| 1. |
- Haghighi, Mona, et al.
(author)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 2. |
- Ahlgren, Cecilia, 1946, et al.
(author)
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The effect of live, attenuated measles vaccine and measles infection on measles antibody levels in serum and CSF of patients with multiple sclerosis or clinically isolated syndrome.
- 2011
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In: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 235:1-2, s. 98-103
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Journal article (peer-reviewed)abstract
- High occurrence of measles, rubella and varicella zoster antibodies has been used as a biomarker for MS (the MRZ test). We analyzed measles antibody titres with respect to measles infection/measles vaccination status in 166 patients with MS or clinically isolated syndrome. Fifty blood donors served as controls. Measles vaccination yielded CSF measles antibodies in fewer patients (62%) than measles infection did (87%, p=0.001) and yielded lower measles titres in both serum and CSF (p<0.001). Controls had lower CSF measles titres than patients with measles vaccination alone (p<0.001). Childhood vaccinations probably reduce the sensitivity of the MRZ diagnostic test for MS.
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| 3. |
- Ahmadpour, Doryaneh, 1973, et al.
(author)
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Inventory study of an early pandemic COVID- 19 cohort in South-Eastern Sweden, focusing on neurological manifestations
- 2023
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 18:1 January
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Journal article (peer-reviewed)abstract
- Background Neurological manifestations in patients with COVID-19 have been reported previously as outcomes of the infection. The purpose of current study was to investigate the occurrence of neurological signs and symptoms in COVID-19 patients, in the county ofÖstergötland in southeastern Sweden. Methods This is a retrospective, observational cohort study. Data were collected between March 2020 and June 2020. Information was extracted from medical records by a trained research assistant and physician and all data were validated by a senior neurologist. Results Seventy-four percent of patients developed at least one neurological symptom during the acute phase of the infection. Headache (43%) was the most common neurological symptom, followed by anosmia and/or ageusia (33%), confusion (28%), hallucinations (17%), dizziness (16%), sleep disorders in terms of insomnia and OSAS (Obstructive Sleep Apnea) (9%), myopathy and neuropathy (8%) and numbness and tingling (5%). Patients treated in the ICU had a higher male presentation (73%). Several risk factors in terms of co-morbidities, were identified. Hypertension (54.5%), depression and anxiety (51%), sleep disorders in terms of insomnia and OSAS (30%), cardiovascular morbidity (28%), autoimmune diseases (25%), chronic lung diseases (24%) and diabetes mellitus type 2 (23%) founded as possible risk factors. Conclusion Neurological symptoms were found in the vast majority (74%) of the patients. Accordingly, attention to neurological, mental and sleep disturbances is warranted with involvement of neurological expertise, in order to avoid further complications and long-term neurological effect of COVID-19. Furthermore, risk factors for more severe COVID-19, in terms of possible co-morbidities that identified in this study should get appropriate attention to optimizing treatment strategies in COVID-19 patients.
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| 4. |
- Axelsson, M, et al.
(author)
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Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis.
- 2011
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In: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 258:5, s. 882-8
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Journal article (peer-reviewed)abstract
- The major intermediate cytoskeletal protein of astrocytes, glial fibrillary acidic protein (GFAP), and that of axons, neurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). Patients with relapsing-remitting MS (RRMS, n = 15) or secondary progressive MS (SPMS, n = 10) and healthy control subjects (n = 28) were examined twice with an interval of 8-10 years apart. Neurological deficits were scored with the Expanded Disability Status Scale (EDSS). GFAP and NFL levels were determined in CSF by enzyme-linked immunosorbent assay (ELISA). GFAP levels and NFL levels correlated with age (r and r (s) = 0.50, p = 0.006). Adjusting for age, MS patients had increased GFAP levels compared with controls (p = 0.03) and GFAP levels correlated with neurological disability (EDSS, r = 0.51, p < 0.05) and disease progression [Multiple Sclerosis Severity Score (MSSS), r = 0.47, p < 0.05]. The mean annual increase of GFAP was 6.5 ng/L for controls, 8.1 ng/L for RRMS patients, and 18.9 ng/L for SPMS patients. GFAP level at the first examination had predictive value for neurological disability 8-10 years later (EDSS, r = 0.45, p < 0.05) but not for EDSS increase between the examinations. NFL levels were not significantly increased in MS patients compared with controls and had no relationship to disability or progression and no prognostic value for disability development. GFAP, a marker for astrogliosis, is a potential biomarker for MS progression and may have a role in clinical trials for assessing the impact of therapies on MS progression.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Haghighi, Sara, et al.
(author)
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Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls.
- 2000
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In: Journal of neurology. - 0340-5354 .- 1432-1459. ; 247:8, s. 616-22
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Journal article (peer-reviewed)abstract
- We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3-4% recurrence risk for manifest MS reported for sibs.
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| 9. |
- Haghighi, Sara, et al.
(author)
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Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients
- 2013
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In: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 326:1-2, s. 35-39
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Journal article (peer-reviewed)abstract
- A proportion of healthy siblings of multiple sclerosis (MS) patients have an oligodonal immunological reaction in their cerebrospinal fluid (CSF) termed the "MS oligoclonal trait". The CSF levels of the major myelin glycosphingolipid sulfatide and serum antibodies against the glycosphingolipids sulfatide and galactosylceramide were recently reported to be increased in MS patients. We studied the levels of these substances in pairs of 46 patients and their 46 healthy siblings and 50 unrelated healthy blood donors (HBD). The sulfatide concentration in CSF was assayed by thin layer chromatography and immunostaining, and the concentration of galactosylceramide by densitometry after thin layer chromatography. Anti-glycosphingolipid antibody levels were assayed by ELISA. In the healthy siblings, the CSF sulfatide concentrations were markedly increased (p<0.001, age adjusted p = 0.025), and the serum IgM anti-GalCer antibodies were increased in healthy siblings compared with HBD (p = 0.02). The increased sulfatide or antibody levels did not co-segregate with the "MS oligoclonal trait" or the HLA-DR15 phenotype. In conclusion, a proportion of healthy siblings of MS patients have increased CSF sulfatide and anti-glycosphingolipid antibody levels, which may, analogous to the "MS oligoclonal trait", constitute an "MS glycosphingolipid endophenotype". Endophenotypes could potentially simplify the genetics of complex disorders
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| 10. |
- Haghighi, Sara
(author)
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Investigation of immunological preconditions in MS patients "MS immunopathic trait"
- 2004
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Doctoral thesis (other academic/artistic)abstract
- We examined 47 MS patients, 47 healthy siblings and 50 healthy unrelated individuals with blood and CSF analysis and found that 19 % (9/47) of healthy siblings of clinically definite multiple sclerosis patients had an intrathecal immunological reaction to ¡Ý 2 CSF-enriched OCB, in contrast to 4% (2/50) of the unrelated healthy controls. We termed this condition ¡°MS immunopathic trait¡±. We challenged whether this subgroup with the MS immunopathic trait was really asymptomatic, using a more stringent method, high-pass resolution perimetry (HRP). With this method, siblings as a group did not differ from the healthy controls. We measured CSF neurofilament light protein (NFL), and glial fibrillary acidic protein (GFAp), in MS patients and their healthy siblings. There was no increase in CSF GFAp and NFL in the healthy siblings of MS patients, nor in the subgroup of the healthy siblings with the MS immunopathic trait. The verification of the MS immunopathic trait was the precondition for the subsequent aims. The next aim was to clarify whether MS immunopathic trait as a phenotype segregates with any particular pattern, and to examine whether there is any candidate gene or genes. We studied two extended families in which MS not only segregates but also approximately 18% of the CSF investigated blood relatives have the MS immunopathic trait, but with no neurological symptoms. Both families fit a genetic model for autosomal dominant inheritance for the MS immunopathic trait. We performed a genome scan using 285 successful markers, to test the hypothesis that a single gene is causing the MS immunopathic trait in these families. Using a parametric method, we identified regions with suggestive linkage at chromosome 6q12 with a LOD-score of 2.4, and suggestive linkage at chromosome 19q13.2 with a LOD-score of 2.2 when family A was analysed alone. In family B, all MS patients, one individual with the MS immunopathic and all blood relatives had the rare HLA type DRB1*0103, which is associated with other autoimmune diseases. However, the suggestive linkage to chromosome 6q21 raises the question whether this suggestive linkage is a protective gene for MS immunopathic trait or a new susceptibility gene for MS disease. A further aim was to examine whether this phenotype had further neurochemical and immunological characteristics, which could be identical or different from MS. In the healthy siblings group, we found significantly increased CSF levels of sulfatide, CSF galactosylceramide (GalCer), TNF-alpha, and CSF IgG antibodies to measles, and serum IgM antibodies to sulfatide and GalCer, as compared to the controls. It was recently shown that GalCer increases and sulfatide reduces the level of the proinflammatory cytokines IL-1beta, IL-6 and TNF-alpha. The occurrence of this differential effect in MS was supported by a significant correlation between CSF GalCer and IL-6 levels in the MS immunopathic trait group. This finding may indicate a greater likelihood for individuals with the higher levels of GalCer to have increased level of IL-6. The absence of axonal damage markers as CSF GFAp and NFL in the healthy siblings, in combination with increased CSF levels of sulfatide, allowed for the tentative conclusion that myelin damage is an earlier event than axonal damage. The present material should give us an opportunity to study whether antiviral or antimyelin antibodies are the earlier event and to further redefine the MS immunopathic trait phenotype.
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| 11. |
- Haghighi, Sara, et al.
(author)
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Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis.
- 2012
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 125:1, s. 64-70
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Journal article (peer-reviewed)abstract
- Objectives- Patients with multiple sclerosis were reported to harbour antibodies not only against proteins and glycoproteins but also against glycolipids, including sulfatide and galactosylceramide (GalCer), the two major glycosphingolipids of myelin. However, previous results were inconsistent concerning glycosphingolipid levels, antibody type, dominance of serum or Cerebrospinal fluid compartments and relationship to the multiple sclerosis (MS) course. Results- We hereby report that the cerebrospinal fluid levels of sulfatide were increased in patients with MS (n=46) compared with controls (n=50, P<0.001). In addition, patients had higher serum IgM anti-glycosphingolipid titres than controls (P=0.03 for sulfatide, <0.001 for GalCer), while the anti-glycosphingolipid IgM antibodies in the cerebrospinal fluid were essentially normal. However, in seven of 46 patients cerebrospinal fluid IgG antibodies against GalCer (P=0.004) could be detected, which was not found in any of the control individuals, and this finding might mirror the occurrence of more specific B-cell clones behind the blood-brain barrier. Conclusions- The IgM immunoreactivity in serum did not show any relationship to the type of course or severity of MS, arguing against a phenomenon secondary to myelin damage. Thus, the IgM antibody findings are compatible with an early antigen challenge or autoimmunity associated with natural antibodies.
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| 12. |
- Haghighi, S., et al.
(author)
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Open-label study with the monoamine stabilizer (-)-OSU6162 in myalgic encephalomyelitis/chronic fatigue syndrome
- 2021
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In: Brain and Behavior. - : Wiley. - 2162-3279. ; 11:4
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Journal article (peer-reviewed)abstract
- Objectives The purpose of the present study was to investigate the safety and tolerability of the monoaminergic stabilizer (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In addition, a potential therapeutic effect of (-)-OSU6162 in ME/CFS was evaluated by means of observer-rated scales and self-assessment rating scales. Materials and Methods In the current study using an open-label single-arm design ME/CFS patient received treatment with (-)-OSU6162 during 12 weeks. The patients received the following doses of (-)-OSU6162: 15 mg b.i.d. during the first 4-week period, up to 30 mg b.i.d. during the second 4-week period and up to 45 mg b.i.d. during the third 4-week period, with follow-up visits after 16 and 20 weeks. Results Out of 33 included patients, 28 completed the 12 weeks treatment period. (-)-OSU6162 was well tolerated; only one patient discontinued due to an adverse event. Vital signs and physical examinations showed no abnormal changes. Blood analyses showed an increase in serum prolactin. Therapeutically, improvements were seen on the Clinical Global Impression of Change scale, the FibroFatigue scale, the Mental Fatigue Scale, the Fatigue Severity Scale, Beck Depression Inventory, and the Short Form 36 Health Survey Questionnaire. Conclusions (-)-OSU6162 is well tolerated in ME/CFS patients and shows promise as a novel treatment to mitigate fatigue and improve mood and health-related quality of life in ME/CFS. Obviously, the present results need to be confirmed in future placebo-controlled double-blind trials.
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| 13. |
- Haghighi, S., et al.
(author)
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Open study with (-)-OSU6162 in multiple sclerosis-related fatigue
- 2018
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 138:6, s. 482-489
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Journal article (peer-reviewed)abstract
- Objectives The main objective of this study was to investigate the tolerability and safety of the monoaminergic stabilizer (-)-OSU6162 in patients with multiple sclerosis (MS). In addition, a potential therapeutic effect of (-)-OSU6162 with focus on MS-related fatigue was estimated by means of various self-assessment rating scales as well as a clinical investigator-rated scale. Materials and methods In this open-label, single-arm study, 30 MS patients received treatment with the monoaminergic stabilizer (-)-OSU6162 during 12 weeks. The dose of (-)-OSU6162 was 15 mg twice daily during the first 4-week period, up to 30 mg twice daily during the second 4-week period and up to 45 mg twice daily during the third 4-week period, with follow-up visits after 16 and 20 weeks. MS-related fatigue was rated by the clinical investigator or by self-assessments, using mainly established rating scales. Twenty-five patients completed the study. Results (-)-OSU6162 was well tolerated by all patients, and no serious adverse events were observed. Therapeutically, improvements were observed with respect to fatigue and mood, as judged by ratings on the Mental Fatigue Scale (MFS), Short Form-36 (SF-36) scale and Beck Depression Inventory (BDI). Furthermore, the large majority of patients were rated as globally improved in the medical observers' rating scale Clinical Global Impression of Change (CGI-C). Conclusions In view of its good tolerability, (-)-OSU6162 may offer a new treatment option for alleviating mental fatigue, as well as depression, in MS. Larger, randomized double-blind controlled trials are warranted to confirm the present preliminary observations.
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| 14. |
- Hansson, Sarah, 1976, et al.
(author)
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Cystatin C in cerebrospinal fluid and multiple sclerosis.
- 2007
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In: Annals of neurology. - : Wiley. - 0364-5134. ; 62:2, s. 193-196
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Journal article (peer-reviewed)abstract
- OBJECTIVE: A recent study using surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid identified a 12.5 kDa truncated isoform of cystatin C (CysC) as a specific biomarker for multiple sclerosis (MS). METHODS: Surface-enhanced laser desorption/ionization time-of-flight analysis of cerebrospinal fluid samples from 43 MS patients and 46 healthy control subjects. RESULTS: Full-length CysC (13.4 kDa) concentration was similar in MS and control samples. The 12.5 kDa CysC protein was produced from full-length CysC by N-terminal cleavage during storage at -20 degrees C. INTERPRETATION: The 12.5 kDa CysC isoform is a storage-related artifact and is not useful as a diagnostic marker for MS.
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| 15. |
- Hestvik, Anne Lise K., et al.
(author)
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Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes
- 2022
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In: Multiple Sclerosis and Related Disorders. - : ELSEVIER SCI LTD. - 2211-0348 .- 2211-0356. ; 63
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Journal article (peer-reviewed)abstract
- Background: Teriflunomide 14 mg (Aubagio (R)) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting. Methods: Teri-LIFE was a prospective, open label, non-interventional, observational, multi-centre study that enrolled 200 teriflunomide-treated patients from three Nordic countries. The primary outcome measure changes in patient-reported QoL over 24 months as measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, fatigue, safety, treatment satisfaction (Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM-1.4)), treatment adherence, and health economic outcomes. Most assessments were made at baseline and then at 6-monthly intervals. Results: Overall, changes in SF-36 scores from baseline to last visit indicated a stable QoL during treatment with teriflunomide for up to 24 months. Relapse activity decreased during the study compared to the pre-baseline period (p<0.001), patient-reported disability increased marginally, and no substantial change was seen in fatigue scores. The mean scores for TSQM domains increased nominally though not significantly from Month 6 to Month 24. The convenience and side effects TSQM domains recorded the highest median scores, indicating the acceptability of oral teriflunomide in this cohort. This was reflected in a generally high treatment adherence and decreased healthcare utilization during the study period. Some differences were seen between treatment-naive and previously treated patients, likely reflecting different patient demographics and disease status at study entry, along with different treatment expectations. Conclusion: Teri-LIFE offers a reliable snapshot of QoL, efficacy, safety, and health economic outcomes in persons with relapsing MS treated with teriflunomide in routine clinical practice in Nordic countries The results were consistent with previous clinical trials and real-world studies.
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| 16. |
- Jons, Daniel, 1974, et al.
(author)
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Follow-up after infectious mononucleosis in search of serological similarities with presymptomatic multiple sclerosis
- 2021
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In: Multiple Sclerosis and Related Disorders. - : Elsevier BV. - 2211-0348 .- 2211-0356. ; 56
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Journal article (peer-reviewed)abstract
- Background: : A two- to three-fold increase in the risk of multiple sclerosis (MS) after infectious mononucleosis (IM) has been observed in cohort and case control studies. However, this association has not been investigated prospectively from IM. It remains to be determined whether long-term immunospecific sequelae with features consistent with presymptomatic MS occur after IM. Methods: : Sera were obtained from individuals with acute IM from 2003-2007 (n = 42) and from the same individuals at a follow-up (FU) study approximately 10 years after IM. These were assayed for antibodies against a variety of Epstein-Barr virus (EBV) antigens, including gp350, a novel recombinant glycoprotein from the EBV envelope. Similarly, single-protein antigens were used to assess measles and varicella-zoster reactivity (Ncore and varicella-zoster glycoprotein E [VZVgE]). The FU study also included cerebrospinal fluid (CSF) samples from 21 of these individuals to test for IgG antibodies against the same viral antigens. As controls, CSF and serum samples were obtained from 15 EBV-seropositive volunteers who denied a history of IM, and serum samples were obtained from 24 EBV-seropositive blood donors. Anti-gp350, anti-Ncore and anti-VZVgE IgG levels were also analysed in sera and CSF samples from 22 persons with MS. Results: : The FU assays showed higher anti-gp350 IgG (p = 0.007, univariate) than among healthy controls, with no difference in serum anti-VCA or anti-EBNA1 IgG levels and no difference in anti-gp350 in the CSF samples. Anti-Ncore IgG and anti-VZVgE were higher in acute IM samples (p < 0.001 and p < 0.0001, respectively) than at FU, although anti-Ncore remained heightened in an age-adjusted analysis at FU (p = 0.014) compared to the control group. In the MS group, the serum anti-gp350 and anti-Ncore IgG levels were significantly higher than among the control group, but the anti-VZVgE levels were not. The CSF anti-gp350 and VZVgE levels were slightly higher among persons with MS than among the control group, whereas anti-Ncore IgG was markedly higher in persons with MS than in the control group. Conclusion: : In the present study IM showed certain similarities with MS. Increased anti-gp350 reactivity persisted more than a decade after IM, reminiscent of the established increased anti-EBV reactivity in presymptomatic MS. Acute IM was associated with increased anti-measles and anti-VZV immunoreactivity, similar to the MRZ reaction in MS, with some evidence suggesting that this measles reactivity persisted after a decade.
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| 17. |
- Kloberg, A., et al.
(author)
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Tolerability and efficacy of the monoaminergic stabilizer (-)-OSU6162 (PNU-96391A) in Huntington's disease: A double-blind cross-over study
- 2014
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In: Acta Neuropsychiatrica. - : Cambridge University Press. - 0924-2708 .- 1601-5215. ; 26:5, s. 298-306
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Journal article (peer-reviewed)abstract
- Objective To evaluate the safety (primary objective) and efficacy (secondary objective) of (-)-OSU6162 in Huntington's disease (HD). Methods In a double-blind, cross-over trial, patients with HD were randomly assigned to start treatment on either (-)-OSU6162 or placebo. After 4 weeks, those patients who initially received active drug were switched to placebo for another 4 weeks, and vice versa. During the first week the (-)-OSU6162 dose was 15 mg twice daily, during the second week 30 mg twice daily, and during the last 2 weeks 45 mg twice daily. Motor, cognitive, mental and social functions were rated by the clinical investigator or by self-assessment, using established rating scales. Results Fifteen patients fulfilling inclusion and exclusion criteria completed the study. (-)-OSU6162 was well tolerated by all patients and no adverse effects were observed. (-)-OSU6162 treatment significantly improved the Short Form 36 Vitality score, mainly due to an improvement of the individual item 'worn-out' (VT3). In addition, an improvement of depressive symptoms was found using Beck Depression Inventory. In contrast to a general trend of improvement in several non-motor variables only small and non-significant differences between (-)-OSU6162 and placebo were found regarding motor functions. Conclusions (-)-OSU6162 offers promise for the treatment of HD, as a drug with good tolerability, capable of improving the patients' experienced non-motor functions such as energy and mood and thus alleviating symptoms of great importance for their quality of life. © © Scandinavian College of Neuropsychopharmacology 2014.
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| 18. |
- Landtblom, Anne-Marie, et al.
(author)
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RebiQoL : A randomized trial of telemedicine patient support program for health-related quality of life and adherence in people with MS treated with Rebif
- 2019
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:7
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Journal article (peer-reviewed)abstract
- RebiQoL was a phase IV multicenter randomized study to assess the impact of a telemedicine patient support program (MSP) on health-related quality of life (HRQoL) in patients with relapsing-remitting MS (RRMS) being administered with Rebif with the RebiSmart device. The primary endpoint was to assess the impact of MSP compared to patients only receiving technical support for RebiSmart on HRQoL at 12 months, using the psychological part of Multiple Sclerosis Impact Scale (MSIS-29), in patients administered with Rebif. A total of 97 patients diagnosed with RRMS were screened for participation in the study of which 3 patients did not fulfill the eligibility criteria and 1 patient withdrew consent. Of the 93 randomized patients, 46 were randomized to MSP and 47 to Technical support only. The demographic characteristics of the patients were well-balanced in the two arms. There were no statistical differences (linear mixed model) in any of the primary (difference of 0.48, 95% CI: -8.30-9.25, p = 0.91) or secondary outcomes (p>0.05). Although the study was slightly underpowered, there was a trend towards better adherence in the MSP group (OR 3.5, 95% CI 0.85-14.40, p = 0.08) although not statistically significant. No unexpected adverse events occurred. This study did not show a statistically significant effect of the particular form of teleintervention used in this study on HRQoL as compared to pure technical support, for MS patients already receiving Rebif with the RebiSmart device.
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| 19. |
- Lundin, Anders, et al.
(author)
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Efficacy and Safety of the Dopaminergic Stabilizer Pridopidine (ACR16) in Patients With Huntington's Disease
- 2010
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In: Clinical neuropharmacology. - 0362-5664 .- 1537-162X. ; 33:5, s. 260-264
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Journal article (peer-reviewed)abstract
- Objectives: To evaluate the efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington's disease (HD). Methods: In a randomized, double-blind, placebo-controlled, 4-week trial, patients with HD received pridopidine (50 mg/d, n = 28) or placebo (n = 30). The primary outcome measure was the change from baseline in weighted cognitive score, assessed by cognitive tests (Symbol Digit Modalities, verbal fluency, and Stroop tests). Secondary outcome measures included changes in the Unified Huntington's Disease Rating Scale, Hospital Anxiety and Depression Scale, Leeds Sleep Evaluation Questionnaire, Reitan Trail-Making Test A, and Clinical Global Impression of Change. Safety assessments were also performed. Results: There was no significant difference between pridopidine and placebo in the change from baseline of the weighted cognitive score. However, secondary measures such as affective symptoms showed trends toward improvement, and there was significant improvement in voluntary motor symptoms compared with placebo (P<0.05). Pridopidine was well tolerated, with a safety profile similar to placebo. Conclusions: Pridopidine shows promise as a treatment for some of the symptoms of HD. In this small-scale study, the most notable effect was improvement in voluntary motor symptoms. Larger, longer-term trials are warranted.
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| 20. |
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| 21. |
- Malmeström, Clas, 1965, et al.
(author)
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Relapses in multiple sclerosis are associated with increased CD8+ T-cell mediated cytotoxicity in CSF.
- 2008
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In: Journal of neuroimmunology. - : Elsevier BV. - 0165-5728. ; 196:1-2, s. 159-65
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Journal article (peer-reviewed)abstract
- MS is thought to be mediated by CD4(+) T-helper cells. To investigate the importance of CD8(+) cytotoxic T-cells in MS we analyzed peripheral blood T-cells by DNA microarray, and plasma and CSF levels of granzymes from MS patients and controls. Cytotoxic gene expression was decreased in peripheral T-cells from RRMS patients whereas plasma levels of granzymes were unchanged. However, granzyme levels were elevated in the CSF of RRMS patients at relapse compared with controls and remission. Thus, CD8+ T-cell-mediated cytotoxicity is confined to the CSF/CNS compartment in RRMS patients and may be involved in the immunopathogenesis of clinical relapses.
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| 22. |
- Mattsson, Niklas, 1979, et al.
(author)
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Cerebrospinal fluid concentrations of peptides derived from chromogranin B and secretogranin II are decreased in multiple sclerosis
- 2007
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 103:5, s. 1932-1939
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Journal article (peer-reviewed)abstract
- Novel biomarkers for multiple sclerosis (MS) could improve diagnosis and provide clues to pathogenesis. In this study surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to analyze protein expression in CSF from 46 MS patients, 46 healthy siblings to the patients, and 50 unrelated healthy controls. Twenty-four proteins in the mass range 2–10 kDa were expressed at significantly different levels (p < 0.01) in a robust manner when comparing the three groups. Identities of three proteins were determined using biochemical purification followed by tandem mass spectrometric analysis. Immunoprecipitation experiments confirmed the identities for two peptides derived from chromogranin B (m/z 6252) and from secretogranin II (m/z 3679). These peptides were all decreased in MS when compared with siblings or controls. Radioimmunoassays specific for each peptide confirmed these differences. The lowered concentrations did not correlate to the axonal damage marker neurofilament light protein and may thus reflect functional changes rather than neurodegeneration. Further studies will investigate the involvement of these peptides in MS pathogenesis.
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| 23. |
- Mattsson, Niklas, 1979, et al.
(author)
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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
- 2010
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
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Journal article (peer-reviewed)abstract
- Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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| 24. |
- Mattsson, Niklas, 1979, et al.
(author)
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Elevated cerebrospinal fluid F2-isoprostane levels indicating oxidative stress in healthy siblings of multiple sclerosis patients.
- 2007
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In: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 414:3, s. 233-6
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Journal article (peer-reviewed)abstract
- Lipid peroxidation has been implicated in the pathogenesis of multiple sclerosis (MS). Isoprostanes, isomers of prostaglandins, are produced by free radical-mediated peroxidation of fatty acids in vivo and can be quantified in biological fluids. This study examines the levels of cerebrospinal fluid (CSF) F2-isoprostanes (F2-iPs) in MS patients (n=46), their healthy siblings (n=46) and unrelated controls (n=50). The median CSF F2-iP concentration (range) was significantly higher in siblings of MS patients, as compared to healthy controls (40.0 [7.1-68.7] and 29.1 [6.4-60.3] pg/mL, respectively, p=0.031). MS patients demonstrated F2-iP levels intermediate between siblings and controls. F2-iP levels in MS patients and siblings correlated significantly (R=0.360, p=0.012). These results suggest that siblings of MS patients have an increased oxidative stress response to environmental and/or genetic factors that may be involved in MS pathogenesis.
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| 25. |
- Mattsson, Niklas, 1979, et al.
(author)
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Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in multiple sclerosis.
- 2009
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In: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 265:4, s. 459-64
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To test the hypothesis that the arachodinic acid metabolites prostaglandin E2 (PGE2) and 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in cerebrospinal fluid (CSF) are elevated and reflect neuroinflammation and degenerative changes in multiple sclerosis (MS). PATIENTS AND METHODS: We measured PGE2 and 15(S)-HETE concentrations, as well as markers of axonal and astroglial injury in CSF from 46 MS patients, 46 healthy siblings and 50 controls. RESULTS: We found elevated levels of both PGE2 and 15(S)-HETE in MS compared with the control and sibling groups. Siblings had lower PGE2 levels and higher 15(S)-HETE levels than controls. There were no correlations between either PGE2 or 15(S)-HETE and clinical scores of MS severity or biochemical markers of axonal or astroglial injury. CONCLUSION: These data suggest no direct involvement of PGE2 and 15(S)-HETE in the MS disease process. Rather, the elevated levels reflect a general up-regulation of arachidonic acid metabolism and neuroinflammation.
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| 26. |
- Mattsson, Niklas, 1979, et al.
(author)
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Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.
- 2009
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 448-54
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P = 0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group (P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS: These results suggest an involvement of BACE1 in the MS disease process.
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| 27. |
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| 28. |
- Törnell, Andreas, 1994, et al.
(author)
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Impact of CYBA genotypes on severity and progression of multiple sclerosis
- 2022
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:5, s. 1457-1464
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Journal article (peer-reviewed)abstract
- Background and purpose: The NOX2 enzyme of myeloid cells generates reactive oxygen species (ROS) that have been implicated in the pathology of multiple sclerosis (MS). We aimed to determine the impact of genetic variation within CYBA, which encodes the functional CYBA/p22phox subunit of NOX2, on MS severity and progression. Methods: One hundred three MS patients with up to 49 (median = 17) years follow-up time from first MS diagnosis were genotyped at the single nucleotide polymorphisms rs1049254 and rs4673 within CYBA. Results were matched with disease severity and time to diagnosis of secondary progressive MS (SPMS). NOX2-mediated formation of ROS was measured by chemiluminescence in blood myeloid cells from healthy donors (n=55) with defined genotypes at rs1049254 and rs4673. Results: The rs1049254/G and rs4673/A CYBA alleles were associated with reduced formation of ROS and were thus defined as low-ROS alleles. Patients carrying low-ROS alleles showed reduced multiple sclerosis severity score (p=0.02, N=103, linear regression) and delayed onset of SPMS (p=0.02, hazard ratio [HR] = 0.46, n=100, log-rank test). In a cohort examined after 2005, patients carrying low-ROS CYBA alleles showed >20years longer time to secondary progression (p=0.003, HR = 0.29, n=59, log-rank test). Conclusions: These results implicate NOX2 in MS, in particular for the development of secondary progressive disease, and point toward NOX2-reductive therapy aiming to delay secondary progression.
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