A missense polymorphism in the putative pheromone receptor gene VN1R1 is associated with sociosexual behavior.

Pheromones regulate social and reproductive behavior in most mammalian species. These effects are mediated by the vomeronasal and main olfactory systems. Effects of putative pheromones on human neuroendocrine activity, brain activity and attractiveness ratings suggest that humans may communicate via similar chemosignaling. Here we studied two samples of younger and older individuals, respectively, with respect to one nonsynonymous polymorphism in the gene encoding the human vomeronasal type-1 receptor 1, VN1R1, and one nonsynonymous polymorphism in the gene encoding the olfactory receptor OR7D4. Participants in both samples had self-reported their sociosexual behavior using the sociosexual orientation inventory, including questions regarding lifetime number of one-night stands, number of partners last year and expected number of partners the coming 5 years. In women, there was a significant association between the VN1R1 polymorphism and sociosexual behavior in both samples, driven specifically by the question regarding one-night stands. Our results support the hypothesis that human social interaction is modulated by communication via chemosignaling.

A 10-year follow-up of the European multicenter trial of interferon ß-1b in secondary-progressive multiple sclerosis.

OBJECTIVES: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). METHODS: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. RESULTS: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R(2): 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R(2): 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. CONCLUSIONS: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.

Long-term follow-up of pediatric patients treated with mitoxantrone for multiple sclerosis.

The chemotherapeutic agent mitoxantrone is approved for the treatment of aggressive multiple sclerosis (MS) in adults. Its use, however, is limited by the risk of severe adverse events including cardiotoxicity, myelosuppression, liver toxicity and secondary leukemia. The aim of this retrospective study is to present data on the safety, tolerability and efficacy of mitoxantrone in a small cohort of children with MS. 4 pediatric MS patients with a high relapse rate or severe, disabling relapses were treated with mitoxantrone and followed for 3.8-18 years. The cumulative dose of mitoxantrone was 36, 68, 84 and 120 mg/m (2), respectively. The frequency and severity of relapses as well as disability scores, decreased in the year after treatment onset. Short-term adverse events were transient in all cases. Cardiac monitoring by transthoracic echocardiography (TTE) showed asymptomatic left ventricular dysfunction during treatment in 1 patient, which was again normal at the next assessment. Long-term adverse events, including late-onset mitoxantrone-induced cardiotoxicity or secondary leukemia did not occur during the follow-up period. In our cohort of pediatric MS patients, mitoxantrone showed short-term reduction of disease activity and no long-term adverse events on follow-up. However, the risk of mitoxantrone-induced cardiotoxicity or toxic leukemia remains a life-long threat.

Patient-reported quality of life in multiple sclerosis differs between cultures and countries: a cross-sectional Austrian-German-Polish study.

BACKGROUND: Patient-reported quality of life (QOL) is an outcome measure in clinical trials in multiple sclerosis (MS), but translated QOL instruments may affect the actual comparability of data. OBJECTIVES: We aimed to investigate possible differences in QOL in MS between cultures and countries. We employed the Functional Assessment of Multiple Sclerosis (FAMS) Version 4 questionnaire, which is a state-of-the-art QOL instrument. METHODS: Some 484 MS patients from Austria (145), Germany (144), and Poland (195) aged 20-60 years, and stratified for sex and disease severity as measured by the Expanded Disability Status Scale (EDSS) score completed the respective FAMS translation and a socio-demographic questionnaire. RESULTS: Analysis of variance and post-hoc Scheffé-test showed that 64% of the FAMS items were answered significantly differently (p < 0.001) between the three countries. A multivariate regression analysis including all the available disease-related and socio-demographic variables revealed the factors age, EDSS score, employment, social contacts, MS course, and country to be significant predictors of both the total FAMS score and the score for items answered differently between the three countries. CONCLUSIONS: Differences exist in the QOL of MS patients from Austria, Germany, and Poland which seem to lie beyond the impact of disease severity. They appear to be related to culture or other country-specific factors, as country was an independent predictor of differently answered items of the FAMS and thus also of the whole FAMS. QOL instruments should consider this aspect to faithfully reflect subjective information such as patient-reported benefit of treatment in multinational clinical trials.

Decision-making for and impact of early immunomodulatory treatment: the Austrian Clinically Isolated Syndrome Study (ACISS).

BACKGROUND AND PURPOSE: When to start disease-modifying treatment (DMT) in patients with a clinically isolated syndrome (CIS) requires individual weighing of benefits versus possible burden of side effects and costs. How this occurs in a routine setting is barely known. The aim of the study was to investigate the decision-making process regarding immediate or later DMT and the ensuing impact on CIS patients in Austria. METHODS: Demographic and (para) clinical characteristics of 296 CIS patients were recorded in 29 multiple sclerosis (MS) centres, and the patients' overall condition was rated on a visual analogue scale (VAS). Clinical follow-up and VAS ratings were repeated at 6-month intervals over 2 years. The decision for initiation of DMT was at the physician's and patient's discretion. RESULTS: In 29% of patients, DMT was started within 3 months and this decision was independently associated with a T2-lesion number >or=9 on MRI and a worse VAS rating by the physician. DMT initiation in the subsequent 6 months was additionally associated with the presence of oligoclonal bands and rarely occurred thereafter. Adapted to the clinical course, later treatment was associated with the highest rate of conversion to clinically definite MS and greatest disability after 2 years whilst never treated patients fared best. Patient VAS ratings significantly improved during follow-up independently of treatment decisions. CONCLUSION: The management of Austrian CIS patients relies strongly on MRI findings and the physicians' interpretation of the patients' overall situation which, after 2 years, depends primarily on the course of the disease.

A longitudinal study on effects of a six-week course for energy conservation for multiple sclerosis patients.

OBJECTIVE: Fatigue management and energy conservation are effective strategies to minimize fatigue in multiple sclerosis (MS). Sustained results have not yet been reported. METHODS: A fatigue management course was provided for 32 MS patients. They were tested prior to, directly after participation in the course and in a 7-9 month follow-up with the Fatigue Severity Scale, the MS-specific Fatigue Scale, the Modified Fatigue Impact Scale (MFIS), the Pittsburgh Sleep Quality Index and a self-rating scale for depression. The Expanded Disability Status Score (EDSS) and the MS functional composite (MSFC) were evaluated before and after participation in the course. RESULTS: The total score and the Cognitive and Physical subscores of the MFIS showed significant improvements on both points of time. Scores in the Fatigue Severity Scale, MS-specific Fatigue Scale and Psychosocial Fatigue Impact Scale did not improve significantly. MS functional composite and EDSS remained unchanged after six weeks of course participation. Subjective sleep quality improved directly after participation in the course and after 7-9 months. The depression score decreased significantly to a normal level at the end of training and in the 7-9 month follow-up. CONCLUSION: Fatigue management enables MS patients to cope with their fatigue and energy more effectively. Follow-up evaluations showed stable results after 7-9 months.

The differential diagnosis of foot lumps: 101 cases treated surgically in North Glasgow over 4 years.

INTRODUCTION: There are a wide variety of different lesions which present as lumps of the foot. There have been very few studies which look at the presenting characteristics or the differential diagnosis of such lesions. PATIENTS AND METHODS: All patients who underwent excision or biopsy of a foot lump over a period of 4 years were studied in order to determine patient demographics, presenting characteristics, diagnoses encountered and to assess the diagnostic accuracy of the surgeon. RESULTS: In total, 101 patients were identified. Average age was 47.3 years (range, 14-79 years); there was a marked female preponderance with 73 females and 28 males. Thirty different histological types were identified; ganglion cysts were the most commonly encountered lesions and there was only one malignant lesion encountered in this study. Only 58 out of the 101 lumps were correctly diagnosed prior to surgery. Certain lesions were more commonly encountered in specific zones of the foot. CONCLUSIONS: We have shown that there are a wide variety of potential diagnoses which have to be considered when examining a patient with a foot lump. There is a low diagnostic accuracy for foot lumps and, therefore, surgical excision and histological diagnosis should be sought if there is any uncertainty.

Mutations in the CLCN2 gene are a rare cause of idiopathic generalized epilepsy syndromes.

Mutations in the chloride channel gene CLCN2 have been reported in families with generalized and focal epilepsy syndromes. To evaluate the contribution of mutations in the CLCN2 gene to the etiology of epilepsies in our population, we screened 96 patients with different epilepsy syndromes and a putative genetic background. No definite mutations were found in our study population. We conclude that mutations in the CLCN2 gene are only a rare cause of idiopathic generalized epilepsy.

Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene.

Mutations in the valosin-containing protein (VCP) on chromosome 9p13-p12 were recently found to be associated with hereditary inclusion body myopathy, Paget disease of the bone, and frontotemporal dementia (IBMPFD). We identified a novel missense mutation in the VCP gene (R159H; 688G>A) segregating with this disease in an Austrian family of four affected siblings, who exhibited progressive proximal myopathy and Paget disease of the bone but without clinical signs of dementia.

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Factors influencing quality of life in multiple sclerosis patients: disability, depressive mood, fatigue and sleep quality.

OBJECTIVES: In a series of 504 patients with multiple sclerosis (MS), quality of life (QOL) and its main clinical and demographic determinants were assessed in comparison with healthy individuals. MATERIALS AND METHODS: A postal questionnaire with self-completed measures of disability (Expanded Disability Status Scale, EDSS), QOL (Quality of Life Index, QLI), depressive mood (Self-rating Depression Scale, SDS), fatigue severity (Fatigue Severity Scale, FSS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) was sent to this sample of MS patients. RESULTS: Most patients were severely disabled; almost half were mildly to severely depressed, suffering from reduced sleep quality and/or fatigue. The multiple sclerosis patients had significantly lower QLI scores than healthy controls. EDSS and SDS scores were found to be predictors of global QLI score. Regarding the different QLI domains, mean SDS scores remained predictive for all QLI items, while mean EDSS, PSQI and FSS scores were only predictive for physical domains. CONCLUSION: Our study clearly demonstrates that depressive mood is the main factor influencing QOL. The disability status, fatigue and reduced sleep quality have an impact mainly on physical domains of life quality.

[Health care costs of multiple sclerosis in Austria. Cross-sectional study including consideration of quality of life]. / Krankheitskosten der multiplen Sklerose in Osterreich. Querschnittstudie unter Berücksichtigung der Lebensqualität.

A retrospective, cross-sectional study was performed to evaluate direct and indirect costs related to multiple sclerosis (MS) in Austria in a representative cohort of patients ( n=895) with typical symptoms. Demographic, socioeconomic, and disease-related data including degree of disability and health-related quality of life as well as consumption of medical and nonmedical resources were recorded and mean total costs per patient and year were calculated (based on 1999 figures). Total direct costs borne by public sources were 15,684 euro per MS patient per year. Overall societal costs increased disproportionately with the progression of the disease, from 12,990 euro per year in patients with mild disability to 69,554 euro per year in patients with severe disability. Increasing disability was reflected by substantial deterioration of health status-related quality of life. Direct costs of MS in Austria are similar to those in other countries.

Iron(II) sulfate release from drop-formed lipophilic matrices developed by special hot-melt technology.

Iron(II) sulfate-containing lipophilic matrices were developed by a special hot-melt technology (melt solidification in drops), using stearin, white wax and their mixture as conventional bed materials. The special technology resulted in spherical particles which can be filled directly into capsules; these store iron as a depot and ensure a slow and uniform release, whereby the irritation of the gastric mucosa by the iron can be decreased. The rates of dissolution of the iron(II) sulfate from the various lipophilic matrices were different, but fundamentally low. Kinetic calculations demonstrated that the rate of dissolution of the iron(II) sulfate was of approximately zero kinetic order. The results of in vivo experiments on rabbits correlated well with the in vitro data. The plasma curves for the animals treated with the iron(II) sulfate preparations varied with the excipients in the depot products. The properties and ratio of the bed materials influenced the release of the iron(II) sulfate. In all probability, the release of the active agent can be regulated through the use of a melt of stearin and white wax in different ratios. The development products functioned as a sustained-release system and ensured elimination of the irritation of the gastric mucosa. At the same time, the results justified the applicability of the special hot-melt technology in the development of the solid dosage form.

Prevalence of multiple sclerosis in Austria. Results of a nationwide survey.

The epidemiology of multiple sclerosis (MS) in Austria is almost unknown. We evaluated the prevalence of MS in Austria using data from questionnaires completed by neurologists, comprising information on a total of 1,006 MS patients who attended 30 out-patient specialized clinics nationwide. Additional data were collected from 2,414 MS patients, who received questionnaires from the Austrian MS Society or their doctor. A novel extrapolation model, based on frequencies of patients visits at MS clinics, was used to estimate the overall prevalence of MS. Considering either disability or the course of the disease, the prevalence of MS patients in Austria was estimated to be 98.5 per 100,000 people. The prevalence of MS in Austria was found to be similar to that of other countries in Central Europe. Epidemiological studies, such as this, provide a unique source of data from which key features of a disease and its impact on patients may be examined.

Apolipoprotein E epsilon 4 is associated with rapid progression of multiple sclerosis.

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is known to impact on various neurologic disorders and has differential effects on the immune system and on CNS repair. Previous findings concerning a possible modulation of the clinical course of MS have been inconsistent, however. METHODS: In a cross-sectional study, the authors investigated 374 patients with clinically definite MS and a disease duration of at least 3 years and related their clinical and demographic findings to the allelic polymorphism of the APOE gene. The genotype distribution of patients with MS was compared with a cohort of 389 asymptomatic, randomly selected elderly volunteers. RESULTS: The authors found no significant differences in the distribution of genotypes between patients with MS and controls. However, patients with MS with the epsilon4 allele (n = 85) had a significantly higher progression index of disability (0.46 +/- 0.4 versus 0.33 +/- 0.26; p < 0.004) and a worse ranked MS severity score (5.1 +/- 1.9 versus 5.7 +/- 1.7; p = 0.05) than their non-epsilon4 counterparts, despite significantly more frequent long-term immunotherapy in epsilon4 carriers (74% versus 58%; p < 0.007). The annual relapse rate in epsilon4 carriers (0.87 +/- 0.56) was significantly higher than in patients with MS without an epsilon4 allele (0.71 +/- 0.47; p = 0.03). CONCLUSIONS: These results suggest no effect of the APOE genotype on susceptibility to MS, but indicate an association of the APOE epsilon4 allele with a more severe course of the disease.

Hypertrophic chronic pachymeningitis as a localized immune process in the craniocervical region.

Hypertrophic chronic pachymeningitis (HCP) is a rare disorder that causes intracranial or spinal thickening of the dura mater. This report describes a patient with progressive HCP in the craniocervical region associated with signs of rheumatic disease. A ventricular-atrial shunt had to be inserted because of increased intracranial pressure. The patient improved after suboccipital craniotomy, C1 to C6 laminectomy, and removal of the thickened dura. Additional therapy with methotrexate stopped progression, which was documented by MRI and PET.

Neurological rehabilitation of severely disabled cardiac arrest survivors. Part I. Course of post-acute inpatient treatment.

BACKGROUND: Some survivors of out-of-hospital cardiac arrest (CA) sustain anoxic brain injury. The aim of this study was to offer these patients a new treatment approach, to describe the course and outcome of rehabilitation, and to judge whether rehabilitation provided benefit. METHODS: Twenty severely disabled patients (mean age 47.6 years, 17 M:3 F) were admitted for inpatient rehabilitation after sustaining anoxic brain damage secondary to CA. The multidisciplinary treatment approach aimed at orientation, communication, mobility, and self care. Function was assessed using Barthel index (BI) score. On discharge, placement and global outcome was noted. Medical charts of consecutive patients were reviewed retrospectively. RESULTS: Inpatient rehabilitation lasted on for average 12 weeks. Improvement in function was slow with a median increase of 1.88 BI score per week. Patients achieved clinically significant functional improvement as measured by pre-post comparison of BI (P<0.001). On discharge, overall disability was mild in 2 (10%), moderate in 7 (35%), and severe in 11 (55%) patients. CONCLUSION: Rehabilitation of selected CA survivors is appropriate, reducing the subsequent burden of care. Although in 55%, only minor dependence on care persisted, on a group level, the potential for rehabilitation was modest, and recovery curve was flat. Before admission, families should be given realistic information about the possible outcome, because independence was rarely achieved.

Electrophysiological, neuropsychological and clinical findings in multiple sclerosis patients receiving interferon beta-1b: a 1-year follow-up.

We assessed serial event-related potentials (ERPs) as well as neuropsychological and clinical test findings in a group of multiple sclerosis (MS) patients (n = 14) treated with interferon beta-1b (INF-beta-1b) compared to normal controls (n = 14). All investigations were done within 1 week before INF-beta-1b therapy was started and 12 months later. An auditory oddball paradigm was employed. No significant differences in the N100, P200, N200 or P300 latencies between patients and control group were found, but 3 out of 14 MS patients developed abnormal P300 latencies (more than 2 standard errors from the mean) after 1 year of INF-beta-1b therapy. This was not reflected by the respective neurological impairment as assessed by the Expanded Disability Status Scale score. ERPs might be a useful tool in clinical studies in order to evaluate drug effects on cognition, but for a final statement, the analysis of ERPs in a larger group of patients is required.