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Background It is unclear whether recombinant β interferons (IFNb) can be effective in secondary progressive multiple sclerosis (SPMS). The aim was to determine whether IFNb can reduce the risk of disability and cognitive impairment progression in SPMS. Methods Using Cochrane methodology, we reviewed all randomised placebo controlled trials of IFNb in SPMS patients (1995eMarch 2012). Results 5 trials (3082 patients) were included. After 3 years, interferons did not reduce disability progression, confirmed at 6 months (RR 0.98, 95% CI 0.82 to 1.16). A small reduction in the number of patients who had relapses during the first 3 years of treatment (RR 0.91, 0.84 to 0.97) was found. No analysis of cognitive data was possible. More treated than placebo patients dropped out for adverse events. Conclusion 3 year treatment with IFNb does not delay permanent disability in SPMS but reduces relapse risk, indicating that the anti-inflammatory effect of IFNb is unable to prevent MS progression once it has become established. [ABSTRACT FROM AUTHOR]

With increasing availability of magnetic resonance imaging (MRI), there is also an increase in incidental abnormal findings. MRI findings suggestive of multiple sclerosis in persons without typical multiple sclerosis symptoms and with normal neurological findings are defined as radiologically isolated syndrome (RIS). Half of the persons with RIS have their initial MRI because of headache, and some have a subclinical cognitive impairment similar to that seen in multiple sclerosis. Radiological measurements also show a similarity between RIS and multiple sclerosis. Approximately two-thirds of persons with RIS show radiological progression and one-third develop neurological symptoms during mean follow-up times of up to five years. Cervical cord lesions are important predictors of clinical conversion. Management has to be individualised, but initiation of disease modifying therapy is controversial and not recommended outside of clinical trials since its effects have not been studied in RIS. Future studies should try to establish the prevalence and long-term prognosis of RIS, its impact on quality of life, and define the role of disease modifying therapy in RIS. [ABSTRACT FROM AUTHOR]

Background: Glatiramer acetate (GA) and interferon-beta (INFb) are first-line disease modifying drugs for relapsing remitting multiple sclerosis (RRMS). Treatment with INFb is associated with a significant increase in health-related quality of life (HR-QoL) in the first 12 months. It is not known whether HR-QoL increases during treatment with GA. Methods: 197 RRMS patients, 106 without and 91 with prior immunomodulation/immunosuppression, were studied for HR-QoL (Leeds Multiple Sclerosis-QoL [LMS-QoL] scale, score range 0 - 32), fatigue (Fatigue Impact Scale [FIS]) and depressed mood (Beck Depression Inventory-Short Form [BDI-SF]) at baseline and 6 and 12 months after start of GA treatment. Results: At 6 and 12 months mean LMS-QoL scores were significantly increased in the treatment-naive patient group (p < 0.001), not in the pre-treated group. At month 12 43% of treatment-naïve patients had improved HRQoL (increase LMS-QoL score 3 or more points) (p < 0.001). Likewise, mean FIS scores were decreased at months 6 and 12 in the treatment-naïve group (p < 0.01), not in the pre-treated group. In both groups mean BDI-SF scores did not change. No demographic or clinical baseline factor was predictive of HR-QoL increase. HR-QoL changes were zero to negative for patients who had discontinued GA before month 12 (28.4% of patients). Conclusions: In RRMS patients without prior immunomodulation/immunosuppression treatment with GA was associated with an increase in HR-QoL in the first 6 months, that was sustained at 12 months. In 4 out of 10 patients HR-QoL improved. Increase in HR-QoL was associated with decrease in fatigue. [ABSTRACT FROM AUTHOR]

Background: In multiple sclerosis (MS), multiple periventricular lesions are commonly the first findings on MRI. However, most of these MS lesions are clinically silent. The brain atrophy rate has shown better correlation to physical disability, but it is not clear how atrophy develops over decades. Corpus callosum forms the roof of the third and lateral ventricles. The corpus callosum area (CCA) in a midsagittal image is age independent in a normal adult population up to the seventh decade; therefore it can be used as a marker for non-age-related, pathological brain atrophy.Objectives: To investigate whether and how CCA decreases in size over time in patients with MS.Methods: In a clinical observational study, 37 patients with MS with a wide range of disease duration at baseline (1-33 years) were followed. Three different MS courses were represented. The mean of individual MRI follow-up was 9 years. Multiple sclerosis severity score (MSSS) was also applied to evaluate disability at baseline and after 9 years of follow-up.Results: A significant decrease in CCA over 9 years (p<0.001) and a persisting association between CCA and the disability status were found. The atrophy rate was similar ever four decades of MS for all MS courses. The mean annual CCA decrease was 9.25 mm2 (1.8%). Surprisingly, atrophy rate did not correlate with sex, disease duration, age at MS onset or MS course.Conclusions: Serial evaluations of CCA might be a robust method in monitoring a non-age-related decrease in CCA, reflecting progression of irreversible destructive changes in MS. [ABSTRACT FROM AUTHOR]

We describe the age- and sex-specific incidence of Guillain-Barré syndrome (GBS) in Harbin, China, based on the information from a prospective survey among a well-defined large population during one year. A network of physicians reported incident patients with a GBS diagnosis from a general population of 5.4 million inhabitants in Harbin, China, during the period from 1 October 1997 to 30 September 1998. Each reported patient was examined by senior neurologists and the GBS diagnosis was validated according to standard diagnostic criteria. All GBS patients were followed-up for six months after onset. Admission registers at all hospitals in Harbin were also checked afterwards for screening patients with a GBS diagnosis who might have been missed. During the study period, 79 patients with a GBS diagnosis were reported. After validation, the GBS diagnosis was confirmed in 70 patients. Another GBS patient was found through the screening of admission registers at hospitals. Among them, 36 GBS patients were residents in Harbin and the other 35 patients were from geographical areas out of Harbin. The GBS incidence, age-adjusted to the European standard population, was 0.66 (95 % CI 0.46–0.91) per 100,000 person-years, with a male to female ratio of 1.4. The highest GBS incidence was found in the youngest age-group and the incidence among the elderly was remarkably lower than those reported from other populations in Western countries. Possible explanations for the distinct pattern of age-specific incidence of GBS are discussed. Further studies are needed. [ABSTRACT FROM AUTHOR]

Four recent genome-wide screen studies in multiple sclerosis (MS) identified a number of candidate regions for susceptibility genes in addition to the HLA complex in 6p21. However, none of these regions provided formally significant evidence for genome-wide linkage. We have investigated such regions in 46 Swedish multiplex MS families, 28 singleton families, 190 sporadic MS patients and 148 normal controls by parametric and nonparametric linkage and association analysis. One microsatellite marker, in 12q23, provided evidence for association in addition to suggestive transmission distortion and slightly positive linkage. In addition, a marker in 7ptr–15 showed a significant transmission distortion as well as a highly significant score in affected pedigree member analysis, but not quite significant deviations in association analysis. One of three markers in 5p, a region implicated in all four previous studies, showed a weakly positive lod score, but no other evidence of importance. Markers in 2p23, 5q11–13, 6q25, 7q21–22, 11q21–23, 13q33–34, 16p13.2, 18p11.32–23, Xp21.3 provided little or no evidence of importance for MS. In summary, these data support the importance of genome-wide screens in the identification of new candidate loci in polygenic disorders. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about a study which examines the association between human leukocyte antigen (HLA) composition and disability in patients with multiple sclerosis (MS) by B. G. Weinshenker and colleagues in a 1998 issue.

Alemtuzumab (Lemtrada™) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or more disease-modifying therapies (DMTs). In clinical trials, alemtuzumab demonstrated efficacy in treatment-naïve patients with active RRMS and those relapsing on prior DMTs, with a consistent and manageable safety and tolerability profile. The European Union indication provides physicians with significant flexibility regarding treatment decisions, affording the opportunity for individualized treatment. Thus, alemtuzumab may be an appropriate treatment choice across a broad range of patients with RRMS, including, for example, treatment-naïve patients with active disease, patients with highly active disease, or for patients relapsing on prior DMTs. There are several practicalities to consider when using alemtuzumab, including the unique dosing regimen, administered via intravenous infusion on 5 consecutive days at baseline and on 3 consecutive days 12 months later, and as-needed retreatment (3 consecutive days at least 12 months after the last course) in cases of disease recurrence. Additionally, routine monthly monitoring is required for up to 48 months after the last infusion to promptly identify potentially serious autoimmune adverse events. Given these considerations, it is beneficial to gain insight into how alemtuzumab is being used in the real-world clinical setting. Here, we report recommendations from European multiple sclerosis experts regarding best practices for alemtuzumab treatment, including management of adverse events and compliance with ongoing safety monitoring requirements. [ABSTRACT FROM AUTHOR]

Background and Purpose: Evidence of brain gadolinium retention has affected gadolinium‐based contrast agent usage. It is, however, unclear to what extent macrocyclic agents are retained and whether their in vivo detection may necessitate nonconventional MRI. Magnetization transfer (MT) could prove suitable to detect gadolinium‐related signal changes since dechelated gadolinium ions bind to macromolecules. Therefore, this study aimed to investigate associations of prior gadolinium administrations with MT and T1 signal abnormalities. Methods: A cohort of 23 persons with multiple sclerosis (MS) (18 females, 5 males, 57 ± 8.0 years) with multiple past gadolinium administrations (median 6, range 3‐12) and 23 age‐ and sex‐matched healthy controls underwent 1.5 Tesla MRI with MT, T1‐weighted 2‐dimensional spin echo, and T1‐weighted 3‐dimensional gradient echo. The signal intensity index was assessed by MRI in gadolinium retention predilection sites. Results: There were dose‐dependent associations of the globus pallidus signal on gradient echo (r =.55, p <.001) and spin echo (r =.38, p =.013) T1‐weighted imaging, but not on MT. Relative to controls, MS patients had higher signal intensity index in the dentate nucleus on T1‐weighted gradient echo (1.037 ± 0.040 vs. 1.016 ± 0.023, p =.04) with a similar trend in the globus pallidus on T1‐weighted spin echo (1.091 ± 0.034 vs. 1.076 ± 0.014, p =.06). MT detected no group differences. Conclusions: Conventional T1‐weighted imaging provided dose‐dependent associations with gadolinium administrations in MS, while these could not be detected with 2‐dimensional MT. Future studies could explore newer MT techniques like 3D and inhomogenous MT. Notably, these associations were identified with conventional MRI even though most patients had not received gadolinium administrations in the preceding 9 years, suggestive of long‐term retention. [ABSTRACT FROM AUTHOR]

Introduction. Daytime sleepiness is a common nonmotor symptom in Parkinson's disease (PD) which is associated with decreased quality of life and perceived health. However, experiences of daytime sleepiness in people with PD have not been explored. The aim of this qualitative study was to explore experiences of daytime sleepiness in people with PD. Materials and Methods. Five women and seven men (42–82 years) with PD for 1.5 to 21 years and excessive daytime sleepiness (i.e., a score of >10 on the Epworth Sleepiness Scale) participated in the study. Data were collected through individual, semistructured, face-to-face interviews and analyzed with qualitative content analysis. Results Three themes of the experience of daytime sleepiness were revealed: (1) not an isolated phenomenon, (2) something to struggle against or accept, and (3) something beyond sleepiness. Conclusion. Daytime sleepiness is a complex nonmotor symptom in PD which manifests itself in several ways. Some experiences are similar, for instance, the attribution of daytime sleepiness to PD and its medical treatment. Differences depend on how sleepiness manifests itself, affects the person, and impacts daily life, as well as whether it causes feelings of embarrassment. Some participants needed to struggle against daytime sleepiness most of the time, and others had found a way to handle it, for example, with physical activity. However, sleepiness may also be used to benefit the person, for example, if they allow themselves to take a power nap to regain energy. The health care professionals can easily underestimate or misinterpret the prevalence and burden of daytime sleepiness because people with PD may describe daytime sleepiness as tiredness, drowsiness, or feeling exhausted, not as sleepiness. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate differences in socio-economic characteristics between CAM users and CAM non-users among people with MS in Denmark as well as differences in characteristics related to the use of CAM among CAM users and the use of conventional treatments among CAM non-users. Methods: An internet-based questionnaire was used to collect data from 3361 patient members of the Danish MS society. A letter with a personal code was sent to all respondents, asking them to fill out the questionnaire online. Reminders to non-respondents were sent twice and the final response rate was 55.5%. Statistical associations were presented as odds ratios and with respective 95% confidence intervals. Results: People with MS in Denmark use a wide range of CAM treatments for a variety of reasons. CAM users were more likely to be of female gender, 18–40 years of age, educated at bachelor level or above, and have a high income compared to CAM non-users (p < 0.05). CAM users more often addressed non-specific/preventive treatment purposes through their use of CAM treatments, they communicated less often with a medical doctor about the CAM treatments used, and they experienced less side effects as well as less positive effects from the CAM treatments used when compared with the use of conventional treatments among CAM non-users (p < 0.05). Conclusions: People with MS in Denmark reported use of a large range of CAM treatments. CAM users differed from CAN non-users in relation to socio-economic factors as well as treatment characteristics. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). Methods: A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. Results: In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Conclusion: Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs. [Copyright &y& Elsevier]

Background and Objective: Comparable data are sparse for inflammatory demyelinating diseases of the central nervous system (CNS) in the Asia-Pacific region, and we aimed to establish a registry of patients with such diseases in the region. Methods: A network of neurologists in the Asia-Pacific Region was established to register patients with the targeted diseases. A standardized register form and relevant instructions in English, translated into the local language when needed, were prepared before the study start and used for data collection. Results: Eight study centres from different countries/areas participated in the study. In total, 857 patients with a validated diagnosis of different inflammatory demyelinating diseases of the CNS were registered, 591 females and 266 males with a female-to-male ratio 2.2. The mean age at onset for all patients was 35.9 (SD: 12.9) years, significantly younger (p = 0.010) for females (35.1 years, SD: 12.6 years) than for males (37.6 years, SD: 13.4 years). Conclusion: Patients with different inflammatory demyelinating diseases of the CNS were in the first time registered in a multi-centre study from eight countries/areas in the Asia-Pacific region. A platform and basis has been established for further study in the field. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) which commonly leads to disability. We reviewed articles on MS from Pakistan using PubMed, Google Scholar and Pak Medinet to present different aspects of the disease and the status of disease modifying treatments in Pakistan and South Asia. MS is not as uncommon in Pakistan as it has been previously thought to be. Estimated prevalence of MS in Pakistan may be 10 per 100,000 population. Data suggests that most features of MS found in Pakistan are similar to those found in the West. These features include a female preponderance, mean age of onset in the third decade of life and similar risk factors including viral infections, smoking, and vitamin D deficiency, as well as genetic risk factors. Relapsing-remitting multiple sclerosis (RRMS) is the most common disease pattern seen in Pakistan which is also consistent with data from other regions. Treatment modalities in Pakistan include immunomodulatory and immunosuppressive drugs. In order to improve care for MS patients in Pakistan, it is extremely important to obtain a population-based prevalence of MS in the country and a national MS registry, along with implementing programs for patients' awareness and the training of doctors, especially internists. There are many disease modifying therapies (DMT) available in Pakistan but no data is available on the utilization and impact of these DMTs. • Estimated prevalence of MS in Pakistan may be 10 per 100,000 population. • Preponderance to MS include a female gender, mean age of onset in the third decade of life and similar risk factors including viral infections, smoking, and vitamin D deficiency, as well as genetic risk factors • Relapsing-remitting multiple sclerosis (RRMS) is the most common disease pattern seen in Pakistan • Limited data available for MS in Pakistan • Disease modifying treatments use is limited due to awareness, limited availability of neurologists and cost of treatment [ABSTRACT FROM AUTHOR]

Aims: To study incident narcolepsy in first- and second-generation immigrant groups using Swedish-born individuals and native Swedes as referents., Methods: The study population included all individuals registered and alive in Sweden at baseline. Narcolepsy was defined as having at least one registered diagnosis of narcolepsy in the Swedish National Patient Register. The incidence of narcolepsy in different immigrant groups was assessed by Cox regression, with hazard ratios (HRs) and 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, co-morbidities, and neighbourhood socioeconomic status., Results: In the first-generation study, 1225 narcolepsy cases were found; 465 males and 760 females, and in the second-generation study, 1710 cases, 702 males and 1008 females. Fully adjusted HRs (95% CI) in the first-generation study was for males 0.83 (0.61-1.13) and females 0.83 (0.64-1.07), and in the second-generation study for males 0.76 (0.60-0.95) and females 0.91 (95% CI 0.76-1.09). Statistically significant excess risks of narcolepsy were found in first-generation males from North America, and second-generation males with parents from North America, and second-generation females with parents from Latin America., Conclusions: There were only significant differences in incident narcolepsy between native Swedes and second-generation male immigrants. The observed differences can partly be explained by differences in Pandemrix® vaccinations and are probably not attributable to genetic differences between immigrants and natives., (© 2022 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background: There is a lack of studies of amyotrophic lateral sclerosis (ALS) in immigrants., Objective: The objective is to study the association between country of birth and incident ALS in first-generation immigrants versus Swedish-born individuals, and in second-generation immigrants versus native Swedes., Methods: Study populations included all adults aged 18 years and older in Sweden, in the first-generation study 6,128,698 individuals (2,975,141 men, 3,153,557 women) with 5,344 ALS cases (3017 men, 2327 women), and in the second-generation study 4,588,845 individuals (2,346,855 men and 2,241,990 women) with 3,420 cases (2027 men and 1393 women). ALS was defined as having at least one registered diagnosis of ALS in the National Patient Register 1998-2017. The incidence of ALS in different first-generation immigrant groups versus Swedish-born individuals was assessed by Cox regression, expressed as hazard ratios (HRs) with 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status., Results: After adjusting for potential confounders, the HRs were lower in foreign-born men, 0.71 (95% CI 0.63-0.81), and women, 0.80 (95% CI 0.70-0.92). The ALS risk was lower among men and women from most Western countries (Europe outside Nordic countries, and North America), and from other regions of the world (Africa, Asia, and Latin America). Among men and women with foreign-born parents, the risk of ALS did not differ significantly from native Swedes., Significance: In general, the risk of ALS was lower in first-generation men and women but did not differ in second-generation individuals., (© 2021. The Author(s).)

Parkinson's disease (PD) is a neurodegenerative disease linked with the loss of dopaminergic neurons in the brain region called substantia nigra and caused by unknown pathogenic mechanisms. Two currently recognized prominent features of PD are an inflammatory response manifested by glial reaction and T-cell infiltration, as well as the presence of various toxic mediators derived from activated glial cells. PD or parkinsonism has been described after infection with several different viruses and it has therefore been hypothesized that a viral infection might play a role in the pathogenesis of the disease. We investigated formalin-fixed post-mortem brain tissue from 9 patients with Parkinson's disease and 11 controls for the presence of Ljungan virus (LV) antigen using a polyclonal antibody against the capsid protein of this recently identified picornavirus with neurotropic properties, suspected of being both a human and an animal pathogen. Evidence of viral antigen was found in 7 out of 9 Parkinson's disease cases and in only 1 out of 11 controls ( p = 0.005). The picornavirus antigen was present in dopamine-containing neurons of the substantia nigra. We propose that LV or an LV-related virus initiates the pathological process underlying sporadic PD. LV-related picornavirus antigen has also been reported in patients with Alzheimer's disease. Potentially successful antiviral treatment in Alzheimer's disease suggests a similar treatment for Parkinson's disease. Amantadine, originally developed as an antiviral drug against influenza infection, has also been used for symptomatic treatment of patients with PD for more than 50 years and is still commonly used by neurologists today. The fact that amantadine also has an antiviral effect on picornaviruses opens the question of this drug being re-evaluated as potential PD therapy in combination with other antiviral compounds directed against picornaviruses.

Background: There is a lack of studies of Huntington's disease (HD) in immigrants., Objective: To study the association between country of birth and incident HD in first-generation immigrants versus Swedish-born individuals and in second-generation immigrants versus Swedish-born individuals with Swedish-born parents., Methods: Study populations included all adults aged 18 years and older in Sweden, i.e., in the first-generation study 6,042,891 individuals with 1034 HD cases and in the second-generation study 4,860,469 individuals with 1001 cases. HD was defined as having at least one registered diagnosis of HD in the National Patient Register. The incidence of HD in different first-generation immigrant groups versus Swedish-born individuals was assessed by Cox regression, expressed as hazard ratios (HRs) and 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighborhood socioeconomic status., Results: Mean age-standardized incidence rates per 100,000 person-years were for all Swedish-born 0.82 and for all foreign born 0.53 and for all men 0.73 and for all women 0.81, with the highest incidence rates for the group 80-84 years of age. After adjusting for potential confounders, the HRs were lower in women in the first- and second-generation, i.e., 0.49 (95% CI 0.36-0.67) and 0.63 (95% 0.45-0.87), respectively, and also among women from Finland or with parents from Finland., Significance: In general, the risk of HD was lower in first-generation and second-generation immigrant women but not among male immigrants., (© 2021. The Author(s).)

Purpose: We aimed to study the association between country of birth and incident epilepsy in several immigrant groups using Swedish-born individuals as referents., Method: The study population included all adults aged 18 years and older in Sweden, living and deceased, 6,690,598 in the first-generation and 6,683,125 in the second-generation sub-study. Epilepsy was defined as having at least one registered diagnosis of epilepsy in the National Patient Register. The incidence of epilepsy in different immigrant groups, using Swedish-born as referents, was assessed by Cox regression, expressed as hazard ratios (HRs) and 95 % confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighbourhood socioeconomic status., Results: In the first-generation sub-study, totally 76,541 individuals had at least one registered diagnosis of epilepsy (1.14 % in total; men 1.22 % and women 1.07 %), and in the second-generation study 72,545 (1.09 %; men 1.18 % and women 0.99 %). After adjusting for confounders, in first-generation immigrants compared to their Swedish-born counterparts the incidence was somewhat lower among both men (HR 0.92, 0.90-0.96) and women (HR 0.93, 0.90-0.96), and in the second-generation immigrants among women (HR 0.95, 0.92-0.99) but not men (HR 0.99; 0.96-1.02). Among immigrant groups, a higher incidence of epilepsy was observed among first-generation women from Africa and Iraq, and second-generation men and women from Bosnia, and women from Finland., Conclusions: Risk of epilepsy was lower in immigrants in general compared to the Swedish-born population; but with higher incidence in some specific groups., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the long-term progression of cognitive dysfunction and its neuroanatomical correlates and predictors in multiple sclerosis (MS)., Methods: A cohort of 37 MS patients reflecting five decades of disease duration and all subtypes was followed over 17.5 years. Matched controls were recruited at the last follow-up. Global cognitive functioning was assessed using a principal component cognitive index based on comprehensive neuropsychological testing. During the last 8.5 years of the study, brain MRI was performed to analyze normalized volumetrics of three global tissue compartments (white and gray matter, lesions) and strategic regions (corpus callosum, thalamus, hippocampus)., Results: Cognitive decline progressed continuously throughout the study paralleled by atrophy and lesion accumulation. The cognitive index partly correlated with Expanded Disability Status Scale (ρ = -0.47, p < 0.001) and was mainly associated with the lesion fraction (β = -0.48, p < 0.001) and callosal fraction (β = 0.39, p = 0.002) in multiple linear regression analysis. The lesion fraction was an independent predictor of the cognitive performance 8.5 years later (β = -0.35, p = 0.008). Symbol Digit Modalities Test was most frequently abnormal (40%), while Rey-Osterrieth Complex Figure Test was more sensitive to detect cognitive decline., Conclusions: Cognitive impairment progresses continuously in MS, associated with atrophy and lesion accumulation, suggesting that interventions targeting these processes could be beneficial at all disease stages. Widespread cognitive functions are more profoundly affected, associated with lesions and corpus callosal atrophy, supporting the idea of an underlying disconnection mechanism for cognitive decline in MS., (Copyright © 2018 Elsevier B.V. All rights reserved.)