- Email: [email protected]
Pitfalls in calculating and comparing prevalence and incidence of multiple sclerosis
GENETIC SUSCEPTIBILITY
TO MULTIPLE
PITFALLS
SCLEROSIS
INCIOENCE
G.C. Ebers, A.D. Sadovnick, N. Risch and the Canadian Collaborative Study
IN CALCULATING AND COtlPARING OF BULTIPLE SCLEROSIS.
PREVALENCE
AND
Kahana E.. (L,2) Zilber N.. (1,3). (1)Neuroepidemiol. Unit, tiadassah Uni How, Jerusalem; (2)Neurol Dept. Barzilai Hedical Center, Ashkelon, affiliated to Ben Gurion Uni.; (3) and Centre de Recherche Francais de Jerusalem, Israel.
Kecogmtion that M.S. susceptibility has a genetic basis has been slow to develop. The reasoning by analogy with polio and slow virus diseaseshas dominated the &inking about M.S. for more than two decades and led to heavy emphasis on identifying a specific environmental agent causing the disease. The tools of genetic epidemiology which have only recently been applied to MS. are rapidly changing concepts of the disease.
Several factors may influence the results of an epidemiological study: patient ascertainment sources, inclusion diagnostic criteria, choice of appropriate denominator and availability of diagnostic tests. The calculated prevalence rate of HS increases with due mainly to problems of time of patient collection, ascertaining patients with long remissions. Thus. in the prevalence on 1.1.60 was 15.2/100,000 population year collection period and 26.6/100,000 Popuidtion for year period. The minimal period of collection should
Studies of age of onset of sibling pairs, reanalysis of geographical prevalence rates, studies of twins, recurrence risk in some families, and more recently investigation of conjugal pairs and their offspring, half siblings and of adoptees clearly indicate that genes play an important role and shed considerable light on the nature of any environmental factors.
length in Israel for a 5 a 37 be 15-
20 years. The length of time between the prevalence day and the end the collection period also affects the calculated for a 21 yearcollection period prevalence. Thus, in Israel, (1.1.55 - 31.12.75), the prevalence rate increased from 15.4/100,000 population when the prevalence day Was 1.1.76 to 23.7/100,000 uhen the prevalence day was 1.1.60. The prevalence day should be about 10 years before the end of the ascertainnent period. For optimal data on the frequency of the disease we need to have a registry which includes up-to-date information on any newly suspected case as well as all chronic historical cases. Pitfalls in the statistical evaluation uf the results wiii also be discussed. of
Analysis of pedigrees supports a complex inheritance pattern. At present the only locus for which there is unambiguous support is HLA. The contribution from this locus is minor. Other enthusiastically supported loci have hugely withered on the vine. A modest association is present for the immuqlobulin variable region which needs confirmation. Microsatellite screening of the genome is progress.
EPICEMIOLOGICAL FEATURES OF TN0 IflMUNOLOGICALLY DISTINCT FORMS OF MULTIPLE SCLEROSIS (MS): ANTI-!lYELIN BASIC (XBP) ASSOCIATED MS VS AXTI-PROTEOLIPZD (PLP) ASSOCIATED MS Sharon Warren and K.G. Warren 9S Patient Care and Research
llnivcrsity
of
Alberta,
Edmonton,
Clinic Canada
Researchers have suggested t!,at there arc at least two ~awutulucicdiiy aisrincr forms oi :-is: a common form associated with increased cerebrospinal fluid (CSF) and tissue anti-NBP and a less frequent form associated with elevated levels of anti-PLP. The purpose of this study lias to determine whether personal and disease features of antiMBP differ from anti-PLP associated MS. Human MBP and I’1.P were used as antigens in a solid phase radioimmunoassay to determine the relative occurrence of anti-MBP and anti-SLP in CSF of patients at the University of Alberta MS Clinic (Edmonton, Canada). Of 808 patients examined to date, onl) 2. 75(22) had elevated anti-PLP; no patient was found to haw both simultaneously. The 22 antl-PLP patients were compared to a systematic random sample of 22 patients with increased antl-MBP on: gender, onset age, first symptom, disability status, illness duration, MS Eamily history and evidence of CNS inflammation (IgG index, igG synthesis and oligoclonal banding). There were significantly more males in the antiI’LP group than the anti-MBP group (64% vs 27%, p*:.O5). Pho onset age curve peaked later for‘ anti-PLP patients ~5 antinRI’ patients (40-49 vs 30-39 yrs). The majority of patients in each group presented with sensory symptoms and were ambulatory; however< !; of the ambulatory patients in each group had experienced symptoms for > 10 years, so that tentative classification on benign vs disabling cow.se was not feasible. More anti-MB I’ than anti-PLP patients had an \IS Eamily history (22% vs OZ, ~7.05). The anti-MBP group showed mope evidence of C\IS inflammation: mote anti-MBP than antiPLP patients had an elevated IgG index (68% YS 18%, p(.Ol), showed increased daily IgG synthesis (68% YS 32Z, pC.05) and uerv positive for oligoclonal banding (731 YS 362, p/.05). Some epidemioloGica features vary between these distinct xmiwnological forms of ?I.5 and so may environmental trigi:ers.
-9-
TO MULTIPLE
PITFALLS
SCLEROSIS
INCIOENCE
G.C. Ebers, A.D. Sadovnick, N. Risch and the Canadian Collaborative Study
IN CALCULATING AND COtlPARING OF BULTIPLE SCLEROSIS.
PREVALENCE
AND
Kahana E.. (L,2) Zilber N.. (1,3). (1)Neuroepidemiol. Unit, tiadassah Uni How, Jerusalem; (2)Neurol Dept. Barzilai Hedical Center, Ashkelon, affiliated to Ben Gurion Uni.; (3) and Centre de Recherche Francais de Jerusalem, Israel.
Kecogmtion that M.S. susceptibility has a genetic basis has been slow to develop. The reasoning by analogy with polio and slow virus diseaseshas dominated the &inking about M.S. for more than two decades and led to heavy emphasis on identifying a specific environmental agent causing the disease. The tools of genetic epidemiology which have only recently been applied to MS. are rapidly changing concepts of the disease.
Several factors may influence the results of an epidemiological study: patient ascertainment sources, inclusion diagnostic criteria, choice of appropriate denominator and availability of diagnostic tests. The calculated prevalence rate of HS increases with due mainly to problems of time of patient collection, ascertaining patients with long remissions. Thus. in the prevalence on 1.1.60 was 15.2/100,000 population year collection period and 26.6/100,000 Popuidtion for year period. The minimal period of collection should
Studies of age of onset of sibling pairs, reanalysis of geographical prevalence rates, studies of twins, recurrence risk in some families, and more recently investigation of conjugal pairs and their offspring, half siblings and of adoptees clearly indicate that genes play an important role and shed considerable light on the nature of any environmental factors.
length in Israel for a 5 a 37 be 15-
20 years. The length of time between the prevalence day and the end the collection period also affects the calculated for a 21 yearcollection period prevalence. Thus, in Israel, (1.1.55 - 31.12.75), the prevalence rate increased from 15.4/100,000 population when the prevalence day Was 1.1.76 to 23.7/100,000 uhen the prevalence day was 1.1.60. The prevalence day should be about 10 years before the end of the ascertainnent period. For optimal data on the frequency of the disease we need to have a registry which includes up-to-date information on any newly suspected case as well as all chronic historical cases. Pitfalls in the statistical evaluation uf the results wiii also be discussed. of
Analysis of pedigrees supports a complex inheritance pattern. At present the only locus for which there is unambiguous support is HLA. The contribution from this locus is minor. Other enthusiastically supported loci have hugely withered on the vine. A modest association is present for the immuqlobulin variable region which needs confirmation. Microsatellite screening of the genome is progress.
EPICEMIOLOGICAL FEATURES OF TN0 IflMUNOLOGICALLY DISTINCT FORMS OF MULTIPLE SCLEROSIS (MS): ANTI-!lYELIN BASIC (XBP) ASSOCIATED MS VS AXTI-PROTEOLIPZD (PLP) ASSOCIATED MS Sharon Warren and K.G. Warren 9S Patient Care and Research
llnivcrsity
of
Alberta,
Edmonton,
Clinic Canada
Researchers have suggested t!,at there arc at least two ~awutulucicdiiy aisrincr forms oi :-is: a common form associated with increased cerebrospinal fluid (CSF) and tissue anti-NBP and a less frequent form associated with elevated levels of anti-PLP. The purpose of this study lias to determine whether personal and disease features of antiMBP differ from anti-PLP associated MS. Human MBP and I’1.P were used as antigens in a solid phase radioimmunoassay to determine the relative occurrence of anti-MBP and anti-SLP in CSF of patients at the University of Alberta MS Clinic (Edmonton, Canada). Of 808 patients examined to date, onl) 2. 75(22) had elevated anti-PLP; no patient was found to haw both simultaneously. The 22 antl-PLP patients were compared to a systematic random sample of 22 patients with increased antl-MBP on: gender, onset age, first symptom, disability status, illness duration, MS Eamily history and evidence of CNS inflammation (IgG index, igG synthesis and oligoclonal banding). There were significantly more males in the antiI’LP group than the anti-MBP group (64% vs 27%, p*:.O5). Pho onset age curve peaked later for‘ anti-PLP patients ~5 antinRI’ patients (40-49 vs 30-39 yrs). The majority of patients in each group presented with sensory symptoms and were ambulatory; however< !; of the ambulatory patients in each group had experienced symptoms for > 10 years, so that tentative classification on benign vs disabling cow.se was not feasible. More anti-MB I’ than anti-PLP patients had an \IS Eamily history (22% vs OZ, ~7.05). The anti-MBP group showed mope evidence of C\IS inflammation: mote anti-MBP than antiPLP patients had an elevated IgG index (68% YS 18%, p(.Ol), showed increased daily IgG synthesis (68% YS 32Z, pC.05) and uerv positive for oligoclonal banding (731 YS 362, p/.05). Some epidemioloGica features vary between these distinct xmiwnological forms of ?I.5 and so may environmental trigi:ers.
-9-