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Potassium and sudden death
1457
schools compared with 12
cases
in 11"vaccinated schools". The
vaccine
efficacy was calculated, by school, as protection 1- (11/690)/(24/645) 57-2%. Bjune et al comment that "During the trial, there were only 2 cases at the same school. Therefore we have no indication that herd immunity contributed to the protective efficacy of the vaccine. School randomisation, though possibly reducing statistical power, has had an important function in reducing to a minimum recording error". Although the design may indeed have reduced recording errors, it may be argued that herd immunity almost certainly did play a part, and that the design most probably increased the efficacy of the trial to detect an effect of the rate or
=
vaccine. The conventional vaccine efficacy statistic is defined in terms of direct protection of vaccine recipients by the vaccine, and is calculated on the assumption that the vaccinated and unvaccinated individuals are equally exposed to infection (not just disease). Since
only
a
small
proportion
of individuals infected with group B
Neisseria meningitidis will manifest disease, the 36 clinical cases observed in the trial must have reflected a much larger number of infected individuals in the study population.2 If the vaccine provided any protection at all against infection or transmission, then it is to be expected that, even if the infection were introduced equally into vaccinated and unvaccinated populations (schools), the vaccinated individuals were on average less exposed than were the unvaccinated, given that all their contacts had also been vaccinated. Thus the overall difference in incidence seen between the two populations reflects not only the direct effect of the vaccine in protecting exposed vaccinated individuals, but also its indirect "herd immunity" effect in reducing the risk of exposure among the vaccinees. Such argument leads to three comments. First, it appears likely that randomisation by schools in the Norway trial led to overestimates of vaccine efficacy, at least in its conventional usage as a measure of direct protection of individual vaccinees. One might argue that the statistic estimated in the trial, which represents the combination of direct and indirect vaccine effects in protection of institutions, is also relevant to public health, given that vaccines are usually allocated to groups and not at random, and they often do have indirect as well as direct effects. On the other hand, such group protection measures are heavily dependent upon the particular population conditions examined, and thus are less generalisable than is the traditional vaccine efficacy measure. Second, it may be noted that designs such as used in the Norway trial increase the power of a trial to detect a vaccine’s effect, by measuring both direct and indirect protection together. Third, there is increasing recognition that vaccines act, and that their actions may be measured, in various ways.3-S Comparisons of the Norway trial result with other studies of meningococcal vaccines must take such differences into account. Communicable Disease Epidemiology Unit,
Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
PAUL E. M. FINE
1. Orenstein WA, Bernier RH, Hinman AR. Assessing vaccine efficacy m the field: further observations. Epidemiol Rev 1988; 10: 212-41. 2. Cartwright KAV, Stuart JM, Robinson PM. Meningococcal carriage in close contacts of cases. Epidemiol Infect 1991; 106: 133-41. 3. Smith PG, Rodrigues LC, Fine PEM. Assessment of the protective efficacy of vaccines against common diseases using case-control and cohort studies. Int J Epidemiol 1984; 13: 87-93. 4 Fine PEM, Clarkson JA. Reflections of the efficacy of pertussis vaccines. Rev Infect Dis
1987; 9: 866-83. 5. Haber M,
Longini I, Halloran ME. Measures of the effects of vaccination 1991; 21: 300-10. randomly mixing population. Int Epidemiol J
in
a
Potassium and sudden death SIR,-Sudden unexplained nocturnal death (SUND) tends to be where hypokalaemic periodic paralysis (HPP) is endemic. Professor Nimmannit and colleagues (Oct 12, p 930) suggest potassium deficiency as the prime factor responsible for seen in populations
both clincial entities and claim that HPP resemble those of SUND.
some
clinical manifestations of
In primary HPP muscle membrane abnormality, demonstrable electrophysiologically,l shifts potassium from extracellular to intracellular muscle space during attacks. However, total body potassium, and muscle potassium between attacks, are only slightly below normal.2 In primary HPP potassium depletion may contribute to the frequency of attacks but it is only a provocative component, not a primary factor in pathogenesis. In patients without primary HPP severe potassium depletion can lead to weakness, necrotising myopathy, and, very rarely, to periodic paralysis.3 In this situation total body potassium is very low, as are intracellular erythrocyte potassium concentrations, as in the patients mentioned by Nimmanit et al.’ However, in primary HPP the erythrocyte potassium concentration is not changeds and no erythrocyte membrane abnormality has been demonstrated.6 Despite the similarity in provocative factors, SUND does not occur in HPP. Several cases of HPP with fatal paralytic attacks were reported in the first half of this century: the course before death was usually not clear, but in most cases death was not sudden. More recently fatal respiratory paralysis after 3 days of paralysis has been described.’ A close relation between serum potassium and degree of paralysis has never been confirmed.6 We have described a large family with HPP, 8 now consisting of 64 patients. 2 died in an attack; 2 had cardiac arrhythmias (asystole, bradycardia); and 2 others had respiratory difficulties. All these patients were male and had severe paralytic attacks, always at night. However, the patients noticed the muscle weakness at an early stage and were awakened by their inability to turn in bed. The 2 deaths happened after 2 days of severe paralysis, before the diagnosis was known, and potassium was not given. There may be a relation between potassium depletion, endemic
distal renal tubular acidosis, and SUND, but HPP should be regarded as a separate clinical entity. Department of Internal Medicine and Neurology, University Hospital Groningen, 9700RB Groningen, Netherlands
TH. P. LINKS A. J. SMIT H. J. G. H. OOSTERHUIS
1. Zwarts MJ, van Weerden TW, Links TP, et al. The muscle fiber conduction velocity and power spectra in familial hypokalemic periodic paralysis. Muscle Nerve 1988; 11: 166-73. 2. Gordon AM, Green JR, Lagunoff D. Studies on a patient with hypokalemic periodic paralysis. Am J Med 1970; 48: 185-95. 3. Engel AG. Periodic paralysis. In: Engel AG, Banker BQ, eds. Myology: basic and clinical. New York: McGraw Hill, 1986: 1843-70. 4. Nimmannit S, Malasit P, Chaovakul V. Susaengrat W, Nilwarangkur S. Potassium and sudden unexplained nocturnal death. Lancet 1990; 336: 116-17. 5. Danowsky TS, Elkington JR, Burrows BA, et al. Exchanges of sodium and potassium in familial periodic paralysis. J Clin Invest 1947; 27: 65-73. 6. Burumo OJS. Familial hypokalemic periodic paralysis, a clinical histological and experimental study. Thesis, University of Leiden, 1978. 7. Ionasescu V, Schochet SS, Powers JM, et al. Hypokalaemic periodic paralysis. J Neurol Sci 1974; 21: 419-29. 8. Links TP, Zwarts MJ, Oosterhuis HJGH, et al. Permanent muscle weakness in familial hypokalaemic penodic paralysis. Brain 1990; 113: 1873-89.
"Headbanging" and fatal subdural haemorrhage SiR,-"Headbanging" is the slang term for violent movements of the head to the beat of rock music. Jackson et all described a fatal case of carotid artery dissection associated with headbanging. We report here a case of fatal subdural haemorrhage. A 20-year-old man spent the evening drinking and headbanging to rock music. On the way home he complained of severe occipital headache. He was found unconscious with seizures a few hours later. He had a respiratory arrest and died about 36 hours after he had been found unconscious. He had an extensive acute subdural haematoma over the right cerebral convexity with considerable midline shift; in places the haematoma was 1 cm thick (figure). Necropsy revealed no evidence of notable injury to scalp, skull or brain, but 80 g or more fresh subdural blood was present over the right cerebral convexity and in the right middle cranial fossa. The brain was swollen, with right-to-left shift and bilateral uncal and cerebellar tonsillar herniation. There was no evidence of an aneurysm of the circle of Willis or an arteriovenous malformation. In the absence of craniocerebral trauma or a vascular lesion death must be ascribed to acute subdural haemorrhage consequent to headbanging.
schools compared with 12
cases
in 11"vaccinated schools". The
vaccine
efficacy was calculated, by school, as protection 1- (11/690)/(24/645) 57-2%. Bjune et al comment that "During the trial, there were only 2 cases at the same school. Therefore we have no indication that herd immunity contributed to the protective efficacy of the vaccine. School randomisation, though possibly reducing statistical power, has had an important function in reducing to a minimum recording error". Although the design may indeed have reduced recording errors, it may be argued that herd immunity almost certainly did play a part, and that the design most probably increased the efficacy of the trial to detect an effect of the rate or
=
vaccine. The conventional vaccine efficacy statistic is defined in terms of direct protection of vaccine recipients by the vaccine, and is calculated on the assumption that the vaccinated and unvaccinated individuals are equally exposed to infection (not just disease). Since
only
a
small
proportion
of individuals infected with group B
Neisseria meningitidis will manifest disease, the 36 clinical cases observed in the trial must have reflected a much larger number of infected individuals in the study population.2 If the vaccine provided any protection at all against infection or transmission, then it is to be expected that, even if the infection were introduced equally into vaccinated and unvaccinated populations (schools), the vaccinated individuals were on average less exposed than were the unvaccinated, given that all their contacts had also been vaccinated. Thus the overall difference in incidence seen between the two populations reflects not only the direct effect of the vaccine in protecting exposed vaccinated individuals, but also its indirect "herd immunity" effect in reducing the risk of exposure among the vaccinees. Such argument leads to three comments. First, it appears likely that randomisation by schools in the Norway trial led to overestimates of vaccine efficacy, at least in its conventional usage as a measure of direct protection of individual vaccinees. One might argue that the statistic estimated in the trial, which represents the combination of direct and indirect vaccine effects in protection of institutions, is also relevant to public health, given that vaccines are usually allocated to groups and not at random, and they often do have indirect as well as direct effects. On the other hand, such group protection measures are heavily dependent upon the particular population conditions examined, and thus are less generalisable than is the traditional vaccine efficacy measure. Second, it may be noted that designs such as used in the Norway trial increase the power of a trial to detect a vaccine’s effect, by measuring both direct and indirect protection together. Third, there is increasing recognition that vaccines act, and that their actions may be measured, in various ways.3-S Comparisons of the Norway trial result with other studies of meningococcal vaccines must take such differences into account. Communicable Disease Epidemiology Unit,
Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
PAUL E. M. FINE
1. Orenstein WA, Bernier RH, Hinman AR. Assessing vaccine efficacy m the field: further observations. Epidemiol Rev 1988; 10: 212-41. 2. Cartwright KAV, Stuart JM, Robinson PM. Meningococcal carriage in close contacts of cases. Epidemiol Infect 1991; 106: 133-41. 3. Smith PG, Rodrigues LC, Fine PEM. Assessment of the protective efficacy of vaccines against common diseases using case-control and cohort studies. Int J Epidemiol 1984; 13: 87-93. 4 Fine PEM, Clarkson JA. Reflections of the efficacy of pertussis vaccines. Rev Infect Dis
1987; 9: 866-83. 5. Haber M,
Longini I, Halloran ME. Measures of the effects of vaccination 1991; 21: 300-10. randomly mixing population. Int Epidemiol J
in
a
Potassium and sudden death SIR,-Sudden unexplained nocturnal death (SUND) tends to be where hypokalaemic periodic paralysis (HPP) is endemic. Professor Nimmannit and colleagues (Oct 12, p 930) suggest potassium deficiency as the prime factor responsible for seen in populations
both clincial entities and claim that HPP resemble those of SUND.
some
clinical manifestations of
In primary HPP muscle membrane abnormality, demonstrable electrophysiologically,l shifts potassium from extracellular to intracellular muscle space during attacks. However, total body potassium, and muscle potassium between attacks, are only slightly below normal.2 In primary HPP potassium depletion may contribute to the frequency of attacks but it is only a provocative component, not a primary factor in pathogenesis. In patients without primary HPP severe potassium depletion can lead to weakness, necrotising myopathy, and, very rarely, to periodic paralysis.3 In this situation total body potassium is very low, as are intracellular erythrocyte potassium concentrations, as in the patients mentioned by Nimmanit et al.’ However, in primary HPP the erythrocyte potassium concentration is not changeds and no erythrocyte membrane abnormality has been demonstrated.6 Despite the similarity in provocative factors, SUND does not occur in HPP. Several cases of HPP with fatal paralytic attacks were reported in the first half of this century: the course before death was usually not clear, but in most cases death was not sudden. More recently fatal respiratory paralysis after 3 days of paralysis has been described.’ A close relation between serum potassium and degree of paralysis has never been confirmed.6 We have described a large family with HPP, 8 now consisting of 64 patients. 2 died in an attack; 2 had cardiac arrhythmias (asystole, bradycardia); and 2 others had respiratory difficulties. All these patients were male and had severe paralytic attacks, always at night. However, the patients noticed the muscle weakness at an early stage and were awakened by their inability to turn in bed. The 2 deaths happened after 2 days of severe paralysis, before the diagnosis was known, and potassium was not given. There may be a relation between potassium depletion, endemic
distal renal tubular acidosis, and SUND, but HPP should be regarded as a separate clinical entity. Department of Internal Medicine and Neurology, University Hospital Groningen, 9700RB Groningen, Netherlands
TH. P. LINKS A. J. SMIT H. J. G. H. OOSTERHUIS
1. Zwarts MJ, van Weerden TW, Links TP, et al. The muscle fiber conduction velocity and power spectra in familial hypokalemic periodic paralysis. Muscle Nerve 1988; 11: 166-73. 2. Gordon AM, Green JR, Lagunoff D. Studies on a patient with hypokalemic periodic paralysis. Am J Med 1970; 48: 185-95. 3. Engel AG. Periodic paralysis. In: Engel AG, Banker BQ, eds. Myology: basic and clinical. New York: McGraw Hill, 1986: 1843-70. 4. Nimmannit S, Malasit P, Chaovakul V. Susaengrat W, Nilwarangkur S. Potassium and sudden unexplained nocturnal death. Lancet 1990; 336: 116-17. 5. Danowsky TS, Elkington JR, Burrows BA, et al. Exchanges of sodium and potassium in familial periodic paralysis. J Clin Invest 1947; 27: 65-73. 6. Burumo OJS. Familial hypokalemic periodic paralysis, a clinical histological and experimental study. Thesis, University of Leiden, 1978. 7. Ionasescu V, Schochet SS, Powers JM, et al. Hypokalaemic periodic paralysis. J Neurol Sci 1974; 21: 419-29. 8. Links TP, Zwarts MJ, Oosterhuis HJGH, et al. Permanent muscle weakness in familial hypokalaemic penodic paralysis. Brain 1990; 113: 1873-89.
"Headbanging" and fatal subdural haemorrhage SiR,-"Headbanging" is the slang term for violent movements of the head to the beat of rock music. Jackson et all described a fatal case of carotid artery dissection associated with headbanging. We report here a case of fatal subdural haemorrhage. A 20-year-old man spent the evening drinking and headbanging to rock music. On the way home he complained of severe occipital headache. He was found unconscious with seizures a few hours later. He had a respiratory arrest and died about 36 hours after he had been found unconscious. He had an extensive acute subdural haematoma over the right cerebral convexity with considerable midline shift; in places the haematoma was 1 cm thick (figure). Necropsy revealed no evidence of notable injury to scalp, skull or brain, but 80 g or more fresh subdural blood was present over the right cerebral convexity and in the right middle cranial fossa. The brain was swollen, with right-to-left shift and bilateral uncal and cerebellar tonsillar herniation. There was no evidence of an aneurysm of the circle of Willis or an arteriovenous malformation. In the absence of craniocerebral trauma or a vascular lesion death must be ascribed to acute subdural haemorrhage consequent to headbanging.