Low plasma thiamine and phosphate in male patients with Parkinson's disease is associated with mild cognitive impairment.

OBJECTIVES: Thiamine deficiency (TD) and phosphate depletion increase the risk for cognitive disturbances. This study investigates whether plasma levels of thiamine (P-THIAM), thiamine-monophosphate (P-TMP), and phosphate (P-PHOS) are associated with mild cognitive decline (MCI) in patients with Parkinson's disease (PD). DESIGN AND STUDY POPULATION: This case-control study includes baseline data from a cohort of newly diagnosed patients identified in the New Parkinsonism in Umeå study (NYPUM) (N = 75) and an age and sex matched control group (n = 24). MEASUREMENTS: Mini Nutritional Assessment (MNA-score) and concentrations of P-THIAM, P-TMP, and P-PHOS at baseline were compared between PD patients with mild cognitive impairment (PD-MCI) and PD patients with normal cognition (PD-NC). Neuropsychological assessments of MCI were performed at time of diagnosis. RESULTS: Compared to patients with NC, patients with MCI had lower levels of P-THIAM and P-TMP as well as lower scores on both the Mini Mental State Examination (MMSE) and MNA-screening test. In addition, patients with MCI were older and had more motor problems. The multiple logistic regressions adjusted for age and sex revealed that higher levels of P-THIAM and the MNA-total score were associated with a lower risk of having MCI. Higher MNA-total score and higher P-THIAM and P-PHOS concentrations decreased the risk of MCI in male patients, but not in female patients. The decreased risk of MCI with higher P-TMP levels was lost after adding age and sex to the model. Bivariate correlations between P-PHOS and P-TMP were shown for the total PD population and controls as well as for males with MCI (r = 0.533; n = 22; p = 0.011), but not for males with NC (r = 0.314; n = 19; p = 0.204). An inverse partial correlation (adjusted for age, sex and UPDRS III) was shown for P-THIAM and MNA-total (r = -0.315,p = 0.009) and -final (part II) (r = -0.395,p = 0.001) score for the PD population (n = 75). CONCLUSIONS: Higher P-THIAM and P-PHOS concentrations and higher MNA-total score were associated with a lower risk of MCI in male PD patients, findings that indicate that nutritional factors may influence cognitive function in males in the early phase of PD.

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease.

OBJECTIVES: Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2-receptor availability (Catechol-O-methyltransferase [COMT] Val158 Met genotype and DRD2 C957 T genotype) affect the development of cognitive deficits in PD. MATERIALS AND METHODS: One hundred and 34 patients with idiopathic PD, participating in a regional, population-based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6-10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD-MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome. RESULTS: Both genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT 158 Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P = .023), the DRD2 957 T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P < .001). The poorer cognitive performance in DRD2 957 T/T carriers with PD occurred mainly in episodic memory and attention. CONCLUSIONS: The results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas.

Gender differences in Parkinson's disease: A clinical perspective.

Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta-analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor-dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross-sectional. Good-quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD.

Intake of vitamin B before onset of Parkinson's disease and atypical parkinsonism and olfactory function at the time of diagnosis.

BACKGROUND/OBJECTIVES: To investigate whether vitamin-B density in the diet 2-8 years before diagnosis is associated with olfactory function at the time of diagnosis. SUBJECTS/METHODS: This prospective nested case-control study included patients with Parkinson's disease (PD), multiple system atrophy and progressive supranuclear paralysis identified between 2004 and 2009 in the county of Västerbotten in northern Sweden. The case database (NYPUM study; Newly Diagnosed Parkinson in Umeå; n=147) was cross-linked to the Northern Sweden Health and Disease Study (NSHDS). Identified patients (n=96) and controls (n=375) were matched for sex, age, year of health survey, sub-cohort and geographical area. Dietary intake was assessed by a food frequency questionnaire, and the brief smell identification test (B-SIT) was used to measure olfactory function at the time of diagnosis. RESULTS: There was no difference in vitamin-B or any other macro- or micro-nutrient densities, energy intake or body mass index (kg/m2; BMI) between patients and controls at baseline at the time of the healthcare survey. A lower thiamin and folate density, amount per 1 megajoule, was reported in patients who scored below median on B-SIT (<7) when compared with that in patients who scored ⩾7 at the time of diagnosis. After adjusting for age, sex and BMI using linear and logistic regressions, an even stronger association was found between thiamin density and olfactory function. CONCLUSIONS: A low thiamin and folate density in the reported diet, 2-8 years before PD diagnosis, was significantly associated with olfactory dysfunction at the time of PD diagnosis.

Frontal white matter injuries predestine gait difficulties in Parkinson's disease.

OBJECTIVES: This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinson's disease. MATERIAL AND METHODS: One hundred and twenty-two patients (47 females, mean age = 70.3 years) were included at baseline. Forty patients were tremor dominant (TD), 64 had postural imbalance and gait difficulty (PIGD), and 18 patients were indeterminate. The DTI was repeated after one, three and 5 years, including reassessment of phenotype. DTI was quantified using fractional anisotropy (FA), and mean, radial and axial diffusion. Targeted white matter involved six regions of interests (ROIs) in prefrontal cortex (PFC), the entrance to the external capsule (EEC) and lateral to the horn of the anterior ventricle (LVAH). Grey matter involved the basal ganglia. Data were analysed using mixed linear models with P < 0.05 (Bonferroni corrected) as significance threshold. RESULTS: PIGD and Indeterminate had reduced FA and axial diffusion in PFC, EEC and LVAH compared to Tremor dominant (P < 0.05). Basal ganglia showed no differences. Post hoc analysis showed that FA correlated negatively, and mean and radial diffusion positively, to PIGD symptoms in EEC, LVAH and four ROIs in PFC (P < 0.05). Tremor symptoms showed no correlations. Patients converting to PIGD and Indeterminate had lower FA, and higher mean and radial diffusion, at baseline in EEC, LVAH and four areas in PFC compared to non-converting patients (P < 0.05). CONCLUSION: Degeneration in frontal white matter is connected to PIGD symptoms in Parkinson's disease and if present at an early stage, the risk for conversion to the PIGD phenotype increases.

Management of dystonia in Europe: a survey of the European network for the study of the dystonia syndromes.

BACKGROUND AND PURPOSE: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. METHODS: A survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. RESULTS: Lack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. CONCLUSIONS: Internationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.

Olfactory Function, Eating Ability, and Visceral Obesity Associated with MMSE Three Years after Parkinson's Disease Diagnosis.

OBJECTIVES: This study examines whether risk factors for poor nutrition are associated with global cognitive function three years after confirmed Parkinson's disease (PD) diagnosis. DESIGN: The follow-up investigations for this prospective community-based study were conducted three years after PD diagnosis. SETTING: The study participants lived in Västerbotten County, a region in northern Sweden with 142,000 inhabitants. PARTICIPANTS: This study population consisted of 118 PD outpatients from the study of Newly Diagnosed PD in Umeå (NYPUM). MEASUREMENTS: Global cognition was assessed with the Mini Mental State Examination (MMSE) at baseline and at follow-up. Anthropometry, nutrition (Mini Nutritional Assessment, MNA, 3-day food registration, 3-FDR), olfactory function (Brief Smell Identification Test, B-SIT), and swallowing, cutting food, and salivation (single questions from the Unified Parkinson's Disease Rating Scale, UPDRS) were used as markers for nutritional status. RESULTS: The MMSE score decreased over three years (-1.06±3.38, p=0.001). Olfactory function at baseline was associated to MMSE at three years (B=0.365, p=0.004). Changes in waist/hip ratio (B=113.29, p=0.017), swallowing (B=1.18, P=0.033), and cutting food (B=-1.80, p=0.000) were associated with MMSE at follow-up. CONCLUSION: This study indicates that olfactory function, cutting food, swallowing, and visceral obesity are associated with MMSE three years after PD diagnosis.

Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture.

BACKGROUND AND PURPOSE: This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinson's disease (PD) with healthy controls using longitudinal data. METHODS: One-hundred and twenty-two patients and 34 controls were included at baseline. The MRI investigations were repeated after 1, 3 and 5 years. The diffusion measures were quantified using fractional anisotropy and mean, radial and axial diffusion (FA, MD, RD, AD). Regions of interest included the anterior, middle and posterior substantia nigra (SN), but also other areas. Linear models were used to test for the effect of disease and hemispheric lateralization. The P value was set at 0.05 (Bonferroni corrected). RESULTS: Fractional anisotropy and AD were increased in the three nigral subareas in PD (P < 0.01), but MD and RD were unaltered. The right SN had higher FA than the left in all subareas (P < 0.01). MD and AD were increased in the right anterior part (P < 0.04), whereas MD and RD were decreased in the right middle and posterior parts (P < 0.001). The left middle cerebellar peduncle had increased FA and AD (P < 0.001) and decreased MD and RD (P < 0.01) compared to the right. Diffusion measures did not progress over time and side differences were not related to disease or lateralization of symptoms. CONCLUSIONS: Increased FA in the SN in PD indicates gliosis and inflammation in the nuclei, but possibly also intrusion of surrounding fibres into the shrinking structure. The hemispheric side differences of diffusion might reflect natural lateralization of connectivity, but their relation to PD must be studied further.

Cognitive function in the early phase of Parkinson's disease, a five-year follow-up.

BACKGROUND: Presence of mild cognitive impairment (MCI) as a predictor for Parkinson's disease dementia (PDD) has been discussed from a clinical perspective. Recently, a Movement Disorder Society (MDS) commissioned Task Force published guidelines for PD-MCI. However, long-term follow-ups of the PD-MCI guidelines for the prediction of PDD have been sparse. METHOD: In a community-based cohort of PD, the MDS guidelines for PD-MCI and consensus criteria for PDD were applied on 147 subjects. The predictive ability of PD-MCI for PDD was investigated. Additionally, baseline comparisons were conducted between MCI that converted to PDD and those who did not, and evolvement of motor function was investigated. RESULTS: One fourth of the population developed PDD. MCI and age at baseline predicted later occurrence of PDD, and baseline results of tests measuring episodic memory, visuospatial function, semantic fluency, and mental flexibility differed between MCI converters and non-converters. Postural instability/gait (PIGD) phenotype and education did not predict later occurrence of PDD, but increased postural/gait disturbances were shown across time in those developing dementia. CONCLUSION: The new PD-MCI guidelines are useful to detect patients at risk for developing PDD. The PIGD phenotype at diagnosis was not a predictor of PDD within 5 years, but the study supports a temporal association between postural/gait disturbances and PDD. Older patients with PD-MCI at baseline with decline in episodic memory, semantic fluency, and mental flexibility need to be carefully monitored regarding cognition and likely also for fall risk.

Cardiovascular risk factors and the risk of Parkinson's disease.

BACKGROUND/OBJECTIVES: The objective of this study was to investigate whether serum triglycerides (S-TG), cholesterol, blood pressure and waist/height ratio are risk factors for Parkinson's disease (PD). SUBJECTS AND METHODS: A population-based sample within the Northern Sweden Health and Disease Study (NSHDS) was used in this study (n=101 790 subjects). Cases with PD were identified prospectively in a community-based study of idiopathic Parkinsonism in the period 2004-2009 in the county of Västerbotten in northern Sweden. The case database obtained was crosslinked to the NSHDS. Eighty-four of 147 patients with PD had visited the primary health care 2-8 years before diagnosis for participation in the NSHDS. For each case, four referents from the NSHDS population were selected, matched for sex, age, year of health survey, subcohort and geographic area. RESULTS: Cases had lower mean S-TG levels (P=0.007). After stratification for sex, the lower S-TG remained significant for men (P=0.006) but not for women (P=0.450), and these were confirmed by the conditional logistic regression for all cases, none adjusted (hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.42, 0.99) and after adjusting for age, body mass index (BMI) and physical activity (HR: 0.61; 95% CI: 0.39, 0.96). Systolic blood pressure (SBP) was negatively associated with PD risk after adjustments for age, BMI and physical activity (HR: 0.98; 95% CI: 0.97-0.99). Smoking and former smoking were associated with a reduced risk for PD. CONCLUSIONS: We found lower S-TG and SBP 2-8 years before a diagnosis of PD. Smoking was confirmed to be negatively associated with PD, whereas recreational activity indicates a risk for women.

Retigabine as add-on treatment of refractory epilepsy--a cost-utility study in a Swedish setting.

OBJECTIVES: To calculate comparative incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) and net marginal benefits for retigabine as add-on treatment for patients with uncontrolled focal seizures as compared to add-on lacosamide treatment and no add-on treatment, respectively. MATERIALS & METHODS: Calculations were performed using a validated decision-tree model. The study population consisted of adult patients with focal-onset epilepsy in published randomized placebo-controlled add-on trials of retigabine or lacosamide. Healthcare utilization and QALY for each treatment alternative were calculated. Probabilistic sensitivity analysis was performed using the specification of this model as a basis for Monte Carlo simulations. 2009 prices were used for all costs. RESULTS: Results were reported for a 2-year follow-up period. Retigabine add-on treatment was both more effective and less costly than lacosamide add-on treatment, and the cost per additional QALY for the retigabine no add-on (standard) therapy comparison was estimated at 2009€ 15,753. Using a willingness-to-pay threshold for a QALY of € 50,000, the net marginal values were estimated at 2009€ 605,874 for retigabine vs lacosamide and 2009€ 2,114,203 for retigabine vs no add-on, per 1,000 patients. The probabilistic analyses showed that the likelihood that retigabine treatment is cost-effective is at least 70%. CONCLUSIONS: The estimated cost per additional QALY, for the retigabine vs no add-on treatment comparison, is well within the range of newly published estimates of willingness to pay for an additional QALY. Thus, add-on retigabine treatment for people with focal-onset epilepsy with no/limited response to standard antiepileptic treatment appears to be cost-effective.

Anal sphincter electromyography in patients with newly diagnosed idiopathic parkinsonism.

OBJECTIVES: The differential diagnosis of patients with idiopathic parkinsonism is difficult, especially early in the course of the disease. External anal sphincter electromyography (EAS-EMG) has been reported to be of value in the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA). Patients with MSA are reported to have pathological EAS-EMG and patients with PD are reported to have significantly less pathological EAS-EMG results. Comparisons between patients with parkinsonian disorders have usually been made many years into the disease, and thus it is largely unknown if the results of EAS-EMG can be used to distinguish the different diagnoses in the early phase of the disease. MATERIALS AND METHODS: We investigated 148 newly diagnosed patients with idiopathic parkinsonism from a population-based incidence cohort (100 definite PD, 21 probable PD, 16 MSA, 11 progressive supranuclear palsy, and 40 controls) with EAS-EMG within 3 months of their first visit and, in the majority of patients, before start of treatment with dopaminergic drugs. The clinical diagnoses were made using established clinical diagnostic criteria after a median follow-up of 3 years. RESULTS: All patient groups had more pathological EAS-EMG results than controls. No EAS-EMG differences were found between the patient groups, especially not between PD and MSA. CONCLUSIONS: External anal sphincter electromyography examination cannot separate the different parkinsonian subgroups from each other in early course of the diseases.

Activities of daily living and quality of life in persons with newly diagnosed Parkinson's disease according to subtype of disease, and in comparison to healthy controls.

OBJECTIVE: To describe activity of daily living (ADL) and quality of life (QoL) at first visit to a neurological centre, in patients subsequently diagnosed with Parkinson's disease (PD), according to subtype of disease and compared to healthy controls. MATERIALS AND METHODS: 99 patients and 31 controls were included. Patients were classified into three groups according to predominant symptoms: 50 Postural instability-gait difficulties (PIGD), 37 tremor dominant, 12 indeterminate. Evaluations included ADL-taxonomy, SF-36, and the Parkinson disease questionnaire (PDQ-39). RESULTS: Patients experienced early on limitations in ADL and QoL compared to controls. Patients with PIGD subtype had already at first visit a worse status, clinically and in ADL and QoL, than patients with tremor dominant type. CONCLUSIONS: Already at first visit to a neurological centre, patients who will eventually receive the diagnosis of PD exhibited restrictions in ADL and QoL. Patients with axial symptoms were affected most.

Lacosamide as treatment of epileptic seizures - cost utility results for Sweden.

OBJECTIVES: To calculate cost per additional quality-adjusted life-year (QALY) for lacosamide as adjunctive treatment for patients with uncontrolled partial-onset seizures as compared to no adjunctive treatment. MATERIALS AND METHODS: A decision-tree simulation model was constructed to calculate the number of seizures and health-care utilization for treated and untreated with lacosamide, respectively. Prices from 2007 were used for all costs. RESULTS: All results were calculated for a 24-, 18-, 12- and 6-months follow-up. The cost per additional QALY was estimated to euro 27,641 (24 months). Using a willingness-to-pay threshold for a QALY of euro 50,000 the net marginal value of using lacosamide was estimated to about euro 850,000 per 1000 patients. CONCLUSIONS: The estimated cost per QALY gained falls within the range of reported estimates of the willingness-to-pay for an additional QALY. The results imply that lacosamide is cost-effective in the treatment of uncontrolled partial-onset seizures (1 euro approximately 9.6 SEK).

Cognitive function in early Parkinson's disease: a population-based study.

BACKGROUND AND PURPOSE: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson's disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls. METHODS: Patients were identified in a longitudinal population based study of idiopathic non-drug induced parkinsonism. Eighty-eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age- and sex-matched healthy control subjects underwent a comprehensive neuropsychological assessment. RESULTS: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in > or =1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with > or =2 cognitive domains affected. CONCLUSION: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.

Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients.

Peripheral immune responses can be sensitive indicators of disease pathology. We evaluated the autoimmune reactions to endocrine (insulin) and astrocytical (S100B) biomarkers in the blood sera of 26 Parkinson's disease (PD) patients compared with controls by using ELISA. We found a statistically significant increase of the autoimmune responses to both antigens in PD patients compared with controls with a mean increase of 70% and 50% in the autoimmune reactions towards insulin and S100B, respectively. Heterogeneity of the immune responses observed in patients may reflect the modulating effect of multiple variables associated with neurodegeneration and also changes in the basic mechanisms of individual autoimmune reactivity. We did not detect any pronounced immune reactions towards insulin amyloid fibrils and oligomers in PD patients, indicating that an amyloid-specific conformational epitope is not involved in immune recognition of this amyloid type, while sequential epitope of native insulin is hidden within the amyloid structures. Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD.

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.

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.

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.

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.