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N Koch-Henriksen

Publications and source records attributed to N Koch-Henriksen.

At least 19 recordsLinked to original sources
PubMed2001

Correlations of brain MRI parameters to disability in multiple sclerosis.

OBJECTIVES: The objective was to correlate magnetic resonance imaging (MRI) T2-weighted lesion load and measures of white matter atrophy in the brain to disability in a population-based sample of patients with multiple sclerosis (MS). MATERIAL AND METHODS: A well defined cohort of patients was drawn at random from the general MS population by using the Danish Multiple Sclerosis Registry. A semi-automated local thresholding technique was used to quantify T2-weighted lesions on MRI; whereas manual tracing was applied to measure the corpus callosum brain ratio (CCR) and the ventricle brain ratio (VBR). RESULTS: A sample of 86 patients with a mean age of 43.3 years (SD 4.3), mean disease duration of 13.6 years (SD 4.4) and a median Expanded Disability Status Score (EDSS) of 6.0 was identified. The correlation between total lesion area of the brain (TLA) and disability (EDSS) for the whole sample was moderate (Spearman rank correlation coefficient r=0.48, P<0.001). Also correlations of CCR and VBR to disability (r=0.32-0.46) were significant. CONCLUSIONS: Correlations of TLA and disability in this study were rather strong. Hence, T2-weighted MRI lesion load in the brain still plays an important role as a surrogate marker of disease and as a secondary outcome measure in phase III treatment trials.

Adult↗
PubMed2001

The Danish Multiple Sclerosis Registry. History, data collection and validity.

The Danish Multiple Sclerosis Registry was formally established in 1956 but started operating in 1949 with a nationwide prevalence survey. Since then, the Registry has continued collecting data on new and old cases of multiple sclerosis (MS) or suspected MS from multiple sources. The Registry reclassifies cases according to standardized diagnostic criteria (currently those of Poser et al). A total of 14,441 cases fulfilling the diagnostic criteria had been registered at the most recently completed follow-up by 1 January 1997; 10,851 had onset from 1948 to 1996 and 3560 before 1948. The completeness has formerly been estimated at about 90%, higher for cohorts with older onset and lower for cohorts with onset close to follow-up. The estimated validity of the diagnosis for autopsy cases classified as definite MS in the Registry is 94%. A long-term nationwide Registry has proved to be a valuable instrument for monitoring incidence and prevalence, analysing survival, performing genetic analysis, providing unselected patient samples for clinical analyses, performing case-control studies and prospective studies and estimating the need for treatment and care.

Age Distribution↗
PubMed2000

The Danish National Project of interferon-beta treatment in relapsing-remitting multiple sclerosis. The Danish Multiple Sclerosis Group.

After approval by the European Union in 1996 of interferon-beta for treatment of relapsing-remitting multiple sclerosis (RRMS), 862 patients in Denmark have received treatment (by April 1999), and 304 of those were enrolled into an open labelled randomised trial to compare the efficacy and tolerability of treatment with interferon-beta-1b (Betaferon) 8 MIU subcutaneous every other day and interferon-beta-1a (Rebif) 6 MIU subcutaneous once a week. Primary and secondary end-points included: (1) the relapse rate, (2) tolerability, (3) neutralizing antibody formation using the same specialised laboratory and validated assay, (4) time to first relapse, (5) time to sustained progression, and (6) number of gadolinium-enhancing lesions in T1-weighted MRI and the total lesion load in T2-weighted MRI. All the records are kept in a nationwide clinical database connected with the Danish Multiple Sclerosis Registry. The randomised trial will be completed by the end of 1999, and the results are not yet available. The annual relapse rate in all treated patients until April 1999 was 0.73, the annual rate of steroid treated relapses was 0.21. By 1 April 1999 8.8% of the patients had discontinued treatment and 10.4% had changed to another interferon-beta preparation. It has been planned to extend the follow-up of all patients treated according to the Danish National Protocol for a period of several years. The continuous and nation-wide registration of the course of the disease in interferon-beta treated RRMS patients may provide valuable knowledge of the treatment-modified long-term course of the disease in a cohort of patients, selected on the basis of well-defined criteria.

Adjuvants, Immunologic↗
PubMed2000

Immunogenicity of interferon-beta in multiple sclerosis patients: influence of preparation, dosage, dose frequency, and route of administration. Danish Multiple Sclerosis Study Group.

A total of 754 consecutive patients with relapsing-remitting multiple sclerosis were investigated for interferon-beta (IFNbeta) antibodies by protein-G affinity chromatography and antiviral neutralization bioassay during 24 months on 6 MIU (22 microg) of subcutaneous IFNbeta-1a once weekly (n = 143) or three times weekly (n = 160), 6 MIU (30 microg) of intramuscular IFNbeta-1a once weekly (n = 140), or 8 MIU every other day of IFNbeta-1b (n = 311). The proportion of binding antibodies was higher in those receiving IFNbeta-1b compared with 6 MIU of IFNbeta-1a three times weekly (97 vs 89% at 12 months), and fewer became positive if 6 MIU of IFNbeta-1a was administered once weekly (58 vs 89%). Fewer patients on intramuscular than subcutaneous IFNbeta-1a became positive (33 vs 58%). The binding and neutralizing capacities were higher in the IFNbeta-1b group than in the IFNbeta-1a groups; these differences, however, were not significant after 12 months. The number of positive patients varied considerably and depended on the amount of IFN added to the bioassay; adding 10 LU/ml or more masked antibody detection. Antibodies induced by either preparation neutralized both IFNbeta species but not IFNalpha. In conclusion, IFNbeta-induced antibodies are frequently found in multiple sclerosis patients, and IFNbeta-1b is more immunogenic than IFNbeta-1a. The immunogenicity of IFNbeta-1a increases with the frequency of administration and if it is given subcutaneously.

Adolescent↗
PubMed1999

Reporting delay and corrected incidence of multiple sclerosis.

The incidence of multiple sclerosis can be adjusted for reporting delay in a way similar to that for AIDS incidence as described in this paper. Two models are applied to data from the Danish Multiple Sclerosis Registry. The first simply describes the delay distribution, the second is a regression model. For the latter it is shown how goodness-of-fit assessment for both time-dependent and time-independent covariates can be handled using ideas from the Cox proportional hazards model. The goodness-of-fit analysis shows that people with onset age below 40 years and people with onset age from 40 years and above should be analysed separately and this is done throughout the paper. The incidences are adjusted with the two estimated delays and an estimate of the variance for the adjusted incidence is given. Finally the crude incidences are compared with the adjusted ones. We find that the incidence has been increasing since 1965 but mostly for people with onset age below 40 years.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

Linkage and association analysis of susceptibility regions on chromosomes 5 and 6 in 106 Scandinavian sibling pair families with multiple sclerosis.

In the genetically homogeneous Scandinavian population, we have investigated chromosome 5 and the HLA (human leukocyte antigen) region on chromosome 6p21 by applying linkage and association analyses on 106 white sibling pair families with multiple sclerosis. The importance of genes within the HLA region for the susceptibility of multiple sclerosis has previously been reported. More recently, findings have suggested importance of regions on chromosome 5. Half of chromosome 5 was analyzed by using 14 microsatellite markers and a susceptibility region with a maximum LOD score of 1.1 was identified. Chromosome 6 was analyzed by HLA-DR typing and using the TNF alpha microsatellite marker. A peak maximum LOD score of 2.0 was found at the HLA-DR marker. Association studies were made for all the markers, comparing 106 probands from the sibling pairs with 100 unrelated controls. None of the markers on chromosome 5 showed significant association with multiple sclerosis, whereas strong association between multiple sclerosis and DR2 was found, with an odds ratio of 3.7 (p < 10(-5)). It is surprising that association was not seen for any of the TNF alpha alleles including the 121-bp allele, although this allele was in positive linkage disequilibrium with DR2 in both patients and controls. Our results support the existence of multiple sclerosis susceptibility loci on chromosomes 5p and 6p21.

Chromosome Mapping↗
PubMed1998

Underlying cause of death in Danish patients with multiple sclerosis: results from the Danish Multiple Sclerosis Registry.

OBJECTIVES: To determine the underlying causes of death in a large population based register series of patients with multiple sclerosis. METHODS: The Danish Multiple Sclerosis Registry, which contains virtually all diagnosed cases of multiple sclerosis in Denmark who were alive in 1949 plus cases with onset of multiple sclerosis in the period 1949-93, who have been diagnosed and notified by 1 January 1994, was linked with the Danish Registry of Causes of Death, in which ICD codes for causes of death from the death certificate are stored for all Danish citizens. RESULTS: 6068 register cases of multiple sclerosis, who had died in the period 1951-93, were included. Multiple sclerosis was noted on the death certificate as the underlying cause of death in 55.4%; cardiac or vascular diseases in 17.6%; cancers in 8.6%; respiratory or infectious diseases in 5.1%; other natural causes in 9.5%; accident or suicide in 3.8%. The distribution varied with age at death. Standardised mortality ratios (SMRs) were computed on the basis of the 8142 incident cases, who had onset of multiple sclerosis within the period 1951-93; the SMRs for causes of death other than multiple sclerosis were highest for infectious or pulmonary diseases: 2.46 (95% confidence interval (95% CI) 2.04-2.94); suicide: 1.62 (95% CI 1.29-2.01); cardiac or vascular diseases: 1.34 (95% CI 1.22-1.48); accidents 1.34 (95% CI 1.02-1.71); and significantly lower than unity for cancers: 0.79 (95% CI 0.70-0.90), lower for men than for women. CONCLUSIONS: More than half of the patients with multiple sclerosis die from multiple sclerosis or complications of the disease. Among other causes, patients with multiple sclerosis have an increased risk of dying from heart or vascular diseases but a reduced risk of dying from cancer. An increased risk of death from suicide and accidents can be indirectly attributed to multiple sclerosis. The diminished risk of dying from cancer may be a result of incomplete ascertainment of cancers in disabled patients with multiple sclerosis.

Accidents↗
PubMed1997

EBV-positive primary central nervous system lymphomas in monozygote twins with common variable immunodeficiency and suspected multiple sclerosis.

Common variable immunodeficiency represents the most frequently occurring primary immunodeficiency disorder and is usually detected sporadically in patients with no family history of immunodeficiency. We present the case stories of two monozygote twins, who following a period of decreasing serum immunoglobulins developed primary central nervous system lymphomas. One twin had clinical and paraclinical features mimicking multiple sclerosis. Immunohistochemical investigations on biopsy tissue showed expression of the bcl-2 and p53 gene products, and Epstein-Barr virus (EBV) encoded small RNA's (EBER) indicating latent infection were detected in lymphoma cells using in situ hybridisation techniques. The pathogenetic role of EBV in oncogenesis is discussed.

Adult↗
PubMed1995

Multiple sclerosis in Scandinavia and Finland.

Review of studies of incidence of MS over several decades in seven geographical areas scattered over Scandinavia and Finland have shown that incidence rates fluctuate significantly with time in most of the areas but in an inconsistent pattern. The incidence appeared to the lowest in the northernmost parts of Norway indicating that the well-known north-south gradient for risk of MS does not hold true for high latitudes.

Denmark↗
PubMed1995

Increased risk of multiple sclerosis after late Epstein-Barr virus infection: a historical prospective study.

An association between infectious mononucleosis (IM) and MS has been proposed. In a historical prospective study we used records from the Danish State Serum Institute on heterophile antibody (HA) tests for IM performed in all Danish patients over a number of years. Included in the analysis were 6853 HA-positive persons analyzed from 1968 to 1978 (except 1975) and 12,886 HA-negative per sons analyzed in the years 1968, 1969, 1970 and 1978. A search for these persons in the central nationwide Danish Multiple Sclerosis Registry (DMSR) was performed. Among the HA-positive persons 16 cases of MS which met the diagnostic criteria were found with onset of MS after the year of the HA test and before follow-up on 1 January 1991. The expected number for a Danish population, matched by sex, age and year at start of observation, was 5.70 (P < 0.05), the risk ratio being 2.81. No patient had developed MS before contracting IM. Among the HA-negative persons 12 were registered with onset of MS after the year of the HA test and before follow-up, the expected number being 10.47 (P > > 0.05). Although Epstein-Barr virus is not suggested in itself to be the cause of MS, we propose that it is a co-factor in the pathogenesis of this disease.

Adolescent↗
PubMed1994

Survival of patients with multiple sclerosis in Denmark: a nationwide, long-term epidemiologic survey.

We estimated survival probability and excess death rates for patients with MS on the basis of data from the Danish Multiple Sclerosis Registry, which includes virtually all patients diagnosed with MS in Denmark (population, five million) since 1948. We reviewed and reclassified all case records according to standardized diagnostic criteria. By linkage to the Danish Central Population Registry, we lost to follow-up only 25 patients who had emigrated. The median survival time from onset of the disease was 28 years in men (compared with 40 years in the matched general male population) and 33 years in women (versus 46 years). The median survival time from diagnosis was 22 years in men (versus 37 years) and 28 years in women (versus 42 years). The excess death rate between onset and follow-up (observed deaths per 1,000 person-years minus the expected number of deaths in a matched general population) was 14.3 in men, which was significantly higher than in women (12.0). Excess mortality increased with age at onset of MS in people of each sex. The 10-year excess death rate has decreased significantly in recent decades. Excess mortality was highest in cases with cerebellar symptoms at onset.

Adult↗
PubMed1992

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.

Adaptation, Psychological↗
PubMed1992

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.

Adolescent↗
PubMed1988

Epidemiology of multiple sclerosis: incidence and prevalence rates in Denmark 1948-64 based on the Danish Multiple Sclerosis Registry.

The Danish Multiple Sclerosis Registry (DMSR) is a national register based upon the ethnically homogeneous Danish population of about 5 millions. The DMSR was founded in 1956 following a nationwide Danish prevalence survey of MS in 1949 and a continuous registration of incident cases of MS since January 1, 1948. Included in DMSR are all Danish cases of MS (or suspicion of MS) diagnosed by a neurologist or a department of neurology. The sources of notification are the 22 neurological departments in Denmark, the National Patient Registry, the neuropathological departments, the Registry of Causes of Death, and, up to 1975, the Disablement Insurance Court. Notified cases which do not comply with the standardized diagnostic criteria of the DMSR are excluded. An estimate of the completeness of the DMSR is 90-95% and the validity is around 94%. Age- and sex-specific incidence rates of MS for the interval 1948-64 are presented. The crude annual incidence rate of MS in Denmark was in the year 1948-64 4.42 per 100,000 population, 22% higher in females than males. There was a significant geographical variation of incidence rates and a significant downward trend in incidence rates during the interval, whereas the prevalence rates showed a slight increase.

Adolescent↗
PubMed1986

Chronic headache related to nasal obstruction.

A study of the occurrence of chronic headache in 444 patients suffering from nasal obstruction is presented. The localization, frequency, severity of the headache and differences between men and women are described. All the patients were treated with rhinoplastic surgery and examined just prior to surgery and 12 months post-operatively, applying exactly the same scheme of questioning and examination on the two occasions. The investigation shows a very strong association between the establishment of a normal nasal passage and the cure of headache. The study stresses the viewpoint that a negative sinus X-ray cannot rule out the possibility that a headache is of nasal origin, and that careful rhinologic examination is essential.

Adolescent↗