- Email: [email protected]
Was Aesop a chronobiologist?
1606
THE LANCET
As a demographer with a quarter of a century’s experience I know that if I encounter finite numbers of a supposedly rare occurrence, the true rate is higher. I also know to trust the observations of well-trained observers in the field. My advice is: avoid mefloquine, advise patients to take chloroquine, and add Paludrine when they reach a country where it is obtainable. Standing Oak Court, Cupertino, California 95014, USA
22996
B. MEREDITH BURKE
Ultrasonic detection of cerebral emboli in carotid stenosis SIR,-Dr Parmet and colleagues’ (April 24, p 1057) demonstration of venous emboli detected during knee arthroplasty illustrates the use of a technique that may have much wider applications in the study of embolism. It relies on emboli acting as ultrasound reflectors, resulting in high intensity signals that can be localised on a 2-dimensional image, as these researchers show. However, emboli can also be detected in arteries, including the intracranial arteries, with doppler ultrasound alone without B-mode imaging, when they appear as short-duration highintensity signals in the doppler spectrum (figure). This technique has proved sensitive enough to detect pathological embolic materials such as thrombus, atheroma, and platelet aggregates,1 and the characteristics of the resulting signal provide information on the size of the embolus.2,3 The ability to detect symptomless arterial cerebral emboli may have major benefits in the management of patients with cerebrovascular disease, as shown by the following case report. A 44-year-old man, who presented with an abrupt onset of weakness in the right arm, was shown by computerised tomography to have a left lentiform nucleus infarct. He recovered fully but had repeated transient ischaemic symptoms affecting the right arm lasting a few minutes despite aspirin therapy, with twenty episodes occurring during 6 months. An angiogram showed only minimum irregularity of the wall contour at the right carotid bifurcation. Aspirin therapy alone was continued; however, he continued to have transient ischaemic attacks. With the use of a standard transcranial ultrasound machine the doppler signal was recorded from both middle cerebral arteries for 20 min each. Recordings were stored on digital audio tape and visually analysed by an observer blinded to the side or clinical diagnosis (the recording was interspersed with recordings from control patients). In the left middle cerebral artery, frequent high-intensity signals were seen (figure). These embolic signals were noted at the very frequent rate of4’8/min during the 20 min recording time. They are very similar to those seen when emboli are introduced into experimental models, although they are of lower intensity (mean 5-61 dB, maximum 7-16 dB), suggesting a size much smaller than the 400 um or larger experimental emboli studied.1,3 No embolic signals were seen on recording from the right middle cerebral artery. On re-examination of the carotid bifurcation with carotid duplex ultrasound, a large smooth plaque was found in the bulb, causing a 30% stenosis, but
parallel with the carotid bulb wall, explaining why the size of the plaque was not detected on angiography. Warfarin was started and transcranial doppler recordings were repeated 1 month later; he had had only one transient ischaemic attack in the interim, when his international normalised ratio had been only 1 3. By contrast with the previous recording, only one embolic signal was detected in the left middle cerebral artery during the whole 20 min; again none were detected on the right side. This case illustrates the potential of this technique to detect symptomless emboli in the cerebral circulation. It will prove useful in localising the embolic source in patients with stroke and may allow identification of subgroups of patients at risk of subsequent embolic stroke. It may aid in monitoring therapy; in our patient the institution of warfarin therapy was followed by a striking reduction in the frequency of emboli. This technique may also provide valuable information on the pathogenesis of cerebral embolism, and our case shows the large number of apparently symptomless emboli that may arise in such patients. HUGH S. MARKUS DIRK DROSTE MARTIN M. BROWN
Division of Clinical Neuroscience St George’s Hospital Medical School, London SW17 0RE, UK
1. Russell D, Madden KP, Clark WM, Sandset PM, Zivin JA. Detection of arterial emboli using Doppler ultrasound in rabbits Stroke 1991; 22: 253-58. 2. Russell D, Brucher R, Madden K, Clark WM, Sandset PM, Zivin J. The intensity of the Doppler signal caused by arterial emboli depends on emblous size. In: Oka M, von Reutern GM, Furuhata H, Kodaira K, eds. Recent advances in neurosonology. Amsterdam: Elsevier Science Publications, 1992: 57-60. 3. Markus HS, Brown MM. Differentation between different pathological cerebral embolic materials using transcranial Doppler in an in vitro model. Stroke 1993; 24: 1-5.
Was Aesop
a
chronobiologist?
SIR,-Among the best known of Aesop’s fables is the story of the tortoise and the hare. When the hare belittled the tortoise for his slow ways, the tortoise responded that he could nevertheless win a race between them. At the start, the hare dashed off and built such a commanding lead that he decided to relax briefly and lay down for a nap. By the time the hare awoke, the tortoise was already at the finish and even the hare’s fastest running proved fruitless. For over 2000 years, the moral-slow and steady wins the race-has lauded the tortoise’s perserverance and dedication while condemning the hare’s arrogance and laziness. With modern knowledge, however, we suspect that the outcome of this historic race depended less on the character traits of these two species and more on differences in their innate 24 h activity cycles. Tortoises are diurnally active, ambulating mainly over the course of the day.1 Hares, on the other hand, are active in a crepuscular pattern—ie, they restrict their running between their feeding sites to dawn and dusk.2 Aesop must have been a keen observer of natural animal rhythms. Rather than agreeing to a daytime race, the hare should have countered the tortoise’s challenge by proposing a sprint at
twilight. We believe the moral of the fable should be modified to reflect the
importance of the internal biological clock that regulates such behavioural rhythmicity. In man also, performance capabilities for various tasks vary with time of day, with some abilities peaking in the morning and others in the evening.3 Ignoring these rhythmicities may be perilous, and some of the symptoms of jet lag, shiftwork, ageing, insomnia, and affective disorders may be due to their temporal disorganisation.4 Thus, slow and steady wins the race, but timing is everything. Department of Neurology, University of Massachusetts Medical School,
JUNICHI TAKEUCHI
Worcester, Massachusetts 01655, USA
WILLIAM J. SCHWARTZ
Gourley EV. Circadian activity rhythm of the gopher tortoise (Gopherus polyphemus). Anim Behav 1972; 20: 13-20. 2. Nuboer JFW, van Nuys WM, van Steenbergen JC. Colour changes in a light regimen as synchronizers of circadian activity. JComp Physiol A 1983; 151: 359-66. 3. Folkard S. Circadian performance rhythms: some practical and theoretical implications. Phil Trans R Soc Lond B 1990; 327: 543-53. 4. Schwartz WJ. A clinician’s primer on the circadian clock: its localization, function, and resetting. Adv Intern Med 1993; 38: 81-106. 1.
Recording of Doppler spectrum
from
right
middle cerebral
artery before warfarin introduction. An embolic signal is seen as a short duration high intensity signal is coded on colour scale with red indicating high intensity and blue low intensity.
Intensity
THE LANCET
As a demographer with a quarter of a century’s experience I know that if I encounter finite numbers of a supposedly rare occurrence, the true rate is higher. I also know to trust the observations of well-trained observers in the field. My advice is: avoid mefloquine, advise patients to take chloroquine, and add Paludrine when they reach a country where it is obtainable. Standing Oak Court, Cupertino, California 95014, USA
22996
B. MEREDITH BURKE
Ultrasonic detection of cerebral emboli in carotid stenosis SIR,-Dr Parmet and colleagues’ (April 24, p 1057) demonstration of venous emboli detected during knee arthroplasty illustrates the use of a technique that may have much wider applications in the study of embolism. It relies on emboli acting as ultrasound reflectors, resulting in high intensity signals that can be localised on a 2-dimensional image, as these researchers show. However, emboli can also be detected in arteries, including the intracranial arteries, with doppler ultrasound alone without B-mode imaging, when they appear as short-duration highintensity signals in the doppler spectrum (figure). This technique has proved sensitive enough to detect pathological embolic materials such as thrombus, atheroma, and platelet aggregates,1 and the characteristics of the resulting signal provide information on the size of the embolus.2,3 The ability to detect symptomless arterial cerebral emboli may have major benefits in the management of patients with cerebrovascular disease, as shown by the following case report. A 44-year-old man, who presented with an abrupt onset of weakness in the right arm, was shown by computerised tomography to have a left lentiform nucleus infarct. He recovered fully but had repeated transient ischaemic symptoms affecting the right arm lasting a few minutes despite aspirin therapy, with twenty episodes occurring during 6 months. An angiogram showed only minimum irregularity of the wall contour at the right carotid bifurcation. Aspirin therapy alone was continued; however, he continued to have transient ischaemic attacks. With the use of a standard transcranial ultrasound machine the doppler signal was recorded from both middle cerebral arteries for 20 min each. Recordings were stored on digital audio tape and visually analysed by an observer blinded to the side or clinical diagnosis (the recording was interspersed with recordings from control patients). In the left middle cerebral artery, frequent high-intensity signals were seen (figure). These embolic signals were noted at the very frequent rate of4’8/min during the 20 min recording time. They are very similar to those seen when emboli are introduced into experimental models, although they are of lower intensity (mean 5-61 dB, maximum 7-16 dB), suggesting a size much smaller than the 400 um or larger experimental emboli studied.1,3 No embolic signals were seen on recording from the right middle cerebral artery. On re-examination of the carotid bifurcation with carotid duplex ultrasound, a large smooth plaque was found in the bulb, causing a 30% stenosis, but
parallel with the carotid bulb wall, explaining why the size of the plaque was not detected on angiography. Warfarin was started and transcranial doppler recordings were repeated 1 month later; he had had only one transient ischaemic attack in the interim, when his international normalised ratio had been only 1 3. By contrast with the previous recording, only one embolic signal was detected in the left middle cerebral artery during the whole 20 min; again none were detected on the right side. This case illustrates the potential of this technique to detect symptomless emboli in the cerebral circulation. It will prove useful in localising the embolic source in patients with stroke and may allow identification of subgroups of patients at risk of subsequent embolic stroke. It may aid in monitoring therapy; in our patient the institution of warfarin therapy was followed by a striking reduction in the frequency of emboli. This technique may also provide valuable information on the pathogenesis of cerebral embolism, and our case shows the large number of apparently symptomless emboli that may arise in such patients. HUGH S. MARKUS DIRK DROSTE MARTIN M. BROWN
Division of Clinical Neuroscience St George’s Hospital Medical School, London SW17 0RE, UK
1. Russell D, Madden KP, Clark WM, Sandset PM, Zivin JA. Detection of arterial emboli using Doppler ultrasound in rabbits Stroke 1991; 22: 253-58. 2. Russell D, Brucher R, Madden K, Clark WM, Sandset PM, Zivin J. The intensity of the Doppler signal caused by arterial emboli depends on emblous size. In: Oka M, von Reutern GM, Furuhata H, Kodaira K, eds. Recent advances in neurosonology. Amsterdam: Elsevier Science Publications, 1992: 57-60. 3. Markus HS, Brown MM. Differentation between different pathological cerebral embolic materials using transcranial Doppler in an in vitro model. Stroke 1993; 24: 1-5.
Was Aesop
a
chronobiologist?
SIR,-Among the best known of Aesop’s fables is the story of the tortoise and the hare. When the hare belittled the tortoise for his slow ways, the tortoise responded that he could nevertheless win a race between them. At the start, the hare dashed off and built such a commanding lead that he decided to relax briefly and lay down for a nap. By the time the hare awoke, the tortoise was already at the finish and even the hare’s fastest running proved fruitless. For over 2000 years, the moral-slow and steady wins the race-has lauded the tortoise’s perserverance and dedication while condemning the hare’s arrogance and laziness. With modern knowledge, however, we suspect that the outcome of this historic race depended less on the character traits of these two species and more on differences in their innate 24 h activity cycles. Tortoises are diurnally active, ambulating mainly over the course of the day.1 Hares, on the other hand, are active in a crepuscular pattern—ie, they restrict their running between their feeding sites to dawn and dusk.2 Aesop must have been a keen observer of natural animal rhythms. Rather than agreeing to a daytime race, the hare should have countered the tortoise’s challenge by proposing a sprint at
twilight. We believe the moral of the fable should be modified to reflect the
importance of the internal biological clock that regulates such behavioural rhythmicity. In man also, performance capabilities for various tasks vary with time of day, with some abilities peaking in the morning and others in the evening.3 Ignoring these rhythmicities may be perilous, and some of the symptoms of jet lag, shiftwork, ageing, insomnia, and affective disorders may be due to their temporal disorganisation.4 Thus, slow and steady wins the race, but timing is everything. Department of Neurology, University of Massachusetts Medical School,
JUNICHI TAKEUCHI
Worcester, Massachusetts 01655, USA
WILLIAM J. SCHWARTZ
Gourley EV. Circadian activity rhythm of the gopher tortoise (Gopherus polyphemus). Anim Behav 1972; 20: 13-20. 2. Nuboer JFW, van Nuys WM, van Steenbergen JC. Colour changes in a light regimen as synchronizers of circadian activity. JComp Physiol A 1983; 151: 359-66. 3. Folkard S. Circadian performance rhythms: some practical and theoretical implications. Phil Trans R Soc Lond B 1990; 327: 543-53. 4. Schwartz WJ. A clinician’s primer on the circadian clock: its localization, function, and resetting. Adv Intern Med 1993; 38: 81-106. 1.
Recording of Doppler spectrum
from
right
middle cerebral
artery before warfarin introduction. An embolic signal is seen as a short duration high intensity signal is coded on colour scale with red indicating high intensity and blue low intensity.
Intensity