829 SUBACUTE SCLEROSING PANENCEPHALITIS IN SARDINIA
SIR,-Subacute sclerosing panencephalitis (S.S.P.E.) is as a rare disease, with an incidence of z11
generally regarded
per 1 million inhabitants per year in the U.S.A.’ However, outbreaks of the disease have been recorded in some parts of the world (North Island of New ZealandCape Province of South AfricaIran,4,5 Lebanon,6 and Syria6). We have observed 20 cases of S.S.P.E. among the resident population of the island of Sardinia (Italy) between 1975 and 1978: 4 in 1975, 5 in 1976, 7 in 1977, and 4 in 1978. 16 patients were males and 4 were females, aged 4-12 years at the clinical onset of S.S.P.E. 19 had a history of measles, at least 7 having had measles at age 8-24 months. Except in 1 case, measles did not occur within 6 months after (or before) chickenpox or other apparent viral diseases, an observation at variance with one report.7 Survival after onset ranged from 2 months (1case, confirmed at necropsy) to over 40 months (9 patients are still alive). All cases save 2 ran a typical clinical course: 1 had pseudotumoral cases
presentation (S.S.P.E. confirmed
at
necropsy) and the other had
had chorioretinitis 1 year before neurological manifestations. All cases showed typical E.E.G. features at least at one stage of the disease, very high C.S.F. IgG with oligoclonal pattern, and increased c.s.F./serum ratio of anti-measles antibody titres. Sardinia has a population of about 1-Lmillion (1976), so the S.S.P.E. incidence from 1975 to 1978 is about 3 cases per million inhabitants per year-i.e., 30 times the U.S.A. incidence.1 A reliable Sardinian S.S.P.E. incidence figure for earlier years cannot be exactly calculated. However, data from hospital records (C.S.F. immunology often unavailable), suggest that there were at least 14 cases in the seventeen years from 1958 to 1974 in the southern part of the island alone. The annual distribution was clearly irregular, there being no new cases for several consecutive years with clustering of cases in a few years. There have been no reports of comparable S.S.P.E. outbreaks in other parts of Italy, where, although sufficient data are lacking, the incidence seems to be similar to that in U.S.A. The geographical distribution of the 20 cases in Sardinia is not homogeneous, there being a clear prevalence in the southeastern part: 7 cases from metropolitan Cagliari (about 290 000 inhabitants), 4 from the surrounding rural villages area of (about 90 000 inhabitants), and 6 from the km2. with about 60 000 in 1854 There inhabitants Ogliastra seems to be no correlation between this distribution and climate or economy. However, most cases came from poor families. 2 unrelated children were living in the same two-apartment house: measles as well as S.S.P.E. clinical onset (9 months later) occurred in both children in the same period (reminiscent of reports of S.S.P.E. in siblings in Iran 4. and other coun-
hilly
tries:9-’z)., The presence of S.S.P.E. outbreaks in some parts of the world, with striking irregularities in the incidence in successive years, favours the hypothesis12-14 that there’is an environmental factor causing the individual susceptibility to the disease. In Sardinia sheep-rearing is common: in the light of the posJabbour, J. T., Duenas, D. A., Sever, J. L., Krebs, H. M., Horta-Barbosa, L. J. Am. med. Ass. 1972, 220, 959. 2 Baguley, D. M., Glasgow, G. L. Lancet, 1973, ii, 763. 3. Kipps, A., MacKenzie, D. J. M., DuT.Naudé, W., McDonald, R. ibid., 1973, ii, 1388. 4. Bnmani, D. J., Sabeti, A., A., Farzadegan, H., Krourian, M., Akabari, Gh. 11th Wld Congr. Neurol. 1977, abstr. 814(A4). 5. Lofti, J., Derarhshan, I., Abbassioun, K., Mirchamsi, H. ibid. abstr. 817(A4). 6. Haddad, F. S., Risk, W. S., Jabbour, J. T. Lancet, 1974, ii, 1025. 7 Detels, R., Brody, J. A., McNew, J., Edgra, A. H. ibid. 1973, ii, 11. 8. Zamndjam, A., Prtovi, P. Electroencephalogr. clin. Neurophysiol. 1977, 43, 1
E494. 9 10
Lorand, B., Nagy, T., Tanska, S. Wld Neurol. 1962, 3, 376. Clark, N. S.,Best, P.V. Archs Dis. Childh. 1964, 39, 376. 11. Kennedy, C. Neurology, 1968, 18, suppl. 1, 58. 12. Agnarsdòttir, G. in Recent Advances in Clinical Virology (edited by A. P. Waterson); p. 21, Edinburgh, 1977. 13 Brody, J.A., Detels, R.Lancet, 1970, ii, 500. 14 Johnson, R. T., terMeulen, V. Adv. intern. Med. 1978, 23, 353.
sible zoonotic genesis of S.S.P.E.,13 this might be an important factor Sardinia has in common with the other countries where prominent S.S.P.E. outbreaks have been noted. Insegnamento di Neuropsichiatna Infantile e Clinica Pediatrica II, Universitá di Cagliari; Istituto di Neuropsichiatria Infantile, Universitä di Sassari; Clinica Pediatrica I, Universitä di Cagliari,
Sardinia, Italy
CARLO CIANCHETTI ANTONIO CAO CAMILLO MASTROPAOLO ROBERTO CORDA
CARRIER-DETECTION RATE AND AGE IN DUCHENNE MUSCULAR DYSTROPHY
SIR,-Dr Nicholson and his colleagues (March 31, p. 692) that, in our study,’ we "assumed a 100% carrier-detection rate in young D.M.D. [X-linked Duchenne muscular dystrophy] carriers and hence regarded all normal S.C.K. [serumstate
creatine-kinase] results as representing non-carriers". We made no such assumptions. Our paper offered evidence that D.M.D. is myogenic, not neurogenic, and part of that evidence was the linear regression of log S.C.K. on age in D.M.D. carriers.
girls from the direct maternal carrier line pedigrees, who had persistent highly abnormal increases of S.C.K., and who were (and still are) regarded by us as carriers of the gene. The converse would be an impossible assumption. These values were incorporated with those from the older carriers, and the regression estabSome of these in established
were
D.M.D.
lished. In such pedigrees it is necessary to regard, as carriers, adult females with abnormal S.C.K. increases; and younger females cannot be excepted. In our present state of knowledge, the only certain way to detect 100% of carriers is to wait until the proband bears a D.M.D. son. The purpose of genetic clinics is to prevent this if possible. Nicholson et al. report, in daughters of known carriers, a general detection-rate of 90% of theoretical. The theoretical maximum is exceeded in those under 16 years of age, suggesting too low an upper normal limit for S.C.K. in younger subjects, and some possibility of misdiagnosis. This accords with our findings in a recently completed study of S.C.K. in 494 normal females (including 52 under 16 years), which shows a marked inverse relationship between age and S.C.K. in younger girls, particularly premenarchal, with a non-parametric 95 percentile upper limit nearly double that for adult women. Research
Laboratory,
Knightswood Hospital, Glasgow G13 2XG University Medical Computing and Statistics Unit, Edinburgh EH8 9AG
W. H. S. THOMSON
IAN SMITH R. A. ELTON
PREDICTING WARFARIN REQUIREMENTS
SIR, You have lately had some correspondence on the prediction of requirements for warfarin (Jan. 20, p. 167, and March 10, p. 552). Following the original paper by Routledge et al. I looked at the relation between maintenance dose and response to a loading-dose in 32 unselected inpatients. The loading dose was 30 mg warfarin; the first prothrombin estimation (Manchester comparative reagent) was’ done at 48 h and the aim was a prothrombin-time ratio of 2.0-3-5. The correlation between response to loading dose and These pamaintenance dose was good (r=0-78, p
SIR,-Subacute sclerosing panencephalitis (S.S.P.E.) is as a rare disease, with an incidence of z11
generally regarded
per 1 million inhabitants per year in the U.S.A.’ However, outbreaks of the disease have been recorded in some parts of the world (North Island of New ZealandCape Province of South AfricaIran,4,5 Lebanon,6 and Syria6). We have observed 20 cases of S.S.P.E. among the resident population of the island of Sardinia (Italy) between 1975 and 1978: 4 in 1975, 5 in 1976, 7 in 1977, and 4 in 1978. 16 patients were males and 4 were females, aged 4-12 years at the clinical onset of S.S.P.E. 19 had a history of measles, at least 7 having had measles at age 8-24 months. Except in 1 case, measles did not occur within 6 months after (or before) chickenpox or other apparent viral diseases, an observation at variance with one report.7 Survival after onset ranged from 2 months (1case, confirmed at necropsy) to over 40 months (9 patients are still alive). All cases save 2 ran a typical clinical course: 1 had pseudotumoral cases
presentation (S.S.P.E. confirmed
at
necropsy) and the other had
had chorioretinitis 1 year before neurological manifestations. All cases showed typical E.E.G. features at least at one stage of the disease, very high C.S.F. IgG with oligoclonal pattern, and increased c.s.F./serum ratio of anti-measles antibody titres. Sardinia has a population of about 1-Lmillion (1976), so the S.S.P.E. incidence from 1975 to 1978 is about 3 cases per million inhabitants per year-i.e., 30 times the U.S.A. incidence.1 A reliable Sardinian S.S.P.E. incidence figure for earlier years cannot be exactly calculated. However, data from hospital records (C.S.F. immunology often unavailable), suggest that there were at least 14 cases in the seventeen years from 1958 to 1974 in the southern part of the island alone. The annual distribution was clearly irregular, there being no new cases for several consecutive years with clustering of cases in a few years. There have been no reports of comparable S.S.P.E. outbreaks in other parts of Italy, where, although sufficient data are lacking, the incidence seems to be similar to that in U.S.A. The geographical distribution of the 20 cases in Sardinia is not homogeneous, there being a clear prevalence in the southeastern part: 7 cases from metropolitan Cagliari (about 290 000 inhabitants), 4 from the surrounding rural villages area of (about 90 000 inhabitants), and 6 from the km2. with about 60 000 in 1854 There inhabitants Ogliastra seems to be no correlation between this distribution and climate or economy. However, most cases came from poor families. 2 unrelated children were living in the same two-apartment house: measles as well as S.S.P.E. clinical onset (9 months later) occurred in both children in the same period (reminiscent of reports of S.S.P.E. in siblings in Iran 4. and other coun-
hilly
tries:9-’z)., The presence of S.S.P.E. outbreaks in some parts of the world, with striking irregularities in the incidence in successive years, favours the hypothesis12-14 that there’is an environmental factor causing the individual susceptibility to the disease. In Sardinia sheep-rearing is common: in the light of the posJabbour, J. T., Duenas, D. A., Sever, J. L., Krebs, H. M., Horta-Barbosa, L. J. Am. med. Ass. 1972, 220, 959. 2 Baguley, D. M., Glasgow, G. L. Lancet, 1973, ii, 763. 3. Kipps, A., MacKenzie, D. J. M., DuT.Naudé, W., McDonald, R. ibid., 1973, ii, 1388. 4. Bnmani, D. J., Sabeti, A., A., Farzadegan, H., Krourian, M., Akabari, Gh. 11th Wld Congr. Neurol. 1977, abstr. 814(A4). 5. Lofti, J., Derarhshan, I., Abbassioun, K., Mirchamsi, H. ibid. abstr. 817(A4). 6. Haddad, F. S., Risk, W. S., Jabbour, J. T. Lancet, 1974, ii, 1025. 7 Detels, R., Brody, J. A., McNew, J., Edgra, A. H. ibid. 1973, ii, 11. 8. Zamndjam, A., Prtovi, P. Electroencephalogr. clin. Neurophysiol. 1977, 43, 1
E494. 9 10
Lorand, B., Nagy, T., Tanska, S. Wld Neurol. 1962, 3, 376. Clark, N. S.,Best, P.V. Archs Dis. Childh. 1964, 39, 376. 11. Kennedy, C. Neurology, 1968, 18, suppl. 1, 58. 12. Agnarsdòttir, G. in Recent Advances in Clinical Virology (edited by A. P. Waterson); p. 21, Edinburgh, 1977. 13 Brody, J.A., Detels, R.Lancet, 1970, ii, 500. 14 Johnson, R. T., terMeulen, V. Adv. intern. Med. 1978, 23, 353.
sible zoonotic genesis of S.S.P.E.,13 this might be an important factor Sardinia has in common with the other countries where prominent S.S.P.E. outbreaks have been noted. Insegnamento di Neuropsichiatna Infantile e Clinica Pediatrica II, Universitá di Cagliari; Istituto di Neuropsichiatria Infantile, Universitä di Sassari; Clinica Pediatrica I, Universitä di Cagliari,
Sardinia, Italy
CARLO CIANCHETTI ANTONIO CAO CAMILLO MASTROPAOLO ROBERTO CORDA
CARRIER-DETECTION RATE AND AGE IN DUCHENNE MUSCULAR DYSTROPHY
SIR,-Dr Nicholson and his colleagues (March 31, p. 692) that, in our study,’ we "assumed a 100% carrier-detection rate in young D.M.D. [X-linked Duchenne muscular dystrophy] carriers and hence regarded all normal S.C.K. [serumstate
creatine-kinase] results as representing non-carriers". We made no such assumptions. Our paper offered evidence that D.M.D. is myogenic, not neurogenic, and part of that evidence was the linear regression of log S.C.K. on age in D.M.D. carriers.
girls from the direct maternal carrier line pedigrees, who had persistent highly abnormal increases of S.C.K., and who were (and still are) regarded by us as carriers of the gene. The converse would be an impossible assumption. These values were incorporated with those from the older carriers, and the regression estabSome of these in established
were
D.M.D.
lished. In such pedigrees it is necessary to regard, as carriers, adult females with abnormal S.C.K. increases; and younger females cannot be excepted. In our present state of knowledge, the only certain way to detect 100% of carriers is to wait until the proband bears a D.M.D. son. The purpose of genetic clinics is to prevent this if possible. Nicholson et al. report, in daughters of known carriers, a general detection-rate of 90% of theoretical. The theoretical maximum is exceeded in those under 16 years of age, suggesting too low an upper normal limit for S.C.K. in younger subjects, and some possibility of misdiagnosis. This accords with our findings in a recently completed study of S.C.K. in 494 normal females (including 52 under 16 years), which shows a marked inverse relationship between age and S.C.K. in younger girls, particularly premenarchal, with a non-parametric 95 percentile upper limit nearly double that for adult women. Research
Laboratory,
Knightswood Hospital, Glasgow G13 2XG University Medical Computing and Statistics Unit, Edinburgh EH8 9AG
W. H. S. THOMSON
IAN SMITH R. A. ELTON
PREDICTING WARFARIN REQUIREMENTS
SIR, You have lately had some correspondence on the prediction of requirements for warfarin (Jan. 20, p. 167, and March 10, p. 552). Following the original paper by Routledge et al. I looked at the relation between maintenance dose and response to a loading-dose in 32 unselected inpatients. The loading dose was 30 mg warfarin; the first prothrombin estimation (Manchester comparative reagent) was’ done at 48 h and the aim was a prothrombin-time ratio of 2.0-3-5. The correlation between response to loading dose and These pamaintenance dose was good (r=0-78, p
