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- Haghighi, Mona, et al.
(författare)
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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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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)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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- Ahlgren, Cecilia, 1946, et al.
(författare)
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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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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 235:1-2, s. 98-103
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Tidskriftsartikel (refereegranskat)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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- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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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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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 18:1 January
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Tidskriftsartikel (refereegranskat)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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- Axelsson, M, et al.
(författare)
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Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis.
- 2011
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 258:5, s. 882-8
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Tidskriftsartikel (refereegranskat)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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- Haghighi, Sara, et al.
(författare)
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Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls.
- 2000
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Ingår i: Journal of neurology. - 0340-5354 .- 1432-1459. ; 247:8, s. 616-22
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Tidskriftsartikel (refereegranskat)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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- Haghighi, Sara, et al.
(författare)
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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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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 326:1-2, s. 35-39
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Tidskriftsartikel (refereegranskat)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
(författare)
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Investigation of immunological preconditions in MS patients "MS immunopathic trait"
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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