Revision of the brief international classification of functioning, disability and health core set for multiple sclerosis: a study of the comprehensive icf core set for multiple sclerosis with participants referred for work ability assessment.

OBJECTIVE: To evaluate the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for multiple sclerosis with regard to the Brief ICF Core Set for multiple sclerosis. DESIGN: Descriptive cross-sectional single-centre study. SUBJECTS: A total of 151 participants (99 females/52 males, mean age 49 years) referred for work ability assessment. METHODS: Data were collected from clinical recordings and by telephone interview. RESULTS: Among 33 Body Functions, 14 were impaired in over 60% of the participants, and 6 in over 75%. These 6 most impaired functions were related to exercise tolerance (b455), urination (b620), muscle power (b730), motor reflex (b750), control of voluntary movement (b760) and gait pattern (b770). Among 54 Activities and Participation categories, 8 were impaired in over 60% of the participants, and 3 were impaired in over 75%. The latter activities were related to walking (d450), moving around (d455) and moving around using equipment (d465). Among the 36 Environmental categories, most were facilitators, except for temperature (e2250) and employment (e590). The latter category was both a facilitator and a barrier. CONCLUSION: These results suggest additional categories that should be included into the Brief ICF Core Set, to improve its representation of the complex disability of multiple sclerosis.

Four Swedish cases of CSF1R-related leukoencephalopathy: Visualization of clinical phenotypes.

Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare, genetic disease caused by heterozygous mutations in the CSF1R gene with rapidly progressive neurodegeneration, behavioral, cognitive, motor disturbances. OBJECTIVE: To describe four cases of CSF1R-related leukoencephalopathy from three families with two different pathogenic mutations in the tyrosine kinase domain of CSF1R and to develop an integrated presentation of inter-individual diversity of clinical presentations. METHODS: This is an observational study of a case series. Patients diagnosed with CSF1R encephalopathy were evaluated with standardized functional estimation scores and subject to analysis of cerebrospinal fluid biomarkers. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were evaluated. We performed a functional phosphorylation assay to confirm the dysfunction of mutated CSF1R protein. RESULTS: Two heterozygous missense mutations in the CSF1R gene were identified, c.2344C>T; p.Arg777Trp and c.2329C>T; p.Arg782Cys. A phosphorylation assay in vitro showed markedly reduced autophosphorylation in cells expressing mutations. According to ACMG criteria, both mutations were pathogenic. A radiological investigation revealed typical white matter lesions in all cases. There was inter-individual diversity in the loss of cognitive, motor-neuronal, and extrapyramidal functions. CONCLUSIONS: Including the present cases, currently three CSF1R mutations are known in Sweden. We present a visualization tool to describe the clinical diversity, with potential use for longitudinal follow-up for this and other leukoencephalopathies.

Neuroimaging phenotypes of CSF1R-related leukoencephalopathy: Systematic review, meta-analysis, and imaging recommendations.

Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare but fatal microgliopathy. The diagnosis is often delayed due to multifaceted symptoms that can mimic several other neurological disorders. Imaging provides diagnostic clues that help identify cases. The objective of this study was to integrate the literature on neuroimaging phenotypes of CSF1R-related leukoencephalopathy. A systematic review and meta-analysis were performed for neuroimaging findings of CSF1R-related leukoencephalopathy via PubMed, Web of Science, and Embase on 25 August 2021. The search included cases with confirmed CSF1R mutations reported under the previous terms hereditary diffuse leukoencephalopathy with spheroids, pigmentary orthochromatic leukodystrophy, and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. In 78 studies providing neuroimaging data, 195 cases were identified carrying CSF1R mutations in 14 exons and five introns. Women had a statistically significant earlier age of onset (p = 0.041, 40 vs 43 years). Mean delay between symptom onset and neuroimaging was 2.3 years. Main magnetic resonance imaging (MRI) findings were frontoparietal white matter lesions, callosal thinning, and foci of restricted diffusion. The hallmark computed tomography (CT) finding was white matter calcifications. Widespread cerebral hypometabolism and hypoperfusion were reported using positron emission tomography and single-photon emission computed tomography. In conclusion, CSF1R-related leukoencephalopathy is associated with progressive white matter lesions and brain atrophy that can resemble other neurodegenerative/-inflammatory disorders. However, long-lasting diffusion restriction and parenchymal calcifications are more specific findings that can aid the differential diagnosis. Native brain CT and brain MRI (with and without a contrast agent) are recommended with proposed protocols and pictorial examples are provided.

Socioeconomic consequences of multiple sclerosis-A systematic literature review.

Multiple sclerosis (MS) is a challenging and disabling condition, predominantly affecting individuals in their early life, and has an impact functionally, financially, and on quality of life. However, there is a lack of systematic approach towards assessing socioeconomic consequences of MS. Our objective was to systematically review observational analytical studies investigating the socioeconomic consequences of MS. We conducted a systematic review on socioeconomic consequences of MS with a focus on employment-, income-, work ability- and relationship-related outcomes between MS and the general population. Additionally, the educational characteristics were extracted. From 4958 studies identified, 187 were assessed for eligibility and a total of 27 studies from eight countries were included in this qualitative assessment; 32 different outcomes were identified. All studies indicated pronounced differences between MS patients and the general population, for example 15%-30% lower employment, lower earnings and higher social benefits, higher absenteeism and presenteeism proportions, higher work disability (eg, sick-leave days) among MS patients. Some studies also indicated differences in the family or relationship characteristics. There were no apparent differences with regard to educational level. In conclusion, socioeconomic data can serve as robust outcome measures to study various aspects of MS reflecting the broader consequences of the disease.

Systematic Review of the Socioeconomic Consequences in Patients With Multiple Sclerosis With Different Levels of Disability and Cognitive Function.

Multiple sclerosis (MS) is a challenging and disabling condition, predominantly affecting individuals in early adulthood. MS affects the physical, cognitive, and mental health of persons suffering from the disease as well as having a great impact on their financial status and quality of life. However, there is a lack of systematic approach toward assessing the socioeconomic consequences of MS. Our objective was to systematically review analytical observational studies investigating the socioeconomic consequences in persons with MS with different levels of physical disability and cognitive function. We conducted a systematic review on socioeconomic consequences of MS with a focus on employment-, income-, work ability-, and relationship-related outcomes in persons with MS with special focus on disability and cognition. Additionally, the educational characteristics were examined. From 4,957 studies identified, 214 were assessed for eligibility and a total of 19 studies were included in this qualitative assessment; 21 different outcomes were identified. All identified studies reported higher unemployment, higher early retirement, and higher risk of unemployment in relation to higher physical disability. Also, cognitive function was found to be a predictor of employment (unemployment). The studies pointed out significant correlations between greater disability and lower earnings and higher income from benefits. A study found the same correlation in relation to cognitive function. The studies reported higher work disability in relation to higher physical disability and lower cognitive function. In conclusion, this systematic review summarizes the pronounced differences in various socioeconomic outcomes between patients with MS with regards to their physical disability and cognitive function. In addition, we identified a lack of studies with longitudinal design in this field that can provide more robust estimates with covariate adjustments, such as disease modifying treatments.

Machine Learning and Multiparametric Brain MRI to Differentiate Hereditary Diffuse Leukodystrophy with Spheroids from Multiple Sclerosis.

BACKGROUND AND PURPOSE: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and multiple sclerosis (MS) are demyelinating and neurodegenerative disorders that can be hard to distinguish clinically and radiologically. HDLS is a rare disorder compared to MS, which has led to occurrent misdiagnosis of HDLS as MS. That is problematic since their prognosis and treatment differ. Both disorders are investigated by MRI, which could help to identify patients with high probability of having HDLS, which could guide targeted genetic testing to confirm the HDLS diagnosis. METHODS: Here, we present a machine learning method based on quantitative MRI that can achieve a robust classification of HDLS versus MS. Four HDLS and 14 age-matched MS patients underwent a quantitative brain MRI protocol (synthetic MRI) at 3 Tesla (T) (scan time <7 minutes). We also performed a repeatability analysis of the predicting features to assess their generalizability by scanning a healthy control with five scan-rescans at 3T and 1.5T. RESULTS: Our predicting features were measured with an average confidence interval of 1.7% (P = .01), at 3T and 2.3% (P = .01) at 1.5T. The model gave a 100% correct classification of the cross-validation data when using 5-11 predicting features. When the maximum measurement noise was inserted in the model, the true positive rate of HDLS was 97.2%, while the true positive rate of MS was 99.6%. CONCLUSIONS: This study suggests that computer-assistance in combination with quantitative MRI may be helpful in aiding the challenging differential diagnosis of HDLS versus MS.

Cognitive function is a major determinant of income among multiple sclerosis patients in Sweden acting independently from physical disability.

BACKGROUND: In multiple sclerosis (MS), various aspects of cognitive function can be detrimentally affected, thus patients' employment and social functioning is commonly impacted. OBJECTIVE: To analyse income among MS patients in relation to cognitive function, assessed with the Symbol Digit Modalities Test (SDMT). METHODS: A cross-sectional study including 2080 MS patients was conducted linking national register-based data. Descriptive statistics and a two-part model were used to estimate differences in earnings and social benefits. RESULTS: MS patients in the highest SDMT score quartile earned more than twice annually compared to patients in the lowest quartile, whereas patients in the lowest quartile received three times more income through social benefits. The difference in earnings and benefits across the SDMT performance quartiles remained statistically significant after adjusting for various clinical and socio-demographic variables, including physical disability. The corrected prevalence ratios for MS patients in the highest quartile for having income from earnings and benefits were 1.40 (95% confidence interval (CI): 1.29-1.49) and 0.81 (95% CI: 0.71-0.90), respectively, when compared to the patients in the lowest quartile. CONCLUSION: Cognitive function affects the financial situation of MS patients negatively and independently of physical disability. This warrants cognitive testing as a routine measure in health care services for MS patients.

Income in Multiple Sclerosis Patients with Different Disease Phenotypes.

BACKGROUND: Multiple sclerosis (MS) is a disease with profound heterogeneity in clinical course. OBJECTIVE: To analyze sources and levels of income among MS patients in relation to disease phenotype with a special focus on identifying differences/similarities between primary progressive MS (PPMS) and secondary progressive MS (SPMS). METHODS: A total of 6890 MS patients aged 21-64 years and living in Sweden in 2010 were identified for this cross-sectional study. Descriptive statistics, logistic, truncated linear, and zero-inflated negative binomial regression models were used to estimate differences in income between SPMS, PPMS and relapsing-remitting MS (RRMS) patients. RESULTS: RRMS patients earned almost twice as much as PPMS and SPMS patients (on average SEK 204,500, SEK 114,500, and SEK 79,800 in 2010, respectively). The difference in earnings between PPMS and SPMS was not statistically significant when analyzed with multivariable regression. The estimated odds ratio for PPMS patients to have income from earnings was not significantly different from SPMS patients (95% CI 0.98 to 1.59). PPMS and RRMS patients were less likely to receive benefits when compared to SPMS patients (by 6% and 27% lower, respectively). CONCLUSION: Our findings argue for similarities between PPMS and SPMS and highlight the socioeconomic importance of preventing RRMS patients convert to SPMS.