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Objectives: To determine whether treatment with autologous hematopoietic stem cell transplantation (HSCT) can induce sustained complete remission in patients with multiple sclerosis (MS). Material and methods: Case series of patients with relapsing‐remitting MS (n = 10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patients were treated with a BEAM/ATG conditioning regimen (n = 9) or a cyclophosphamide/ATG conditioning regimen (n = 1) followed by infusion of unmanipulated autologous hematopoietic stem cells. The primary endpoint was sustained complete remission. Sustained complete remission was defined as “no evidence of disease activity‐4,” sustained for a period of at least 5 years without any ongoing disease‐modifying treatment. Furthermore, MS was considered as “resolved” if intrathecal IgG production and cerebrospinal fluid neurofilament light levels were normalized as well. Results: Five out of 10 patients were in sustained complete remission at the end of the study. In three of them, MS was resolved. Conclusions: Our data demonstrate that sustained complete remission after autologous HSCT for MS is possible.

Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses. Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL inc

IMPORTANCE Hematopoietic stem cell transplantation (HSCT) represents a potentially useful approach to slow or prevent progressive disability in relapsing-remitting multiple sclerosis (MS). OBJECTIVE To compare the effect of nonmyeloablative HSCT vs disease-modifying therapy (DMT) on disease progression. DESIGN, SETTING, AND PARTICIPANTS Between September 20, 2005, and July 7, 2016, a total of 110 patients with relapsing-remitting MS, at least 2 relapses while receiving DMT in the prior year, and an Expanded Disability Status Scale (EDSS; score range, 0-10 [10 = worst neurologic disability]) score of 2.0 to 6.0 were randomized at 4 US, European, and South American centers. Final follow-up occurred in January 2018 and database lock in February 2018. INTERVENTIONS Patients were randomized to receive HSCT along with cyclophosphamide (200mg/kg) and antithymocyte globulin (6mg/kg) (n = 55) or DMT of higher efficacy or a different class than DMT taken during the previous year (n = 55). MAIN OUTCOMES AND MEASURES The primary end point was disease progression, defined as an EDSS score increase after at least 1 year of 1.0 point or more (minimal clinically important difference, 0.5) on 2 evaluations 6 months apart, with differences in time to progression estimated as hazard ratios. RESULTS Among 110 randomized patients (73 [66%] women; mean age, 36 [SD, 8.6] years), 103 remained in the trial, with 98 evaluated at 1 year and 23 evaluated yearly for 5 years (median follow-up, 2 years; mean, 2.8 years). Disease progression occurred in 3 patients in the HSCT group and 34 patients in the DMT group. Median time to progression could not be calculated in the HSCT group because of too few events; it was 24 months (interquartile range, 18-48 months) in the DMT group (hazard ratio, 0.07; 95% CI, 0.02-0.24; P < .001). During the first year, mean EDSS scores decreased (improved) from 3.38 to 2.36 in the HSCT group and increased (worsened) from 3.31 to 3.98 in the DMT group (between-gro

Importance: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure: The cNfL levels adjusted for age and sex across diagnoses.Results: Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was

INTRODUCTION: Huntington's disease (HD) is a neurodegenerative disorder, but evidence also suggests neuroinflammation in the pathogenesis. The immune mechanisms involved and the timing of their activation need further clarification. METHODS: A clinically well-characterized HD cohort and gene negative controls were enrolled. YKL-40 reflecting innate immunity and sCD27, a marker of adaptive immunity, were measured across disease stages. Comparisons were made with markers of neurodegeneration: neurofilament light (NFL), total-tau (T-tau), and phospho-tau (P-tau). RESULTS: 52 cross-sectional cerebrospinal fluid samples and 23 follow-up samples were analyzed. sCD27 was elevated in manifest HD and premanifest gene expansion carriers, whereas controls mostly had undetectable levels. YKL-40 showed a trend toward increase in manifest HD. sCD27 correlated with YKL-40 which in turn was closely associated to all included markers of neurodegeneration. YKL-40, NFL, and both forms of tau could all independently predict HD symptoms, but only NFL levels differed between groups after age-adjustment. CONCLUSION: Increased sCD27 in premanifest HD is a sign of T cell-mediated neuroinflammation. This finding is novel since other reports almost exclusively have found early involvement of innate immunity. Validation of sCD27 in a larger HD cohort is needed. The role of adaptive immunity in HD needs further clarification, as it may hasten disease progression.

OBJECTIVES: Off-label use of rituximab to treat MS patients in Sweden is high, and the need for long-term safety data may not be met. Our objectives were to assess the rate of rituximab prescription in patients with multiple sclerosis in Sweden and, in addition, to evaluate the safety of rituximab in a single centre for patients with multiple sclerosis. MATERIAL AND METHODS: Review of the Swedish MS register was performed to study the number of MS patients treated with rituximab during the last 6 years. Investigation also included a retrospective review of medical files in search for possible side effects/adverse events in all adult patients with MS treated with rituximab at Uppsala University Hospital. RESULTS: Presently, in Sweden the rate of rituximab prescriptions in relation to other annually started of disease- modifying drugs in MS is 53.5%. CONCLUSIONS: The share of MS patients in Sweden who are treated with rituximab is very high, and also rapidly increasing. Taken into account the off-label use, cases with adverse medical conditions that could possibly be related to rituximab use should be reported thoroughly.

Purpose: The prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden. Method: We retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017. Results: We identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0-80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects. Conclusion: Seizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS.

Background and purposeThe 2014 International League Against Epilepsy clinical definition of epilepsy allows diagnosis after a single unprovoked seizure if the 10-year recurrence risk exceeds 60%. Multiple sclerosis (MS) carries an increased risk of epilepsy, but the risk after a first seizure is unknown. We aimed to investigate the risk of epilepsy in patients with MS who had suffered a first seizure. MethodsWe cross-referenced data from the Swedish MS register with the national patient register for 15810 patients with MS and 43635 controls and included 289 patients with MS and 222 controls with a first diagnosis of seizure or status epilepticus (SE) without prior epilepsy or presumed symptomatic aetiology. Kaplan-Meier curves were used to estimate the risk of epilepsy. ResultsThe 10-year risk of epilepsy was 51.4% [95% confidence interval (CI), 44.0-58.9] for patients with MS and 41.3% (95% CI, 33.5-49.1) for controls. The risk was 46.1% (95% CI, 35.3-56.9) for patients with relapsing-remitting MS and 60.7% (95% CI, 46.6-74.8) for patients with secondary progressive MS. For patients with MS with SE, the 10-year risk of epilepsy was 85.9% (95% CI, 67.9-100). ConclusionsOur data indicate that patients with relapsing-remitting MS have a similar risk as controls of developing epilepsy after a single seizure. Patients with secondary progressive MS could run a greater risk of subsequent epilepsy, but our data do not indicate a risk that, with certainty, exceeds the threshold specified by the International League Against Epilepsy. Patients with SE have a high risk of epilepsy, possibly motivating diagnosis and treatment.

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index (P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10(-5)), relapse/ progression (P < 10(-5)), and nonrelapse mortality (P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFSwas associated with experience (>= 23 transplants for AD, P = .001), learning (time from first HSCT for AD >= 6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status (P = .02). Despite improved survival over time (P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD.

Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. There was no treatment-related mortality, although one patient needed intensive care. aHSCT may be a therapeutic option for children with disease that does not respond to standard care.

In: Abstracts From The 43RD Annual Meeting Of The Europeansociety For Blood And Marrow Transplantation:Physicians—Posters Session (P001-P738).Meeting Abstract: P571

Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.