G Comi

San Raffaele Scientific Institute, Milano, Lombardy, Italy

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Publications (628)2661.89 Total impact

  • [Show abstract] [Hide abstract]
    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; · 1.50 Impact Factor
  • R. Chieffo, F. Ferrari, P. Battista, E. Houdayer, A. Nuara, F. Alemanno, J. Abutalebi, A. Zangen, G. Comi, S.F. Cappa, L. Leocani
    Clinical Neurophysiology 06/2014; 125:S145. · 2.98 Impact Factor
  • S. Guerrieri, G. Di Maggio, R. Santangelo, L. Ferrari, S. Medaglini, M. Rodegher, B. Colombo, L. Moiola, U. Del Carro, V. Martinelli, G. Comi, L. Leocani
    Clinical Neurophysiology 06/2014; 125:S204. · 2.98 Impact Factor
  • Clinical Neurophysiology 06/2014; 125:S131-S132. · 2.98 Impact Factor
  • M. Fichera, F. Spagnolo, E. Houdayer, R. Chieffo, D. Dalla Libera, L. Straffi, E. Coppi, A. Nuara, L. Ferrari, G. Di Maggio, M. Bianco, S. Velikova, A. Zangen, G. Comi, M.A. Volonté, L. Leocani
    Clinical Neurophysiology 06/2014; 125:S131. · 2.98 Impact Factor
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    ABSTRACT: Introduction: To assess abnormalities of fMRI activity during a sustained attention task in pediatric patients with traumatic brain injury (TBI). Methods: FMRI scans were acquired from 22 pediatric TBI patients (mean age=14.3 years; mean time from TBI=1.96 years) and 7 healthy controls (mean age=10.8 years) during the administration of the Conners’ CPT. Patients underwent the Wechsler Intelligence Scale for Children (WISC-IV) and the Functional Independence Measure (FIM) evaluation. Results: In both groups, significant activations during the different conditions of the CPT task were found in the right somatosensory cortex, supplementary motor area, middle cingulate cortex, inferior frontal gyrus (pars opercularis) and left cerebellum. With increasing task difficulty (“load effect”) both groups had increased fMRI activity in the bilateral middle occipital gyrus. During this condition, compared to TBI patients, controls also had an increased recruitment of the middle occipital gyrus as well as temporal and parietal regions. Patients having better performances at the CPT, better scores at WISC-IV and FIM scales and a longer time from TBI showed a reduced activity of the anterior cingulate cortex, superior frontal and middle frontal gyri during the CPT task. Patients having better scores at WISC-IV and a longer time from TBI showed also higher activity of frontal and temporal regions during the “load” condition. Conclusions: Pediatric TBI patients experience an inability to optimize the recruitment of the attentional network, which might contribute to explain the attentional deficits frequently observed in this condition.
    EUROPEAN JOURNAL OF NEUROLOGY, Meeting Abstract: OS1229; 05/2014
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    ABSTRACT: The use of complementary alternative medicine (CAM) in paediatric populations is considerably increased, especially for pain and chronic conditions, as demonstrated by epidemiological surveys both in Europe and in the USA. In our study, CAM was used in 76 % patients of a cohort of 124 children affected by headache (age 4-16 years; 67 % female; 70 % migraine without aura, 12 % migraine with aura, 18 % tensive headache according to IHS criteria) consecutively recruited at a Pediatric Headache University Center. CAM was used as preventive treatment in 80 % cases. The main reasons for seeking CAM were: the wish of avoiding chronic use of drugs with their related side effects, the desire of an integrated approach, the reported inefficacy of conventional medicine, and a more suitable children disposition to CAM than to pharmacological compound. Female gender, younger age, migraine without aura, parents' higher educational status, maternal use of CAM and other associated chronic conditions, correlated with CAM use (p < 0.05). 73 % patients chose CAM also to treat other diseases (i.e. allergies, colitis, asthma, insomnia, muscle-scheletric disorders and dysmenorrhoea). The most assumed CAM were: herbal remedies (64 %) such as Valeriana, Ginkgo biloba, Boswellia serrata, Vitex agnus-castus, passion flower, Linden tree; vitamins/minerals supplements (40 %) with magnesium, 5-Hydroxytryptophan, vitamin B6 or B12, Multivitamin compounds; Homeopathy (47 %) with Silicea, Ignatia Amara, Pulsatilla, Aconitum, Nux Vomica, Calcarea phosphorica; physical treatment (45 %) such as Ayurvedic massage, shiatsu, osteopathy; yoga (33 %); acupuncture (11 %). CAM-often integrated with conventional care-was auto-prescribed in 30 % of the cases, suggested by non-physician in 22 %, by the General Practitioner in 24 % and by paediatrician in 24 %. Both general practitioners and neurologists were mostly unaware of their patients' CAM use. In conclusion, neurologists should inquire for CAM use and be prepared to learn about CAM therapies or to directly interact with CAM trained experts, in order to coordinate an integrative approach to health, as especially required in paediatric headache patients and their parents. Further studies are required to investigate safety and efficacy of CAM in pediatric headache, as a possible side-medicine to conventional pharmacological approach.
    05/2014; 35 Suppl 1:145-8.
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    ABSTRACT: Introduction: We applied DT MRI to analyze damage to the supra- and infra-tentorial districts in pediatric patients with vegetative state (VS) or minimally conscious state (MCS) and their correlations with clinical scales of disease severity. Methods: Seven pediatric patients in a VS and six in a MCS, suffering from severe acquired brain injury due to non-traumatic origin and 10 pediatric healthy controls underwent a DT MRI scan and patients were assessed using the Glasgow Coma Scale and Disability Rating Scale. We obtained fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivities (RD) from the corpus callosum (CC), inferior (ICP), middle (MCP), and superior (SCP) cerebellar peduncles. Results: Compared to controls, patients had lower FA of the CC and SCP, and higher MD, AD and RD of the CC and cerebellar peduncles. Compared to acute patients, those in the chronic stage had lower FA and higher MD, AD and RD of the anterior part of the MCP. Differences of FA, MD and RD between supra- vs. infra- tentorial compartments differentiated patients from controls. Furthermore, the difference of FA between supra- vs. infra- tentorial compartments distinguished VS from MCS patients (p<0.01). Significant correlations were found between DT MRI indexes and clinical scales (r ranging from -0.77 to 0.73). Conclusions: In pediatric patients with VS/MCS due to non-traumatic origin, the severity of clinical disability correlates with structural damage to both infratentorial and the long-range cortico-cortical tracts, suggesting that global, rather than focal damage, contributes to the clinical severity of these patients.
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    ABSTRACT: Using diffusion tensor magnetic resonance imaging (DT MRI), we analyzed the architectural integrity of the brain white matter (WM) from a large cohort of MS patients to identify the structural substrates of the concomitant presence of depression and fatigue. Brain dual-echo, 3D T1-weighted and DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched healthy controls (HCs). Patients were stratified by the presence of depression (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses were run in brain WM tracts using standard-space templates. Whole-brain voxel-wise analysis yielded no significant differences between patient subgroups. At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of the forceps minor. Reduced FA of the right anterior thalamic radiation and right uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for depression. No significant differences were found between D vs not D-MS patients, after correcting for fatigue. This study provides evidence for partially overlapping damage to frontal and fronto-temporal pathways underlying depression and fatigue in MS.
    Multiple Sclerosis 04/2014; · 4.86 Impact Factor
  • Neurological Sciences 03/2014; · 1.50 Impact Factor
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    ABSTRACT: BACKGROUND: Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing or relapsing-remitting multiple sclerosis. We aimed to provide further evidence for the safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis. METHODS: This international, randomised, double-blind, placebo-controlled, phase 3 study enrolled adults aged 18-55 years with relapsing multiple sclerosis, one or more relapse in the previous 12 months or two or more in the previous 24 months but no relapse in the previous 30 days, and an Expanded Disability Status Scale (EDSS) score of 5.5 points or less. Patients were recruited from 189 sites in 26 countries and randomly assigned (1:1:1) to once-daily placebo, teriflunomide 7 mg, or teriflunomide 14 mg via an interactive voice recognition system. Treatment duration was variable, ending 48 weeks after the last patient was included. The primary endpoint was annualised relapse rate (number of relapses per patient-year) and the key secondary endpoint was time to sustained accumulation of disability (an EDSS score increase of at least 1 EDSS point sustained for a minimum of 12 weeks), both analysed in the modified intention-to-treat population (all patients who received at least one dose of assigned study medication). This study is registered with ClinicalTrials.gov, number NCT00751881. FINDINGS: Between Sept 17, 2008, and Feb 17, 2011, 1169 patients were randomly assigned to a treatment group, of whom 388, 407, and 370 patients received at least one dose of placebo, teriflunomide 7 mg, or teriflunomide 14 mg, respectively. By the end of the study, the annualised relapse rate was higher in patients assigned to placebo (0.50 [95% CI 0.43-0.58]) than in those assigned to teriflunomide 14 mg (0.32 [0.27-0.38]; p=0.0001) or teriflunomide 7 mg (0.39 [0.33-0.46]; p=0.0183). Compared with placebo, teriflunomide 14 mg reduced the risk of sustained accumulation of disability (hazard ratio [HR] 0.68 [95% CI 0.47-1.00]; log-rank p=0.0442); however, teriflunomide 7 mg had no effect on sustained accumulation of disability (HR 0.95 [0.68-1.35]; log-rank p=0.7620). The most common adverse events were alanine aminotransferase increases (32 [8%] of 385 patients in the placebo group vs 46 [11%] of 409 patients in the teriflunomide 7 mg group vs 52 [14%] of 371 patients in the teriflunomide 14 mg group), hair thinning (17 [4%] vs 42 [10%] vs 50 [13%]), and headache (42 [11%] vs 60 [15%] vs 46 [12%]). Incidence of serious adverse events was similar in all treatment groups (47 [12%] vs 52 [13%] vs 44 [12%]). Four deaths occurred, none of which was considered to be related to study drug (respiratory infection in the placebo group, traffic accident in the teriflunomide 7 mg group, and suicide and septicaemia due to Gram-negative infection complicated by disseminated intravascular coagulopathy in the teriflunomide 14 mg group). INTERPRETATION: Teriflunomide 14 mg was associated with a lower relapse rate and less disability accumulation compared with placebo, with a similar safety and tolerability profile to that reported in previous studies. These results confirm the dose effect reported in previous trials and support the use of teriflunomide 14 mg in patients with relapsing multiple sclerosis.
    The Lancet Neurology 03/2014; 13(3):247-256. · 21.82 Impact Factor
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    ABSTRACT: Cerebrospinal fluid (CSF) biomarkers (protein tau, phosphorylated tau and amyloid Beta 1-42) are recognized as a supportive feature in diagnosis of Alzheimer's disease (AD) and their role in identifying atypical variants of AD is currently under investigation. We dosed these proteins in nine patients clinically and instrumentally affected by posterior cortical atrophy (PCA), a rare disorder characterized by a progressive neurodegenerative process that involves primarily the posterior brain regions. We compared the obtained values with a large group of AD patients (N = 117), recruited in our neurological department. Our data revealed no differences in the CSF profile between PCA and AD, showing abnormal values of protein tau, phosphorylated tau and amyloid Beta 1-42 in both groups of patients. This study underlines the diagnostic importance of CSF biomarkers in PCA patients, supporting the hypothesis that PCA is an atypical variant of AD with an onset before the age of 65.
    Neurological Sciences 02/2014; · 1.50 Impact Factor
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    ABSTRACT: Background: In experimental autoimmune encephalomyelitis, inhibition of the renin-angiotensin system with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors resulted in a significantly ameliorated disease course. We evaluated the effects of ARBs and ACE inhibitors on the efficacy of interferon beta-1b in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: In this post hoc analysis of the BEYOND (Betaferon Efficacy Yielding Outcomes of a New Dose) study, clinical and MRI end points were compared between patients treated with interferon beta-1b 250 or 500 µg and concomitant ARBs or ACE inhibitors and patients treated with interferon beta-1b 250 or 500 µg only (reference group). Results: Patients in the ARB group (n = 22) tended to have a higher relapse rate (0.48 vs. 0.23, p = 0.051) and a higher number of new gadolinium-enhancing lesions (0.6 vs. 0.3, p = 0.057) than patients in the reference group. Patients in the ACE inhibitor group (n = 49) also tended to have a higher relapse rate (0.29 vs. 0.22, p = 0.357). No differences were observed for the other end points. Conclusion: In the BEYOND study cohort, a concomitant medication with ARBs or ACE inhibitors did not have a beneficial effect in patients with RRMS treated with interferon beta-1b. As patients appeared to have a higher relapse rate, our results warrant further investigation. © 2014 S. Karger AG, Basel.
    European Neurology 01/2014; 71(3-4):173-179. · 1.36 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) deposition, which activates microglia, induces neuroinflammation and drives neurodegeneration. Recent evidence indicates that soluble pre-fibrillar Aβ species, rather than insoluble fibrils, are the most toxic forms of Aβ. Preventing soluble Aβ formation represents, therefore, a major goal in AD. We investigated whether microvesicles (MVs) released extracellularly by reactive microglia may contribute to AD degeneration. We found that production of myeloid MVs, likely of microglial origin, is strikingly high in AD patients and in subjects with mild cognitive impairment and that AD MVs are toxic for cultured neurons. The mechanism responsible for MV neurotoxicity was defined in vitro using MVs produced by primary microglia. We demonstrated that neurotoxicity of MVs results from (i) the capability of MV lipids to promote formation of soluble Aβ species from extracellular insoluble aggregates and (ii) from the presence of neurotoxic Aβ forms trafficked to MVs after Aβ internalization into microglia. MV neurotoxicity was neutralized by the Aβ-interacting protein PrP and anti-Aβ antibodies, which prevented binding to neurons of neurotoxic soluble Aβ species. This study identifies microglia-derived MVs as a novel mechanism by which microglia participate in AD degeneration, and suggest new therapeutic strategies for the treatment of the disease.Cell Death and Differentiation advance online publication, 13 December 2013; doi:10.1038/cdd.2013.180.
    Cell death and differentiation 12/2013; · 8.24 Impact Factor
  • Neurological Sciences 11/2013; · 1.50 Impact Factor
  • Clinical Neurophysiology 11/2013; 124(11):e216. · 2.98 Impact Factor
  • Clinical Neurophysiology 11/2013; 124(11):e197. · 2.98 Impact Factor
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    ABSTRACT: To identify clinical predictors of effectiveness of a motor rehabilitation treatment in a cohort of multiple sclerosis (MS) patients. We analysed 212 consecutive patients who underwent a short-term (3-7 weeks) intensive (two hours per day, five days per week), individualised, goal-oriented inpatient rehabilitation program. Activity limitation and impairment were measured on admission and discharge of the rehabilitation trial using the motor sub-items of the Functional Independence Measure (mFIM) and the Expanded Disability Status Scale (EDSS) score. Multivariate logistic regression models have been tested to evaluate the role of clinical baseline features on rehabilitation effectiveness. According to pre-defined outcome measures, 75.1% of MS patients improved in either activity limitation (≥5 points delta mFIM) or impairment (≥1.0 delta EDSS score if baseline EDSS was ≤5.5, or ≥0.5 if baseline EDSS was >5.5), and 35.4% of MS patients improved in both outcomes. A relapsing-remitting course of disease, a more severe baseline impairment and activity limitation level, a shorter disease duration and a less severe balance dysfunction were predictive of the effectiveness of rehabilitation. These data confirm that an intensive inpatient rehabilitation program is able to produce a short-term relevant improvement on clinical and functional outcome measures and suggest some clinical features which can be considered as potential predictors of the outcome of rehabilitative intervention.
    Multiple Sclerosis 10/2013; · 4.86 Impact Factor
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    ABSTRACT: Among postural abnormalities in Parkinson's disease (PD), striatal hand (SH) is a particularly underexplored phenomenon. It leads to extreme abnormalities of hand posture, causing altered dexterity, pain and disfigurement. In our study, three blinded investigators examined several pictures of the hands of individuals with PD (N = 40) and controls (N = 15). The investigators quantified postural alterations using the Striatal Hand Score. Demographic and clinical data were also collected. As no differences were detected among investigators agreement, a final Hand Score (HS, range 0-4) was obtained for each hand. The Striatal Hand Score in both the left and right hand was significantly different in PD compared to controls (p < 0.001 for both left and right hand). Striatal hand was significantly worse on the side of PD onset, and on the side with greater PD symptomatology. The finding of a striatal hand was 100 % specific for a diagnosis of PD. Nine PD subjects were evaluated both on and off medication, and dopaminergic treatment did not significantly change the Striatal Hand Score. Our findings suggest that in patients without any explanation for hand deformities other than PD, striatal hand occurs very often, and is highly specific for the side of worst PD involvement. We recommend including an evaluation for SH as part of routine practice. This study emphasizes the importance of a careful observation of the patient in order to improve diagnostic accuracy.
    Journal of Neurology 10/2013; · 3.84 Impact Factor

Publication Stats

14k Citations
2,661.89 Total Impact Points


  • 1995–2014
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
    • Ospedale Santa Maria della Misericordia, Rovigo
      Rovigo, Veneto, Italy
  • 2013
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 1982–2013
    • University of Milan
      • Department of Neurological Sciences
      Milano, Lombardy, Italy
  • 2012
    • University of Leicester
      • Department of Cardiovascular Sciences
      Leiscester, England, United Kingdom
  • 2009–2012
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 2002–2012
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
  • 2011
    • Centre Hospitalier Universitaire de Rennes
      • Service de neurologie
      Roazhon, Brittany, France
  • 2008–2011
    • University of Florence
      • Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino
      Florence, Tuscany, Italy
  • 2010
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 2006–2009
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy
  • 1985–2009
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      • Division of Neuroscience
      Milano, Lombardy, Italy
  • 2001
    • Sapienza University of Rome
      • Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science
      Roma, Latium, Italy
  • 2000
    • The University of Western Ontario
      London, Ontario, Canada
  • 1989–2000
    • Politecnico di Milano
      • • Department of Bioengineering
      • • Department of Electronics, Information, and Bioengineering
      • • Department of Electrical Engineering
      Milano, Lombardy, Italy
  • 1999
    • IRCCS Multimedica
      Milano, Lombardy, Italy
  • 1996
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
    • University of Helsinki
      Helsinki, Southern Finland Province, Finland
  • 1995–1996
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
  • 1992
    • Hospital of Saint Raphael
      New Haven, Connecticut, United States
  • 1991
    • Università degli Studi di Urbino "Carlo Bo"
      • Department of Biomolecular Science
      Urbino, The Marches, Italy