Multiple Sclerosis: Fazekas F

Comi G, Kappos L, Clanet M, Ebers G, Fassas A, Fazekas F, Filippi M, Hartung HP, Hertenstein B, Karussis D, Martino G, Tyndall A, van der Meché FG. · Multiple Sclerosis Centre, San Raffaele Scientific Institute, Milan, Italy. · J Neurol. · Pubmed #10896270 No free full text.

Abstract: Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Fazekas F, Thompson A. · No affiliation provided · Mult Scler. · Pubmed #19244394 No free full text.

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Fazekas F, Kieseier BC. · No affiliation provided · J Neurol Sci. · Pubmed #19200857 No free full text.

This publication has no abstract.

Rovaris M, Barkhof F, Calabrese M, De Stefano N, Fazekas F, Miller DH, Montalban X, Polman C, Rocca MA, Thompson AJ, Yousry TA, Filippi M. · Multiple Sclerosis Centre, Scientific Institute Santa Maria Nascente, Fondazione Don Gnocchi, Milan, Italy. · Neurology. · Pubmed #19433744 No free full text.

Abstract: It is well known that the current classification of patients with benign multiple sclerosis (BMS), i.e., those with absent or minimal locomotor disability several years after disease onset, suffers from not having any prognostic value for the subsequent evolution of multiple sclerosis (MS). The identification of markers predictive of the longer-term course of MS will help define BMS more reliably and would allow better counseling of patients, particularly when advising on the initiation of a disease-modifying treatment. MRI-based evidence suggests that there are three potential, but not mutually exclusive, explanations for the scarce clinical impact of BMS: 1) the paucity of tissue damage within and outside MS lesions; 2) the relative sparing of clinically eloquent regions; and 3) the presence of effective compensatory mechanisms. In addition, the results of correlative MRI/neuropsychology studies underpin the need for a new definition of BMS, which should consider the maintenance of a normal cognitive profile as an additional criterion.

Ropele S, Fazekas F. · Department of Neurology, Medical University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. · Neuroimaging Clin N Am. · Pubmed #19064197 No free full text.

Abstract: We introduce the fundamental aspects of MT, of MT MR imaging, and the respective analysis techniques. We then review the applications of MT MR imaging to multiple sclerosis. Finally we review the technique's contribution to our understanding of this disease.

Sailer M, Fazekas F, Gass A, Kappos L, Radue EW, Rieckmann P, Toyka K, Wiendl H, Bendszus M. · Neurologische Universitätsklinik, Otto-von-Guericke-Universität, Magdeburg. · Rofo. · Pubmed #18937154 No free full text.

Abstract: PURPOSE: Magnetic resonance imaging (MRI) has become a valuable tool for diagnosing and monitoring multiple sclerosis (MS). The high sensitivity for the detection of hyperintense lesions in T 2-weighted scans contributes substantially to diagnosis. The initial lesion number or lesion volume stands for an increased probability of further accumulation of lesion burden, an earlier conversion to clinically definite MS and progression of disability in the next 5 - 15 years. This diagnostic and prognostic information gained from MRI early in the disease course lead in 2001 to a revision of the diagnostic criteria. MATERIALS AND METHODS: For the first time MRI criteria were defined in addition to the clinical and paraclinical criteria using the clinical terms for dissemination with respect to space and time. In particular, the defined MRI criteria are based on lesion number and location, the appearance of new lesions and lesion enhancement using contrast agent. RESULTS: Reliable detection and description of older and new lesions in the disease course by MRI represents subclinical disease activity which can substitute the clinical confirmation of a relapse leading to an earlier diagnosis. This places importance on the assessment of the subclinical disease activity in sequential MR scans requiring a standardized and reproducible approach to minimize variability despite different MR scanners. CONCLUSION: This review provides an updated proposal for the approach and management of cranial and spinal MR scans in patients with MS. We describe the influence of variables which cannot be standardized (scanner, field strength, manufacturer and software) and outline potential pitfalls of clinical MR imaging in MS resulting from a non-standardized approach. This updated proposal for slice positioning, sequences and documentation is a result of a consensus process targeting systematic and standardized use in clinical MR evaluations of MS.

Seewann A, Enzinger C, Filippi M, Barkhof F, Rovira A, Gass A, Miller D, Montalban X, Thompson A, Yousry T, Tintore M, de Stefano N, Palace J, Rovaris M, Polman C, Fazekas F, Anonymous00221. · Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria. · J Neurol. · Pubmed #18004634 No free full text.

Abstract: BACKGROUND : Idiopathic inflammatory demyelinating lesions (IIDL) of the brain usually present with a morphologic pattern characteristic of multiple sclerosis (MS). Atypical appearances of IIDLs also exist, however, and can pose significant diagnostic problems and uncertainty regarding prognosis and adequate therapy. We attempted to improve upon this situation by reviewing the literature. METHODS : We performed a PubMed search from January 1984 through December 2004 for articles in English reporting on IIDLs which had been considered as morphologically atypical (66 articles; 270 cases reported). From these publications 69 individual patient reports allowed the extraction of adequate information on magnetic resonance imaging (MRI) and associated disease characteristics. RESULTS : Reported atypical IIDLs most frequently manifested as large ring-like lesions (n = 27) which are now considered quite suggestive of an antibodymediated form of MS. Truly atypical IIDLs were less common and exhibited appearances which we termed megacystic (n = 8), Balolike (n = 11) and diffusely infiltrating (n = 11). Despite limitations imposed by the absence of original data the inter-rater agreement in defining these subtypes of atypical IIDLs was moderate to substantial (kappa 0.48-0.68) and we noted trends for their association with certain demographic, clinical and paraclinical variables. INTERPRETATION : We suggest that IIDLs reported as atypical in the literature can be segregated into several distinct subtypes based on their MRI appearance. The recognition of these patterns may be useful for the differential diagnosis and for a future classification. Because of the limitations inherent in our review this will have to be confirmed by a prospective registry.

Fazekas F, Strasser-Fuchs S, Hommes OR. · Department of Neurology, Medical University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. · J Neurol Sci. · Pubmed #17449063 No free full text.

Abstract: There is an established role for intravenous immunoglobulin (IVIG) in the treatment of certain neurologic autoimmune disorders which affect the peripheral nervous system and a variety of immunomodulatory properties of IVIG have been proposed. This prompted an intense research into the efficacy of IVIG in central nervous system autoimmune disorders and until now several well-controlled clinical trials have been performed in different stages and phenotypes of multiple sclerosis (MS). The results were mixed. Speculations that IVIG might be able to reverse fixed neurologic deficits from MS could not be confirmed. Adding IVIG to the conventional treatment of MS relapses with high-dose IVMP also did not provide any additional benefits. Similarly, trials failed to establish a role for IVIG in the treatment of secondary or primary progressive MS. Most consistent beneficial results with a reduction of relapse rates and a slowing of disability have been obtained in relapsing-remitting MS including clinically isolated syndromes although a most recent study did not confirm a reduction of disease activity based on clinical and MRI findings. Trial results also suggest that IVIG might serve to suppress an increased recurrence of relapses immediately after delivery. Consequently, IVIG treatment may be considered as second line option for these indications although there is still uncertainty regarding the actual mechanism(s) of action and optimal dosage of this treatment.

Fazekas F, Soelberg-Sorensen P, Comi G, Filippi M. · Department of Neurology, Medical University of Graz, Austria. · J Neuroimaging. · Pubmed #17425736 No free full text.

Abstract: It is the primary goal of disease modifying treatments in multiple sclerosis (MS) to prevent the occurrence of new clinical deficits and lessen or prevent accumulation of disability. As a consequence, clinical aspects constitute the major outcome variables in treatment trials and are also the leading factor for treatment decisions in individual patients. However, determining treatment efficacy by clinical evaluation suffers from limited objectivity, sensitivity, and specificity for the underlying pathophysiologic aspects, which may constitute the target of a given therapy. Magnetic resonance imaging (MRI) can partly overcome these limitations by showing morphologic aspects of the disease with clinical relevance and responsiveness to therapy. Within the past 10 years sufficient data have been collected to establish the accumulation of new/enlarging T2 lesions and gadolinium enhancing lesions, T2 lesion load, T1-hypointense lesions, and brain volume changes as reasonably well-defined markers of disease processes, which may serve to monitor treatment efficacy. Accordingly, these variables have been extensively used for probing the efficacy of disease modifying treatments. In part they are also suited to guide therapeutic decisions in the individual patient. Further options may come from the use of advanced techniques like magnetization transfer MRI, diffusion-weighted MRI, and proton magnetic resonance spectroscopy, which detect more subtle MS related tissue abnormalities. Irrespective of the technique employed, great care has to be given to the standardization and reproducibility of both data acquisition and interpretation when using MRI to monitor treatment efficacy. For the individual patient therapeutic decisions based on MRI need experience and caution.

Charil A, Yousry TA, Rovaris M, Barkhof F, De Stefano N, Fazekas F, Miller DH, Montalban X, Simon JH, Polman C, Filippi M. · Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy. · Lancet Neurol. · Pubmed #16987731 No free full text.

Abstract: Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.

Fazekas F, Enzinger C, Ropele S, Schmidt H, Schmidt R, Strasser-Fuchs S. · Department of Neurology, Medical University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. · J Neurol Sci. · Pubmed #16631796 No free full text.

Abstract: Epidemiological studies provide strong evidence that susceptibility to multiple sclerosis (MS) is in part genetically determined. Likewise the heterogeneity in clinical manifestations, temporal course, severity, and in the pathological processes of MS are probably also influenced by our genes. Apolipoprotein E (apoE) polymorphism has been considered a candidate for impacting on MS because of its numerous functions related to brain tissue and evidence for an association with a variety of cerebral disorders, specifically Alzheimer's disease (AD). The apoE alleles epsilon2, epsilon3, and epsilon4 are known to impact differently on aspects such as neuronal growth and repair, neuroprotection and inflammation. After a review of the strong association of the apoE polymorphism with AD, we review the results on MS. These are far less homogenous but have gained support from morphologic and metabolic measures obtained with magnetic resonance imaging indicating a greater extent of brain destruction with the apoE epsilon4 allele. Evidence for a protective role of the epsilon2 allele in MS is weak. In view of the association with AD it is tempting to speculate that neuropsychologic functioning in MS might be even more strongly related to the apoE polymorphism and especially to the epsilon4 allele than other deficits, but few data on this issue are yet available. While part of the association of the apoE polymorphism with AD is supposed to be caused by apoE-isoform dependent effects on amyloid-beta deposition, no single pathogenetically relevant mechanism has yet been confirmed for MS. In summary we presently may assume only subtle effects of the apoE polymorphism on the course of MS. These effects are probably further modulated by other genes and need further investigation.

Schmidt R, Enzinger C, Ropele S, Schmidt H, Fazekas F. · Department of Neurology, Medical University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. · J Neurol Sci. · Pubmed #16626755 No free full text.

Abstract: Subcortical vascular cognitive impairment is caused by lacunes and widespread ischemic white matter damage which closely resembles white matter abnormalities seen in multiple sclerosis. Recent evidence suggests that the progression rate of ischemic white matter lesions on MRI is very similar to that observed in multiple sclerosis. Consequently, it has been proposed to use MRI for monitoring disease activity not only in multiple sclerosis but also in vascular dementia trials. There is first evidence from magnetization transfer imaging studies that other than in MS normal appearing white matter is not affected in cerebral small vessel disease. This contrasts the hypothesis that ischemic white matter damage extends far beyond changes visible on conventional MR. The cognitive consequences of both diseases are strikingly similar which is at least partly caused by damage to frontal-subcortical circuits. Involvement of these common functional anatomical structures and their modulatory transmitter systems has now led to common interventional approaches such as the use of cholinesterase inhibitors.

Karussis D, Biermann LD, Bohlega S, Boiko A, Chofflon M, Fazekas F, Freedman M, Gebeily S, Gouider R, Havrdova E, Jakab G, Karabudak R, Miller A, Anonymous00555. · Department of Neurology, Hadassah Hebrew University Hospital, Ein-Karem, Jerusalem, Israel. · Eur J Neurol. · Pubmed #16420394 No free full text.

Abstract: An International Working Group for Treatment Optimization in MS met to recommend evidence-based therapeutic options for the management of suboptimal responses or intolerable side-effects in patients treated with disease-modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed. However, even after having identified criteria for a suboptimal response to current treatments, clinicians require guidance on how to improve the outcomes. This report summarizes the conclusions from a workshop at which this issue was addressed. We suggest treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side-effects on their current therapy.

Seifert T, Enzinger C, Ropele S, Storch MK, Strasser-Fuchs S, Fazekas F. · Department of Neurology, Graz Medical University, Graz, Austria. · Eur J Neurol. · Pubmed #16128868 No free full text.

Abstract: Acute transverse myelitis (ATM) not related to systemic disease may present in a relapsing manner. Data in the literature about this condition are scarce. We describe three patients suffering from relapsing myelitis in whom no association with systemic disease, i.e. infectious or connective tissue disease was found. Magnetic resonance imaging (MRI) findings were also distinctly different from multiple sclerosis and consistent with a necrotizing type of inflammation. Despite various treatment strategies, all patients became severely disabled. Relapsing ATM not related to systemic disease appears to be a specific entity which accounts for severe disability and currently lacks effective treatment.

Filippi M, Falini A, Arnold DL, Fazekas F, Gonen O, Simon JH, Dousset V, Savoiardo M, Wolinsky JS, Anonymous00084. · Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Milan, Italy. · J Magn Reson Imaging. · Pubmed #15906322 No free full text.

Abstract: On October 9-11, 2003, the third meeting of the White Matter Study Group of the International Society for Magnetic Resonance in Medicine was held in Venice, Italy. This article is the report of the meeting on how to use MRI in the diagnostic workup of multiple sclerosis (MS) and allied white matter disorders, and to define the nature and the extent of MS pathology in vivo. Both of these steps are central to the design of future treatment strategies aimed at limiting the functional consequences of the most disabling aspects of this disease.

Rieckmann P, Toyka KV, Bassetti C, Beer K, Beer S, Buettner U, Chofflon M, Götschi-Fuchs M, Hess K, Kappos L, Kesselring J, Goebels N, Ludin HP, Mattle H, Schluep M, Vaney C, Baumhackl U, Berger T, Deisenhammer F, Fazekas F, Freimüller M, Kollegger H, Kristoferitsch W, Lassmann H, Markut H, Strasser-Fuchs S, Vass K, Altenkirch H, Bamborschke S, Baum K, Benecke R, Brück W, Dommasch D, Elias WG, Gass A, Gehlen W, Haas J, Haferkamp G, Hanefeld F, Hartung HP, Heesen C, Heidenreich F, Heitmann R, Hemmer B, Hense T, Hohlfeld R, Janzen RW, Japp G, Jung S, Jügelt E, Koehler J, Kölmel W, König N, Lowitzsch K, Manegold U, Melms A, Mertin J, Oschmann P, Petereit HF, Pette M, Pöhlau D, Pohl D, Poser S, Sailer M, Schmidt S, Schock G, Schulz M, Schwarz S, Seidel D, Sommer N, Stangel M, Stark E, Steinbrecher A, Tumani H, Voltz R, Weber F, Weinrich W, Weissert R, Wiendl H, Wiethölter H, Wildemann U, Zettl UK, Zipp F, Zschenderlein R, Izquierdo G, Kirjazovas A, Packauskas L, Miller D, Koncan Vracko B, Millers A, Orologas A, Panellus M, Sindic CJ, Bratic M, Svraka A, Vella NR, Stelmasiak Z, Selmaj K, Bartosik-Psujik H, Mitosek-Szewczyk K, Belniak E, Mochecka A, Bayas A, Chan A, Flachenecker P, Gold R, Kallmann B, Leussink V, Mäurer M, Ruprecht K, Stoll G, Weilbach FX, Anonymous00046. · Dept. of Neurology, Josef-Schneider-Str. 11, 97080, Würzburg, Germany. · J Neurol. · Pubmed #15592728 No free full text.

Abstract: Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Miller DH, Filippi M, Fazekas F, Frederiksen JL, Matthews PM, Montalban X, Polman CH. · NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, United Kingdom. · Ann Neurol. · Pubmed #15293279 No free full text.

Abstract: The diagnosis of multiple sclerosis (MS) has been improved in recent decades with the incorporation of paraclinical investigations in diagnostic workup. In the last 15 years, magnetic resonance imaging (MRI) has become an especially valuable tool for supporting MS diagnosis, and specific imaging criteria became fundamental to the guidelines for the diagnosis of MS published in 2001 by an international panel (IP). The new IP criteria include MRI evidence of dissemination in space and time, making it possible to diagnose MS after a single clinical episode. This review considers current evidence concerning the reliability of the new IP criteria for the diagnosis of relapsing-onset MS, discusses strengths and weaknesses of the criteria, and outlines areas which may need modification or should be the focus of future research directed toward improving diagnostic accuracy. It also makes practical recommendations when using MRI and the IP criteria in MS diagnosis, especially in patients with clinically isolated syndromes or atypical presentations. The IP criteria are timely and concrete and introduce an important concept to MS diagnosis. Future modifications, based on emerging evidence, should further facilitate their implementation and improve their accuracy.

Bammer R, Fazekas F. · Lucas MRS/I Center, Stanford University, Stanford, CA 94305-5488, USA. · Top Magn Reson Imaging. · Pubmed #14872166 No free full text.

Abstract: During the last decade, diffusion-weighted imaging (DWI) has matured from an experimental tool to a clinically useful modality that has not only significantly impacted the diagnosis of (acute) cerebral stroke but has also shown utility in other abnormalities of the brain. Although DWI should be equally sensitive to changes in the spine, it has been used far less frequently in this region of the body. This is mainly because of the inhomogeneous magnetic environment, the small size of the spinal cord, and increased motion in and around the spine. However, once these limitations are overcome, a whole range of applications can be envisioned. Already now, DWI promises to be able to differentiate between benign and malignant vertebral compression fractures. As in the brain, the immediate reduction of diffusivity following ischemic damage in the spinal cord may provide an early identification of patients with infarction. The study of diffusion anisotropy may open new avenues for the detection and better understanding of damage to the long fiber tracts with important clinical implications for disorders like multiple sclerosis and amyotrophic lateral sclerosis. It may also be possible to address, in a more refined manner, mechanisms of damage such as occur with spondylotic myelopathy. To lay the basis for future research in these areas, we will discuss the most appropriate DWI methods for the spine. Following an overview of the basic principles of DWI and associated pitfalls, the most commonly used imaging methods are addressed. Finally, experimental and clinical applications in the spinal cord and the vertebral column and their clinical relevance thus far are reviewed.

Fazekas F, Barkhof F, Filippi M, Grossman RI, Li DK, McDonald WI, McFarland HF, Paty DW, Simon JH, Wolinsky JS, Miller DH. · Department of Neurology and MRI Center, Karl-Franzens University, Graz, Austria. · Neurology. · Pubmed #10449103 No free full text.

Abstract: MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS.

Filippi M, Rocca MA, Arnold DL, Bakshi R, Barkhof F, De Stefano N, Fazekas F, Frohman E, Wolinsky JS. · Neuroimaging Research Unit, Department of Neurology Scientific Institute and University Ospedale San Raffaele, Milan, Italy. · Eur J Neurol. · Pubmed #16643308 No free full text.

Abstract: Magnetic resonance (MR)-based techniques are widely used for the assessment of patients with suspected and definite multiple sclerosis (MS). However, despite the publication of several position papers, which attempted to define the utility of MR techniques in the management of MS, their application in everyday clinical practice is still suboptimal. This is probably related, not only, to the fact that the majority of published guidelines focused on the optimization of MR technology in clinical trials, but also to the continuing development of modern, quantitative MR-based techniques, that have not as yet entered the clinical arena. The present report summarizes the conclusions of the 'EFNS Expert Panel of Neuroimaging of MS' on the application of conventional and non-conventional MR techniques to the clinical management of patients with MS. These guidelines are intended to assist in the use of conventional MRI for the diagnosis and longitudinal monitoring of patients with MS. In addition, they should provide a foundation for the development of more widespread but rational clinical applications of non-conventional MR-based techniques in studies of MS patients.

Grabner R, Popotnig F, Ropele S, Neuper C, Gorani F, Petrovic K, Ebner F, Strasser-Fuchs S, Fazekas F, Enzinger C. · Institute of Psychology, University of Graz, Austria, Section of Neuroradiology, Department of Radiology, Medical University of Graz, Austria. · Mult Scler. · Pubmed #18208887 No free full text.

Abstract: The Faces Symbol Test (FST) has recently been proposed as a brief and patient-friendly screening instrument for the assessment of cognitive dysfunction in patients with multiple sclerosis (MS). However, in contrast to well-established MS screening tests such as the Paced Auditory Serial Addition Test, the neural correlates of the FST have not been investigated so far. In the present study, we developed a functional MRI (fMRI) version of the FST to provide first data on brain regions and networks involved in this test. A sample of 19 healthy participants completed a version of the FST adapted for fMRI, requiring matching of faces and symbols in a multiple choice test and two further experimental conditions drawing on cognitive subcomponents (face matching and symbol matching). Imaging data showed a differential involvement of a fronto-parieto-occipital network in the three conditions. The most demanding FST condition elicited brain activation patterns related with sustained attention and executive control. These results suggest that the FST recruits brain networks critical for higher-order cognitive functions often impaired in MS patients.

Fazekas F, Sørensen PS, Filippi M, Ropele S, Lin X, Koelmel HW, Fernandez O, Pozzilli C, O'Connor P, Enriquez MM, Hommes OR, Anonymous00202. · Department of Neurology, Medical University of Graz, Graz, Austria. · Mult Scler. · Pubmed #16042226 No free full text.

Abstract: BACKGROUND: Monthly application of high-dose intravenous immunoglobulin (IVIG) to patients with secondary progressive multiple sclerosis (MS) showed no clinical benefit in the European Study on Immunoglobulin in MS (ESIMS). Magnetic resonance imaging (MRI) results may provide insights into the morphologic consequences of such treatment. METHODS: A total of 318 patients (mean age 44 +/- 7 years) were enrolled in 31 European and Canadian centres and treated monthly with 1 g/kg body weight of IVIG or equivalent amounts of albumin 0.1% for 27 months. MRI was performed at baseline and after 12 and 24 months and comprised of conventional dual-echo T2-weighted and T1-weighted scans before and after application of 0.1 mmol/kg Gd-DTPA. RESULTS: Similar to clinical variables, MRI measures at baseline were well comparable between treatment groups except for a somewhat lower mean number of contrast-enhancing lesions and number of active scans in IVIG-treated patients. Over the trial period there was almost no change of the T2-lesion load and the 'black hole' volume in both treatment groups and the cumulative number of contrast-enhancing lesions were similar. There was only a trend for fewer new or enlarged T2-lesions in IVIG patients, which disappeared after correction for the imbalance in the number of contrast-enhancing lesions at baseline. Brain volume in terms of a partial cerebral fraction decreased significantly less with IVIG than placebo treatment (final visit: -0.62 -/+ 0.88% versus -0.88 +/- 0.91%; P=0.009). This difference remained statistically significant with correction for active lesions at baseline (P=0.02) and was seen primarily in male patients and those with an Expanded Disability Status Scale score > or = 6 and no relapses in the two years before the study. CONCLUSION: The absence of significant differences in conventional MRI measures between both treatment groups parallels the negative clinical results of ESIMS. The causes for and possible long-term clinical effects of a lower rate of brain volume loss in IVIG patients should be explored further.

Hommes OR, Sørensen PS, Fazekas F, Enriquez MM, Koelmel HW, Fernandez O, Pozzilli C, O'Connor P. · European Charcot Foundation, Nijmegen, Netherlands. · Lancet. · Pubmed #15451222 No free full text.

Abstract: BACKGROUND: Several double-blind placebo-controlled trials of relapsing-remitting multiple sclerosis have shown beneficial effects of intravenous immunoglobulin (IVIG) on relapse rate and disability. The European Study on Intravenous Immunoglobulin in Multiple Sclerosis set out to test IVIG in the secondary progressive phase of the disease. METHODS: 318 patients with clinically definite secondary progressive multiple sclerosis (mean age 44 years [SD 7]) were randomly assigned IVIG 1 g/kg per month (n=159) or an equivalent volume of placebo (albumin 0.1%; n=159) for 27 months. After baseline investigation, clinical assessments were made every 3 months and MRI was repeated after 12 months and 24 months. The primary outcome was confirmed worsening of disability as defined by the time to first confirmed progression on the expanded disability status scale (EDSS). Analyses were by intention to treat. FINDINGS: 19 patients in the IVIG group and 39 in the placebo group terminated study treatment prematurely but were included in the analyses. IVIG treatment had no beneficial effect on time to confirmed EDSS progression (hazard ratio 1.11 [95% CI 0.80-1.53] for IVIG versus placebo). The annual relapse rate was 0.46 in both groups. No significant differences between the treatment groups were found in any of the other clinical outcome measures or in the change of T2-lesion load over time. The treatment was generally well tolerated, although deep venous thrombosis, pulmonary embolism, or both occurred in seven patients with risk factors for thromboembolism (IVIG six, placebo one). INTERPRETATION: Treatment with IVIG in this study did not show any clinical benefit and therefore cannot be recommended for patients with secondary progressive multiple sclerosis.

Filippi M, Rocca MA, Pagani E, Iannucci G, Sormani MP, Fazekas F, Ropele S, Hommes OR, Comi G. · Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy. · Arch Neurol. · Pubmed #15364687 links to  free full text

Abstract: BACKGROUND: Magnetization transfer magnetic resonance imaging (MT MRI) can provide in vivo markers reflecting the severity of multiple sclerosis-related brain damage occurring within and outside T2-visible lesions. OBJECTIVE: To investigate the effect of intravenous immunoglobulin (IVIG) treatment on the accumulation of brain damage in patients with secondary progressive multiple sclerosis (SPMS), measured using MT MRI.Design, Patients, and Intervention Seventy patients with SPMS participating in the European, multicenter, randomized, double-blind, placebo-controlled trial of IVIG in SPMS underwent brain T2-weighted and MT MRI at baseline and after 12 and 24 months. The MT MRI scans were post-processed and analyzed to obtain MT ratio values from T2-visible lesions and MT ratio histograms from the normal-appearing brain tissue (NABT). RESULTS: At baseline, a significant difference was found for NABT MT ratio histogram peak height (P =.003) between treated patients and patients receiving placebo. No significant differences between treated patients and those receiving placebo were found for any of the considered MT MRI-derived metrics in terms of treatment x time interaction. Nevertheless, over the 24-month period, the placebo patients experienced a 6.75% reduction of the NABT MT ratio histogram peak height, whereas treated patients experienced only a 0.92% reduction of the NABT MT ratio histogram peak height. CONCLUSIONS: This study did not show any statistically significant effect of IVIG on MT MRI quantities. Nevertheless, the markedly different percentage change of the NABT MT ratio histogram peak height over time between patients receiving placebo and treated patients suggests a possible role of IVIG treatment in preventing the loss of "truly" normal brain tissue in SPMS patients.

Fazekas F, Ropele S, Enzinger C, Seifert T, Strasser-Fuchs S. · Department of Neurology, Karl-Franzens-University Graz, Auenbruggerplatz 22, A-8036 Graz, Austria. · Mult Scler. · Pubmed #12474987 No free full text.

Abstract: OBJECTIVE: Previous magnetization transfer (MT) studies in multiple sclerosis (MS) suggest a reduction of the MT ratio (MTR) precedes new lesion development. To gain further insight into pre-lesional tissue abnormalities, we investigated the time course of additional quantitative MT parameters. METHODS: Serial magnetic resonance imaging (MRI), including a gadolinium-enhanced T1 scan and MT imaging by means of a FastPACE sequence, was performed on 12 patients (4 males, 8 females) with relapsing-remitting MS. Quantitative MT values including the magnetization exchange rate (kfor) and the native relaxation time (T1free were analysed in the six months prior to the appearance of 44 enhancing lesions and in 88 control regions of persistently normal-appearing white matter (NAWM). RESULTS: Appearance of new active lesions was preceded by a significant decrease of the MTR (F7,166=91.5; p<0.0001) and of kfor (F7,166=105.2; p<0.0001), and by an increase of T1free (F7,166=57.3; p<0.0001). The drop of kfor was the most pronounced pre-lesional change and together with the MTR was statistically significant already four months before the appearance of new lesion. The observed increase of T1free was relatively small. MT variables of reactivated lesions were always different from NAWM but showed no characteristic time course. CONCLUSIONS: Multiparametric MT measurements suggest both a reduction of macromolecular material and a focal increase of free water to occur several months before the appearance of an active lesion. Reduction of the magnetization exchange rate, which may result from primary damage to myelin, appears to be the leading event