Multiple Sclerosis: Comi G

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.

Comi G. · Institute of Experimental Neurology, University Vita-Salute San Raffaele, Via Olgettina 48, I-20132 Milan, Italy. · Neurol Sci. · Pubmed #16688591 No free full text.

This publication has no abstract.

Comi G, Rocca MA, Filippi M. · No affiliation provided · Eur Neurol. · Pubmed #15159597 links to  free full text

This publication has no abstract.

Comi G. · No affiliation provided · Curr Opin Neurol. · Pubmed #10871245 No free full text.

Abstract: Class 1 clinical trials demonstrated that immunomodulatory treatments (interferon beta and glatiramer acetate) reduce the disease activity and the accumulation of disability in relapsing remitting multiple sclerosis. Moreover interferon beta-1b also had similar positive effects in secondary progressive multiple sclerosis. The magnitude of these clinical effects was modest, but the reduction of inflammatory activity, as revealed by magnetic resonance imaging, was marked. Converging evidence from new pathological studies and new magnetic resonance techniques, characterized by increased pathological specificity, has shown that already in the early phases of the disease inflammatory activity determines irreversible axonal damage. Moreover, the amount of inflammatory activity at the clinical presentation of the disease has some value in predicting long-term disability. Taken together, these data indicate that patients may benefit from early treatment; the positive results of the Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study support this conclusion.

Comi G. · Department of Neurology, Scientic Institute San Raffaele, Via Olgettina 60, 20132, Milano, Italy. · Neurol Sci. · Pubmed #18690509 No free full text.

Abstract: Most of the Consensus Groups in Europe and America support an early decision-making therapeutic approach in patients with a diagnosis of Multiple Sclerosis, either with IFNbeta or GA which have been demonstrated to be a reasonable therapeutic strategy because of their benefit. The treat-early approach within disease management is based on the assumption, particularly during the early phase of the disease, on the reduction of both relapse rate and of the ongoing inflammatory processes. As soon as the MS diagnosis is certain or even in patients with a first episode suggestive of MS, with negative prognostic factors and a typical presentation, the induction therapy, which is more aggressive on the immune system, seems to have more relevant short-and long-lasting beneficial effects. However, if the disease course is suboptimally controlled, an escalating strategy, using either Mitoxantrone, Cyclophosphamide, various other immuno-active agents, or the combination of different drugs, is suggested. The current challenge in therapeutic strategy is to identify the most effective drug, or combination of drugs, during a specific phase of the disease of each single patient. Nevertheless, the decision to adopt a combination therapy in patients with a low response to monotherapy should not be delayed until severe irreversible disability is evident.

Leocani L, Colombo B, Comi G. · Institute of Experimental Neurology Dept. of Neurology, Clinical Neurophysiology, Neurorehabilitation, Univ. Vita-Salute and Scientific Institute San Raffaele, Via Olgettina 60, 20132, Milan, Italy. · Neurol Sci. · Pubmed #18690505 No free full text.

Abstract: Fatigue is an overwhelming sense of tiredness or lack of energy, affecting both mental and physical domains. Fatigue is reported by about 50% of patients with multiple sclerosis (MS), and may be independent from depressed mood or weakness. Recently, the importance of distinguishing between subjective complaint and objective signs of fatigue has been emphasized, since the self-reported increase of subjective cognitive fatigue may not be related to a decline of cognitive performances. There is a general consensus that fatigue in MS is a central phenomenon, related to several factors. Neurophysiological studies revealed an impairment of volitional drive to the descending motor pathways and functional imaging studies indicated a selective involvement of frontal cortex and basal ganglia. Thus, the physiopathology of fatigue may rely on dysfunction of circuits involving thalamus, basal ganglia, and frontal cortex, which, affected by the MS lesions or disturbed in their function by the products of inflammation, could be the substrate of fatigue. The abnormal subjective fatigue observed in MS and perhaps in other neurological disorders could be due to a higher brain working load required to perform a given mental or physical activity, or to an internal overestimation of such load.

Leocani L, Comi G. · Institute of Experimental Neurology Dept. of Neurology, Clinical Neurophysiology, Neurorehabilitation, Univ. Vita-Salute and Scientific Institute San Raffaele, Via Olgettina 60, 20132, Milan, Italy. · Neurol Sci. · Pubmed #18690497 No free full text.

Abstract: After the advent of immunomodulatory treatment in Multiple Sclerosis and after several options for early treatment have become available, the early identification of patients non responder has become a very important issue. Therefore, methods are needed for the detection of disease activity and, particularly in more advanced phases of the disease, of disease progression. Neurophysiological methods, mainly evoked potentials (EPs), are widely used in the functional assessment of sensory and motor pathways. Their usefulness in the assessment of disease activity is limited by the fact that, although they can also reveal clinically silent lesions, EPs abnormalities are present only if their corresponding pathway is involved. With this respect, EPs have been extensively replaced by magnetic resonance imaging (MRI), with the exception of optic nerve in which the sensitivity of EPs and MRI is similar. Nevertheless, EPs can be useful for the assessment of disease progression, since their abnormalities have been demonstrated to be more strictly related to disability than MRI lesion burden. With this perspective, EPs can still be useful in the identification of non responder by providing the clinician with objective functional assessment of eloquent pathways in patients with ambiguous new symptoms, for the confirmation of a dubious relapse, and by providing a method for detecting worsening of nervous conduction for the confirmation of disease progression.

Comi G. · Department of Neurology, Vita-Salute San Raffaele University, Milan, Italy. · Nat Clin Pract Neurol. · Pubmed #18364723 No free full text.

This publication has no abstract.

Comi G. · Institute of Experimental Neurology, Department of Neurology, University Vita-Salute, Scientific Institute S.Raffaele, Via Olgettina 48, 20132 Milan, Italy. · J Neurol Sci. · Pubmed #17950360 No free full text.

Abstract: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, predominantly, but not exclusively, involving the normal appearing white matter. Until very recently we believed that nervous dysfunction in MS was completely depending on the accumulation of lesions in the white matter of the CNS. As a consequence, lesions seen by magnetic resonance imaging (MRI) have been considered a potential surrogate end point in clinical trials assessing new MS treatments. More recently, this concept have been challenged by the emerging evidences, mostly from pathological and MRI studies, that lesions may be located also in grey matter and that the white and grey matter not affected by lesions is abnormal. The causes of this normal appearing grey and white matter damage are still debated and there is the possibility that such a damage is largely independent from the lesions. There are accumulating evidences that the pathogenetic mechanisms in MS may differ in the early and in the late phases of the disease. Early MS is associated with recruitment of systemically derived immune cell populations and inflammatory lesions. Late MS results characterised by a predominantly compartimentalised immunological response. These recent modifications on our views of the MS pathogenesis and pathophysiology do have major implications on the therapeutic strategies, including the use of treatments aiming to enhance the recovery, such as stem cell therapy.

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.

Leocani L, Comi G. · Department of Neurology, Clinical Neurophysiology and Neurorehabilitation, University Vita-Salute, Scientific Institute Hospital San Raffaele, Milan, Italy. · Prog Brain Res. · Pubmed #17071242 No free full text.

Abstract: The analysis of event-related desynchronization (ERD) and event-related synchronization (ERS) provides information on the dynamics of cortical activation during cognitive and motor tasks and has been applied in a variety of neurological and psychiatric disorders. In this chapter, we focus on studies concerning movement-related activity, which showed changes in amount, topography, or time course in relation to not only involvement of the motor system--such as Parkinson's disease (PD), dystonia, and stroke affecting the sensorimotor (SM) pathways--but also physiological aging, degenerative dementia, obsessive-compulsive disorder (OCD), and fatigue associated with multiple sclerosis (MS). In these disorders, the extent of abnormality in the pattern of ERD/ERS is related to the severity of the underlying pathology. Moreover in MS, a correlation with the severity of brain tissue has been found. While there is consistency in changes related to ipokinetic disorders, mainly consisting of delayed appearance of ERD to movement preparation, changes occurring in other brain disorders need to be replicated or raise doubts on the specificity of changes across different diseases. Further studies are needed in order to validate the usefulness of this methodology in the assessment of the single patient for diagnosis and monitoring of the natural course of the disease and of treatment efficacy.

Comi G. · Department of Neurology and Neurorehabilitation, Università Vita-Salute, Istituto Scientifico San Raffaele, Via Olgettina 60, I-20132 Milan, Italy. · Neurol Sci. · Pubmed #16708191 No free full text.

Abstract: Class I clinical trials demonstrated that immunomodulatory treatments (interferon-beta and glatiramer acetate) reduce the disease activity and the accumulation of disability in relapsing-remitting multiple sclerosis (MS). Moreover, interferon-beta-1b had similar positive effects also in secondary progressive MS. The magnitude of these clinical effects was modest, but the reduction of inflammatory activity, as revealed by magnetic resonance imaging, was marked. There is converging evidence from new pathological studies and from new magnetic resonance techniques, characterised by an increased pathological specificity, that already in the early phases of the disease the inflammatory activity determines irreversible axonal damage. Moreover, the amount of inflammatory activity at clinical presentation of the disease has some value for predicting long-term disability. Taken together, these data indicate that patients may benefit from early treatment; the positive results of three double-blind placebo-controlled clinical trials (Early Treatment of Multiple Sclerosis and Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study and BENEFIT) support this conclusion.

Zaffaroni M, Ghezzi A, Comi G. · Centro Studi Sclerosi Multipla, Az. Osp. S. Antonio Abate, Via Pastori 4, I-21013 Gallarate (VA), Italy. · Neurol Sci. · Pubmed #16708175 No free full text.

Abstract: Immunosuppressive drugs have been used out of label in multiple sclerosis (MS) for over 30 years and around 10% of patients are actually under immunosuppressive treatment. The rationale for immunosuppression in MS lies in the hypothesis that MS is an inflammatory immune-mediated disease that can take advantage of strong anti-inflammatory activity. Azathioprine, methotrexate, cyclophosphamide and mitoxantrone are the most utilised agents, but only the latter has been approved for clinically active MS. Many of them are safe in combination with interferon-beta and are under investigation in controlled trials. Plasma exchange is limited to catastrophic attacks in refractory MS whilst bone marrow transplantation is considered in patients with an extremely severe, active disease as the final option in escalation therapy. Although immunosuppressants are best effective in induction therapy, their use is limited by toxicity and potential long-term risk.

Rovaris M, Comi G, Filippi M. · Department of Neurology, Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy. · J Neurol Sci. · Pubmed #16626748 No free full text.

Abstract: Studies with conventional magnetic resonance imaging (MRI) indicate that cognitive impairment in multiple sclerosis (MS) patients is not fully explained by the burden of T2-visible lesions in the brain. Other non-conventional MRI techniques with increased specificity to the more destructive aspects of MS pathology, such as magnetization transfer MRI, diffusion-weighted MRI and proton magnetic resonance spectroscopy, have recently been applied to MS cognitive studies. The results suggest that the presence and extent of "occult" MS pathological features in the normal-appearing brain tissue and the location of lesions in eloquent sites play a central role in the pathogenesis of MS neuropsychological impairment.

Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. · Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy. · Lancet Neurol. · Pubmed #16545751 No free full text.

Abstract: The secondary progressive phase of multiple sclerosis (MS), which is characterised by a steady accrual of fixed disability after an initial relapsing remitting course, is not clearly understood. Although there is no consensus on the mechanisms underlying such a transition to the progressive phase, epidemiological and neuroimaging studies indicate that it is probably driven by the high prevalence of neurodegenerative compared with inflammatory pathological changes. This notion is lent support by the limited efficacy of available immunomodulating and immunosuppressive treatment strategies, which seems to be further decreased in the late stages of secondary progressive MS. No established clinical or paraclinical predictors of the transition from relapsing remitting to secondary progressive MS have been described. However, the use of quantitative MRI-derived measures is warranted to monitor natural history studies and therapeutic trials of secondary progressive MS with increased reliability. In view of the small effects of immunomodulating and immunosuppressive treatments in preventing the transition to secondary progression, the development of treatments promoting neuroaxonal repair remains an important goal in this disease.

Martinelli V, Comi G. · Department of Neurology, Scientific Institute H San Raffaele, Via Olgettina 48, I-20132, Milan, Italy. · Neurol Sci. · Pubmed #16388357 No free full text.

Abstract: Most of the consensus groups in Europe and America support an early decision-making therapeutic approach in patients with a diagnosis of multiple sclerosis (MS), either with interferon-beta or glatiramer acetate, which have been demonstrated to be a reasonable therapeutic strategy because of their benefit. The "treat-early approach" within disease management is based on the assumption, particularly during the early phase of the disease, of the reduction of both relapse rate and of the ongoing inflammatory processes may delay irreversible neurological damages. As soon as the MS diagnosis is certain or even in patients with a first episode suggestive of MS, with negative prognostic factors and a typical presentation, "induction therapy", which is more aggressive on the immune system, seems to have more relevant short- and long-lasting beneficial effects. However, if the disease course is suboptimally controlled, an "escalating strategy", using mitoxantrone, cyclophosphamide, various other immunoactive agents or a combination of different drugs, is suggested. The current challenge in therapeutic strategy is to identify the most effective drug, or combination of drugs, during a specific phase of the disease for each single patient. Anyhow, the decision to adopt a combination therapy in patients with a low response to monotherapy should not be delayed until severe irreversible disability is evident.

Comi G, Martino G. · Department of Neurology and Clinical Neurophysiology, Università Vita-Salute, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. · Clin Neurol Neurosurg. · Pubmed #16386359 No free full text.

Abstract: Immunomodulating and immunosuppressive treatments for multiple sclerosis patients are directed against the inflammatory process and are only partially effective. This partial failure could be explained by mechanisms of axonal damage at least partially independent from acute or chronic inflammation. This suggests that there is a need for better use of available treatments and the necessity of alternative new therapeutic options to halt disease progression and enhance recovery mechanisms. Concerning actual treatments, two strategies are quite interesting: early treatment and combination therapy. The former approach is based on converging epidemiological, immunological and pathological studies and is proved by some recent clinical trials. The second one is under evaluation on ongoing clinical trials. Progress in understanding the mechanisms of T cell activation, inactivation and modulation has been translated into new therapeutic strategies aiming at inducing selective immunosuppression. Such an approach is now tested in phase II-III clinical trials.

Rocca MA, Hickman SJ, Bö L, Agosta F, Miller DH, Comi G, Filippi M. · Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, via Olgettina 60, 20132 Milan, Italy. · J Neuroimaging. · Pubmed #16254392 No free full text.

Abstract: During the past 2 decades, the considerable improvement of magnetic resonance (MR) technology and the development of new MR strategies capable of providing an in vivo overall assessment of multiple sclerosis (MS) pathology have allowed us to obtain important novel pieces of information on disease evolution in the brain. However, despite this, the correlation between brain MR imaging metrics and clinical disability are still suboptimal. A reason for this discrepancy might be the involvement of clinically eloquent structures, such as the spinal cord, which owing to technical challenges have not been extensively studied using MR imaging until very recently. An objective and accurate estimate of the presence and extent of spinal cord damage might indeed contribute to increasing the strength of the correlations between clinical and MRI metrics. This review summarizes the main results obtained from the application of conventional and modern MR-based techniques for the evaluation of spinal cord damage in MS.

Martinelli Boneschi F, Rovaris M, Capra R, Comi G. · Scientific Institute Ospedale San Raffaele, Nerological Department, Via Olgettina, 48, Milano, Italy 20132. · Cochrane Database Syst Rev. · Pubmed #16235298 No free full text.

Abstract: BACKGROUND: Mitoxantrone (MX) has been shown to be moderately effective in reducing the clinical outcome measures of disease activity in multiple sclerosis (MS) patients. OBJECTIVES: The objective was to assess the efficacy and safety of MX in relapsing-remitting MS (RRMS), progressive relapsing MS (PRMS) and secondary progressive MS (SPMS). SEARCH STRATEGY: We searched the Cochrane MS Group Trials Register (searched April 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004), MEDLINE (Pub Med) (January 1966 to April 2005), EMBASE (January 1974 to April 2005), and reference lists of articles. We also undertook hand searching and contacting trialists and pharmaceutical companies. SELECTION CRITERIA: The trials were selected if double-blinded, placebo-controlled, randomised, irrespective of eventual additive therapy (such as steroids). DATA COLLECTION AND ANALYSIS: Three reviewers independently selected articles for inclusion, assessed trials' quality and extracted data. MAIN RESULTS: Four trials involving 270 participants were included. MX was found to reduce the progression of disability at 2 years follow-up (proportion of participants with 6-months confirmed progression of disability: Odds Ratios (OR) 0.3, p = 0.05). Similar figures were found regarding the reduction in annualised relapse rate and the proportion of patients free from relapses at 1 and 2 years, as well as the number of patients with active MRI lesions at 6 months/ 1 year only. Side effects reported in the trials were more frequent in treated patients than in controls. Caution must be exercised in drawing conclusions from such data because of the heterogeneous quality and characteristics of the included trials, which are different in terms of treatment schedule and type of enrolled patients. More than half of the included patients came from a single study. Moreover, from the included trials, it was not possible to estimate the long-term efficacy and safety of MX, which may raise concerns about the risk of cardiotoxicity and therapy-related leukemias, which is increasingly reported in the literature. AUTHORS' CONCLUSIONS: MX is moderately effective in reducing the disease progression and the frequency of relapses in patients affected by RR, PR and SP MS in the short-term follow-up (2 years), even if the results are based on trials heterogeneous in terms of drug dosage and inclusion criteria. No major neoplastic or symptomatic cardiotoxicity related to MX have been reported from the trials. However, longer follow-up studies are highly warranted to better explore the efficacy and safety of the drug, mainly as regards the long-term risk of therapy-related leukemias and cardiotoxicity.As a conclusion, MX has a partial efficacy, but, due to its unclear long-term safety profile, it should be used to treat patients with worsening RR and SP MS with evidence of worsening disability.

Rocca MA, Hickman SJ, Bö L, Agosta F, Miller DH, Comi G, Filippi M. · Neuroimaging Research Unit, Scientific Institute and University Ospedale San Raffaele, Milan, Italy. · Mult Scler. · Pubmed #16193891 No free full text.

Abstract: Although multiple sclerosis (MS) frequently involves the optic nerves, imaging this structure is not yet performed routinely in clinical practice. The recent improvement of magnetic resonance (MR) technology and the development of new MR strategies, capable of providing an, in vivo, overall assessment of MS pathology has allowed objective metrics to be obtained for monitoring disease evolution, essentially in the brain. However, despite this progress, the correlation between brain MR metrics of the disease and clinical disability are still disappointing. An objective and accurate estimate of the presence and extent of optic nerve involvement might help to overcome this clinical/MRI paradox. This review summarizes the main results obtained from the application of conventional and modern MR-based techniques for the evaluation of optic nerve damage in MS.

Rovaris M, Comi G, Filippi M. · Neuroimaging Research Unit, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, via Olgettina 60-20132 Milan, Italy. · J Neurol Sci. · Pubmed #15949501 No free full text.

Abstract: The assessment of brain volume changes on serial magnetic resonance imaging (MRI) scans can provide an objective measure of progressive atrophy reflecting the neurodegenerative aspects of multiple sclerosis (MS) pathology. The present article reviews the results of studies assessing the effect of glatiramer acetate (GA) treatment in preventing MS-related, MRI-measurable brain volume decrease. Whilst data from the extended, open-label follow-up of the US trial seem to indicate that long-term treatment with GA might prevent the loss of brain parenchyma in relapsing-remitting MS patients, longitudinal data from the European/Canadian MRI trial suggest that, over a short-term period of treatment, GA does not have a clear-cut impact on the decrease of brain volume. The effect of GA on MS-related brain atrophy might, therefore, be delayed and dissociated in time from those exerted on other clinical and MRI measures of disease activity. However, the modest magnitude of this effect makes it difficult to evaluate its impact on the actual disease progression. Further studies of adequate duration are now required to address this issue, as well as to confirm the sustained efficacy of GA treatment over long periods of follow-up.

Comi G, Filippi M. · Department of Neurology and Clinical Neurophysiology, Milan, Italy. · Curr Opin Neurol. · Pubmed #15891407 No free full text.

Abstract: PURPOSE OF REVIEW: The availability of partially effective immunomodulatory and immunosuppressive treatments for relapsing multiple sclerosis (MS) opens important ethical, methodological and practical issues in the design and conduct of new clinical trials in these patients. RECENT FINDINGS: The recommendation of the National Health Authorities to prioritize phase III clinical trials using placebo arm raises ethical questions. In addition, patients are reluctant to be involved in such trials. Alternative clinical trial designs will be discussed. Relapses and active lesions are accepted measures of disease activity; new/enlarging T2 lesions and/or enhancing lesions are accepted surrogate markers of disease activity in phase II clinical trials. On the contrary, there are no accepted magnetic resonance imaging (MRI) surrogate markers of disease progression and also the clinical measures to monitor the degenerative aspects of the disease are not without important limitations. New scales of impairment, disability and quality of life will be reviewed extensively. We will also focus on the value of modern and quantitative MRI techniques, which hold substantial promise as tools to estimate the extent of MS-related irreversible tissue loss. SUMMARY: The use of an active comparator in a superior clinical-trial design is becoming an attractive option for testing the efficacy of new drugs in relapsing MS. At present there are no fully reliable and sensitive clinical markers of the accumulation of irreversible tissue damage in MS. Although additional extensive application in longitudinal studies is needed, modern MRI techniques are promising tools to monitor the neurodegenerative aspects of MS.

Comi G. · Department of Neurology and Clinical Neurophysiology, Via Olgettina 60, I-20132 Milan, Italy. · Neurol Sci. · Pubmed #15883679 No free full text.

This publication has no abstract.

Comi G. · Unità di Neurologia e Neuroriabilitazione, Istituto di Neurologia Sperimentale, Università Vita Salute S. Raffaele, Via Olgettina 60, I-20132 Milan, Italy. · Neurol Sci. · Pubmed #15727238 No free full text.

Abstract: The pseudotumoral forms of multiple sclerosis often represent a diagnostic problem. In this paper, the main clinical, radiological and pathological characteristics of these forms are described. A short overview on the main treatments used in these cases is also provided.

Martinelli V, Rodegher M, Moiola L, Comi G. · Department of Neurology, HS Raffaele Scientific Institute, Via Olgettina 48, I-20132 Milan, Italy. · Neurol Sci. · Pubmed #15727232 No free full text.

Abstract: Late onset multiple sclerosis (LOMS), defined as the first presentation of clinical symptoms in patients over 50, is not a rare phenomenon as previously thought, since the prevalence ranges between 4% and 9.6% in different studies. The course of the disease is often primary progressive and pyramidal or cerebellar involvement is observed in 60%-70% of the patients at presentation. LOMS is usually associated with a faster progression to disability compared to young adult multiple sclerosis (MS) patients. Moreover in patients over 50, MS variants and atypical forms which present a difficult diagnostic problem, may be frequently encountered. The differential diagnosis may be sometimes difficult and includes cerebro-spinal vascular syndromes, hypertension-related disorders, compressive myelopathies, primary or secondary vasculitis, metabolic diseases, degenerative and nutritional syndromes. Clinical characteristics, magnetic resonance imaging (MRI) pattern of abnormalities, evoked potential studies and cerebrospinal fluid (CSF) oligoclonal band analysis are of high diagnostic yield in LOMS patients, but expertise in interpreting their results is strongly required.