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L Forsgren

Publications and source records attributed to L Forsgren.

At least 19 recordsLinked to original sources

The epidemiology of epilepsy in Europe - a systematic review.

Population-based epidemiological studies on epilepsy are available mainly from the UK and the Nordic, Baltic and western Mediterranean countries. No studies were identified from large areas of Europe, especially from the former eastern Europe (except the Baltic countries) and the eastern Mediterranean countries. Based on the prevalence of epilepsy in different studies and accounting for incomplete case identification the estimated number of children and adolescents in Europe with active epilepsy is 0.9 million (prevalence 4.5-5.0 per 1000), 1.9 million in ages 20-64 years (prevalence six per 1000) and 0.6 million in ages 65 years and older (prevalence seven per 1000). Approximately 20-30% of the epilepsy population have more than one seizure per month. Based on the age-specific incidence rates in European studies, the estimated number of new cases per year amongst European children and adolescents is 130,000 (incidence rate 70 per 100,000), 96,000 in adults 20-64 years (incidence rate 30 per 100,000) and 85,000 in the elderly 65 years and older (incidence 100 per 100,000). The proportion of both new and established cases with epilepsy in the young, adults and elderly in individual countries may differ substantially from total European distribution because of differences in age structure.

Age Distribution↗

An altered immune response to Epstein-Barr virus in multiple sclerosis: a prospective study.

OBJECTIVE: To investigate the association between human herpesviruses and multiple sclerosis (MS), as well as between measles virus and MS. METHODS: The authors identified prospectively collected serum samples from 73 MS cases and retrospective sera from 161 MS cases in two population-based serum bank registers. Analyses of IgG antibody responses in cases and matched referents were performed for Epstein-Barr virus (EBV [EBNA-1 and VCA]), human herpesvirus 6 (HHV-6), herpes simplex virus (HSV), varicella zoster virus (VZV), and measles. RESULTS: All cases showed signs of past EBV infection. High activity to EBNA-1 and HHV-6 significantly (borderline significance for HHV-6) increased the risk for MS in prospective sera. A discrepancy between activities to EBNA-1 and VCA was striking in MS samples collected less than 5 years before relapsing-remitting MS onset, where high activity to EBNA-1 significantly increased, and high VCA activity significantly decreased the risk for MS. There was no support for major causal roles for HSV, VZV, or measles. CONCLUSION: Individuals who will develop MS exhibit an altered immune response against the EBV virus characterized by a high IgG activity to EBNA-1 in the absence of high activity to VCA, this being most pronounced in the 5-year period preceding MS onset.

Adolescent↗

Teaching of neuroepidemiology in Europe: time for action.

Many epidemiological and clinical studies in Europe, especially in Eastern Europe and countries in transition, are of poor methodological quality because of lack of background knowledge in clinical epidemiology methods and study designs. The only way to improve the quality of epidemiological studies is to provide adequate undergraduate and/or postgraduate education for the health professionals and allied health professions. To facilitate this process, the European Federation of Neurological Societies (EFNS) Task Force on teaching of clinical epidemiology in Europe was set up in October 2000. Based on analyses of the current teaching and research activities in neuroepidemiology in Europe, this paper describes the Task Force recommendations aimed to improve these activities.

Education, Medical↗

Clinical characteristics of multiple sclerosis in Västerbotten County in northern Sweden.

BACKGROUND: Most clinical data for multiple sclerosis are hospital based-that is, derived from patients referred to clinics specialising in the disease. OBJECTIVES: To present data derived from two population based multiple sclerosis populations, an incidence cohort and a prevalence population, from Västerbotten County, northern Sweden. METHODS: The two populations were identified from multiple sources, and case ascertainment was assured through a personal clinical review, including interviews and examination of the patients. RESULTS: Characteristics at onset for the different clinical subtypes of multiple sclerosis are presented, including the clinical spectrum of the first attack, the anatomical correlation between the first and second attacks, sex distribution, and disability distribution. CONCLUSIONS: Based on the comparison of present and earlier natural history data, multiple sclerosis appears to be a slightly more benign disease than previously recognised.

Adult↗

Leisure time and social activity after a newly diagnosed unprovoked epileptic seizure in adult age. A population-based case-referent study.

PURPOSE: To investigate leisure time activity and factors that influence it in an adult cohort having newly diagnosed unprovoked epileptic seizures. PATIENTS AND METHODS: A cohort of 62 patients > or =17 years with a newly diagnosed unprovoked epileptic seizure during 1985-87 and 93 sex- and age-matched referents were followed up regarding leisure time activity, marital status and driver's license for 10 years till 1996. Data were questionnaire derived. RESULTS: Patients became significantly less physically active, traveled abroad less often and were generally less active during their leisure time than referents. No other significant differences were observed. CONCLUSION: After a newly diagnosed unprovoked epileptic seizure in adult age, most leisure time activities, marital status and holding of driver's license are not affected. Patients become physically less active than referents. The role of seizures for this difference is unclear and other medical and social factors should be considered.

Adult↗

Incidence (1988-97) and prevalence (1997) of multiple sclerosis in Västerbotten County in northern Sweden.

OBJECTIVE: To investigate the incidence and prevalence of multiple sclerosis in Västerbotten County in northern Sweden. METHODS: Multiple sources were used in the case identification process. Follow up interviews with clinical examinations were undertaken and, when indicated, additional paraclinical investigations were done. In this way case ascertainment was assured and supplemental clinical data were collected. The incidence rate was based on symptom onset. Onset adjusted prevalence was applied. RESULTS: The crude incidence rate of multiple sclerosis in 1988-97 in Västerbotten County was 5.2/10(5) (95% confidence interval, 4.4 to 6.2): 6.7/10(5) (6.0 to 8.3) in women and 3.7/10(5) (2.7 to 4.9) in men. The onset adjusted prevalence for 31 December 1997 was 154/10(5) (139 to 170): 202/10(5) (179 to 228) in women and 105/10(5) (89 to 125) in men. When compared with a previous estimate of prevalence, a yearly 2.6% increase in prevalence between 1990 and 1997 was found, mainly attributable to a higher incidence than mortality. CONCLUSIONS: The present incidence rate and prevalence confirms earlier findings that Västerbotten is a high risk area for multiple sclerosis. The adjusted incidence was twice as high as the incidence from 1974-88 in the only previous Swedish population based study from Göteborg, but comparable with other recent Fennoscandian multiple sclerosis incidence rates.

Adolescent↗

Sick leave and professional assistance for multiple sclerosis individuals in Västerbotten County, northern Sweden.

The aims of this study of a cross-sectional multiple sclerosis (MS) population in Västerbotten County, northern Sweden, were to estimate the prevalence of sick leave, professional assistance and housing; to study risk factors for sick leave; and to estimate the odds for sick leave in comparison with the general population of the county. The consequences of MS-related incapacity on the socioeconomic factors studied were considerable. Almost half (45%) of prevalent MS cases aged 18-64 years were fully sick listed and only one-third (35%) were not sick listed at all. Every fourth individual in the prevalence population received professional assistance, and 9% were living in care homes or special apartments for the disabled. Multiple logistic regression analysis identified the Expanded Disability Status Scale (EDSS) as the strongest predictor of sick leave. The time from symptom onset to full sick leave leading to temporary or permanent disability pension was significantly shorter for cases with progressive onset, higher age at onset and in males. The risk of full sick leave due to MS was six times higher than in the general population.

Adolescent↗

Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1.

Migraine is the most common type of chronic episodic headache. To find novel susceptibility genes for familial migraine with and without aura, a genomewide screen was performed in a large family from northern Sweden. Evidence of linkage was obtained on chromosome 6p12.2-p21.1, with a maximum two-point lod score of 5.41 for marker D6S452. The patients with migraine shared a common haplotype of 10 Mb between markers D6S1650 and D6S1960.

Adult↗

Heteroplasmy of the human mtDNA control region remains constant during life.

In a longitudinal, retrospective study, we monitored the level of heteroplasmy at nucleotide position (nt) 309 and nt 16189 of the control region of human mtDNA. As a unique source of DNA, we analyzed multiple cervical-cell samples collected, during 1 or 2 decades, from four women with heteroplasmy at either nt 309 or nt 16189. According to accurate, quantitative analysis by solid-phase minisequencing, the level of heteroplasmy remained stable in the cervical-cell samples from all four women during the time studied. We also analyzed autopsy samples from several different tissues, all containing nt 309 in heteroplasmic form, of one of the women, who was deceased. On the basis of our results, heteroplasmy in the control region of mtDNA seems to be inherited and is not the result of somatic age-related accumulation.

Autopsy↗

Seizure recurrence in adults after a newly diagnosed unprovoked epileptic seizure.

PURPOSE: To investigate the risk of seizure recurrence after a newly diagnosed unprovoked epileptic seizure in an adult population-based cohort. MATERIAL AND METHODS: A total of 107 patients aged >or=17 years with a newly diagnosed unprovoked epileptic seizure (index seizure) were prospectively identified for the period 1985-87. Patients were followed until the date of death or to the end of 1996 with a median follow-up of 10.3 years for surviving cases. Overall cumulative recurrence rates and possible influencing variables were calculated. RESULTS: At 750 days after the index seizure the recurrence was 58%, and after that no events occurred. Recurrence risk was significantly higher when index seizure was remote symptomatic or preceded by two or more seizures. No other study variable predicted seizure recurrence. CONCLUSION: Etiology and the occurrence of seizures before the index seizure after a newly diagnosed unprovoked epileptic seizure predict seizure recurrence. Thus, particular consideration should be given to these factors in the decision of whether or not to initiate antiepileptic treatment.

Adolescent↗

Remission of seizures in a population-based adult cohort with a newly diagnosed unprovoked epileptic seizure.

PURPOSE: To investigate the probability of achieving remission of seizures after a newly diagnosed unprovoked epileptic seizure in an adult population-based cohort. METHODS: 107 patients aged 17 years or older with a newly diagnosed unprovoked epileptic seizure (index seizure) in 1985 through 1987 were followed up until the date of death or to the end of 1996. The proportion of cases during follow-up that attained a 1-year, 3-year, 5-year remission was calculated by actuarial analyses. Variables for stratification were age at diagnosis, seizure type, etiology, EEG, and the occurrence of seizures within 1 year of initiation of antiepileptic drug (AED) therapy. RESULTS: Cumulative 1-, 3- and 5-year remission rates were 68, 64, and 58%. There was no statistically significant difference regarding time points of achieving a 1-year remission after epilepsy diagnosis and the subsequent probability during follow-up of attaining a 5-year remission. Having seizures within 1 year after beginning with an AED was a statistically significant predictor of never achieving 1-year remission of seizures during follow-up (refractory seizures). Other stratified variables were not statistically significant predictors. CONCLUSIONS: Seizure prognosis for the majority of patients with newly diagnosed epilepsy is good. The time required after epilepsy diagnosis to achieve a 1-year remission of seizures does not affect the probability of additionally achieving a 5-year remission. Patients with refractory seizures can be identified within a few years from diagnosis of epilepsy. These patients must be targeted early for optimization of pharmacologic treatment, possible surgery, and psychosocial intervention.

Actuarial Analysis↗

An incident case-control study of first unprovoked afebrile seizures in children: a population-based study of pre- and perinatal risk factors.

PURPOSE: The aim of this prospective incident community-based study was to assess the influence of pre- and perinatal risk factors in children in whom an unprovoked afebrile epileptic seizure later developed. METHODS: From November 1, 1985, until June 30, 1987, 75 children aged 0-15 years with a first unprovoked afebrile seizure were identified. After exclusion of cases with neonatal seizures (n = 14), two controls per case were selected from the same province in northern Sweden matched by age and sex. Files from maternity wards and pediatric clinics could be traced for 58 cases and 109 controls. These formed the study group. RESULTS: In the univariate analysis, the risk for an unprovoked afebrile seizure was significantly elevated for birth order (OR = 9.3; CI, 2.2-39), vaginal bleeding (OR = 17; 95% CI, 3.5-85), onset of hypertension during pregnancy (OR = 4.8; CI, 1.3-17), cesarean section (OR = 18; 95% CI, 3.7-88), short or long gestational age (OR = 6.7; 95% CI, 2.0-22), and an Apgar score < or =6 at any time (OR = 3.8; 95% CI, 1.2-12). None of these six factors was present in 48.3% of the cases and 89% in the controls. A combination of two or more risk factors found to be significant in the univariate analysis showed a pronounced increased risk for seizures (OR = 19; 95% CI, 5.6-65). In the multivariate analysis, the following characteristics remained statistically significant: vaginal bleeding, gestational age, and Cesarean section. Furthermore, smoking also was identified as a risk factor in the multivariate analysis (OR = 3.4; 95% CI, 1.1-10). CONCLUSIONS: Both pre- and perinatal factors may be associated with later development of epileptic seizures in children. However, in many of the cases, no such factors were identified.

Adolescent↗

Superoxide dismutase in CSF from amyotrophic lateral sclerosis patients with and without CuZn-superoxide dismutase mutations.

Mutations in CuZn-superoxide dismutase (CuZn-SOD) have been linked to familial amyotrophic lateral sclerosis (ALS), and motor neurone death is caused by the gain of a toxic property of the mutant protein. Here we determined amounts, activity and molecular forms of CuZn-SOD in CSF from ALS patients carrying the D90A and other CuZn-SOD mutations and patients without such mutations. There were no differences in amount of protein and enzymic activities of CuZn-SOD between 37 neurological controls, 54 sporadic and 12 familial ALS cases, and 10 cases homozygous for the D90A mutation. Three cases heterozygous for the A89V, S105L and G114A CuZn-SOD mutations showed low amounts of CuZn-SOD. There was no evidence for accumulation of inactive protein in any of the groups. Immunoblots showed no evidence for the presence of any precipitates or other molecular forms of CuZn-SOD with higher molecular weight in the groups. About 25% of the CuZn-SOD subunits in CSF from controls shows an N-terminal truncation. This truncated portion does not differ between controls and ALS groups not carrying CuZn-SOD mutations, but is 70% larger in samples from D90A homozygous ALS patients. The findings suggest an essentially normal amount and activity of D90A mutant CuZn-SOD in CNS tissues of ALS cases. The increased occurrence of N-terminally truncated mutant subunits may indicate a difference in degradation routes compared with the wild-type enzyme, resistance against subsequent proteolytic steps and/or a compromised downstream proteolytic machinery. Molecular fragments accumulated to a greater extent from the D90A mutant enzyme might contribute to the motor neurone degeneration. We also determined the other SOD isoenzymes: in the controls, CuZn-SOD contributed 75%, extracellular SOD 25% and Mn-SOD <5% of the total SOD activity. There was no difference in the amount of extracellular SOD between any of the groups.

Adult↗

Prevalence of multiple sclerosis in Västerbotten County in northern Sweden.

OBJECTIVE: To estimate the prevalence and clinical characteristics of multiple sclerosis (MS) in Västerbotten County in northern Sweden. METHODS: Individuals with MS were identified from several sources. A follow-up interview and/or examination was performed in 94% of cases still living in the area during 1997-99. Onset adjusted prevalence and a definition of onset symptoms were applied. RESULTS: A total of 313 cases were identified, resulting in an onset adjusted crude prevalence of MS for January 1990 of 125/105 (95% confidence interval (CI): 112-140). Female predominance was evident (163/105 (95% CI: 142-187) vs 86/105 (95% CI: 71-104)). Diagnostic coding registers were the most important source for identification of cases. CONCLUSIONS: The crude prevalence of MS in Västerbotten was higher than previous reports from other major areas in Scandinavia. The adjusted prevalence was significantly higher when compared with a previous study from Göteborg, south-western Sweden. The methodology used in this study gives a high degree of case ascertainment and increases the comparability of multiple sclerosis epidemiological studies.

Adolescent↗

A major locus for myoclonus-dystonia maps to chromosome 7q in eight families.

Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21.

Chromosome Mapping↗

Evidence for a common Spinocerebellar ataxia type 7 (SCA7) founder mutation in Scandinavia.

Spinocerebellar ataxia type 7 (SCA7) is a neuro-degenerative disorder characterised by progressive cerebellar ataxia and macular degeneration. SCA7 is one of the least common genetically verified autosomal dominant cerebellar ataxias (ADCAs) in the world (4.5 to 11.6%), but in Sweden and Finland SCA7 is the most commonly identified form of ADCA. In an inventory of hereditary ataxias in Scandinavia (Sweden, Norway, Denmark and Finland) we identified 15 SCA7 families, eight in Sweden and seven in Finland, while no cases of SCA7 could be found in Norway or Denmark. We examined whether the relatively high frequency of SCA7 families in Sweden and Finland was the result of a common founder effect. Only two out of 15 families could be connected genealogically. However, an extensive haplotype analysis over a 10.2 cM region surrounding the SCA7 gene locus showed that all 15 families studied shared a common haplotype over at least 1.9 cM. This strongly suggests that all Scandinavian SCA7 families originate from a common founder pre-mutation.

Ataxin-7↗

Mortality risk in an adult cohort with a newly diagnosed unprovoked epileptic seizure: a population-based study.

PURPOSE: We sought to investigate mortality risk in an adult cohort with newly diagnosed unprovoked epileptic seizures. METHODS: One hundred seven patients who were at least 17 years old and had newly diagnosed unprovoked epileptic seizures were prospectively identified during a period of 20 months between 1985 and 1987. Patients were followed until the date of death or the end of 1996. The standard mortality ratio (SMR) was analyzed in the whole cohort and in the portion of the cohort with recurrent seizures at inclusion. The influences on the SMR of time since diagnosis, sex, age at diagnosis, seizure cause, seizure type, and cause of death were also investigated. RESULTS: The SMR was significantly increased (SMR, 2.5; 95% confidence interval [CI], 1. 2-3.2). This significantly increased risk was found during the first 2 years after diagnosis (year 1: SMR, 7.3; 95% CI, 4.4-12.1; year 2: SMR, 3.6; 95% CI, 1.6-8.1) and at years 9-11 (SMR, 5.4; 95% CI, 2. 7-11.2). The increased mortality risk was most pronounced when the seizures occurred before the age of 60 years. Mortality risk was elevated among patients with remote symptomatic epilepsy (SMR, 3.3; 95% CI, 2.4-4.5) but not idiopathic epilepsy. CONCLUSIONS: There is increased mortality risk in an adult cohort with newly diagnosed unprovoked epileptic seizures. This increase is found in symptomatic patients, young patients, and during the first 2 years after the diagnosis.

Adolescent↗

Evaluation of the role of the D2 dopamine receptor in myoclonus dystonia.

A novel Val154-->Ile mutation in the D2 dopamine receptor (DRD2) on chromosome 11q23 has recently been shown to be associated with myoclonus dystonia (M-D) in one large family. Sequence analysis of the DRD2 gene in 5 M-D patients from different families did not reveal any mutations, nor was there evidence of linkage to the 11q23 region in the DRD2 gene in four other families. Receptor binding and signal transduction assays of the DRD2 mutant and wild-type receptors revealed identical agonist and antagonist affinities and functional responses. These studies suggest that M-D is genetically heterogeneous. The molecular mechanisms through which the Val-->Ile mutation may contribute to M-D remain to be determined.

Adolescent↗