Optic neuritis as onset manifestation of multiple sclerosis: a nationwide, long-term survey.

OBJECTIVE: To determine the predictive value on survival of optic neuritis (ON) as onset manifestation of MS. METHODS: We used data obtained from the Danish Multiple Sclerosis Registry, which includes virtually all patients diagnosed with MS in Denmark. From 1949 to 1990, 7,548 unselected patients fulfilling standardized diagnostic criteria of MS were registered. RESULTS: The onset manifestation of MS was known in 6,923 patients, and was ON in 1,282 patients (19%). The mean age at onset was 31.1 years for these patients compared with 34.8 years for patients with another or unknown onset manifestation of MS (non-ON) (p < 0.001). The mean delay from the first known manifestation of MS to the final diagnosis of MS was 6.1 years (ON) and 4.2 years (non-ON). The median survival time from onset of ON was 30 years in men (compared with 41 years in the matched general male population) and 40 years in women (versus 47 years). The excess death rate increased with age at onset of MS in people of each sex. Excess death rate for women differed significantly between patients with ON as onset manifestation and patients with another or unknown onset manifestation of MS (8.3 versus 13.0). In patients with ON as onset manifestation of MS, the excess death rate was significantly higher in men (14.0) than in women (8.3). CONCLUSION: ON as onset manifestation of MS indicates a more favorable prognosis of survival of MS judged by excess death rate only in women.

Supraorbital neuralgia. Vågå study of headache epidemiology.

In a recent, hospital-based report, we described a small series of 5 patients with unilateral, more or less chronic, severe forehead pain, that could be transitorily abated by anaesthetic blockade of the supraorbital nerve and more permanently abated by 'liberation' operation directed towards the nerve exit area at the supraorbital notch. However, epidemiological data on supraorbital neuralgia are lacking. Among 1838 18-65-year-old inhabitants in Vågå (88.6% of the eligible ones), there were 10 who presented the following clinical picture: (1) Unilateral forehead/ocular pain, not diagnosed or diagnosable as any other, particular, unilateral headache; (2) Steadfast unilaterality; (3) Increased tenderness upon pressure over the exit site of the supraorbital nerve (incisura frontalis) on that side--in those who were in an active phase; (4) Foregoing trauma in the forehead/supraorbital rim area, ipsilaterally. In approximately half the cases, there was a moderate, ipsilateral sensory loss. A striking finding was the occurrence of jabs in the symptomatic area, and in synchrony with the neuralgia pain. These 10 inhabitants correspond to a prevalence of 0.5% (or 0.65% if two nontrauma cases are included).

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.

A discriminant analysis approach to morphological regionalization in the European Late Mesolithic.

The morphological regionalization of European Mesolithic populations was studied by discriminant analysis. Samples from four localities were compared employing craniometric variables. The general conclusion was that there is evidence for regionalization in the Late mesolithic in Europe, and a clinical pattern of variation was not detected. These results are in agreement with archaeological reconstructions of the population structure in the Late Mesolithic Europe.

On statistical methods for comparison of intrasample morphometric variability: Zalavár revisited.

In studies of morphology, methods for comparing amounts of variability are often important. Three different ways of utilizing determinants of covariance matrices for testing for surplus variability in a hypothesis sample compared to a reference sample are presented: an F-test based on standardized generalized variances, a parametric bootstrap based on draws on Wishart matrices, and a nonparametric bootstrap. The F-test based on standardized generalized variances and the Wishart-based bootstrap are applicable when multivariate normality can be assumed. These methods can be applied with only summary data available. However, the nonparametric bootstrap can be applied with multivariate nonnormally distributed data as well as multivariate normally distributed data, and small sample sizes. Therefore, this method is preferable when raw data are available. Three craniometric samples are used to present the methods. A Hungarian Zalavár sample and an Austrian Berg sample are compared to a Norwegian Oslo sample, the latter employed as reference sample. In agreement with a previous study, it is shown that the Zalavár sample does not represent surplus variability, whereas the Berg sample does represent such a surplus variability.

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.

Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study.

BACKGROUND: Biochemical liver function tests are widely used in the clinic and are some of the most frequently used tests in screening for diseases in older age groups. The aim of the present study was to estimate the relative importance of genetic and environmental factors to variations in these tests among the elderly. METHODS: We conducted a survey among Danish twins, 73-102 years of age, identified in the population-based Danish Twin Registry. Among the 2749 individuals in the study population, an interview was conducted with 79%. From these, a blood sample was collected from 290 same-sex twin pairs, total of 580 subjects, within a 6-month period and analyzed for alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and albumin. The interview included questions about alcohol consumption and body mass index (BMI; self-calculated height and weight). Heritability (proportion of the population variance attributable to genetic variation) was estimated using structural-equation analyses before and after correction for alcohol consumption and BMI. RESULTS: Structural-equation analyses revealed a substantial heritability (35-61%) for the four biochemical liver function tests: ALT, GGT, LDH, and bilirubin. The remaining variation could be attributed to individuals' nonfamilial environments. Adjustment for alcohol consumption and BMI had no influence on the heritability for ALT, GGT, LDH, and bilirubin. For albumin, two models fit equally well before adjustment for alcohol and BMI: a model including additive genetic and nonshared environmental factors (AE), and a model including shared and nonshared environmental factors (CE). After adjustment, the model including shared and nonshared environment was clearly the best fitting model. CONCLUSIONS: For both males and females, the effect of genetic factors on the biochemical liver function tests ALT, GGT, LDH, and bilirubin is substantial and accounts for one-third to two-thirds of the variation among individuals 73-102 years of age. The heritability is equal for males and females and does not change notably after controlling for alcohol consumption and BMI. For albumin, no major impact of genetic factors was found independent of BMI and alcohol consumption. An understanding of the genetic mechanisms underlying biochemical liver function tests among the very old may be of value in the interpretation of these tests in this age group.