Ali Manouchehrinia

Karolinska Institutet | KI · Department of Clinical Neuroscience

Background: The Multiple Sclerosis Severity Score (MSSS) is obtained by normalising the Expanded Disability Status Scale (EDSS) score for disease duration and has been a valuable tool in cross-sectional studies. Objective: To assess whether use of age rather than the inherently ambiguous disease duration was a feasible approach. Method: We poo...

Tobacco smoking has been linked to an increased risk of multiple sclerosis. However, to date, results from the few studies on the impact of smoking on the progression of disability are conflicting. The aim of this study was to investigate the effects of smoking on disability progression and disease severity in a cohort of patients with clinically d...

There are inconsistent data on mortality in people with multiple sclerosis (MS). We performed a meta-analysis of all-cause, cause-specific and gender-specific crude mortality rates (CMRs), and standardised mortality ratios (SMRs) in MS, and estimated the rate of change of CMR and SMR over the past 50 years. Medline, Embase and the Cochrane Library...

As patients with multiple sclerosis (MS) have more than 2.5-fold increased mortality risk, we sought to investigate the impact of tobacco smoking on the risk of premature death and its contribution to the excess mortality in MS patients. We studied 1032 patients during the period 1994-2013 in a UK-based register. Cox regression model was used to in...

Since its first comprehensive clinico-pathological description by Charcot, Multiple sclerosis (MS) has remained a mysterious clinical entity and has represented a fascination to scientists and clinicians of the most diverse disciplines. With an incompletely known pathogenesis and aetiology, it has given rise to numerous theories including the more...

Background: The two main phenotypes of multiple sclerosis (MS), primary progressive (PPMS) and relapsing Onset (ROMS), show clinical and demographic differences suggesting possible differential risk mechanisms. Understanding the heritable features of these phenotypes could provide aetiological insight. Objectives: To evaluate the magnitude of fa...

Background: Multiple sclerosis (MS) quality of care guidelines are consensus-based. The effectiveness of the recommendations is unknown. Objective: To determine whether clinic-level quality of care affects clinical and patient-reported outcomes. Methods: This nationwide observational cohort study included patients with adult-onset MS in the Sw...

Objectives: The present study is aimed at determining the effect of cigarette smoking (CS) on serum uric acid (UA) levels quantitatively before and after smoking cessation among people with MS (pwMS). Additionally, a possible correlation between UA levels and both disability progression and disease severity was also investigated. A retrospective cr...

Background To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing–remitting MS (RRMS) and SPMS and may identify situations wh...

Background: Cognitive impairment occurs in 40%-70% of persons with multiple sclerosis (MS). Objective: To examine the effectiveness of natalizumab compared with other disease-modifying treatments (DMTs) on improving cognition as measured by the Symbol Digit Modalities Test (SDMT). Methods: Data were collected as part of Swedish nationwide phas...

Background: Neurofilament light (NfL) levels reflect inflammatory disease activity in multiple sclerosis (MS), but it is less clear if NfL also can serve as a biomarker for MS progression in treated patients without relapses and focal lesion accrual. In addition, it has not been well established if clinically effective treatment re-establishes an a...

Background Most previous multiple sclerosis (MS) brain atrophy studies using MS impact scale 29 (MSIS-29) or symbol digit modalities test (SDMT) have been cross-sectional with limited sets of clinical outcomes. Objectives To investigate which brain and lesion volume metrics show the strongest long-term associations with the expanded disability sta...

Background Timing of disease-modifying therapy affects clinical disability in multiple sclerosis, but it is not known whether patient reported outcomes are also affected. This study investigates the relationship between treatment timing and patient-reported symptoms and health-related quality of life. Methods This was a nationwide observational co...

Objectives High rates of anti-drug antibodies (ADA) to rituximab have been demonstrated in patients undergoing treatment for systemic lupus erythematosus (SLE). However, little is known with regards to their long-term dynamics, impact on drug kinetics and subsequent implications for treatment response. In this study, we aimed to evaluate ADA persis...

Purpose A major limitation of biologic therapy is formation of anti-drug antibodies (ADA). We have demonstrated ADA to Rituximab (RTX) predict subsequent infusion related reactions. However, little is known regarding the longterm dynamics of ADA to RTX in patients undergoing treatment for SLE. In this study we evaluated the longitudinal impact of A...

Background A major limitation of biologic therapy is formation of anti-drug antibodies (ADA). We previously found ADA to rituximab (RTX) are more prevalent in patients undergoing treatment for systemic lupus erythematosus (SLE) than rheumatoid arthritis and vasculitis (1). In addition, we demonstrated that ADA to RTX predict subsequent infusion rel...

Background/Aims A major limitation of biologic therapy is formation of anti-drug antibodies (ADA). We previously demonstrated that ADA to rituximab are more prevalent in patients undergoing treatment for systemic lupus erythematosus (SLE) than rheumatoid arthritis and vasculitis, and predict subsequent infusion reactions. However, little is known r...

Background Early treatment with disease modifying therapies (DMTs) for multiple sclerosis (MS) has been associated with lower disability progression; the aim was to explore its association with cost of illness (COI) in MS. Methods All people with relapsing-remitting MS in the Swedish MS register, aged 20–57 years and receiving their first MS DMT i...

Tobacco smoke is an important modifiable environmental risk factor for multiple sclerosis (MS) risk. The population attributable fraction (AF) of MS due to smoking can be used to assess the contribution of smoking to the risk of MS development. We conducted a matched case-control study, including individuals with MS and population-based controls. O...

Background Serum neurofilament light chain (sNfL) is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs and to prognosticate disease course in people with multiple sclerosis on the group level. The absence of representative reference values to correct for physiological age-dependent increases in s...

Objective To explore the longitudinal relationship between multiple sclerosis (MS) relapses and information processing efficiency among persons with relapsing-remitting MS. Methods Swedish nationwide cohort study of persons with incident relapsing-remitting MS (2001-2019). Relapse information and symbol digit modalities test (SDMT) scores were obt...

Background The latitude gradient in multiple sclerosis incidence indicates that low sun exposure and therefore vitamin D deficiency is associated with multiple sclerosis risk. Objective Investigation of the effect of month of birth, which influences postnatal vitamin D levels, on multiple sclerosis risk and severity in Sweden. Methods Patients an...

Objectives Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. Identifying MS at the population level is important for disease surveillance and allocation of resources. The Swedish National Patient Registry (NPR) has been used to study the epidemiology of MS, but the accuracy of this resource is not known....

Multiple sclerosis (MS) patients with immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) have different genetic backgrounds and brain MRI features compared to those without. In this study, we aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS register data...

Purpose: Observational studies have suggested a protective effect of alcohol intake with autoimmune disorders, which was not supported by Mendelian randomization (MR) analyses that used only a few (<20) instrumental variables. Methods: We systemically interrogated a putative causal relationship between alcohol consumption and four common autoimmune...

Background: Although over a dozen disease modifying treatments (DMTs) are available for relapsing forms of multiple sclerosis (MS), treatment interruption, switching and discontinuation are common challenges. The objective of this study was to describe treatment interruption and discontinuation in the Big MS data network. Methods: We merged informa...

Multiple sclerosis (MS) patients with and without the oligoclonal band (OCB) distribution of immunoglobulin gamma (IgG) in the cerebrospinal fluid (CSF) has a different genetic background and brain MRI features. In this study we have aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS regis...

Depression is common in multiple sclerosis (MS); however, the underlying mechanism for the relationship remains unknown. In this study, we examined a putative causal relationship between depression and MS using a bidirectional Mendelian randomisation (MR) framework. Using the latest genome-wide association study data available, 168 non–major histoc...

Background Existing severity measurements in multiple sclerosis (MS) are often cross-sectional, making longitudinal comparisons of disease course between individuals difficult. Objective The objective of this study is to create a severity metric that can reliably summarize a patient’s disease course. Methods We developed the nARMSS – normalized A...

Background The absence of reliable imaging or biological markers of phenotype transition in multiple sclerosis (MS) makes assignment of current phenotype status difficult. Objective The authors sought to determine whether clinical information can be used to accurately assign current disease phenotypes. Methods Data from the clinical visits of 14,...

Background Early initiation of disease-modifying treatment (DMT) is associated with better disability outcomes in multiple sclerosis (MS). However, little is known of how treatment decisions affect socio-economic outcomes. Objective To estimate the long-term impact of early initiation of DMT on the income of MS patients. Methods In total, 3610 MS...

Background: The β-D-Mannuronic acid (M2000) as a novel immunosuppressive drug, patented (PCT/EP2017/067920), has shown positive effects in experimental model of multiple sclerosis (MS). In this study, our aim was to assess efficacy and safety outcomes in MS treated patients with mannuronic acid compared to the conventional drug. Methods: In a 6-...

Transition from a relapsing-remitting to the secondary progressive phenotype is an important milestone in the clinical evolution of multiple sclerosis. In the absence of reliable imaging or biological markers of phenotype transition, assignment of current phenotype status relies on retrospective evaluation of the medical history of an individual. H...

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are pr...

Objective To investigate the association between plasma neurofilament light chain (pNfL) levels and the risk of developing sustained disability worsening. Methods Concentrations of pNfL were determined in 4,385 persons with multiple sclerosis (MS) and 1,026 randomly selected population-based sex- and age-matched controls using the highly sensitive...

Objective: To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS). Methods: Data including...

Blood Neurofilament light chain (NfL) has been suggested as a promising biomarker in several neurological conditions. Since blood NfL is the consequence of leaked NfL from the cerebrospinal fluid, differences in individuals’ Body Mass Index (BMI) or blood volume (BV) might affect its correlation to other biomarkers and disease outcomes. Here, we in...

Objective: To evaluate quality of life (QoL), measured by the EQ-5D, in adults with pediatric-onset multiple sclerosis (POMS) or adult-onset multiple sclerosis (AOMS) and explore determinants of QoL in both groups. Methods: Data were collected from the nationwide Swedish multiple sclerosis (MS) registry. Demographic characteristics, EQ-5D-3 leve...

Objective: Depression is common in multiple sclerosis (MS), but its impact on disability worsening has not yet been determined. We explored the risk of disability worsening associated with depression in a nationwide longitudinal cohort. Methods: This retrospective cohort study used linked data from 3 Swedish nationwide registries: the MS Registe...

Background: Reductions of the peripapillary retinal nerve fiber layer (pRNFL) thickness has been indicated even in early-stages of multiple sclerosis (MS). The aim was to investigate the association between pRNFL thickness, measured with optical coherence tomography (OCT), and physical disability and cognitive impairment in MS. Methods: 465 MS p...

Background: As the prevalence and incidence of Multiple Sclerosis (MS) are increasing remarkably in Iran, gathering standardized information regarding the individual's diagnosis, care, and outcomes through a uniform registry system would enable policy-makers to systematically plan for care quality improvements. Objective: To design a valid and r...

Patients with the 'aggressive' form of MS accrue disability at an accelerated rate, typically reaching EDSS >= 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive MS, but less research has focused on clinical markers that are present in the first year of disease. The development of early predi...

Importance Cognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term. Objective To compare long-term information-processing efficiency between patients with POMS and adult-...

Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facil...

Objective: To evaluate long-term disability progression in pediatric-onset multiple sclerosis (POMS) and compare to adult-onset multiple sclerosis (AOMS). Methods: This was a retrospective cohort study using prospectively collected clinical information from the Swedish MS Registry. Clinical features were compared and Kaplan-Meier and Cox proport...

Importance Clinicians’ experience and findings from recent natural history studies suggest that multiple sclerosis (MS) may now be running a more slowly progressing course than before. Objective To investigate whether the risk of reaching MS disability milestones has changed over the last decade in Sweden. Design, Setting, and Participants A nati...

Objective Benign multiple sclerosis (BMS) is often defined by the Expanded Disability Status Scale (EDSS) score of ≤3.0 after ≥15 years of disease duration. This classification’s clinical relevance remains unclear as benign patients may suffer other impairments and advance towards a progressive course, prompting our objective to holistically invest...

Background Persons who develop multiple sclerosis (MS) at a young age may bear a higher genetic risk load than persons who develop MS later in life; however, the contribution of familial influence to the risk of MS, in relation to onset age, has not been established. Objective To investigate the familial risk of MS at two extremes of the spectrum...

Cigarette smoking is the most prominent significant cause of death and morbidity. It is recognised as a risk factor for a number of immune mediated, inflammatory diseases including multiple sclerosis (MS). Here, we review the complex immunological effects of smoking on the immune system, which include enhancement of inflammatory responses with a pa...

Objectives: We aimed at designing a nomogram, a prediction tool, to predict the individual's risk of conversion to secondary progressive multiple sclerosis (SPMS) at the time of multiple sclerosis (MS) onset. Methods: One derivation and three validation cohorts were established. The derivation cohort included 8825 relapsing-onset MS patients in...

Both high body mass index (BMI) and smoking tobacco are known risk factors for developing multiple sclerosis (MS). However, it is unclear whether BMI, like smoking, is a risk factor for the secondary progressive (SP) course. We, therefore, sought to determine if high/low BMI at age 20 is associated to risk of SP development, in the context of smoki...

Background Reduced peripapillary retinal nerve fiber layer (pRNFL) and combined ganglion cell and inner plexiform layer (GCIP) thicknesses as measured by optical coherence tomography (OCT) have been observed in multiple sclerosis (MS) patients. The purpose was to determine the most associative OCT measure to level of cognitive and physical disabili...

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 s...

Varicella zoster virus (VZV) infection has been implicated in multiple sclerosis (MS), but direct causal involvement has been disputed. Nevertheless, knowledge of VZV exposure is important, given the risk of serious complications of first exposure while undergoing immunosuppressive treatment, in particular with fingolimod. We distributed questionna...

Purpose Reductions in the retinal nerve fibre layer (RNFL) have been indicated even in early‐stages of multiple sclerosis (MS). The aim was to assess the potential of the RNFL quadrant measurements in differentiating disease phenotypes and their association with cognitive impairment and physical disability. Methods Four hundred and sixty‐five MS p...

Genetic variants within some cytokine receptor genes have been associated with MS susceptibility, including IL7RA and IL2RA. As these genes are expressed by cells targeted by immune-modulatory drugs, we explored the potential role of their gene products as biomarkers in monitoring MS treatment. We assessed the impact of natalizumab followed by fing...

Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical...