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Sleep Apnoea Syndromes
25
relationship between crime in biological parents and their adopted-away offspring, but once again there was a significant correlation between alcoholism in biological parents and in their adopted-out sons.
Sleep Apnoea Syndromes SLEEP apnoea, defined by GUILLEMINAULT et al.1 as cessation of airflow at the nostrils and mouth lasting for at least ten seconds, probably occurs less than ten times a night in normal subjects, and then
Despite deficiencies in both the twin and adoptive studies, it seems likely that genetic factors do contribute to alcoholism in men, although not necessarily in women. Is what is inherited a biochemical predisposition to alcohol dependence or is it some personality inadequacy which may lead to secondary alcoholism. Neither the twin nor the adoptive studies produced any evidence in favour of a personality predisposition and there has been increasing interest in a possible pharmacogenetic mechanism. It is known, for instance, that inbred strains of rats and mice differ in their preference for, or avoidance of, alcohol, and that the drinker strains tend to have higher alcohol-dehydrogenase activity.8 The existence of an atypically active human form of alcohol dehydrogenase has also attracted a great deal of notice. Only a small proportion of Europeans have this enzyme variant but it is found in 85% of the Japanese population.8 The unpleasant flushing reaction which many Orientals have to alcohol could be due to their more active alcohol dehydrogenase, producing higher acetaldehyde levels than in Caucasians; as a consequence could be less attractive to Asian heavy
only during rapid-eye-movement (R.E.M.) sleep. In patients with sleep, apnoea syndromes the apnoeic episodes are more prolonged and more frequent - at least thirty episodes, both during R.E.M. and non-R.E.M. sleep, in a seven-hour nocturnal sleep.1 Sleep apnoea has long been known to arise in rare neurological and otolaryngological disorders, such3 as bulbar poliomyelitis,2 bilateral cordotomy, Ondine’s curse,4 the Shy-Drager syndrome,5-7 muscular dystrophy,8 the Pierre-Robin syndrome,9 and the bird-like face syndrome. 10 Neurologists and sleep experts have doubtless been familiar with these syndromes for many years; but wider recognition of the possibility of a sleep apnoea syndrome in patients presenting to general physicians stems largely from recent work at the Stanford Sleep Research Center, 11and also in Europe. 12 Sleep apnoea has been separated into obstructive syndromes, where air-flow ceases despite continuation of abdominal and thoracic inspiratory movements (implying that the upper airway is occluded),
people.
ably the commoner, the patient may be persuaded to seek medical advice on account of loud snoring and daytime somnolence13—the syndrome of hypersomnia with periodic apnoea (H.P.A.). Alveolar hypoventilation during sleep can occur in heavy snorers with mechanical narrowing of the upper airways, as in people with obesity, with large adenoids or tonsils, with laryngeal stenosis, or, as has now been proven, with failure of the genioglossus muscle to open the pharynx in inspiration during Sleep. 14 Ingenious fibreoptic studies of the upper airway during sleep have demonstrated such episodic narrowing, with rapid vibration of the soft palate accompanying snoring. 15 Obstructive apnoea
drinking
These findings have led to a search for markers which might predict a genetic proneness to alcoholism. An a sociation with colour-vision defect has been reported from time to time,18 but has not been generally confirmed. A more promising lead has been the reported link between alcoholism and nonsecretion of ABH blood-group substances in saliva.19 Alcoholism also seems to have joined the growing list of psychiatric conditions associated with low platelet monoamine-oxidase (M.A.o.), and MAJOR and MURPHy20 have now shown that the first-degree relatives of low-M.A.o. alcoholics have a higher incidence of alcoholism than the relatives of alcoholics with higher M.A.o. Thus, the genetic investigation of alcoholism looks much more promising than it did when SLATER and COWIE4 surveyed the scene a mere seven years ago. The comparative ineffectiveness of expensive psychiatric treatment of the chronic alcoholic has led ORFORD and EDWARDS21 to propose much greater attention towards prevention.One preventive strategy which merits further inves-’ tigation is the detection of individuals at particular risk of becoming dependent on alcohol because ol some
genetic predisposition.
18 Cruz-Coke, R., Varela,A. Lancet, 1965, ii, 1348. 19. Camps, F. E. Dodd. B. E., Lincoln, P. J Br med. J. 1969, iv, 457. 20 Major, L. F , Murphy, D. L. Br. J. Psychiat. 1978, 132, 548. 21 Orford, J, Edw ards, G. Alcoholism. London, 1977.
and central apnoea, with transient cessation of res-
piratory
motor
activity;
some
patients
may have
both types. In obstructive apnoea, which is
prob-
1.
Guilleminault, C., van den Hoed, J., Mitler, M. M. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement); p. 1. New York,
2. 3.
Plum, F., Swanson, A. G. Archs Neurol. Psychiat. 1958, 80, 267. Rosomoff, H. L., Kneger, A. J., Kuperman, A. S. J. Neurosurg. 1969, 31,
1978.
620. 4. Fruhmann, G. Bull. Physiopathol. Respir. 1972, 8, 1173. 5. Shy, G. M., Drager, G. A. Archs Neurol. 1960, 2, 511. 6. Lockwood, A. H. ibid. 1976, 33, 292. 7. Lehrman, K. L., Guilleminault, C, Schroeder, J S., Tilkian, A., Forno, L. N. Archs intern. Med 1978, 138, 206. 8. Coccagna, G., Mantovani, M., Parchi, C., Mironi, F., Lugaresi, E. J. Neurol. Neurosurg. Psychiat 195, 38, 977. 9. Ferguson, C. F. Ann. Otol. Rhinol Lar. 1967, 76, 762. 10. Coccagna, G., Di Donato, G., Verucchi, P., Cirignotta, F., Mantovani, M., Lugaresi, E. Archs Neurol 1976, 33, 769. 11. Guillemmault, C., Tilkian, A., Dement, W. C. A. Rev. Med. 1976, 27, 465. 12. Report of Symposium. Bull. Physic Pathol. Respir 1972, 8. 13. Lugaresi, E., Coccagna, G., Cirignotta, F. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement , p 13. New York, 1978. 14. Remmers, J. E., de Groot, W J., Sauerland, E K , Anch, A. M.J. appl Phy-
siol. 1978, 44, 931
26
the sudden-infant-death syndrome, particularly in family studies. 16 17 As well as the obvious fall in arterial oxygen saturation during the episode of sleep apnoea, cardiac arrhythmias and acute rises in both systemic and pulmonary arterial blood-pressure are seen. The mechanism of central apnoea is less clearly understood. From studies in both man and animals it seems that, during R.E.M. sleep, breathing is often very irregular and unresponsive to chemical and vagal drives, except to hypoxia, which remains a powerful stimulant of respiratory rate and possibly depth. 18 Polygraphic recordings of electroencephalogram, nasal and buccal air-flow, and thoracic and abdominal respiratory movements, with monitoring of arterial oxygen saturation, now allow accurate diagnosis of the presence and type has been related
to
of sleep apnoea. These new techniques have led to the recognition of sleep apncea syndromes in otherwise normal people. In GuiLLEMiNAULT’s experience these are often men who, not necessarily obese, snore loudly and complain of excessive day-time sleepiness. Such patients can suffer from severe intellectual deterioration and personality changes, resulting in disruption of family and social life. Recognition of the potential clinical importance of these syndromes has led GUILLEMINAULT and his colleagues to treat obstructive apnoea by tracheostomy, 19 and they now describe the detailed results of such treatment in six males with predominantly obstructive sleepinduced apnoea, with an average of at least fifty apnceic spells per hour of sleep, along with daytime sleepiness and loud snoring.2° When these patients were awake, their haemodynamic and respiratory variables were normal, but obstructive sleep apnoea produced a striking rise in systemic and pulmonary arterial pressures
value of 45
with
(this
latter to a mean falls in arterial 38 mm Hg. Tra-
Hg), tension, on average to cheostomy, which presents challenging medical, surgical, and social problems,19 was done without preoperative sedation, which these workers believe to be very dangerous in such patients who may have short, thick necks which can make normal intubation impossible. After the tracheostomy there was an impressive reduction in apnceic episodes, although some patients still had central apnoea; the lowest P02 during sleep rose from 38 to 71 mm Hg, with a significant reduction in both mean pulmonary and mean systemic arterial pressures. Traoxygen
15.
mm
severe
Borowiecki, B., Pollak, C. P., Weitzman, E. D., Rakoff, S., Imperato, J. Laryngoscope, 1978, 88, 1310. 16. Strohl, K. P., Saunders, N. A., Feldman, N. T., Hallett, M. New Engl. J. Med. 1978, 299, 969. 17. Weitzman, E. D., Graziani, L. in Advances in Sleep Research, vol I (edited by E. D. Weitzman); p. 327. New York, 1974. 18. Phillipson, E. A., Sullivan, C. E. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement); p. 47. New York, 1978. 19. Hill, M. W., Simmons, F. B., Guilleminault, C. in Advances in Sleep Research (edited by C. Guillemmault and W. C. Dement); p. 347. New York, 1978.
thus prevent obstructive apnoea, a conclusion confirmed by experimental closure of the tracheostomy in two of the six patients during sleep: the obstructive apnoea reappeared. The importance of sleep apncea and/or transient sleep hypoxxmia has been emphasised by the recognition of these syndromes in patients with chronic bronchitis and emphysema, particularly of the "blue and bloated" type;21 and the first article this week records arterial Po2 values falling transiently as low as 27 mm Hg in such patients. These
cheostomy
can
seen mainly during R.E.M. sleep, may last for considerable periods, but apnoea is not always present, and the fall in arterial P02 is not always associated with a rise in Pco2. Recognition of slight rises, during hypoxaemic episodes, in the already high pulmonary arterial pressures, confirming the observations in sleep apnoea in patients with the Shy-Drager syndrome,22 has led to the suggestion 23 that some of the differences between the "blue and bloated" and the "pink and puffing" types of patients with chronic bronchitis24 may arise from more frequent sleep apnoea or transient hypoxaemic episodes in "blue and bloated" patients.
episodes,
RUPTURED INTRACRANIALANEURYSM NEUROSURGEONS do
not
always
agree among them-
selves, let alone with physicians, about the
treatment
of
ruptured intracranial aneurysm. Some reports have even provoked disagreement among the members of one institution, as happened a few years ago at the Mayo Clinic. 12 A new report from the Mayo, by a neurosurgeon and a neurologist,3 describes 310 patients referred a
between 1969 and 1977. The greatest peril in the first 7-10 days after rupture was a further bleed. This happened in a third of the series-in 14% after admission to the Mayo-and was the most important factor in the 10% who died before the planned operation could be performed. Rebleeding affected all categories of patients. By contrast, most of the 14% in whom an ischaemic neurological deficit developed in the same period were still suffering from the effects of the initial haemorrhage. It is widely believed that intracranial surgery for aneurysm has become safer since the adoption of micro-
surgical techniques. Certainly the 30% mortality-rates reported a decade ago4 seem to be a thing of the past. Postoperative deficits related to surgical technique developed in only 4% of the Mayo series. The main source of mortality (5%) and major morbidity (14%) was delayed cerebral ischxmla, which developed after a period in which the patient’s postoperative state seemed satisfactory, and which was almost confined to patients 20. Motta, J., Guilleminault, C., Schroeder, J. S., Dement, W. C. Ann. intern. Med. 1978, 89, 454. 21. Flick, M. R., Block, A. J. ibid. 1977, 86, 725. 22. Schroeder, J. S., Motta, J., Guillemmault, C. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement); p. 177. New York, 1978. 23. Flenley, D. C. Lancet, 1978, i, 542. 24. Domhorst, A. C. ibid. 1955, i, 1185. 1. Millikan, C. H. Archs Neurol. 1975, 32, 433. 2. Miller, R. H., McCarty, C. S., Kerr, F W L., et al. ibid. 1976, 33, 309.
relationship between crime in biological parents and their adopted-away offspring, but once again there was a significant correlation between alcoholism in biological parents and in their adopted-out sons.
Sleep Apnoea Syndromes SLEEP apnoea, defined by GUILLEMINAULT et al.1 as cessation of airflow at the nostrils and mouth lasting for at least ten seconds, probably occurs less than ten times a night in normal subjects, and then
Despite deficiencies in both the twin and adoptive studies, it seems likely that genetic factors do contribute to alcoholism in men, although not necessarily in women. Is what is inherited a biochemical predisposition to alcohol dependence or is it some personality inadequacy which may lead to secondary alcoholism. Neither the twin nor the adoptive studies produced any evidence in favour of a personality predisposition and there has been increasing interest in a possible pharmacogenetic mechanism. It is known, for instance, that inbred strains of rats and mice differ in their preference for, or avoidance of, alcohol, and that the drinker strains tend to have higher alcohol-dehydrogenase activity.8 The existence of an atypically active human form of alcohol dehydrogenase has also attracted a great deal of notice. Only a small proportion of Europeans have this enzyme variant but it is found in 85% of the Japanese population.8 The unpleasant flushing reaction which many Orientals have to alcohol could be due to their more active alcohol dehydrogenase, producing higher acetaldehyde levels than in Caucasians; as a consequence could be less attractive to Asian heavy
only during rapid-eye-movement (R.E.M.) sleep. In patients with sleep, apnoea syndromes the apnoeic episodes are more prolonged and more frequent - at least thirty episodes, both during R.E.M. and non-R.E.M. sleep, in a seven-hour nocturnal sleep.1 Sleep apnoea has long been known to arise in rare neurological and otolaryngological disorders, such3 as bulbar poliomyelitis,2 bilateral cordotomy, Ondine’s curse,4 the Shy-Drager syndrome,5-7 muscular dystrophy,8 the Pierre-Robin syndrome,9 and the bird-like face syndrome. 10 Neurologists and sleep experts have doubtless been familiar with these syndromes for many years; but wider recognition of the possibility of a sleep apnoea syndrome in patients presenting to general physicians stems largely from recent work at the Stanford Sleep Research Center, 11and also in Europe. 12 Sleep apnoea has been separated into obstructive syndromes, where air-flow ceases despite continuation of abdominal and thoracic inspiratory movements (implying that the upper airway is occluded),
people.
ably the commoner, the patient may be persuaded to seek medical advice on account of loud snoring and daytime somnolence13—the syndrome of hypersomnia with periodic apnoea (H.P.A.). Alveolar hypoventilation during sleep can occur in heavy snorers with mechanical narrowing of the upper airways, as in people with obesity, with large adenoids or tonsils, with laryngeal stenosis, or, as has now been proven, with failure of the genioglossus muscle to open the pharynx in inspiration during Sleep. 14 Ingenious fibreoptic studies of the upper airway during sleep have demonstrated such episodic narrowing, with rapid vibration of the soft palate accompanying snoring. 15 Obstructive apnoea
drinking
These findings have led to a search for markers which might predict a genetic proneness to alcoholism. An a sociation with colour-vision defect has been reported from time to time,18 but has not been generally confirmed. A more promising lead has been the reported link between alcoholism and nonsecretion of ABH blood-group substances in saliva.19 Alcoholism also seems to have joined the growing list of psychiatric conditions associated with low platelet monoamine-oxidase (M.A.o.), and MAJOR and MURPHy20 have now shown that the first-degree relatives of low-M.A.o. alcoholics have a higher incidence of alcoholism than the relatives of alcoholics with higher M.A.o. Thus, the genetic investigation of alcoholism looks much more promising than it did when SLATER and COWIE4 surveyed the scene a mere seven years ago. The comparative ineffectiveness of expensive psychiatric treatment of the chronic alcoholic has led ORFORD and EDWARDS21 to propose much greater attention towards prevention.One preventive strategy which merits further inves-’ tigation is the detection of individuals at particular risk of becoming dependent on alcohol because ol some
genetic predisposition.
18 Cruz-Coke, R., Varela,A. Lancet, 1965, ii, 1348. 19. Camps, F. E. Dodd. B. E., Lincoln, P. J Br med. J. 1969, iv, 457. 20 Major, L. F , Murphy, D. L. Br. J. Psychiat. 1978, 132, 548. 21 Orford, J, Edw ards, G. Alcoholism. London, 1977.
and central apnoea, with transient cessation of res-
piratory
motor
activity;
some
patients
may have
both types. In obstructive apnoea, which is
prob-
1.
Guilleminault, C., van den Hoed, J., Mitler, M. M. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement); p. 1. New York,
2. 3.
Plum, F., Swanson, A. G. Archs Neurol. Psychiat. 1958, 80, 267. Rosomoff, H. L., Kneger, A. J., Kuperman, A. S. J. Neurosurg. 1969, 31,
1978.
620. 4. Fruhmann, G. Bull. Physiopathol. Respir. 1972, 8, 1173. 5. Shy, G. M., Drager, G. A. Archs Neurol. 1960, 2, 511. 6. Lockwood, A. H. ibid. 1976, 33, 292. 7. Lehrman, K. L., Guilleminault, C, Schroeder, J S., Tilkian, A., Forno, L. N. Archs intern. Med 1978, 138, 206. 8. Coccagna, G., Mantovani, M., Parchi, C., Mironi, F., Lugaresi, E. J. Neurol. Neurosurg. Psychiat 195, 38, 977. 9. Ferguson, C. F. Ann. Otol. Rhinol Lar. 1967, 76, 762. 10. Coccagna, G., Di Donato, G., Verucchi, P., Cirignotta, F., Mantovani, M., Lugaresi, E. Archs Neurol 1976, 33, 769. 11. Guillemmault, C., Tilkian, A., Dement, W. C. A. Rev. Med. 1976, 27, 465. 12. Report of Symposium. Bull. Physic Pathol. Respir 1972, 8. 13. Lugaresi, E., Coccagna, G., Cirignotta, F. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement , p 13. New York, 1978. 14. Remmers, J. E., de Groot, W J., Sauerland, E K , Anch, A. M.J. appl Phy-
siol. 1978, 44, 931
26
the sudden-infant-death syndrome, particularly in family studies. 16 17 As well as the obvious fall in arterial oxygen saturation during the episode of sleep apnoea, cardiac arrhythmias and acute rises in both systemic and pulmonary arterial blood-pressure are seen. The mechanism of central apnoea is less clearly understood. From studies in both man and animals it seems that, during R.E.M. sleep, breathing is often very irregular and unresponsive to chemical and vagal drives, except to hypoxia, which remains a powerful stimulant of respiratory rate and possibly depth. 18 Polygraphic recordings of electroencephalogram, nasal and buccal air-flow, and thoracic and abdominal respiratory movements, with monitoring of arterial oxygen saturation, now allow accurate diagnosis of the presence and type has been related
to
of sleep apnoea. These new techniques have led to the recognition of sleep apncea syndromes in otherwise normal people. In GuiLLEMiNAULT’s experience these are often men who, not necessarily obese, snore loudly and complain of excessive day-time sleepiness. Such patients can suffer from severe intellectual deterioration and personality changes, resulting in disruption of family and social life. Recognition of the potential clinical importance of these syndromes has led GUILLEMINAULT and his colleagues to treat obstructive apnoea by tracheostomy, 19 and they now describe the detailed results of such treatment in six males with predominantly obstructive sleepinduced apnoea, with an average of at least fifty apnceic spells per hour of sleep, along with daytime sleepiness and loud snoring.2° When these patients were awake, their haemodynamic and respiratory variables were normal, but obstructive sleep apnoea produced a striking rise in systemic and pulmonary arterial pressures
value of 45
with
(this
latter to a mean falls in arterial 38 mm Hg. Tra-
Hg), tension, on average to cheostomy, which presents challenging medical, surgical, and social problems,19 was done without preoperative sedation, which these workers believe to be very dangerous in such patients who may have short, thick necks which can make normal intubation impossible. After the tracheostomy there was an impressive reduction in apnceic episodes, although some patients still had central apnoea; the lowest P02 during sleep rose from 38 to 71 mm Hg, with a significant reduction in both mean pulmonary and mean systemic arterial pressures. Traoxygen
15.
mm
severe
Borowiecki, B., Pollak, C. P., Weitzman, E. D., Rakoff, S., Imperato, J. Laryngoscope, 1978, 88, 1310. 16. Strohl, K. P., Saunders, N. A., Feldman, N. T., Hallett, M. New Engl. J. Med. 1978, 299, 969. 17. Weitzman, E. D., Graziani, L. in Advances in Sleep Research, vol I (edited by E. D. Weitzman); p. 327. New York, 1974. 18. Phillipson, E. A., Sullivan, C. E. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement); p. 47. New York, 1978. 19. Hill, M. W., Simmons, F. B., Guilleminault, C. in Advances in Sleep Research (edited by C. Guillemmault and W. C. Dement); p. 347. New York, 1978.
thus prevent obstructive apnoea, a conclusion confirmed by experimental closure of the tracheostomy in two of the six patients during sleep: the obstructive apnoea reappeared. The importance of sleep apncea and/or transient sleep hypoxxmia has been emphasised by the recognition of these syndromes in patients with chronic bronchitis and emphysema, particularly of the "blue and bloated" type;21 and the first article this week records arterial Po2 values falling transiently as low as 27 mm Hg in such patients. These
cheostomy
can
seen mainly during R.E.M. sleep, may last for considerable periods, but apnoea is not always present, and the fall in arterial P02 is not always associated with a rise in Pco2. Recognition of slight rises, during hypoxaemic episodes, in the already high pulmonary arterial pressures, confirming the observations in sleep apnoea in patients with the Shy-Drager syndrome,22 has led to the suggestion 23 that some of the differences between the "blue and bloated" and the "pink and puffing" types of patients with chronic bronchitis24 may arise from more frequent sleep apnoea or transient hypoxaemic episodes in "blue and bloated" patients.
episodes,
RUPTURED INTRACRANIALANEURYSM NEUROSURGEONS do
not
always
agree among them-
selves, let alone with physicians, about the
treatment
of
ruptured intracranial aneurysm. Some reports have even provoked disagreement among the members of one institution, as happened a few years ago at the Mayo Clinic. 12 A new report from the Mayo, by a neurosurgeon and a neurologist,3 describes 310 patients referred a
between 1969 and 1977. The greatest peril in the first 7-10 days after rupture was a further bleed. This happened in a third of the series-in 14% after admission to the Mayo-and was the most important factor in the 10% who died before the planned operation could be performed. Rebleeding affected all categories of patients. By contrast, most of the 14% in whom an ischaemic neurological deficit developed in the same period were still suffering from the effects of the initial haemorrhage. It is widely believed that intracranial surgery for aneurysm has become safer since the adoption of micro-
surgical techniques. Certainly the 30% mortality-rates reported a decade ago4 seem to be a thing of the past. Postoperative deficits related to surgical technique developed in only 4% of the Mayo series. The main source of mortality (5%) and major morbidity (14%) was delayed cerebral ischxmla, which developed after a period in which the patient’s postoperative state seemed satisfactory, and which was almost confined to patients 20. Motta, J., Guilleminault, C., Schroeder, J. S., Dement, W. C. Ann. intern. Med. 1978, 89, 454. 21. Flick, M. R., Block, A. J. ibid. 1977, 86, 725. 22. Schroeder, J. S., Motta, J., Guillemmault, C. in Sleep Apnea Syndromes (edited by C. Guilleminault and W. C. Dement); p. 177. New York, 1978. 23. Flenley, D. C. Lancet, 1978, i, 542. 24. Domhorst, A. C. ibid. 1955, i, 1185. 1. Millikan, C. H. Archs Neurol. 1975, 32, 433. 2. Miller, R. H., McCarty, C. S., Kerr, F W L., et al. ibid. 1976, 33, 309.