Incidence of multiple sclerosis in Denmark 1948-1982: a descriptive nationwide study.

The incidence rates of multiple sclerosis (MS) in Denmark were estimated as a result of a continuous nationwide epidemiological survey since 1948 by the Danish Multiple Sclerosis Registry (DMSR). Among cases notified to the DMSR, 6,478 met the diagnostic criteria and had onset of MS from 1948 through 1982. The crude annual incidence rate was 4.45/100,000 and the lifetime cumulative incidence rate was 0.32%. The female/male ratio was 1.37:1. Crude incidence rates declined during the period 1952-1967. After 1967 the incidence seemed to rise again but in an irregular pattern. The decline in incidence involved only cases up to the age of 35. The subsequent increase was most marked in females and in the age groups over 45 years.     

The Danish Multiple Sclerosis Registry: a 50-year follow-up.

The Danish Multiple Sclerosis Registry was established in 1948 in continuation with a nationwide survey of the prevalence of Multiple Sclerosis (MS) in Denmark. The register has since collected information on MS patients from all Danish departments of neurology, practising neurologists, MS rehabilitation centres, the National Patient Registry, the Danish MS Society, and departments of neuropathology. The registry is linked with the Danish Central Population Registry. The completeness has been estimated at more than 90%. All cases are reclassified by two neurologists as to diagnosis and year of onset. 12 070 cases with a confirmed diagnosis of MS are kept in the databases. They were prevalent in 1949 or have had onset in the period 1948 - 1993. The registry is continuously updated with new information on registered cases and new cases. The crude average annual incidence rate 1980 - 89 was 4.99/105; the prevalence rate was 112/105 by 1 January 1990. Cross-linking with other registers have enabled analytical prospective epidemiological studies, and the registry has provided population based unbiased samples of patients for a number of clinical studies.     

Evaluating the use and limitations of the Danish National Patient Register in register-based research using an example of multiple sclerosis

Mason K, Thygesen LC, Stenager E, Brønnum‐Hansen H, Koch‐Henriksen N. Evaluating the use and limitations of the Danish National Patient Register in register‐based research using an example of multiple sclerosis.
Acta Neurol Scand: 2012: 125: 213–217.
© 2011 John Wiley & Sons A/S. Background – The Danish National Patient Register, Landspatientregistret (LPR), is a register of all hospital discharges and outpatient treatments in Denmark. Aims – It is increasingly used in research so it is important to understand to what extent this can be used as an accurate source of information. Virtually all patients in Denmark with multiple sclerosis (MS) are reported to the Combined MS Registry (DMSR), so this was used as the standard which the LPR was compared against. Methods – All residents of Denmark are assigned a unique Civil Register (CPR) number; this was used to compare data between registers. The LPR completeness was estimated by the proportion of cases from the DMSR that could be retrieved from the LPR. The LPR validity was estimated by the proportion of cases, listed in the LPR and DMSR, in whom the MS diagnosis could be confirmed as definite/probable/possible by the DMSR. Results – We found that 86.9% of those who were DMSR listed with an approved MS diagnosis were also listed in the LPR with a MS diagnosis. The diagnosis was valid in 96.3% of patients listed in the LPR when compared against the DMSR. Conclusions – The low completeness reduces the usefulness of the LPR in epidemiological MS research, in particular incidence studies. The study also found that the completeness of the LPR could be increased to 92.8% by including LPR records from other departments in addition, but this reduced the validity of the LPR to 95.1%. However, these results cannot uncritically be applied to registration of other diseases in the LPR.     

Suicide attempts in multiple sclerosis

The purposes of the study were (1) to estimate the risk of suicide attempts in multiple sclerosis (MS) patients in Denmark and compare the risk to the background population in the County of Funen, Denmark; (2) to estimate the risk of suicide attempts in MS patients receiving immunomodulating therapy compared with untreated patients. The Danish MS Registry, the Danish MS Treatment Registry and the Suicide Attempt Registry are linked and merged together using a person identification number given to all persons residing in Denmark. Among 404 MS patients, 15 patients had attempted suicide, although no increased risk for suicide attempts was found in MS patients. No difference in number of suicide attempts in treated and untreated patients was found.     

Concordance for multiple sclerosis in Danish twins: an update of a nationwide study

The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study, virtually all Danish MS cases among twins born before 1983 with onset of MS after 1948 and diagnosis before I January 1997 were identified. Of 13 286 MS cases, 178 were twins and, of these 164 twin pairs were discordant and seven were concordant. We found significantly higher proband-wise concordance among monozygotic twins than dizygotic twins, with estimated proband-wise concordances of 24% (95% confidence interval (CI): 5-39%) for monozygotic and 3% (95% CI: 0-8%) for dizygotic twins. Thus, a monozygotic twin whose co-twin has MS has a 24% risk of developing the disease, while the corresponding risk for a dizygotic twin is only 3%. Our results largely confirm previously published concordance estimates and indicate that genetic factors are of importance in susceptibility to MS.     

Multiple sclerosis and poliomyelitis. A Danish historical cohort study

OBJECTIVE: To evaluate whether persons with a history of poliomyelitis are at an increased risk of developing multiple sclerosis (MS). MATERIAL AND METHODS: All patients diagnosed with acute poliomyelitis in the greater capital area of Copenhagen, Denmark, between 1919 and 1954 were identified and followed with respect to MS. Information on vital status and diagnosis of sclerosis was obtained through linkage with the Danish Civil Registration System and The Danish Multiple Sclerosis Registry, respectively. Follow-up started on the date of the establishment of the Danish Civil Registration System (April 1, 1968) until death, emigration or December 31, 1996, whichever came first. The observed incidence of MS among polio patients was compared with the expected incidence calculated according to national gender, age and period specific rates of MS. RESULTS: During 149,364 years of follow-up, 19 cases of multiple sclerosis were observed among 5652 polio patients compared with 11.0 expected (SIR = 1.73 (1.04-2.74)). The increased risk of MS was most pronounced in polio patients hospitalized during adolescence. Neither gender nor the acute severity of poliomyelitis modified the risk of MS. CONCLUSION: Our results are based on small numbers of events, however the findings suggest that the polio patients might be at an increased risk of MS.     

Suicide and multiple sclerosis: an epidemiological investigation.

In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males and for patients with onset of MS before the age of 30 years and those diagnosed before the age of 40. The SMR was highest within the first five years after diagnosis.     

Incidence and prevalence of motor neuron disease in Coastal and Mountainous Regions,Croatia, 1984–1993. A preliminary survey

In the period 1984–1993, we carried out an incidence and prevalence study of motor neuron disease in Coastal and Mountainous Regions, Croatia. This was the first epidemiological study on motor neuron disease in Croatia. A total of 22 incident cases were identified. The crude annual incidence rate was 0.68 (95% confidence interval 0.43-1.03) per 100,000 person-years; 0.95 (95% confidence interval 0.60-1.43) per 100,000 person-years for men and 0.42 (95% confidence interval 0.26-0.63) per 100,000 person-years for women. The rate adjusted to the European population was 0.63 (95% confidence interval 0.39-0.95) per 100,000 person-years. The age-adjusted incidence in our population is similar to the rates, standardized to the European population, observed in Italy, but lower than recent rates in the US and northern European studies. On 31st December 1993, there were 18 prevalent cases. The prevalence adjusted to the European population was 5.24 (95% confidence interval 3.10-8.28) per 100,000 population.     

Estimating the prevalence and incidence of multiple sclerosis in the Lorraine region, France, by the capture-recapture method

OBJECTIVE: The objective of this study was to assess the prevalence and incidence of multiple sclerosis (MS) in the Lorraine region, in France. METHODS: Data from three sources - Regional Health Insurance System, medical records departments and the Lorraine registry of MS - and a capture-recapture method with log-linear models were used to estimate the prevalence and incidence of MS. RESULTS: We identified 7193 records of reported MS corresponding to 4299 unique suspected cases of MS existing on 31 December 2008, in Lorraine. On the basis of the 4001 validated cases, the observed crude prevalence of MS was 170.9 cases per 100,000 inhabitants (95% confidence interval [CI]: 165.7; 176.3), and the observed annual crude incidence of MS was 4.4 cases per 100,000 inhabitants (95% CI: 3.6; 5.4). With the capture-recapture method, the estimated prevalence of MS was 4405.7 (95% CI: 4261.5; 4629.7), so an estimated 405 cases were not identified by the three sources. The estimated prevalence was 188.2 cases per 100,000 inhabitants (95% CI: 182.7; 193.8), and the estimated annual incidence was 8.5 cases per 100,000 inhabitants (95% CI: 7.3; 9.7). CONCLUSIONS: The capture-recapture method allowed us to estimate an additional 10.1% of unobserved prevalent cases and to anticipate 47.5% of unobserved incident cases.     

Incidence and prevalence of epilepsy in Denmark

PURPOSE: To estimate the occurrence of epilepsy in Denmark between 1977 and 2002, taking gender, age, and secular trends into consideration. METHODS: We used the Danish Civil Registration System to identify all persons born in Denmark and the Danish National Hospital Register to identify persons registered with epilepsy between 1977 and 2002. RESULTS: Between 1977 and 2002 the average incidence of epilepsy was 68.8 new epilepsy patients per 100,000 person-years at risk. However, the incidence changed with calendar time and increased steeply from 1990 to 1995, probably due to changes in diagnostic system and inclusion of outpatients. From 1995 to 2002 the incidence rate was reasonable constant with an average of 83.3 new cases per 100,000 person-years at risk, except for patients over 60 years of age where we observed an increase in incidence with calendar time. The age-specific incidence rates declined from a high level in children to a low level between 20 and 40 years of age, and thereafter a gradual increase was seen. The incidence rate was slightly higher in men than in women except for the age range 10-20 years. About 2% of the population was diagnosed with epilepsy at some point during the first 25 years of life. The overall 5-year prevalence proportion of epilepsy was 0.6% with a slight variation with age and gender between 0.4 and 0.8% of the population. CONCLUSION: The occurrence of epilepsy is age and gender specific. The estimated incidence rate of epilepsy furthermore increased over time for persons older than 60 years of age.     

Trends in risk of stroke in patients with a hospital diagnosis of nonvalvular atrial fibrillation: National Cohort Study in Denmark, 1980-2002

AIM: We examined trends in incidence of stroke of any nature (ischemic and/or hemorrhagic) in subjects with a hospital diagnosis of nonvalvular atrial fibrillation or flutter in Denmark from 1980 to 2002 by sex, age and conditions of comorbidity. METHODS: We identified all individuals, aged 40-89 years, with an incident hospital diagnosis of atrial fibrillation or flutter and no history of stroke or heart valve disease in the Danish National Registry of Patients, and subjects were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any nature (ischemic and/or hemorrhagic) and in the Danish Civil Registration System (emigration and vital status). We used multivariate Cox proportional hazard regression analysis to estimate trends in incidence of stroke. RESULTS: Nonvalvular atrial fibrillation or flutter was diagnosed in 141,493 subjects (75,126 men and 66,367 women), and during follow-up 15,964 subjects had an incident diagnosis of stroke. The hazard ratios for stroke in the last 3-year period compared to the first 5-year period, adjusted for 10-year age group, conditions of comorbidity, and general stroke trend in the Danish population were 0.78 (95% CI 0.70-0.86) in men, and 0.80 (95% CI 0.72-0.88) in women. The reduction in risk of stroke by calendar year was most prominent in patients aged 40-74 years. CONCLUSION: We observed a modest decrease in risk of stroke in subject with atrial fibrillation in Denmark during calendar years 1980-2002. However, we could not control for any changes in diagnostic performance, admission practice, and medical management of patients with atrial fibrillation.     

Multiple sclerosis in southern Europe: Monreale City, Italy. A twenty-year follow-up incidence and prevalence study

BACKGROUND: Several follow-up studies showed increasing prevalence and incidence rates for multiple sclerosis (MS). OBJECTIVE: To ascertain, throughout a follow-up study, the incidence and prevalence of MS in the city of Monreale, Sicily, southern Italy. METHODS: We calculated crude and age- and sex-specific prevalence rates on December 31, 2000, and determined incidence rates for the period January 1, 1992 to December 31, 2000. RESULTS: The prevalence of MS was 71.2 per 100,000 population (48,5/100,000 in men; 93,0/100,000 in women). The incidence rate of MS for the period 1992-2000 was 4.0/100,000 per year. CONCLUSION: This study showed a nonsignificant increase in MS incidence rates in Monreale city for 1992-2000 compared to 1981-1991. Prevalence rates were similar to those of the previous follow-up study. Intervals between onset of symptoms and diagnosis seemed shorter than in prior studies. There is no evidence that the high prevalence and incidence rates have changed in this interval but numbers are too small for firm statements. These findings indicate that in Monreale city MS prevalence is stable and confirm Sicily as a high-risk area for MS.     

Multiple sclerosis in Oslo, Norway: prevalence on 1 January 1995 and incidence over a 25-year period

The Oslo Multiple Sclerosis (MS) Registry was established in 1990, and this is the first report on the prevalence and incidence of MS in the city of Oslo, Norway. The prevalence rate of definite MS on 1 January 1995 was 120.4/10(5). Inclusion of patients of native Norwegian ancestry only and exclusion of non-Norwegian immigrants yielded a prevalence rate of 136.0/10(5). A similar prevalence rate (136.5/10(5)) was found when patients and immigrants from the other Nordic countries (Finland, Sweden, Denmark) were included. Segregation of the native Norwegian patients according to the counties where they were born showed no significant differences except for a disproportionate increase of patients born in the inland county of Oppland. A total of 794 cases were resident in Oslo at the time of a diagnosis of definite MS in the period 1972-99. The crude average annual incidence rate for each 5-year period, between 1972 and 1996, increased significantly from 3.7/10(5) in the 1972-76 to 8.7/10(5) in the 1992-96 period. The increase was more marked in relapsing-remitting (RR) than in primary progressive disease and in female cases.     

Multiple sclerosis among utility workers

The incidence of MS was assessed in a nationwide cohort study of 31,990 employees of Danish utility companies between 1900 and 1993. Overall, 32 cases of MS were diagnosed, as compared with 23.7 expected from national incidence rates, to yield a standardized incidence ratio of 1.35 (95% confidence interval, 0.92 to 1.91). We found no support for the hypothesis of an association between occupational exposure to electromagnetic fields and the risk of MS.     

The risk of multiple sclerosis in Denmark

By means of age specific incidence and death rates for MS, plus age specific death rates all causes, the risk of multiple sclerosis in Denmark has been calculated with a modified life-table method. the cumulative lifetime risk of MS from birth is estimated at 201 per 100,000 (180 in males and 223 in females) - or one chance in 500. the cumulative risk remains about the same from birth until age 25 when it begins to decline toward 0 which is reached at age 60.
Period cumulative risks from various ages and for periods ranging from 5 to 30 years were also calculated. Thus, at age 20, the risk of MS within 10 years is 74 per 100,000 and within twenty years, 142, for both sexes combined.
With the likely equivalence of the duration of the illness throughout the world, and with little major variation expected for most regions for death rates, all causes, within the ages of concern, we may then estimate the risk of MS for parts of the world considered as high frequency MS (like Denmark), medium frequency (like Italy), or low frequency (like Japan). By applying to these regions the factors of 1.0, 0.3, and 0.04 respectively, as reflecting the ratios of their likely prevalence rates, the cumulative lifetime and period risks may be approximated from the Danish data. Thus in 20 years, a group of 100,000 Japanese migrating to Denmark at age 10 would be expected to contain 4 MS if they retained the low risk of their homeland, as opposed to 92 MS if they acquired the high risk of Denmark.     

MULTIPLE SCLEROSIS and HODGKIN''S DISEASE IN DENMARK

There has been a hypothesis that Hodgkin's disease in young adults and multiple sclerosis may have related causes because the age of clinical onset and the geographic distribution of both are similar. This hypothesis was tested for data in Denmark. Detweeen 1943-62, the average annual incidence rate for Hoadgkin's disease in Denmark was 2.25 per 100,000 population (2.68 male and 1.83 female). Between 1951-69, the average annual death rate for Hodgkin's disease was 2.15 per 100,000 (2.66 male and 1.64 female). The average annual incidence rate for multiple sclerosis in Denmark was calculated from age at onset for 2,481 prevalent cases of 1949, the 1940 population, and an average annual incidence of 128.86 cases for 1939-45: the average annual incidence rate per 100,000 was then 3.35 (3.00 male and 3.69 female). Age specific incidence and death rate for Hodgkin's disease in Denmark each showed a bimodal curve, with one peak at age 25-29 and the other at age 70-74; this was found for each sex, with male rates consistently higher than female. The age specific incidence rates for multiple sclerosis were clearly unimodal with a peak at age 25-29 more definite in females than males. Rates for MS were notably higher for young females than males but about equal by sex for those over the age of 30. The geographic distribution of multiple sclerosis within the counties (amter) of Denmark was markedly non-random, with the major concentration of high prevalence areas middle Jutland and on to Fyn. Geographic distribution of Hodgkin's disease, whether for the young or the old, and whether from incident or death cases, showed no significant variation from a homogeneous distribution. In formal testing there was no correlation of any Hodgkin's distribution with that of MS. A review of the Hodgkin's data for distribution in the United States, on which the original hypothesis was based, suggests the variation there may be little more than reporting artifact. Accordingly, we conclude that there is no relation between distributions of these two disorders, and the factors they do appear to have in common are either quite non-specific or of questionable validity. Thus there is no reason to believe that multiple sclerosis and Hodgkin's disease, even in the young, share a common etiology.     

Incidence and prevalence of motor neuron disease in two Danish counties

A total of 186 cases of motor neuron disease (MND) was identified in two Danish counties during the period 1974-1986. The average annual incidence rate was 1.4/100,000 population, and the male:female ratio of incidence rates was 1.5. Mean age at diagnosis was 64.3 +/- 10.0 years. The incidence rates increased significantly with advancing age and reached a maximum at age 60-79 years, followed by a nonsignificant decrease. The average point prevalence was 3.1/100,000 population. Bulbar symptoms were part of the initial symptoms in 65% of cases, and patients with bulbar onset were older than patients with spinal onset. Age- and sex-specific incidence rates indicated a marked male preponderance amongst the youngest patients, in contrast to a female preponderance in patients above 60 years with bulbar onset of MND. Familial MND accounted for 2.7% of cases.     

Prevalence and incidence of multiple sclerosis in Catania, Sicily

OBJECTIVE: An epidemiologic survey was conducted to determine the prevalence and incidence of MS in the city of Catania, Sicily, Italy. Prevalence rate was calculated as point prevalence at January 1,1995, and incidence during 1974 to 1995. METHODS: The authors studied the frequency of MS in the community of Catania in a population of 333,075 inhabitants according to the 1991 census. The primary sources for the case ascertainment were the neurologic and motor rehabilitation departments, the MS Center, the Italian MS Association, private neurologists, and family doctors. All patients who satisfied the Poser criteria for clinically definite MS, laboratory-supported definite MS, clinically probable MS, and laboratory-supported probable MS were considered prevalent and incident cases. RESULTS: One hundred ninety-five patients with MS who had had the onset of disease on prevalence day in a population of 333,075 inhabitants were detected. The prevalence rate was 58.5 per 100,000 (95% CI 50.7 to 67.5). Prevalence was higher in women (62.0/100,000) than in men (54.8/100,000). The age-specific prevalence showed a peak in the group aged 35 to 44 (145.1/100,000). From 1975 to 1994, 170 subjects with MS had the clinical onset of the disease. The mean annual incidence was 2.3 per 100,000 (95% CI 2.0 to 2.6). Age-specific incidence showed a peak in the group aged 25 to 34 (6.32/100,000). Incidence for 5-year intervals increased from 1.3 during 1975 to 1979 to 3.9 during 1990 to 1994. CONCLUSIONS: These prevalence and incidence rates are close to those reported in other similar surveys carried out in Italy and southern Europe.     

Pain in patients with multiple sclerosis: a population-based study

BACKGROUND: Pain is an important symptom in patients with multiple sclerosis (MS). The estimated pain prevalence varies between 30% and 90%. To our knowledge, previous studies do not include a whole population sample of patients with MS. OBJECTIVE: To assess pain prevalence and its clinical characteristics and impact on daily life in a population sample of MS patients and in a reference group. DESIGN: Postal survey. SETTING: Aarhus County, Denmark. PARTICIPANTS: The population of patients with definite MS in Aarhus County (n = 771) and a sex- and age-stratified reference group from the general population (n = 769). MAIN OUTCOME MEASURES: Pain prevalence, intensity, and treatment requirement; and the impact of pain on daily life. RESULTS: Response rates for MS patients and reference subjects were 81.3% and 63.3%, respectively. Pain in the month preceding assessment occurred in 79.4% of MS patients and in 74.7% of reference subjects (prevalence proportion ratio, 1.06; 95% confidence interval, 0.99-1.13). Patients with MS had a higher pain intensity ("when pain is at its least" median visual analog scale score, 20.0 vs 11.0 mm [P<.01];and "when pain is at its worst" median visual analog scale score, 68.0 vs 55.0 mm [P<.01]). Daily intake of analgesics occurred in 24.4% of MS patients and 9.0% of reference subjects (prevalence proportion ratio, 2.7; 95% confidence interval, 2.0-3.6). Patients with MS more often reported that pain interfered with daily life "most of the time" or "all the time." CONCLUSIONS: The frequency of reported pain in MS patients was not higher than in the background population. However, pain intensity, the need for analgesic treatment, and the impact of pain on daily life were higher in MS patients.     

Epidemiology of anorexia nervosa and bulimia nervosa in Bornholm County,Denmark, 1970–1989

In a retrospective study of anorexia nervosa and bulimia nervosa, potential cases were traced, studied, and diagnosed according to ICD-10. Forty-two cases were found in Bornholm County, comprising the island of Bornholm in Denmark, in a population of 47,000 from 1970 to 1989. Less than half of these cases (n= 16) were registered in Danish psychiatric case registers, and 35% (n= 14) could be found only by search in primary care. The incidence rates were stable during most of the study period, but a significant increase occurred during the last 5 years. The prevalence rates, determined by counting the number of cases in the population year by year, also increased during the late part of the study period. In 1989 the incidence rate of the high-risk group of females 10 to 24 years of age was 136 per 100,000 for anorexia nervosa and 45 per 100,000 for bulimia nervosa, and the prevalence rate was 222 per 100,000 for anorexia nervosa and 89 per 100,000 for bulimia nervosa.