Baseline MRI predicts future attacks and disability in clinically isolated syndromes

Tintoré, Mar; Rovira, Àlex; J, Río; Nos, Carlos; Grivé, Elisenda; Téllez, N; Pelayo, R.; Comabella, Manuel; Sastre‐Garriga, Jaume; Montalbán, Xavier

doi:10.1212/01.wnl.0000237354.10144.ec

Cited by 268 publications

(220 citation statements)

References 26 publications

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“…10 A more recent study using equipment better comparable to the standards in the BENEFIT study has reported 60% of patients with more than 10 lesions. 11 More importantly, as reported in our article, the BENEFIT study also found robust treatment effects of interferon beta-1b in patients with CIS with less subclinical disease dissemination (i.e., participants with fewer than nine T2 lesions).…”

Section: Treatment With Interferon Beta-1b Delays Conversion To Clinisupporting

confidence: 80%

Correction

2007

Neurology

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To the Editor: Rakocevic et al. 1 report 5 out of 38 consecutively studied patients with stiff person syndrome (SPS) and high-titer anti-GAD antibodies who also developed cerebellar disease. We would like to highlight the issue of eye movement abnormalities in those patients, and commend them on including that information.The authors reported that in Patient 1, hypometric saccades were prominent; Patient 2 had square-wave nystagmus; Patient 4 had nystagmus and hypometric saccades; and Patient 5 had impaired eye movements. They did not mention ocular motor abnormalities in Patient 3. They again introduced ocular motor abnormalities in the Discussion, stating that "Gait or focal limb ataxia, dysarthria, and visual disturbances were prominent in all patients. Slow and hypometric saccades and sustained lateral gaze-evoked nystagmus were common."Unfortunately, the documentation and discussion of eye movement disturbances in SPS and in cerebellar ataxia with GAD antibodies is rare and is usually based on vague, nonquantitative, clinical descriptions. 2 Economides and Horton 3 were the first to objectively report the presence of gaze-holding nystagmus, limited abduction, ocular misalignment, deficient smooth pursuit, and impaired saccadic initiation in a patient with SPS. They attributed these findings to a dysfunction of GABAergic pathways.Using the magnetic search coil technique, we recently reported a detailed quantitative documentation of a rare saccade velocity profile, downbeat nystagmus, and loss of downward smooth pursuit in a patient with SPS and cerebellar ataxia. 4 Additional studies using precise measurement of eye movements in SPS patients with and without cerebellar signs could be useful in clarifying the link between GAD antibodies and cerebellar dysfunction. The possibility of using quantitative eye measures as a biomarker of neurodegeneration has been discussed 5 regarding the assessment of eye movements in presymptomatic and symptomatic individuals with Huntington disease.We would like to encourage the authors and the neurologic community to quantitatively study eye movements in SPS patients with and without cerebellar signs and in cerebellar ataxia with GAD antibodies. C.R. Gordon, A.Z. Zivotofsky, T. Siman-Tov, N. Gadoth, Kfar Saba, Israel Disclosure: The authors report no conflicts of interest.Reply from the Author: Gordon et al. emphasize that abnormal eye movements can occur in patients with SPS and cerebellar ataxia. We agree. We have observed such abnormalities not only in patients with SPS and cerebellar ataxia reported in our present series, 1 but also in some SPS patients without ataxia. The association is highlighted even further by another patient we have recently seen who presented only with nystagmus and saccadic eye movement abnormalities and positive GAD antibodies, but without signs of SPS.These observations indicate that GABAergic pathways are involved in abnormal eye movements. We also agree with Gordon et al. that the eye movements need to be studied quantitatively and serially in...

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Section: Treatment With Interferon Beta-1b Delays Conversion To Clinisupporting

confidence: 80%

Correction

2007

Neurology

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“…18,59,[90][91][92][93][94][95][96][97][98][99][100] For example, RRMS and CIS patients with elevated Gd+ and T2 lesion activity, in terms of number or volume of lesions before or after therapy, have a greater likelihood of subsequent clinical relapses, disability progression, cognitive impairment, decreased quality of life, and even death as compared with patients with lower or absent MRI activity. 18,59,[90][91][92][93][94][95][96][97][98][99][100] Although most of these studies have been relatively short term, some have followed study cohorts for 20 or more years. [100][101][102] …”

Section: Discussionmentioning

confidence: 99%

Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Cook¹,

Dhib‐Jalbut²,

Dowling³

et al. 2012

International Journal of MS Care

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It has recently been suggested that the Lublin-Reingold clinical classification of multiple sclerosis (MS) be modified to include the use of magnetic resonance imaging (MRI). An international consensus conference sponsored by the Consortium of Multiple Sclerosis Centers (CMSC) was held from March 5to 7, 2010, to review the available evidence on the need for such modification of the Lublin-Reingold criteria and whether the addition of MRI or other biomarkers might lead to a better understanding of MS pathophysiology and disease course over time. The conference participants concluded that evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions and unequivocally new or enlarging T2-weighted lesions (subclinical activity, subclinical relapses) should be added to the clinical classification of MS in distinguishing relapsing inflammatory from progressive forms of the disease. The consensus was that these changes to the classification system would provide more rigorous definitions and categorization of MS course, leading to better insights as to the evolution and treatment of MS. Int J MS Care. 2012;14:105-114. It was recently suggested by Lincoln et al. 1 that the Lublin-Reingold clinical classification of multiple sclerosis (MS) 2 for the assessment of MS phenotypes and patient evolution over time be modified to include magnetic resonance imaging (MRI). It was recommended that the classification incorporate the "conventional," generally available MRI techniques of gadolinium (Gd) T1-weighted sequences and dual-echo and fluid-attenuated inversion recovery (T2-weighted and FLAIR) images ( course over time and, in turn, more informed clinical trials and a better understanding of appropriate therapies.Prior to the meeting, a survey of members of the CMSC was conducted on the need to modify the Lublin-Reingold classification. Over a 1-week period, 141 responses were received, representing 16% of the CMSC members polled. The results were as follows: A total of 70% of respondents indicated that the LublinReingold classification did not sufficiently distinguish the different forms of MS; 87% felt that the LublinReingold classification did not sufficiently distinguish MS disease activity even within a given category of the disease; and 84% indicated that it would be useful to include certain subclinical indices of disease activity in the clinical classification, such as MRI gadoliniumother MRI modalities that are not currently widely available and other validated biomarkers might be added to the classification in the future.In response to the publication of Lincoln et al., 1 the Consortium of Multiple Sclerosis Centers (CMSC) sponsored an international consensus conference, which was held in Short Hills, New Jersey, from March 5 to 7, 2010. Participating in the conference were 28 invited MS experts from North and South America and Europe who were well versed in clinical trials, the management of MS, biostatistics, neuropathology, neuroimaging, and neuroimmunology. The goal of the meeting was to review the available...

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“…Over time, most patients with a clinically isolated syndrome in whom additional clinically silent brain lesions on MRI suggest disseminated infl ammatory CNS disease develop relapsing-remitting multiple sclerosis and have a substantial risk for later progression of disability. [1][2][3] Previous studies in patients with clinically isolated syndromes have shown a benefi cial eff ect of early treatment with interferon beta and glatiramer acetate on the risk of conversion to clinically defi nite multiple sclerosis (CDMS), but they were too short and not prospectively designed to capture any eff ect on disability. [4][5][6][7] More over, these trials did not address whether a delay in starting treatment has a long-term eff ect on disease course.…”

Section: Introductionmentioning

confidence: 99%

Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

Kappos

Freedman

Polman

et al. 2009

The Lancet Neurology

336

283

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BACKGROUND:The Betaferon/Betaseron in newly emerging multiple sclerosis for initial treatment (BENEFIT) trial investigated the effect of treatment with interferon beta-1b after a clinically isolated syndrome. The 5-year active treatment extension compares the effects of early and delayed treatment with interferon beta-1b on time to clinically definite multiple sclerosis (CDMS) and other disease outcomes, including disability progression. METHODS: Patients with a first event suggestive of multiple sclerosis and a minimum of two clinically silent lesions in MRI were randomly assigned to receive interferon beta-1b 250 microg (n=292; early treatment) or placebo (n=176; delayed treatment) subcutaneously every other day for 2 years, or until diagnosis of CDMS. All patients were then eligible to enter a prospectively planned follow-up phase with open-label interferon beta-1b up to a maximum of 5 years after randomisation. Patients and study personnel remained unaware of initial treatment a...

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Baseline MRI predicts future attacks and disability in clinically isolated syndromes

Abstract: Baseline MRI determines the risk for converting to clinically definite multiple sclerosis and correlates with disability at 5 years. The proportion of patients developing disability is low during the first 5 years but rapidly increases shortly after.

Cited by 268 publications

References 26 publications

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Use of Magnetic Resonance Imaging as Well as Clinical Disease Activity in the Clinical Classification of Multiple Sclerosis and Assessment of Its Course

Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial

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