Petra Nilsson

Predicting the Outcome of Optic Neuritis Evaluation of risk factors after 30 years of follow-up.

AbstractBackgroundMultiplensclerosis (MS) is a common diseasenwith considerable risk for disability.nOptic neuritis (ON) is a commonnfirst symptom of MS but itncan also remain an isolatednepisode. Therefore, predicting thenoutcome of ON has gained in importance,nparticularly in light ofncurrent discussions of early diseasenmodifying treatments in individualsnat risk of developing MS. We reportednpreviously on our cohort ofn86 patients with acute monosymptomaticnunilateral ON of whom 33nhad progressed to MS after up to 18nyears. Three patients had died. Thenpresent study extends the observationnperiod to 31 years.MethodsPatients were followed for up to 31nyears or until a diagnosis of MSnwas made. Cerebrospinal fluidn(CSF) was examined at onset. HLAnclass I and II antigens were determined.nMagnetic Resonance Imagingn(MRI) was performed duringnfollow up.FindingsOnly one of 50npatients at risk developed clinicalnmanifestations of MS during thenextended follow up period. The estimatedn15–year–risk of MS wasn40 % (confidence interval [CI]n31%–52%). Most cases, 20 of 34 orn60%, occurred within three years.nAmong factors present at onset,nCSF with mononuclear pleocytosisnand/or oligoclonal Ig increased thenrisk for subsequent MS significantly,n49% (CI 38%–65%) comparednwith 23 % (CI 12%–44%) fornthose with normal CSF, p = 0·02.nYounger patients and those withnwinter onset also had greater risk.nRecurrence of ON similarly elevatednthe risk significantly,np < 0·001. After 19–31 years MRI lesionsnsuggestive of demyelinatingndisease were detected in 20 of 30nindividuals although no clinicalnmanifestations of MS had occurred.ConclusionThe risk of MSnin this large population–basednprospective ON patient series wasn40% and significantly higher innthose with inflammatory CSF abnormalitiesnat onset. Clinicallynsilent MRI lesions suggestive of MSnwere detected in a majority ofnthose with “ON-only”. This findingnshould be taken into account whenndiscussing prognosis and early interventionnin patients with clinicallynisolated ON.

A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis

Background: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010. Methods: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded. Results: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing–remitting MS patients (nu2009=u2009901), mean Expanded Disability Status Scale (EDSS, −10.7%), Multiple Sclerosis Severity Scale (MSSS, −20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical −9.9%, psychological −13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials. Conclusions: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience

Background Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS. Methods Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1u2005year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47u2005months. Results At 5u2005years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%). Conclusions HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

The BrainIT group: concept and core dataset definition

Summary¶Introduction. An open collaborative international network has been established which aims to improve inter-centre standards for collection of high-resolution, neurointensive care data on patients with traumatic brain injury. The group is also working towards the creation of an open access, detailed and validated database that will be useful for post-hoc hypothesis testing. In Part A, the underlying concept, the group coordination structure, membership guidelines and database access and publication criteria are described. Secondly, in part B, we describe a set of meetings funded by the EEC that allowed us to define a “Core Dataset” and we present the results of a feasibility exercise for collection of this core dataset.Methods. Four group meetings funded by the EEC have enabled definition of a “Core Dataset” to be collected from all centres regardless of specific project aim. A paper based pilot collection of data was conducted to determine the feasibility for collection of the core dataset. Specially designed forms to collect the core dataset demographic and clinical information as well as sample the time-series data elements were distributed by both email and standard mail to 22 BrainIT centres. A deadline of two months was set to receive completed forms back from centres. A pilot data collection of minute by minute physiological monitoring data was also performed.Findings. A core-dataset was defined and can be downloaded from the BrainIT web-site (go to “Core dataset” link at: www.brainit.org). Eighteen centres (82%) returned completed forms by the set deadline. Overall the feasibility for collection of the core data elements was high with only 10 of the 64 questions (16%) showing missing data. Of those 10 fields with missing data, the average number of centres not responding was 12% and the median 6%. An SQL database to hold the data has been designed and is being tested. Software tools for collection of the core dataset have been developed. Ethics approval has been granted for collection of multi-centre data as part of a pilot data collection study.Interpretation. The BrainIT network provides a more standardised and higher resolution data collection mechanism for research groups, organisations and the device industry to conduct multi-centre trials of new health care technology in patients with traumatic brain injury.

Costs and quality of life in multiple sclerosis patients with spasticity

The resource use and health‐related quality of life (HRQoL) of patients with multiple sclerosis (MS) spasticity are not well known. The purpose of this study was to obtain estimates of resource utilization, costs, and HRQoL, for patients with different levels of MS spasticity in southern Sweden.

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society.

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.

Tumefactive demyelinating disease treated with decompressive craniectomy.

Background:u2002 Tumefactive demyelinating disease (TDD) is a rare primary demyelinating disease with diagnostic and therapeutic challenges.

Cognitive dysfunction 24-31 years after isolated optic neuritis.

Objective Cognitive dysfunction is common in multiple sclerosis (MS), but long-term data on cognition in patients with clinically isolated syndromes are sparse. Methods We determined cognitive functions in 22 patients 44–75 years old diagnosed with optic neuritis 24–31 years earlier but had no further clinical bouts and had not progressed clinically to MS. We used a neuropsychological test battery covering nine cognitive domains. Magnetic resonance imaging (MRI) of the brain had been performed earlier and was normal in six patients and showed two or more white matter abnormalities compatible with demyelinating lesions in 16 patients. Results On neuropsychological testing, one patient was within normal range on all tests, six subjects showed borderline results, and 15 patients (68%) showed significantly impaired performance in at least one cognitive domain. Seven patients showed significant impairment in two or more domains. Executive function, visuo-spatial ability, and information processing speed were the most frequently affected domains. There was no apparent correlation between MRI findings and cognitive function. Conclusions We conclude that cognitive dysfunction is common in patients many years after clinically isolated optic neuritis. Cognitive dysfunction was found even in patients who had no apparent demyelinating lesions on follow-up MRI.

The role of MRI of the brain and spinal cord, and CSF examination for the diagnosis of primary progressive multiple sclerosis

The clinical applicability of the revised McDonald diagnostic criteria of primary progressive multiple sclerosis (PPMS) was assessed in 17 patients with a longstanding PPMS diagnosis (mean 15u2003years). All patients were re‐evaluated with clinical examinations, magnetic resonance imaging (MRI) of the brain and the spinal cord, extensive laboratory tests, and 12 patients underwent cerebrospinal fluid (CSF) examination. No diagnosis more likely than PPMS was disclosed. All patients had brain and spinal cord lesions on MRI. In 15 patients the brain lesions and in 14 the spinal cord lesions fulfilled the revised McDonald criteria for positive scans. No contrast‐enhancing lesion was observed despite administration of triple doses of gadolinium. In total, 12 patients fulfilled the revised McDonald MRI criteria for PPMS. Of the remaining five patients who incompletely fulfilled the revised MRI criteria, all had CSF findings supporting the diagnosis PPMS. Thus, CSF analysis was required in addition to MRI in about one‐third of the patients to establish the diagnosis of PPMS.

Cognitive functioning following one-year natalizumab treatment : A non-randomized clinical trial

Cognitive impairment is common in multiple sclerosis (MS) and can have serious impact on social and occupational functioning. Natalizumab reduces relapse rates, magnetic resonance imaging (MRI) lesions, and progression of disability. Previous studies on cognitive functioning have not based inclusion on cognitive performance criteria. The aim of the present study was to determine any potential natalizumab‐related cognitive effects on MS patients performing below normal limits on neuropsychological testing.