept 27, 1890)
markers
were
available, by direct DNA sequencing.
Therefore, our current strategy for prenatal diagnosis is screen the parents first to identify the mutations, and
to to
confirm the diagnosis by RFLP linkage analysis whenever
possible. Occasionally, novel mutations will be encountered, and RFLP linkage or, if time permits, direct DNA sequencing provide an alternative approach. This strategy can be adopted for other ethnic groups at risk for &bgr;-thalassaernia, as indeed we have done for the UK Cypriot population. Seven ARMS primers were sufficient to detect the mutation in every case of 73 at-risk couples. In couples where both partners carried the IVSIntl 10 mutation, it was possible to screen for the mutation in the parents first and then carry out a prenatal diagnosis on chorionic villus DNA later the same day. The approach has proved as reliable as haplotype analysis, and in one case more so with the identification of mislabelled samples. We wish to thank Alison Fitches and Debra Valler for their technical assistance in haplotype analysis and direct DNA sequencing. We also thank all clinicians who referred samples for prenatal diagnosis.
REFERENCES 1. Saiki RK, Bugawan TL, Horn
GT, Mullis KB, Erlich HA. Analysis of enzymatically amplified &bgr;-globin and HLA-DQ &agr; DNA with allelicspecific oligonucleotide probes. Nature 1986; 324: 163-66.
Arterial responses
CR, Graham A, Heptinstall LE, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucl Acids Res 1989; 17: 2503-16. 3. Newton CR, Heptinstall LE, Summers C, et al. Amplification refractory mutation system for prenatal diagnosis and carrier assessment in cystic fibrosis. Lancet 1989; ii: 1481-82. 4. Old JM, Higgs DR. Gene analysis. In: Weatherall DJ, ed. Methods in haematology, vol 6. The thalassaemias. Edinburgh: Churchill Livingstone, 1982: 74-102. 5. Thein SL, Hesketh C, Wallace RB, Weatherall DJ. The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis. Br J Haematol 1988; 70: 225-31. 6. Kulozik AE, Lyons J, Kohne E, Geliger H, Bartram CR, Kleihauer E. Rapid and non-radioactive prenatal diagnosis of &bgr;-thalassaemia and sickle cell disease: application of the polymerase chain reaction (PCR). Br J Haematol 1988; 70: 455-58. 7. Semenza GL, Dowling CE, Kazazian HH Jr. Hinf I polymorphism 3’ to the human &bgr;-globin gene detected by the polymerase chain reaction (PCR). Nucl Acids Res 1989; 17: 2376. 8. Thein SL, Hesketh C, Brown JM, Anstey AV, Weatherall DJ. Molecular characterisation of a high A2 &bgr;-thalassaemia by direct sequencing of single strand enriched amplification genomic DNA. Blood 1989; 73: 924-30. 9. Kretz KA, Carson GS, O’Brien JS. Direct sequencing from low-melt agarose with Sequenase. Nucl Acids Res 1989; 17: 5864. 10. Saiki RK, Chang CA, Levenson CH, et al. Diagnosis of sickle cell anaemia and &bgr;-thalassaemia with enzymatically amplified DNA and non-reactive allele-specific oligonucleotide probes. N Engl J Med 1988; 319: 537-41. 11. Chehab FF, Kan YW. Detection of specific DNA sequences by fluorescent amplification: A colour cocomplementation assay. Proc Natl Acad Sci USA 1989; 86: 9178-82. 2. Newton
during migraine headache
The superficial temporal artery has been thought to be the main focus of pain during migraine attacks, but its diameter has never been measured directly. The use of a new, high-resolution ultrasound machine to measure arterial size in 25 migraine patients with unilateral head pain showed that the lumen was wider on the painful than on the non-painful side during a migraine attack. The diameters of both radial arteries and the temporal artery on the non-painful side were smaller during than between attacks. The generalised vasoconstriction was not shared by the temporal artery on the affected side, which suggests a local vasodilatory response. The findings suggest that cephalic arteries may play a role in migraine pathogenesis.
Introduction Studies on the mechanism of migraine have focused on the dilatation and increased pulsations of the external carotid artery and its branches.1-3 So far the diameter of the temporal artery has been measured by indirect methods. A new, high-resolution ultrasound machine has now made it possible to measure directly, yet non-invasively, the luminal diameter of superficial small arteries such as the temporal arteryThe purpose of our investigation was to examine whether the temporal artery dilates on the symptomatic side during a migraine headache.
Patients and methods women with migraine who had unilateral pain-3 with aura (classic migraine) and 22 without aura (common migraine) - entered the study. Their median age was 49 years (range 24-84). The diagnosis was made according to the criteria of the International Headache Society.s Patients were asked to go to the hospital during a spontaneous, unilateral migraine attack. Patients with daily headache were not included. The median monthly frequency of migrainous attacks was 3 (range 1-8) and of tension-type headaches 2 (range 0-20). The study was approved by the local ethical committee and patients gave their informed consent. The luminal diameter of the temporal artery was measured with a high-resolution ultrasound unit (’Dermascan C’, Cortex technology, 20 MHz centre frequency and 15 MHz bandwidth).
25
When the sound beam is directed perpendicular to the skin superficially located arteries such as the temporal artery can be located, since the high amplitudes reflect the interfaces between blood and vessel wall that are seen pulsating (fig 1).The mean of four measurements randomly distributed within the shortest possible interval (within 1 minute) was used to augment precision. The measurements were taken at sound velocity 1605 m/s, reported to be the sound velocity in human blood.4 Patients arrived at the clinic as soon as possible after onset of a migraine attack. No ergotamine or morphine-like agent was allowed for 48 h, and no analgesics for 6 h, before the study. Patients were carefully instructed not to reveal laterality of migraine headache to the investigator. With the patient supine the right and left frontal
Neurology, Gentofte Hospital Olesen) and Bispebjerg Hospital (P. Tfelt-Hansen), University of Copenhagen, Denmark. Correspondence to Dr H. K Iversen, Department of Neurology, Gentofte Hospital, 2900 Hellerup, Denmark
ADDRESSES Department of (H. K Iversen, T H. Nielsen, Prof J
838
TABLE II-LUMINAL DIAMETER OF THE FRONTAL BRANCH OF THE TEMPORAL AN D RADIAL ARTERIES DURING AND BETWEEN MIGRAINE ATTACKS
*p < 0 01 fordifference from non-symptomatic temporal artery
Fig 1-Ultrasound B-mode presentation of the frontal branch of the temporal artery (lower part) and luminal diameter as the peak to peak distance on A-mode (upper part). The peaks represent the tissue interfaces.
branches of the superfical temporal arteries were gently palpated without being compressed. Any palpable difference in size between the sides was noted. The sites at which measurements were made were defmed in terms of the angle and distance relative to the orbitomeatal line to ensure that repeat measurements were made at exactly the same position. After the patient had rested for 30 min, the luminal diameters of both temporal arteries were measured. The two radial arteries were measured at a point 2 cm proximal to the distal volar crest of the wrist. After the measurements had been made, the patients were asked to palpate the frontal branch of their temporal arteries and report any difference in size. When patients had been free from migraine for at least a week, the measurements were repeated at the same positions. The room temperature was
keptat21-23°C. Statistics Wilcoxon’s rank
sum test
for
paired
data
was
used
to
evaluate
differences in diameters of temporal and radial arteries. The sign test was
used for palpation and pain data.
diameter of the temporal artery on the symptomatic side during an attack did not differ from that between attacks (p = 0-75), but on the other side the diameter decreased by 9-4% during attacks (median value) (p < 0-003) (fig 2). The diameter of the radial arteries was measured in 20 of the 25 patients. There was no difference between sides during or between attacks (p =0-4) (table n), but on both sides the diameters were smaller during than between attacks by 4-3% on the symptomatic side and by 4-6% on the non-symptomatic side. Clinically the investigator judged the temporal artery to be larger on the symptomatic side in 15, and on the non-symptomatic side in 3 of 22 patients. In 4 patients no difference was found (p < 0-01) (table III). Palpation reflects the outer diameter of the artery, as opposed to the luminal diameter measured by ultrasound. Of 21 patients, 14 reported the symptomatic side and 1 the non-symptomatic side to be greater, and 6 patients found no difference between the two sides (p < 001). Neither the investigator nor the patients found any significant difference between sides in the attack-free intervals (table III). After the investigation, 23 patients were asked if the gentle palpation caused local pain-15 did not, 7 did, and 1 could not tell (p>0 05). Furthermore, they were asked if the migraine headache changed during palpation-20 patients reported no change, 2 worsening, and 1 relief.
Results Clinical characteristics of migraine patients and of the attacks studied are given in table I. The investigations were done at a median of 5 h (range 2-58) after onset of attacks. Headache was right sided in 14 and left sided in 11patients. During a migraine headache the median luminal diameter of the frontal branch of the temporal artery of the affected side was greater than that on the other side, but during intervals between attacks the diameters were similar (table n). The TABLE I-CHARACTERISTICS OF MIGRAINE ATTACKS
.
Non-symptomatic side
Symptomatic side
Fig 2-Luminal diameter of the frontal branch of the temporal artery during migraine attack. The box
covers
the middle 50% of the values between the lower and
upper quartiles ; the central line is at the median, the "whiskers" extend out to the extremes, but only to those points that are within 1 5 times the interquartiles range.
839
TABLE III-SIZE OF FRONTAL BRANCH OF THE TEMPORAL ARTERY BY PALPATION
migraine pain originates from extracranial perivascular neurogenic inflammation one would expect palpation to aggravate or elicit pain, but this was not observed. A slight but widespread irritation of perivascular nerves could, because of spatial summation, explain pain. There is also the possibility that the extracranial artery dilatation is paralleled by intracranial arterial dilatation which might be an equally or even more important souce of pain. Our findings are important, not because they fully explain migraine pain, but because they show abnormal reactions of the arterial system in migraine. REFERENCES
Discussion Pulse amplitude measurements have been used to evaluate the temporal artery in migraine studies.1-3 The recently developed Korotkov sound microphone displacement transducer and photoplethysmograph systems improve the accuracy of pulse amplitude measurements of the temporal artery and were used in a study3 of 62 patients with unilateral migraine headaches. In a subgroup of 22 patients with "extracranial headache" (headache relieved partly or completely by compression of the superficial temporal artery) the mean pulse amplitude of the frontal branch of the temporal artery was greatest on the symptomatic side. The conclusion was that in only a minority of patients did dilatation of the superficial temporal artery and its branches contribute substantially to migraine headache. These methods of estimating diameters are, however, based on the pulse amplitude measurements and therefore only indirectly reflect the arterial diameter. With the ultrasound technique that we used diameters can be measured accurately and reproducibly.4 The patients were investigated during unilateral migraine attacks. The luminal diameter of the frontal branch of the temporal artery was significantly larger on the symptomatic than on the non-symptomatic side during but not between attacks. The attack was associated with generalised arterial constriction, as indicated by constriction of both radial arteries and the non-symptomatic temporal artery. Raised plasma and noradrenaline concentrations unloading of to induce constriction of seem mainly baroreceptors stimulation of the median nerve arterioles, whereas electrical or of sympathetic fibres and local infusion of serotonin constrict mainly large arteries.6-8 Recently, it has been shown in man that the cold pressor test induces direct neurogenic sympathetic constriction of the brachial arteries, whereas infusion of adrenaline does not.9 The widespread peripheral constriction during migraine attacks could thus be due to generally increased sympathetic activity or to changes in serotonin release from platelets, which have been reported earlier.10-12 The general arterial constriction was not shared by the temporal artery on the symptomatic side, which suggests a local dilatation. Decreased local sympathetic activation and structural changes in the artery are unlikely to account for our fmdings, since migraine changed side from attack to attack in 16 patients. The adventitia of extracranial and intracranial arteries are richly supplied with sympathetic, parasympathetic, and trigeminal nerve fibres. These are near the media and contain monoamines and peptide transmitters with vasoactive and inflammatory properties.13,14 Activity in dilatory nerves is therefore likely to sensitise perivascular nociceptors. Thus our fmdings of local vasodilator effects may also contribute towards understanding of migraine pain mechanisms. If
1. Tunis
MM, Wolfe HG. Studies of headache. Arch Neurol Psychiatry
1953; 70: 551-57. 2. Brazil P, Friedman AP. Craniovascular studies in headache. A report and analysis of pulse volume tracings. Neurology 1956; 6: 96-102. 3. Drummond PD, Lance JW. Extracranial vascular changes and the source of pain in migraine headache. Ann Neurol 1983; 13: 32-37. 4. Nielsen TH, Iversen HK, Tfelt-Hansen P. Determination of the luminal diameter of the radial artery in man by the high frequency unltrasound. A methodological study. Ultrasound Med Biol (in press). 5. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1988; 8 (suppl): 19-28. 6. Abboud FM, Eckstein JW. Comparative changes in segmental vascular resistance in response to nerve stimulation and to norepinephrine. Circulation Res 1966; 18: 263-77.
7. Abboud FM. Vascular responses to norepinephrine, angiotensin, vasopressin and serotonin. Fed Proc 1968; 27: 1391-95. 8. Grega GJ, Adamski SW. Patterns of constriction produced by vasoactive agents. Fed Proc 1987; 46: 270-75. 9. Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation 1989; 79: 93-100. 10. Sicuteri F, Testi H, Ansalmi A. Biochemical investigations in headache: increase in hydroxyindolacetic acid excretion during migraine. Int Arch Allergy 1961; 19: 55-58. 11. Fog-Møller F, Genefke IK, Bryndum B. Changes in concentration of catecholamines in blood during spontaneous migraine attacks and reserpine-induced attacks. In: Greene R (ed). Current concepts in migraine research. New York: Raven, 1978: 115-19. 12. Anthony M. Biochemical indices of sympathetic activity in migraine. Cephalalgia 1981; 1: 83-89. 13. Moskowitz MA. The neurobiology of vascular head pain. Ann Neurol 1984; 16: 157-68. 14. Edvinsson L, MacKenzie ET, McCulloch, Uddman R. Nerve supply and receptor mechanisms in intra- and extracerebral blood vessels. In: Olesen J, Edvinsen L, eds. Basic mechanisms of headache. Amsterdam: Elsevier 1988: 129-44.
From The Lancet Dangers of
London street crossings
It is hardly necessary to recall the fact that street accidents are of frequent occurrence in London in order to assure ourselves that the traffic in public thoroughfares is in dangerous excess of its natural limits. The evil, moreover, shows no sign of abatement, but rather of annual increase. It is time, therefore, to consider how we may best secure the safety of pedestrians, and we shall in this connexion direct attention especially to the useful suggestion of a contemporary, which proposes the formation of subways or bridges at the more frequented crossings. Of these two alternatives, the bridge has this in its favour, that it would form a conspicuous, and sometimes even an ornamental, object, and would by its evident convenience invite the passer-by. On the other hand, it would also assuredly present an obstacle in the course of the busy stream rushing beneath its arches and eddying round its pillars.... In any case, many foot-passengers would use neither, but continue to travel, as now, among the wheels and quadrupeds. A certain number, however, including most of the old, infirm, or timid-those, in a word, more liable to accidentwould observe caution and go by the new and special routes. All conclusions on the subject are doubtless premature, but the practical value of this suggestion might as well be experimentally tested by its application at one or two chosen spots in the metropolis.
(Sept 27, 1890)
