G Comi

Università Vita-Salute San Raffaele, Milano, Lombardy, Italy

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Publications (654)2892.45 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Elevated body temperature was recently reported for the first time in patients with relapsing-remitting multiple sclerosis (RRMS) relative to healthy controls. In addition, warmer body temperature was associated with worse fatigue. These findings are highly novel, may indicate a novel pathophysiology for MS fatigue, and therefore warrant replication in a geographically separate sample. Here, we investigated body temperature and its association to fatigue in an Italian sample of 44 RRMS patients and 44 age- and sex-matched healthy controls. Consistent with our original report, we found elevated body temperature in the RRMS sample compared to healthy controls. Warmer body temperature was associated with worse fatigue, thereby supporting the notion of endogenous temperature elevations in patients with RRMS as a novel pathophysiological factor underlying fatigue. Our findings highlight a paradigm shift in our understanding of the effect of heat in RRMS, from exogenous (i.e., Uhthoff's phenomenon) to endogenous. Although randomized controlled trials of cooling treatments (i.e., aspirin, cooling garments) to reduce fatigue in RRMS have been successful, consideration of endogenously elevated body temperature as the underlying target will enhance our development of novel treatments.
    Journal of Neurology 07/2015; DOI:10.1007/s00415-015-7863-8 · 3.38 Impact Factor
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    ABSTRACT: To assess the long-term benefit-risk profile of repeated courses of rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and related disorders, in everyday clinical practice. This is a prospective observational study performed at San Raffaele Hospital, Milan, Italy. From February 2006, we recruited 21 patients affected by NMO and NMO spectrum of disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.) rituximab and then were followed for at least 2 years. At a mean follow-up time of 48 months, we observed a significant reduction of the annualized relapse rate (ARR), from 2.0 to 0.16 (p < 0.01); and of the median Expanded Disability Status Scale (EDSS), from 5.5 to 4.0 (p < 0.013). There were 12 patients (57%) who remained disease free during the follow-up period. Five patients (24%) reported mild hematological adverse events. Serious infectious adverse events were reported by another four patients: These were all wheelchair bound at the beginning of their rituximab treatment. A fixed treatment scheme of rituximab, with re-treatment every 6 months, was efficacious for NMO and NMOSD, with a good safety profile; however, to obtain an even better benefit-risk ratio, close monitoring of CD19(+) B cells should be performed before the re-treatment of patients with high-level disability, concomitant leukopenia and hypogammaglobulinemia. © The Author(s), 2015.
    Multiple Sclerosis 07/2015; DOI:10.1177/1352458515594042 · 4.82 Impact Factor
  • R Teggi · B Colombo · O Gatti · G Comi · M Bussi
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    ABSTRACT: Vestibular migraine (VM) is one of the most frequent causes of episodic vertigo, with a lifetime prevalence of 0.98 %. Prophylactic therapy includes calcium channel blockers, beta-blockers, antiepileptic drugs and antidepressants. We studied the association of cinnarizine 20 mg and dimenhydrinate 40 mg (Arlevertan©) in a group of 22 patients affected by definite VM. Proposed therapy included one tablet twice a day for 1 month, which was repeated three times with 1 month of interval between drug intake; results were compared with those of a control group of 11 VM patients who asked to observe only lifestyle measures for migraine. The main outcome was the number of vertigo and headache crises in the 6 months before therapy and in the 6 months of follow-up. Subjects performing Arlevertan© presented during the 6 months of therapy a decrease of vertigo attacks from 5.3 to 2.1 and of headaches from 4.3 to 1.7 (p < 0.0001); 68 % of these subjects reported a decrease of at least 50 % of vertigo attacks, while 63 % of headaches. Conversely, vertigo attacks decreased from 3.5 to 2.2 and headaches from 2.6 to 2 in patients observing only lifestyle; 18 % of these subjects reported a decrease of at least 50 % of vertigo crises and 27 % of headaches. Our data do not differ from those of previous works assessing efficacy of different prophylactic therapies for VM and reporting consistent reduction of vertigo spells in a rate of patients ranging from 60 and 80 %.
    Neurological Sciences 06/2015; DOI:10.1007/s10072-015-2270-6 · 1.45 Impact Factor
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    ABSTRACT: In post hoc analyses of an open-label, phase 3b study (FIRST), relapse rates during 4 months of fingolimod therapy were compared in patients with and without previous natalizumab exposure. Reductions in the proportion of patients experiencing relapses and annualized relapse rates (ARRs) from years 1 and 1–2 pre-study were evident between months 1 and 2 of fingolimod treatment, and were most pronounced in natalizumab-naïve patients and those who discontinued natalizumab >6 months pre-study. Patients who discontinued natalizumab 3–6 months pre-study had a peak ARR during month 1 of fingolimod treatment, followed by a decrease during months 2–4. These data indicate that fingolimod has the potential to reduce disease reactivation but that timing of treatment initiation may be critical for achieving an optimal effect.
    Multiple Sclerosis 05/2015; 21(6):786-790. DOI:10.1177/1352458514549404 · 4.82 Impact Factor
  • Physiotherapy 05/2015; 101:e447-e448. DOI:10.1016/j.physio.2015.03.3229 · 1.91 Impact Factor
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    ABSTRACT: Background and purposeThe Rio score (RS) and the modified Rio score (MRS) are two scoring systems that can identify the early predictive factors of disability progression in relapsing−remitting multiple sclerosis (RRMS) patients treated with interferon-β (IFN-β). The objective of the study was to validate the usefulness of the RS and MRS in a large cohort of multiple sclerosis patients treated with IFN-β in daily clinical practice.Methods The analysis included a cohort of RRMS patients treated with different formulations of IFN-β for at least 1 year. The RS and MRS were used to classify the patients after 1 year of treatment. Multivariate analysis was performed to identify predictive variables of suboptimal response at 5 years, defined as Expanded Disability Status Scale confirmed progression or switching to a second-line therapy.ResultsSixty-nine of 416 included patients were considered as suboptimal responders at 5-year evaluation. The possible score range was 0–3. A higher risk of suboptimal response was found for RS and MRS in the presence of ≥2 scores (hazard ratio 3.0, P = 0.002, and hazard ratio 5.0, P < 0.0001, respectively).Conclusions Our study confirmed, in a daily clinical setting, that MRS had a better specificity and accuracy than RS in identifying the patients who will have a poor response to long-term IFN-β treatment.
    European Journal of Neurology 04/2015; 22(6). DOI:10.1111/ene.12695 · 4.06 Impact Factor
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    ABSTRACT: To better characterize brain circuits dysfunctions in normoacousic tinnitus sufferers. 17 normoacousic chronic, unilateral high-pitched tinnitus sufferers (6 females, 43.6±9.8y.o, disease duration 22±35months) underwent a 29-channel resting-state electroencephalography (EEG - 5min opened-eyes, 5min closed-eyes) and auditory oddball paradigm for event-related potentials analyses (ERPs - N1, P2 and P300). Cortical 3D distribution of current source density was computed with sLORETA. Results were compared with 17 controls (9 females, 45.7±15.1y.o). Eyes opened, tinnitus sufferers had lower alpha and beta sources in the left inferior parietal lobule. Eyes closed, tinnitus sufferers had decreased alpha sources in the left inferior temporal and post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG data did not correlate with tinnitus sufferers' clinical features. Subjects with tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups. sLORETA solutions showed decreased sources of these ERPs in the left inferior temporal gyrus in the tinnitus group. We showed cortico-thalamo-cortical involvements in normoacousic tinnitus with hyperexcitability of the left auditory cortex and inferior temporal gyrus. This might reflect processes of maladaptive cortical plasticity and memory consolidation. Further validation is needed to establish the value of this tool in customizing therapeutic approach. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 02/2015; DOI:10.1016/j.clinph.2015.01.027 · 3.10 Impact Factor
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    ABSTRACT: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation. © The Author(s), 2015.
    Multiple Sclerosis 02/2015; 21(8). DOI:10.1177/1352458514568827 · 4.82 Impact Factor
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    ABSTRACT: Background and purposeActive engagement in intellectually enriching activities (e.g. reading, hobbies) builds ‘reserve’ against memory decline in elders and persons with multiple sclerosis (MS), but the neural basis for this protective influence of enrichment is unknown. Herein the neuroanatomical basis of reserve against memory decline in MS patients is investigated.Methods Relapse-onset MS patients (N = 187) underwent 3.0 T magnetic resonance imaging of the brain to quantify T2 lesion volume (T2LV) and normalized volumes of total brain, total white, total grey (using SIENAX) and thalamus, caudate, putamen, pallidum, amygdala and hippocampus (using FIRST). Patients completed a survey quantifying their engagement in early life intellectual enrichment (i.e. reading, hobbies). Verbal and visuospatial episodic memory was assessed with neuropsychological tasks in a representative subsample (N = 97).ResultsControlling for demographics and T2LV, intellectual enrichment was specifically linked to larger normalized hippocampal volume (rp = 0.213, P = 0.004), with no link to other brain volumes/structures. Moreover, greater intellectual enrichment moderated/attenuated the negative relationship between normalized total brain volume (i.e. overall cerebral atrophy) and normalized hippocampal volume (i.e. hippocampal atrophy; P = 0.001) whereby patients who engaged in more early life intellectual enrichment better maintained hippocampal volume in the face of worse overall cerebral atrophy. Finally, the link between greater intellectual enrichment and better memory was partially mediated through larger hippocampal volume.Conclusions These findings support larger hippocampal volume as one key component of the neuroanatomical basis of reserve against memory decline in MS. These findings are consistent with previous literature on experience-dependent neuroplasticity within the hippocampus.
    European Journal of Neurology 02/2015; DOI:10.1111/ene.12662 · 4.06 Impact Factor
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    ABSTRACT: The role of genetic factors in influencing the clinical expression of multiple sclerosis (MS) is unclear. The objective of this paper is to identify genes, pathways and networks implicated in age at onset (AAO) and severity, measured using the Multiple Sclerosis Severity Score (MSSS), of primary-progressive MS (PPMS). We conducted a genome-wide association study (GWAS) of 470 PPMS patients of Italian origin:. Allelic association of 296,589 SNPs with AAO and MSSS was calculated. Pathway and network analyses were also conducted using different tools. No single association signal exceeded genome-wide significance in AAO and MSSS analyses. Nominally associated genes to AAO and MSSS were enriched in both traits for 10 pathways, including: "oxidative phosphorylation" (FDRAAO=9*10(-4); FDRMSSS=3.0*10(-2)), "citrate (TCA) cycle" (FDRAAO=1.6*10(-2); FDRMSSS=3.2*10(-3)), and "B cell receptor signaling" (FDRAAO=3.1*10(-2); FDRMSSS=2.2*10(-3)). In addition, an enrichment of "chemokine signaling pathway" (FDR=9*10(-4)) for AAO and of "leukocyte transendothelial migration" (FDR=2.4*10(-3)) for MSSS trait was observed, among others. Network analysis revealed that p53 and CREB1 were central hubs for AAO and MSSS traits, respectively. Despite the fact that no major effect signals emerged in the present GWAS, our data suggest that genetic variants acting in the context of oxidative stress and immune dysfunction could modulate the onset and severity of PPMS. © The Author(s), 2015.
    Multiple Sclerosis 01/2015; DOI:10.1177/1352458514564590 · 4.82 Impact Factor
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    ABSTRACT: IntroductionHigh levels of autoantibodies directed against glutamic acid decarboxylase (GAD) are associated with stiff-person syndrome (SPS). However, other neurological syndromes have been described in association with anti-GAD antibodies, defining a novel group of syndromes, collectively named “hyperexcitability disorders”. Here, we describe a patient complaining for acute onset of involuntary jerk movements in his legs, associated with pathologically increased level of anti-GAD antibodies.Case reportA 62-year-old man presented with a 4-day history of progressive involuntary jerk movements in his legs with unsteadiness during walking. He denied other focal neurologic or systemic symptoms.He had a medical history of arterial hypertension, diabetes mellitus under insulin treatment, and mild renal impairment. He also referred balance disorder for 2 years, without vestibular impairment, (as evaluated by the otolaryngologist), and a single episode of trunk stiffening lasted 1 month, about ...
    Neurological Sciences 01/2015; 36(4). DOI:10.1007/s10072-014-2058-0 · 1.45 Impact Factor
  • 19th International Congress of the World-Muscle-Society; 10/2014
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    The Journal of Headache and Pain 09/2014; 15(Suppl 1):B22-B22. DOI:10.1186/1129-2377-15-S1-B22 · 2.80 Impact Factor
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    The Journal of Headache and Pain 09/2014; 15(Suppl 1):E18-E18. DOI:10.1186/1129-2377-15-S1-E18 · 2.80 Impact Factor
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    ABSTRACT: Background: RPC1063 is an oral, selective sphingosine 1-phosphate 1 receptor modulator in clinical development for the treatment of relapsing multiple sclerosis (RMS). Objectives: Demonstrate the superior efficacy of low (LD, 0.5 mg) and high (HD, 1.0 mg) dose RPC1063 vs. placebo (PBO), and characterize the safety of RPC1063 in patients with RMS. Methods: RADIANCE is an international, combined Phase 2/3 trial. In the 24-week, Phase 2 portion, 258 patients were randomized (1:1:1) to PBO (n=88), LD (n=87) or HD (n=83). The primary endpoint was the cumulative number of total gadolinium-enhancing (GdE) lesions on MRI at Wks 12, 16, 20 and 24. Key secondary endpoints included number of GdE lesions at Wk 24, cumulative number of new/enlarging T2 lesions from Wks 12-24, and annualized relapse rate (ARR). Safety was assessed using vital signs, labs, ECG, Holter monitoring, PFT, OCT and adverse events (AEs). Patients were titrated to their assigned dose over one week to mitigate first dose heart rate effects. Results: 98% of patients completed the trial. Cumulative total Wk 12-24 GdE lesions was reduced 86% in both RPC1063 arms vs. PBO (mean ± SD: PBO 11.1 ± 29.9, LD 1.5 ± 3.7, HD 1.5 ± 3.4, both p< 0.0001). Numbers of GdE lesions at Wk 24 were significantly reduced 91 and 94% (PBO 3.2 ± 9.8, LD 0.3 ± 0.9, HD 0.2 ± 0.6, both p< 0.0001) and cumulative Wks 12-24 new/enlarging T2 lesions 84 and 91% (PBO 9.0 ± 20.9, LD 1.4 ± 3.2, HD 0.8 ± 1.9, both p< 0.0001). A favorable trend in ARR reduction was observed vs. PBO (LD: 31%, p=0.27; HD: 53%, p=0.053). The AE profiles were comparable between groups. The most common AEs in combined RPC1063 vs. PBO were nasopharyngitis (9.4 vs 13.6%), headache (4.7 vs 9.1%), and urinary tract infection (4.7 vs 2.3%). During the first 6 hours post first dose of RPC1063, maximum reductions in mean hourly heart rate were < 2 bpm from baseline and no patient had a minimum hourly heart rate < 45 bpm. No notable cardiac, pulmonary, ophthalmologic or malignancy AEs were observed. Transient alanine aminotransferase ≥3x upper limit of normal occurred in 3 patients (LD 2 (2.3%), HD 1 (1.2%)) that decreased with continued treatment. Conclusions: Both doses of RPC1063 demonstrated large, significant and consistent reductions of all MRI measures of MS disease activity. The tolerability and safety results suggest a favorable risk-benefit profile of RPC1063 in the treatment of RMS. These results support the ongoing Phase 3 portion of the RADIANCE trial of RPC1063 vs. interferon beta-1a in RMS (NCT02047734).
    ACTRIMS-ECTRIMS MSBoston 2014; 09/2014
  • Clinical Neurophysiology 06/2014; 125:S131-S132. DOI:10.1016/S1388-2457(14)50430-0 · 3.10 Impact Factor
  • Clinical Neurophysiology 06/2014; 125:S81-S82. DOI:10.1016/S1388-2457(14)50271-4 · 3.10 Impact Factor
  • Clinical Neurophysiology 06/2014; 125:S145. DOI:10.1016/S1388-2457(14)50476-2 · 3.10 Impact Factor
  • Clinical Neurophysiology 06/2014; 125:S131. DOI:10.1016/S1388-2457(14)50429-4 · 3.10 Impact Factor

Publication Stats

14k Citations
2,892.45 Total Impact Points


  • 2003–2015
    • Università Vita-Salute San Raffaele
      • Faculty of Psychology
      Milano, Lombardy, Italy
  • 1995–2015
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 2007–2014
    • Università Telematica San Raffaele
      Milano, Lombardy, Italy
  • 2013
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 2004–2013
    • University of Florence
      Florens, Tuscany, Italy
  • 1985–2012
    • University of Milan
      • Department of Neurological Sciences
      Milano, Lombardy, Italy
  • 2011
    • Catholic University of the Sacred Heart
      • Institute of Human Physiology
      Milano, Lombardy, Italy
    • Medical University of Vienna
      • Department of Neurology
      Wien, Vienna, Austria
  • 2009–2011
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      Milano, Lombardy, Italy
  • 2007–2011
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      • Dipartimento di Neurologia
      Milano, Lombardy, Italy
  • 2001
    • Sapienza University of Rome
      Roma, Latium, Italy
    • University of Texas Health Science Center at Houston
      • Department of Neurology
      Houston, Texas, United States
  • 2000
    • The University of Western Ontario
      London, Ontario, Canada
    • Spedali Civili di Brescia
      Brescia, Lombardy, Italy
  • 1989–2000
    • Politecnico di Milano
      • • Department of Bioengineering
      • • Department of Electronics, Information, and Bioengineering
      Milano, Lombardy, Italy
  • 1999
    • IRCCS Multimedica
      Milano, Lombardy, Italy
  • 1996
    • Foundation of the Carlo Besta Neurological Institute
      Milano, Lombardy, Italy
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • Department of Neuroscience & Imaging
      Chieta, Abruzzo, Italy
  • 1992
    • Hospital of Saint Raphael
      New Haven, Connecticut, United States