The association of selected multiple sclerosis symptoms with disability and quality of life: a large Danish self-report survey.

BACKGROUND: People with multiple sclerosis (MS) experience a wide range of unpredictable and variable symptoms. The symptomatology of MS has previously been reported in large sample registry studies; however, some symptoms may be underreported in registries based on clinician-reported outcomes and how the symptoms are associated with quality of life (QoL) are often not addressed. The aim of this study was to comprehensively evaluate the frequency of selected MS related symptoms and their associations with disability and QoL in a large self-report study. METHODS: We conducted a cross-sectional questionnaire survey among all patients at the Danish Multiple Sclerosis Center, Copenhagen University Hospital, Denmark. The questionnaire included information on clinical and sociodemographic characteristics, descriptors of QoL and disability, as well as prevalence and severity of the following MS symptoms: impaired ambulation, spasticity, chronic pain, fatigue, bowel and bladder dysfunction, and sleep disturbances. RESULTS: Questionnaires were returned by 2244/3606 (62%). Participants without MS diagnosis or incomplete questionnaires were excluded, n = 235. A total of 2009 questionnaires were included for analysis (mean age 49.4 years; mean disease duration 11.7 years; and 69% were women). The most frequently reported symptoms were bowel and bladder dysfunction (74%), fatigue (66%), sleep disturbances (59%), spasticity (51%) and impaired ambulation (38%). With exception of fatigue and sleep disturbances, all other symptoms increased in severity with higher disability level. Invisible symptoms (also referred to as hidden symptoms) such as fatigue, pain and sleep disturbances had the strongest associations with the overall QoL. CONCLUSION: We found invisible symptoms highly prevalent, even at mild disability levels. Fatigue, pain and sleep disturbances had the strongest associations with the overall QoL and were more frequently reported in our study compared with previous registry-based studies. These symptoms may be underreported in registries based on clinician reported outcomes, which emphasizes the importance of including standardized patient reported outcomes in nationwide registries to better understand the impact of the symptom burden in MS.

Circulating levels of tight junction proteins in multiple sclerosis: Association with inflammation and disease activity before and after disease modifying therapy.

BACKGROUND: Tight junction proteins contribute to maintenance of epithelial and endothelial barriers such as the intestinal barrier and the blood brain barrier (BBB). Increased permeability of these barriers has been linked to disease activity in MS and there is currently a lack of easily accessible biomarkers predicting disease activity in MS. AIM: To investigate whether levels of circulating tight junction proteins occludin and zonula occludens-1 (ZO-1) are associated with biomarkers of inflammation and disease activity; and to determine whether they could serve as clinical biomarkers. METHODS: We prospectively included 72 newly diagnosed patients with relapsing remitting MS or clinically isolated syndrome with no prior disease modifying therapy (DMT) use and 50 healthy controls (HCs). Patients were followed with blood samples, 3 tesla MRI, and clinical evaluation for 12 months. Occludin, ZO-1, calprotectin and soluble urokinase-type plasminogen activator receptor (suPAR) were measured by ELISA; serum neurofilament light (NfL) and IL-6 by single-molecule array (SIMOA). The mRNA expression of IFNG, IL1R1, IL10, IL1B, ARG1 and TNF was measured by quantitative real time polymerase chain reaction (qPCR) in whole blood. RESULTS: Plasma occludin levels were higher in MS patients compared with HCs. After 12 months on DMT, occludin levels were reduced by approximately 25% irrespective of 1st or 2nd line DMT (p<0.001). Furthermore, NfL and calprotectin levels were significantly reduced by 31% and 29%, respectively. Occludin and ZO-1 did not correlate with biomarkers of inflammation and did not predict disease activity at baseline or after 12 months. CONCLUSIONS: Higher levels of occludin suggest an increased permeability of the BBB and/or the intestinal barrier in MS patients. The reduction of occludin after 12 months on DMTs might reflect repair of these barriers upon treatment. However, plasma levels of ZO-1 and occludin could not predict clinical or MRI disease activity as determined by regression and ROC-curve analysis. Our results do not indicate a clear clinically relevant role for circulating tight junction proteins as biomarkers of disease activity in MS and further investigations in larger cohorts are needed to clarify this issue.

Biomarkers of inflammation and epithelial barrier function in multiple sclerosis.

BACKGROUND: There is a lack of reliable biomarkers predicting disability and disease activity in multiple sclerosis (MS). Recent evidence suggests an involvement of intestinal and pulmonary epithelial barrier function related to immune activation and the pathophysiology of MS. Blood biomarkers of epithelial barrier function have, however, not been widely studied in MS. OBJECTIVE: To examine biomarkers of inflammation and epithelial barrier function in relapsing remitting MS (RRMS) patients compared with healthy controls (HCs), and to assess associations between biomarkers and disease activity. METHODS: A panel of 30 biomarkers were measured in serum or plasma from 49 newly diagnosed, untreated RRMS patients and 58 HCs with electrochemiluminescence or ELISA. Neurofilament light chain (NfL) was measured with single-molecule array. Validation was performed in a second independent cohort of 68 newly diagnosed, treatment naive RRMS patients and 50 HCs. Patients were divided into groups of active and inactive disease based on NfL levels and the presence of gadolinium enhancing magnetic resonance imaging lesions. RESULTS: Patients with active MS showed significantly higher serum levels of calprotectin and soluble urokinase plasminogen activator receptor compared with inactive MS in the exploratory cohort. Validation confirmed higher levels of calprotectin in active compared with inactive MS, and HCs. Biomarkers of intestinal and pulmonary epithelial barrier function did not differ significantly between groups. CONCLUSIONS: The measured biomarkers of epithelial barrier function do not seem to play a major role in the pathophysiology of MS, but serum calprotectin could represent a clinically useful biomarker of innate immune activation and disease activity.

Illegal cannabis use is common among Danes with multiple sclerosis.

BACKGROUND: Use of cannabis to alleviate multiple sclerosis (MS)-related symptoms is increasing. Due to strict regulations, only a minority of MS patients receive cannabis-based prescription drugs. The extent of recreational and medical cannabis use among Danes with MS is unknown. Our aim was to evaluate the prevalence of illegal and legal use of cannabis in MS patients, as well as reasons for use and perceived adverse effects. METHODS: An anonymous questionnaire was sent to all 3606 patients at the Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen. The questionnaire included questions about sociodemographic factors, clinical characteristics and medical or recreational cannabis use. RESULTS: Questionnaires were completed by 2244/3606 (62%), of which 2009 questionnaires from patients with MS or clinical isolated syndrome (CIS) were valid for analysis. Forty-nine percent (980/2009) had used cannabis at least once. Cannabis was used within the past year (current user) by 21%, and only 21% of those received prescribed cannabis-based medicine. Recreational use was reported by 17%. The primary reasons for use were to alleviate pain (61%), spasticity (52%) and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%) and dizziness (13%). Almost half (44%) of the non-cannabis users would consider use of cannabis to alleviate MS symptoms if the drug was legalized. CONCLUSION: This study shows that illegal cannabis use is common among Danes with MS as only 21% of the current cannabis users received prescribed cannabis-based medicine. Current cannabis users reported high efficacy in relieving pain, spasticity and sleep disturbances. In addition, only mild to moderate severity of adverse effects were reported. To the best of our knowledge, this is the most comprehensive survey of cannabis use among MS patients.

Shift work at young age is associated with increased risk of multiple sclerosis in a Danish population.

BACKGROUND: Epidemiological studies suggest an important role for environmental factors in developing multiple sclerosis (MS). Furthermore several studies have indicated that the effect of environmental factors may be especially pronounced in adolescents. Recently only one study investigated and found that shift work at young age is associated with an increased risk of developing MS. In this study we focused on the effect of shift work in the vulnerable period between 15-19 years. OBJECTIVE: The aim of this study was to investigate the association between shift work at young age and the risk of developing MS. METHODS: We performed a large case-control study including 1723 patients diagnosed with MS and 4067 controls. MS patients were recruited from the Danish Multiple Sclerosis Biobank and controls from The Danish Blood Donor Study. Information on working patterns and lifestyle factors was obtained using a comprehensive lifestyle-environmental factor questionnaire with participants enrolled between 2009 and 2014. Logistic regression models were used to investigate the association between shift work at age 15-19 years and the subsequent risk of MS and were controlled for effects due to established MS risk factors. RESULTS: We found a statistically significant association when total numbers of night shifts were compared with non-shift workers. For every additional 100 night shifts the odds ratio (OR) for MS was 1.20 (95% confidence interval (CI), 1.08-1.34, p=0.001). Increasing intensity of shift work also increased MS risk. For every additional night per month the OR was 1.04 (95% CI, 1.01-1.06, p=0.002). Duration of shift work in years was not associated with risk of MS. CONCLUSION: This study supports a statistically significant association between shift work at age 15-19 years and MS risk.

Epidemiology of meningococcal disease in Denmark 1980-1988.

Based on epidemiological data of notified cases of meningococcal disease (MD) in Denmark during the period 1980-88 the recommendations for prophylaxis are evaluated. In 1986 the incidence of MD increased about 60% to 5.5 per 100,000 population. The clinical diagnosis of MD was verified by culture of Neisseria meningitidis in 79% of notified cases. About 40% of all patients were less than 4 years of age. The mortality in 1988 was found to be 10%. Serogroup B disease accounted for about 80% of the cases. Two co-primary and 28 secondary cases were registered. Two major outbreaks of serogroup C disease occurred in 1984 and 1986, respectively. In small clusters of 2-3 cases within socially well-defined groups the recommendations for prophylaxis are sufficient. But for the new pattern of clusters spread over months to years in certain geographical areas or open social groups, especially among teenagers, the existing recommendations are insufficient. The occurrence of localized clusters of serogroup B disease emphasises the need for a vaccine against serogroup B disease.

Outbreak of Salmonella typhimurium infection traced to contaminated chocolate and caused by a strain lacking the 60-megadalton virulence plasmid.

We describe an outbreak of Salmonella typhimurium infection, caused by contaminated chocolate produced by one Norwegian company, which occurred in Norway and Finland in 1987. A total of 349 bacteriologically verified cases were recorded in Norway, and 12 cases were recorded in Finland. There was a predominance of young children among the patients (median age, 6 years), many of whom developed acute hemorrhagic diarrhea. The outbreak strain exhibited a rare phage lysis pattern and a characteristic plasmid profile lacking the 60-MDa virulence-associated plasmid. DNA hybridization failed to demonstrate any DNA sequence homology between the outbreak strain and the virulence plasmid. The outbreak strain was nonlethal for orally infected mice. The finding of only less than or equal to 10 S. typhimurium cells per 100 g of chocolate in about 90% of the positive samples obtained from retail outlets suggested that an inoculum of fewer than 10 organisms may have been sufficient to cause symptomatic disease.

[The contaminated chocolate epidemic of 1987]. / Sjokoladeepidemien i 1987.

The article describes a nationwide outbreak of Salmonella typhimurium infection in 1987 caused by contaminated chocolate products from one particular factory. A total of 349 bacteriologically verified cases were recorded. It was estimated, however, that 20,000-40,000 persons became ill during the outbreak. We describe the epidemiological and bacteriological investigations which led to identification of the source of infection, and discuss two epidemiological models for investigation of food-borne outbreaks. The article emphasizes the importance of collaboration between the community health service and the local food inspection laboratories during investigation of foodborne outbreaks.

Investigation of an outbreak of Salmonella oranienburg infections in Norway, caused by contaminated black pepper.

From November 1981 to August 31, 1982, 126 bacteriologically confirmed cases of Salmonella oranienburg infections were reported in Norway. This paper summarizes the development of the outbreak and describes the epidemiologic and microbiologic investigations leading to the discovery of contaminated black pepper as the source of the outbreak. In an investigation limited to 26 patients in the Trøndelag region, the Trondheim Public Food Control Laboratory isolated S. oranienburg from six samples of black, ground pepper from the patients' households and from 15 samples of black, ground pepper from unopened, original packings having the trademark of the Norwegian Cooperative Association (Co-op).