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SWAYBACK AND MULTIPLE SCLEROSIS
1147
manic-depressive psychosis (unpublished data),
or
with
involutional melancholia.16 Psychiatric Research Centre, University of Uppsala, Ulleråker Hospital, Uppsala 17, Sweden.
ÅKE STENSTEDT.
SWAYBACK AND MULTIPLE SCLEROSIS SIR,-In 1947 Campbell et al.16 reported the appearance of disseminated sclerosis in four of seven workers in Cambridge investigating swayback in sheep. On Dec. 12, 1966, a necropsy was performed in this department on the last survivor (case 4 of Campbell et aJ.16), who was aged 59 years. The findings in brief were those of bronchopneumonia, and typical multiple sclerosis affecting the brain and spinal cord. The histological findings were of variably sized plaques of gliosis with perivascular round-cell infiltration and demyelination. Similar changes were found in the one other case on which a necropsy was
performed. 17
Department of Pathology, University of Cambridge.
PETER R. MILLARD M. J. MITCHINSON.
work that the incubation-period of kuru in man is at least five years. This makes it unlikely that fluctuations in kuru deaths
represent fluctuations in the recent transmission of the kurugenic agent. One cannot exclude the possibility that hormonal or other conditioning factors are secondarily related to climate. Andrewes has stated that climate derived stresses could alter host susceptibility to respiratory infection and disease.24 The concept that marginal malnutrition can shorten the incubation-period of kuru could have practical as well as notional significance. The possible increase in average incubation-period of kuru over the decade 1957-66 18 23 could be related, in part at least, to a general improvement in the nutritional status following pacification of the area.2o If this is so, then continued improvement in nutrition, or perhaps even diet supplementation, might postpone the onset of kuru for some years in a significant proportion of the susceptible population. Identification of the nutritional factor(s) which may be involved is a matter of urgency. Protein deficiency is common amongst the highlanders of New Guinea, especially in women and young children. 25 Folic acid 26 and pyridoxine 27 deficiencies are known to impair immune responses.
planned to give diet supplements to early cases of kuru, but, practical difficulties involved locally, I should welcome any comments or suggestions arising from results in the scrapie or other laboratory-animal systems. It is
because of the
KURU, RAINFALL, AND NUTRITION SIR,-Deaths from kuru have declined during the decade 1957-66, but there have been superimposed fluctuations in annual mortality amongst South Fore females. I have shown that these fluctuations correlate significantly with the annual rainfall
at Okapa about 18 months before.18 Since the clinical of kuru averages 9-12 months from onset to death, and since peaks in kuru prevalence precede the peaks of kuru mortality by about 9 months, this correlation probably reflects an association between rainfall and the onset of kuru 6-9 months later. The observation 11 that the onset of kuru may be more common in the drier months of the year accords with this interpretation. I have also shown that hospital deaths at Okapa and village deaths in infants and young children may be significantly correlated with the rainfall 6-9 months before. Further, there is a local correlation between increased rainfall and decreased availability of sweet potato (the staple food) about 6 months later, which can be accounted for by sociological or agricultural factors. 20 It is suggested that the above correlations could represent causal relations. These are illustrated in the following schema, in which relations 1, 6, and 7 are established, while 2, 3, 4, and 5 are postulated but seem reasonable on other grounds. course
Observations on the natural history of kuru 20 21 are compatible with this view that marginal nutrition and perhaps other non-specific stresses can facilitate the onset of clinical kuru. It may be deduced from experimental22 and genealogical 23 15. Stenstedt, Å. Acta psychiat. scand. 1959, suppl. 127. 16. Campbell, A. M. G., Daniel, P., Porter, R. J., Russell, W. R., Smith, H. V., Innes, J. R. M. Brain, 1947, 70, 50. 17. Campbell, A. M. G. J. Neurol. Neurosurg. Psychiat. 1963, 26, 514. 18. Mathews, J. D. Papua N. Guinea med. J. (in the press). 19. Alpers, M. P., Gajdusek, D. C. Am. J. trop. Med. Hyg. 1965, 14, 852. 20. Mathews, J. D. M.D. thesis, University of Melbourne. Unpublished. 21. Hornabrook, R. W. Personal communication. 22. Gajdusek, D. C., Gibbs, C. J., Alpers, M. Science, N.Y. 1967, 155, 212. 23. Mathews, J. D. Lancet, 1967, i, 821.
Kuru Research Office, Public Health Department, Okapa, Eastern Highlands, New Guinea.
J. D. MATHEWS.
LOSS OF BRAIN POTASSIUM IN KWASHIORKOR SiR,ŇIam interested in Dr. Garrow’s article (Sept. 23, p. 643) and especially in his observation that total body potassium (particularly central-nervous-system potassium) is decreased in infants with kwashiorkor. It is attractive to hypothesise that some metabolic disturbance, or a series of linked disturbances related to protein deficiency, cause an alteration in brain-electrolyte composition, possibly xtiologically associated with the characteristic mental aberrations in these children. Dr. Garrow refers in his Introduction to several articles which are said to indicate that the weight of the severely malnourished child’s brain "is relatively well preserved ".2829 Workers from Kampala, in publications based on nearly 1100 necropsies of Ugandan children from birth to 15 years of age, have analysed brain-weights, categorised into groups with and without overt malnutrition.29 30 Brain-weight standards 31 were used as reference, and for each age-group the mean brainweights in Ugandan children above the age of one year were found to be decreased.3O The major finding was that the mean brain-weight in those Ugandan children with severe malnutrition was significantly lower than in the non-malnourished, a finding somewhat in contradiction to those of other workers cited by Dr. Garrow. It has been pointed out that since human brain-growth seems to attain a plateau at approximately one year after the rate of brain-growth slows considerably, certain influences on brainsize might very well be operative during foetal life and during the first year after birth-i.e., before the time when clinical kwashiorkor is generally observed. Conceivably other workers were concerned with a form of protein deficiency not present at such an early stage of human growth and development. I share with others the firm conviction that this area of research interest deserves special encouragement, and should 24. 25. 26. 27. 28.
29. 30. 31.
Andrewes, C. H. Science, N.Y. 1964, 146, 1274. Bailey, K. V. Trop. geogr. Med. 1963, 15, 389. Axelrod, A. E., Pruzansky, J. Vitams Horm. 1955, 13, 1. Charconnet-Harding, F., Hirsch, A. Annls Inst. Pasteur, Paris, 91, 120. Bodian, D. Am. J. Hyg. 1948, 48, 87. Klose, E. Jb. Kinderheilk. phys. Erzieh. 1914, 80, 154. Kerpel-Fronius, E., von Frank, K. Annls Pœdiat. 1949, 173, 321. Montgomery, R. D. J. clin. Invest. 1962, 41, 1653. Brown, R. E. Devl Med. Child Neurol. 1966, 8, 512. Brown, R. E. E. Afr. med. J. 1965, 42, 584. Copoletta, J. M., Wolbach, S. B. Am. J. Path. 1933, 9, 55.
manic-depressive psychosis (unpublished data),
or
with
involutional melancholia.16 Psychiatric Research Centre, University of Uppsala, Ulleråker Hospital, Uppsala 17, Sweden.
ÅKE STENSTEDT.
SWAYBACK AND MULTIPLE SCLEROSIS SIR,-In 1947 Campbell et al.16 reported the appearance of disseminated sclerosis in four of seven workers in Cambridge investigating swayback in sheep. On Dec. 12, 1966, a necropsy was performed in this department on the last survivor (case 4 of Campbell et aJ.16), who was aged 59 years. The findings in brief were those of bronchopneumonia, and typical multiple sclerosis affecting the brain and spinal cord. The histological findings were of variably sized plaques of gliosis with perivascular round-cell infiltration and demyelination. Similar changes were found in the one other case on which a necropsy was
performed. 17
Department of Pathology, University of Cambridge.
PETER R. MILLARD M. J. MITCHINSON.
work that the incubation-period of kuru in man is at least five years. This makes it unlikely that fluctuations in kuru deaths
represent fluctuations in the recent transmission of the kurugenic agent. One cannot exclude the possibility that hormonal or other conditioning factors are secondarily related to climate. Andrewes has stated that climate derived stresses could alter host susceptibility to respiratory infection and disease.24 The concept that marginal malnutrition can shorten the incubation-period of kuru could have practical as well as notional significance. The possible increase in average incubation-period of kuru over the decade 1957-66 18 23 could be related, in part at least, to a general improvement in the nutritional status following pacification of the area.2o If this is so, then continued improvement in nutrition, or perhaps even diet supplementation, might postpone the onset of kuru for some years in a significant proportion of the susceptible population. Identification of the nutritional factor(s) which may be involved is a matter of urgency. Protein deficiency is common amongst the highlanders of New Guinea, especially in women and young children. 25 Folic acid 26 and pyridoxine 27 deficiencies are known to impair immune responses.
planned to give diet supplements to early cases of kuru, but, practical difficulties involved locally, I should welcome any comments or suggestions arising from results in the scrapie or other laboratory-animal systems. It is
because of the
KURU, RAINFALL, AND NUTRITION SIR,-Deaths from kuru have declined during the decade 1957-66, but there have been superimposed fluctuations in annual mortality amongst South Fore females. I have shown that these fluctuations correlate significantly with the annual rainfall
at Okapa about 18 months before.18 Since the clinical of kuru averages 9-12 months from onset to death, and since peaks in kuru prevalence precede the peaks of kuru mortality by about 9 months, this correlation probably reflects an association between rainfall and the onset of kuru 6-9 months later. The observation 11 that the onset of kuru may be more common in the drier months of the year accords with this interpretation. I have also shown that hospital deaths at Okapa and village deaths in infants and young children may be significantly correlated with the rainfall 6-9 months before. Further, there is a local correlation between increased rainfall and decreased availability of sweet potato (the staple food) about 6 months later, which can be accounted for by sociological or agricultural factors. 20 It is suggested that the above correlations could represent causal relations. These are illustrated in the following schema, in which relations 1, 6, and 7 are established, while 2, 3, 4, and 5 are postulated but seem reasonable on other grounds. course
Observations on the natural history of kuru 20 21 are compatible with this view that marginal nutrition and perhaps other non-specific stresses can facilitate the onset of clinical kuru. It may be deduced from experimental22 and genealogical 23 15. Stenstedt, Å. Acta psychiat. scand. 1959, suppl. 127. 16. Campbell, A. M. G., Daniel, P., Porter, R. J., Russell, W. R., Smith, H. V., Innes, J. R. M. Brain, 1947, 70, 50. 17. Campbell, A. M. G. J. Neurol. Neurosurg. Psychiat. 1963, 26, 514. 18. Mathews, J. D. Papua N. Guinea med. J. (in the press). 19. Alpers, M. P., Gajdusek, D. C. Am. J. trop. Med. Hyg. 1965, 14, 852. 20. Mathews, J. D. M.D. thesis, University of Melbourne. Unpublished. 21. Hornabrook, R. W. Personal communication. 22. Gajdusek, D. C., Gibbs, C. J., Alpers, M. Science, N.Y. 1967, 155, 212. 23. Mathews, J. D. Lancet, 1967, i, 821.
Kuru Research Office, Public Health Department, Okapa, Eastern Highlands, New Guinea.
J. D. MATHEWS.
LOSS OF BRAIN POTASSIUM IN KWASHIORKOR SiR,ŇIam interested in Dr. Garrow’s article (Sept. 23, p. 643) and especially in his observation that total body potassium (particularly central-nervous-system potassium) is decreased in infants with kwashiorkor. It is attractive to hypothesise that some metabolic disturbance, or a series of linked disturbances related to protein deficiency, cause an alteration in brain-electrolyte composition, possibly xtiologically associated with the characteristic mental aberrations in these children. Dr. Garrow refers in his Introduction to several articles which are said to indicate that the weight of the severely malnourished child’s brain "is relatively well preserved ".2829 Workers from Kampala, in publications based on nearly 1100 necropsies of Ugandan children from birth to 15 years of age, have analysed brain-weights, categorised into groups with and without overt malnutrition.29 30 Brain-weight standards 31 were used as reference, and for each age-group the mean brainweights in Ugandan children above the age of one year were found to be decreased.3O The major finding was that the mean brain-weight in those Ugandan children with severe malnutrition was significantly lower than in the non-malnourished, a finding somewhat in contradiction to those of other workers cited by Dr. Garrow. It has been pointed out that since human brain-growth seems to attain a plateau at approximately one year after the rate of brain-growth slows considerably, certain influences on brainsize might very well be operative during foetal life and during the first year after birth-i.e., before the time when clinical kwashiorkor is generally observed. Conceivably other workers were concerned with a form of protein deficiency not present at such an early stage of human growth and development. I share with others the firm conviction that this area of research interest deserves special encouragement, and should 24. 25. 26. 27. 28.
29. 30. 31.
Andrewes, C. H. Science, N.Y. 1964, 146, 1274. Bailey, K. V. Trop. geogr. Med. 1963, 15, 389. Axelrod, A. E., Pruzansky, J. Vitams Horm. 1955, 13, 1. Charconnet-Harding, F., Hirsch, A. Annls Inst. Pasteur, Paris, 91, 120. Bodian, D. Am. J. Hyg. 1948, 48, 87. Klose, E. Jb. Kinderheilk. phys. Erzieh. 1914, 80, 154. Kerpel-Fronius, E., von Frank, K. Annls Pœdiat. 1949, 173, 321. Montgomery, R. D. J. clin. Invest. 1962, 41, 1653. Brown, R. E. Devl Med. Child Neurol. 1966, 8, 512. Brown, R. E. E. Afr. med. J. 1965, 42, 584. Copoletta, J. M., Wolbach, S. B. Am. J. Path. 1933, 9, 55.