46 results on '"Paola, Naldi"'
Search Results
2. Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients
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Eleonora Virgilio, Domizia Vecchio, Ilaria Crespi, Paolo Barbero, Beatrice Caloni, Paola Naldi, Roberto Cantello, Umberto Dianzani, and Cristoforo Comi
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multiple sclerosis ,vitamin D ,cognition ,information processing speed ,IPS ,symbol digit modalities test ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.
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- 2021
- Full Text
- View/download PDF
3. Benign COVID-19 in an Aggressive Case of Aquaporin-4 Neuromyelitis Optica Treated with Tocilizumab
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Domizia Vecchio, Claudio Solaro, Eleonora Virgilio, Paola Naldi, Rugiada Bottero, Fabio Masuccio, Marco Capobianco, and Roberto Cantello
- Abstract
Aggressive neuromyelitis optica spectrum disorders (NMOSDs) with antibodies (Abs) against aquaporin-4 (AQP4) can be treated by blocking the interleukin 6 (IL6) pathways with tocilizumab. This IL6-inhibitor was employed to treat coronavirus disease 2019 (COVID-19) pneumonia with unconclusive results. We present a 52-year-old woman with AQP4 NMOSD, unresponsive to rituximab, that stabilized on tocilizumab one year after the disease onset. She was bed-bound and progressively recovered her mobility. During intensive rehabilitation, she presented fever and cough for one week with nasopharyngeal swabs positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This mild COVID-19 recovered spontaneously without sequelae, and the monthly tocilizumab infusions were continued for another 10 months. Subsequently, serious and prolonged respiratory and urinary infections caused treatment interruption, and then her disease re-activated. In our case, tocilizumab was effective in preventing NMOSD relapse and was safe to use during SARS-CoV-2 infection.
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- 2022
4. The Impact of Lifetime Alcohol and Cigarette Smoking Loads on Multiple Sclerosis Severity
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Andrei Ivashynka, Massimiliano Copetti, Paola Naldi, Sandra D'Alfonso, and Maurizio A. Leone
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multiple sclerosis ,multiple sclerosis severity score ,lifetime alcohol load ,lifetime cigarette smoking load ,risk factors ,cross-sectional study ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background: The association between lifestyle factors and Multiple Sclerosis (MS) disease severity and progression has been investigated to a lesser extent compared with susceptibility to the disease.Objective: We aimed to assess the impact of lifetime alcohol and cigarette smoking load on MS severity.Methods: Design: a cross-sectional study. Three hundred fifty-one patients consecutively admitted to the Department of Neurology were asked to complete the “Questionnaire of Lifestyle” (part of the European Prospective Investigation into Cancer and Nutrition project). An estimation of the cumulative lifetime cigarette smoking and alcohol load was calculated as the weighted sum of the mean number of cigarettes smoked and standard alcoholic drinks consumed per day at different ages. The measure of exposure was expressed in terms of pack-year and drink-year. Disease severity was estimated by the Multiple Sclerosis Severity Score (MSSS). Logistic regression analyses were performed using MSSS (first tertile vs. third tertile) as the outcome.Results: The median MSSS was higher (3.2 vs. 2.3, p = 0.002) in ever- vs. never-smokers, but we did not find a difference between ever- and never-drinkers (2.7 vs. 2.8, p = ns). Ever-smokers were almost twice as likely to fall in the upper MSSS tertile than never-smokers. Ever-drinkers did not show a statistically significant association between alcohol intake and MS severity. The risk of falling in the worst MSSS tertile for smokers was 10.81 (2.0–58.48; p < 0.01) if they were never-drinkers, whereas it was only 1.65 (0.89–3.03, p = 0.11) if they were also drinkers. On the other side, the risk of falling in the worst MSSS tertile for drinkers did not change as much, whether they also were smokers (0.46; 0.13–1.65; p = 0.23) or not (1.49; 0.55–4.04, p = 0.43).Conclusions: Cigarette smoking, unlike alcohol consumption, is associated with MS severity. Alcohol consumption may attenuate the effect of smoking on disease severity, acting as an effect modifier. The biological background of this effect is unknown. The limitations of our study are mostly due to its cross-sectional design.
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- 2019
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5. Susac Syndrome: an uncommon cause of impaired vision
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Paolo Barbero, Domizia Vecchio, Eleonora Virgilio, Paola Naldi, Cristoforo Comi, and Roberto Cantello
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Adult ,Psychiatry and Mental health ,Susac Syndrome ,Retinal Artery Occlusion ,Vertigo ,Brain ,Humans ,Female ,Neurology (clinical) ,Dermatology ,General Medicine ,Magnetic Resonance Imaging - Abstract
A 35-year-old Caucasian woman presented an abrupt onset of bilateral impaired vision, and arrived to our attention two weeks later. She had a previous episode of mild dizziness. She underwent a fluorescein angiography showing branch retinal artery occlusions and a brain magnetic resonance imaging (MRI) revealing several supraand infratentorial FLAIR-hyperintense white matter lesions, two with contrast enhancement. Thrombophilic, autoimmune and infective (including Human Immunodeficiency Virus, Borrelia burgdorferi, Hepatitis B Virus, Hepatitis C Virus, Herpes Simplex Virus 1-2, Varicella Zoster Virus) screening was negative. Cerebrospinal fluid analysis showed intrathecal IgG synthesis. We suspected a Primary Central Nervous System Vasculitis, and intravenous steroids were started. Three months later a second brain MRI showed seven new lesions without contrast enhancement, and she revealed a cognitive impairment and bilateral hearing loss. Reviewing the clinical history and MRI, she fulfilled diagnostic criteria for Susac syndrome. She had two cycles of cyclophosphamide, and recovered in 6 months and then remained stable with metotrexate.
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- 2022
6. Prognostic Role of Visual Evoked Potentials in Non-Neuritic Eyes at Multiple Sclerosis Diagnosis
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Domizia Vecchio, Paolo Barbero, Giulia Galli, Eleonora Virgilio, Paola Naldi, Cristoforo Comi, and Roberto Cantello
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General Medicine - Abstract
Introduction: This study aimed to assess the prognostic role of visual evoked potentials (VEPs) of the non-neuritic eye at the diagnosis of multiple sclerosis (MS). Patients and methods: We enrolled 181 MS patients (62% females, mean age at diagnosis: 38 years, standard deviation: 12) at the time of the first diagnostic work-up, including VEPs. We collected P100 latency and N75-P100 amplitude of non-neuritic eyes at diagnosis, and then we calculated the mean values in 127 patients with no history of optic neuritis (ON) or considered the unaffected eye in the remaining. At last follow-up (minimum: one year), disability was evaluated according to MS Severity Score or MSSS (median: 2.44, range: 0.18–9.63). Statistical analysis included Mann–Whitney descriptive analysis, Spearman correlation for independent samples, and linear regression for significant predictors of MSSS. Results: 38/181 patients had P100 latency >115 ms, and 63/181 showed N75-P100 amplitude < 5 microV in the unaffected eyes at MS diagnosis. At last follow-up, MSSS correlated with P100 latency (rho = 0.21, p = 0.004) and N75-P100 amplitude (rho = 0.19, p = 0.009) collected at diagnosis. P100 latency (not N75-P100 amplitude) resulted in a predictor for disability over time (MSSS) in the regression model (along with age at onset, MS course, and disease-modifying treatments). Conclusions: Our study showed a prognostic value of VEPs in clinically unaffected eyes at MS diagnosis to predict future disability, independently from a history of ON.
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- 2023
7. Cannabinoids in multiple sclerosis: A neurophysiological analysis
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Eleonora Virgilio, Roberto Cantello, Antonio Spagarino, Domizia Vecchio, Claudia Varrasi, and Paola Naldi
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Adult ,Male ,Visual analogue scale ,Modified Ashworth scale ,Analgesic ,Administration, Oral ,Pain ,Pilot Projects ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Cannabidiol ,Humans ,Dronabinol ,030212 general & internal medicine ,Spasticity ,Muscle, Skeletal ,business.industry ,Standard treatment ,Multiple sclerosis ,General Medicine ,Middle Aged ,Multiple Sclerosis, Chronic Progressive ,medicine.disease ,Drug Combinations ,Treatment Outcome ,Neurology ,Muscle Spasticity ,Anesthesia ,Female ,Silent period ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Objectives To investigate the action of cannabinoids on spasticity and pain in secondary progressive multiple sclerosis, by means of neurophysiological indexes. Material and methods We assessed 15 patients with progressive MS (11 females) using clinical scales for spasticity and pain, as well as neurophysiological variables (H/M ratio, cutaneous silent period or CSP). Testing occurred before (T0) and during (T1) a standard treatment with an oral spray containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Neurophysiological measures at T0 were compared with those of 14 healthy controls of similar age and sex (HC). We then compared the patient results at the two time points (T1 vs T0). Results At T0, neurophysiological variables did not differ significantly between patients and controls. At T1, spasticity and pain scores improved, as detected by the Modified Ashworth Scale or MAS (P = .001), 9-Hole Peg Test or 9HPT (P = .018), numeric rating scale for spasticity or NRS (P = .001), and visual analogue scale for pain or VAS (P = .005). At the same time, the CSP was significantly prolonged (P = .001). Conclusions The THC-CBD spray improved spasticity and pain in secondary progressive MS patients. The spray prolonged CSP duration, which appears a promising tool for assessing and monitoring the analgesic effects of THC-CBD in MS.
- Published
- 2020
8. Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients
- Author
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Cristoforo Comi, Paolo Barbero, Roberto Cantello, Beatrice Caloni, Eleonora Virgilio, Ilaria Crespi, Umberto Dianzani, Paola Naldi, and Domizia Vecchio
- Subjects
Serum vitamin ,cognition ,medicine.medical_specialty ,business.industry ,General Neuroscience ,Multiple sclerosis ,IPS ,Symbol digit modalities test ,Cognition ,vitamin D ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Disease ,medicine.disease ,multiple sclerosis ,Article ,symbol digit modalities test ,Correlation ,information processing speed ,Internal medicine ,Vitamin D and neurology ,medicine ,SDMT ,business ,Cognitive impairment ,RC321-571 - Abstract
Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.
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- 2021
9. Post-lumbar puncture headache: an adverse effect in multiple sclerosis work-up
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Cristoforo Comi, Maurizio Leone, Veronica Ferro, Domizia Vecchio, Paola Naldi, and Roberto Cantello
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Multiple Sclerosis ,Neurology ,Adolescent ,Dermatology ,Spinal Puncture ,Young Adult ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Adverse effect ,Neck stiffness ,Neuroradiology ,medicine.diagnostic_test ,Lumbar puncture ,business.industry ,Age Factors ,General Medicine ,Middle Aged ,Work-up ,Psychiatry and Mental health ,Female ,Neurology (clinical) ,Neurosurgery ,Post-Dural Puncture Headache ,business ,Complication ,030217 neurology & neurosurgery - Abstract
Lumbar puncture (LP) is a safe procedure commonly performed in the diagnostic work-up of multiple sclerosis (MS), and its main adverse event is post-LP headache (PLPH). Predictors for PLPH in MS are not established. To describe the occurrence of, and, factors related to PLPH in patients with suspected MS, studied on a daily-basis admission. One hundred patients (70 females) were admitted for a diagnostic LP (standardized with a traumatic 19-G needle), observed for 6 h, and evaluated for adverse events 2 and 7 days later. Descriptive statistics and a multivariate analysis (for PLPH) were performed. Fifty-seven (57%) patients had PLPH at 48 h, which persisted 1 week in 31, and only two presented beyond the first 2 days. Other adverse events were tinnitus and neck stiffness. None required investigations or was hospitalized. Age was the only predictor for PLPH at day 2, whereas the onset of headache within 48 h and female gender were predictors for PLPH at day 7. PLPH is a frequent complication of LP performed on daily-basis admission in MS work-up. The maximum onset is within the first 48 h. Age and gender seem the only predictors for the appearance and persistence of PLPH.
- Published
- 2019
10. Chronic cerebrospinal venous insufficiency is not associated with multiple sclerosis and its severity: a blind-verified study.
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Maurizio A Leone, Olga Raymkulova, Paola Naldi, Piergiorgio Lochner, Laura Bolamperti, Lorenzo Coppo, Alessandro Stecco, and William Liboni
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Medicine ,Science - Abstract
BackgroundChronic Cerebrospinal Venous Insufficiency (CCSVI) has been associated with multiple sclerosis (MS) with a risk ranging from as high as two-hundred-fold to a protective effect. However, not all studies were blinded, and the efficacy of blinding was never assessed.ObjectiveTo evaluate the association of CCSVI with MS in a cross-sectional blinded study and look for any association of CCSVI with the severity of MS.Methodology/principal findingsThe Echo-color Doppler examination was carried out in accordance with Zamboni's five criteria in 68 consecutive MS patients and 68 healthy controls, matched by gender and age (±5 years). Four experienced neurosonologists, blinded to the status of cases and controls, performed the study and were then asked to guess the status (case or control) of each participant. The number of positive CCSVI criteria was similar in the two groups. CCSVI, defined as the presence of two or more criteria, was detected in 21 cases (30.9%) and 23 controls (33.8%), with an OR of 0.9 (95%CL = 0.4-1.8, p = 0.71). The prevalence of CCSVI was related to age in cases (OR increasing from 0.2 to 1.4), but not in controls. CCSVI positive (N = 21) and negative (N = 47) MS patients were similar in clinical type, age at disease onset, disability, and fatigue. Disease duration was longer (16.5±9.8 years) in CCSVI positive than negative patients (11.5±7.4; p = 0.04). The operators correctly guessed 34/68 cases (50%) and 45/68 controls (66%) (p = 0.06), indicating a different success of blinding.Conclusions/significanceCCSVI was not associated with MS itself, nor its severity. We cannot rule out the possibility that CCSVI is a consequence of MS or of aging. Blinding of sonographers is a key point in studying CCSVI and its verification should be a requisite of future studies.
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- 2013
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11. Paraneoplastic neuromyelitis optica spectrum disorders: a case series
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Cristoforo Comi, Eleonora Virgilio, Paola Naldi, Paola Cavalla, Roberto Cantello, Fabiana Tesser, Domizia Vecchio, and Marco Vercellino
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medicine.medical_specialty ,Neurology ,medicine.medical_treatment ,Dermatology ,Myelitis, Transverse ,Transverse myelitis ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Optic neuritis ,030212 general & internal medicine ,Lung cancer ,Neuroradiology ,Aged ,Autoantibodies ,Aquaporin 4 ,business.industry ,Neuromyelitis Optica ,Immunosuppression ,General Medicine ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Etiology ,Female ,Neurology (clinical) ,Neurosurgery ,business ,030217 neurology & neurosurgery - Abstract
Aquaporin-4 antibody (AQP4-IgG) neuromyelitis optica spectrum disorders (NMOSD) are rare idiopathic autoimmune diseases, presenting with optic neuritis (ON), longitudinally extensive transverse myelitis (LETM), and brainstem syndromes and a prevalence range between 0.5 and 4/100,000. Only 3% to 25% of NMOSD have been described as a paraneoplastic (PN) syndrome (PNNMOSD). Both idiopathic NMOSD (INMOSD) and PNNMOSD cases mostly affect females, but PNNMOSD usually presents with a spinal cord or brainstem involvement in elderly patients. Few cases of both malignancies (for the majority breast or lung cancer) and benign tumors (monoclonal gammopathy) were previously reported. Currently, there is no consensus on treatment approach for PNNMOSD (only surgical removal or surgery combined with chronic immunosuppression). Here, we present a series of three newly diagnosed PNNMOSD cases, who differ from each other for demographic and clinical features, tumor association, long-term treatment, and outcome. We propose that a PN etiology should be considered always whenever a new diagnosis of NMOSD is made, not only in patients over 50 years old or in spinal cord/brainstem lesions presentations. Our findings add to existing evidence and raise awareness on PNNMOSD. We enhance the importance for the clinicians of recognizing tumor symptoms and signs whenever a NMOSD is newly diagnosed.
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- 2020
12. Holmes tremor caused by a natalizumab-related progressive multifocal leukoencephalopathy: a case report and brief review of the literature
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Domizia Vecchio, Paola Naldi, Cristoforo Comi, Roberto Cantello, and Luca Magistrelli
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medicine.medical_specialty ,Pediatrics ,Neurology ,business.industry ,Progressive multifocal leukoencephalopathy ,Dermatology ,General Medicine ,medicine.disease ,Holmes tremor ,Psychiatry and Mental health ,Natalizumab ,medicine ,Neurology (clinical) ,Neurosurgery ,business ,Neuroradiology ,medicine.drug - Published
- 2019
13. Benign COVID-19 in an aggressive case of aquaporin-4 Neuromyelitis optica treated with tocilizumab
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Marco Capobianco, Domizia Vecchio, Eleonora Virgilio, Paola Naldi, Claudio Solaro, and Roberto Cantello
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medicine.medical_specialty ,Neuromyelitis optica ,Coronavirus disease 2019 (COVID-19) ,business.industry ,medicine.disease ,Gastroenterology ,Article ,chemistry.chemical_compound ,Tocilizumab ,Aquaporin 4 ,Neurology ,chemistry ,Internal medicine ,medicine ,Neurology (clinical) ,business - Published
- 2021
14. Cannabinoids efficacy in vanishing white matter disease: A case report
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Eleonora Virgilio, Giulia Galli, Riccardo Fornaro, Domizia Vecchio, Roberto Cantello, and Paola Naldi
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medicine.medical_specialty ,Vanishing white matter disease ,Neurology ,business.industry ,medicine ,Neurology (clinical) ,business ,Dermatology - Published
- 2021
15. The Impact of Life-Time Alcohol and Smoking Load on Multiple Sclerosis Severity
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Massimiliano Copetti, Maurizio Leone, Sandra D'Alfonso, Andrei Ivashynka, and Paola Naldi
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business.industry ,Multiple sclerosis ,Etiology ,Medicine ,Odds ratio ,Disease ,Pack-year ,business ,medicine.disease ,Logistic regression ,Confidence interval ,European Prospective Investigation into Cancer and Nutrition ,Demography - Abstract
Background: Investigation on the association of smoking and alcohol consumption with Multiple Sclerosis (MS) disease severity is less advanced compared with susceptibility to the disease. We aimed to assess the impact of life-time alcohol and smoking load on MS severity. Methods: 351 patients consecutively admitted at the Department of Neurology were asked to fill the "Questionnaire of Lifestyle" (part of the European Prospective Investigation into Cancer and Nutrition project). An estimation of the cumulative lifetime smoking and alcohol load was calculated as the weighted sum of the mean number of cigarettes smoked or standard alcohol drinks drunk per day at different ages. The measure of exposure was expressed in terms of pack year and drink year. The disease severity was estimated through the Multiple Sclerosis Severity Score (MSSS). Logistic regression analyses were performed using MSSS (first tertile vs. third tertile) as the outcome. Findings: The median MSSS was higher (3.2 vs. 2.3, p=0.002) in ever compared to never smokers, but we did not find difference between ever and never drinkers (2.7 vs. 2.8, p=ns). Ever smokers were almost two times more likely to fall in the upper MSSS tertile than never smokers. Ever drinkers did not show statistically significant association with MS severity. However, we found an interaction between alcohol consumption and smoke: ever smokers/never drinkers had an Odds Ratio (OR) of 6.4 (Confidence Interval (CI) =1.5-27.1) to fall in the upper MSSS tertile compared with never smokers/never drinkers, but the risk was less in smokers with both lower (1.8, CI=0.6-6.0) or higher drink load (2.6, CI=0.9-7.4). Interpretation: In our pilot study of consecutive MS patients we found a positive trend between the lifetime alcohol and smoking load with disease severity. Knowledge of potentially modifying factors is important from a clinical as well as an etiological point of view. Funding Statement: The fund “Maffeo-Fondazione della Comunita del Novarese” (Novara, Italy) has been supported the fellowship of Dr. Andrei Ivashynka during study design, recruitment and examination of patients. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Declaration of Interests: A. Ivashynka, S. D’Alfonso, M. Copetti, P. Naldi, MA Leone report no conflict of interest related to this study. Ethics Approval Statement: The work was approved by the Ethics Committee of the University Hospital "Maggiore della Carita", Novara, Italy
- Published
- 2018
16. MOG-antibody demyelinating diseases: a case of post-partum severe rhombencephalitis and transverse myelitis
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Cristoforo Comi, Paola Naldi, E Virgilio, Roberto Cantello, and Domizia Vecchio
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Adult ,Pediatrics ,medicine.medical_specialty ,medicine.medical_treatment ,Demyelinating Autoimmune Diseases, CNS ,Fluid-attenuated inversion recovery ,Myelitis, Transverse ,Transverse myelitis ,Myelin oligodendrocyte glycoprotein ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,medicine ,Humans ,Autoantibodies ,biology ,business.industry ,Multiple sclerosis ,Postpartum Period ,Immunosuppression ,General Medicine ,medicine.disease ,Rhombencephalon ,nervous system ,Neurology ,Respiratory failure ,Immunoglobulin G ,030221 ophthalmology & optometry ,biology.protein ,Encephalitis ,Plasmapheresis ,Female ,Myelin-Oligodendrocyte Glycoprotein ,Neurology (clinical) ,business ,Respiratory Insufficiency ,030217 neurology & neurosurgery - Abstract
Introduction Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) associated disorders present with a spectrum of clinical pictures including brainstem involvement. Case report A patient with the sudden onset of a post-partum severe rhombencephalitis causing respiratory failure (12 years after a mild transverse myelitis). Despite the aggressive clinical course, she had an impressive recovery after plasmapheresis, and no further relapses on immunosuppression. Conclusion MOG-IgG disorders could relapse several years after onset and involve brainstem. Good prognosis is possible after treatment.
- Published
- 2017
17. Combined use of Kappa Free Light Chain Index and Isoelectrofocusing of Cerebro-Spinal Fluid in Diagnosing Multiple Sclerosis: Performances and Costs
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Ilaria Crespi, Cristoforo Comi, Riccardo Mora, Giorgio Bellomo, Maria Giovanna Sulas, Paola Naldi, Domizia Vecchio, and Roberto Cantello
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0301 basic medicine ,Immunofixation ,medicine.medical_specialty ,Multiple Sclerosis ,Serum albumin ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Immunoglobulin kappa-Chains ,0302 clinical medicine ,Cerebrospinal fluid ,Nephelometry and Turbidimetry ,Internal medicine ,medicine ,Humans ,Chromatography ,biology ,Chemistry ,Multiple sclerosis ,Oligoclonal Bands ,Albumin ,Gold standard (test) ,medicine.disease ,030104 developmental biology ,Immunoglobulin G ,biology.protein ,Nephelometry ,030217 neurology & neurosurgery ,Kappa ,Biomarkers - Abstract
Background Isoelectrofocusing (IEF) to detect oligoclonal bands (OBCs) in cerebrospinal fluid (CSF) is the gold standard approach for evaluating intrathecal immunoglobulin synthesis in multiple sclerosis (MS) but the kappa free light chain index (KFLCi) is emerging as an alternative marker, and the combined/sequential uses of IEF and KFLCi have never been challenged. Methods CSF and serum albumin, IgG, kFLC and lFLC were measured by nephelometry; albumin, IgG and kFLC quotients as well as Link and kFLC indexes were calculated; OCBs were evaluated by immunofixation. A total of 150 consecutive patients: 48 with MS, 32 with other neurological inflammatory diseases (NID), 62 with neurological non-inflammatory diseases (NNID), and 8 without any detectable neurological disease (NND) were investigated. Results Both IEF and KFLCi showed a similar accuracy as diagnostic tests for multiple sclerosis. The high sensitivity and specificity associated with the lower cost of KFLCi suggested to use this test first, followed by IEF as a confirmative procedure. The sequential use of IEF and KFLCi showed high diagnostic efficiency with cost reduction of 43 and 21%, if compared to the contemporary use of both tests, or the unique use of IEF in all patients. Conclusions The "sequential testing" using KFLCi followed by IEF in MS represents an optimal procedure with accurate performance and lower costs.
- Published
- 2017
18. Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy?
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Lucia Moiola, Marco Capobianco, Ruggero Capra, Chiara Rosa Mancinelli, Nicola De Rossi, Simonetta Gerevini, Cristina Scarpazza, Alessandra Lugaresi, Luca Prosperini, Paola Naldi, Luisa Imberti, Scarpazza, Cristina, Prosperini, Luca, Mancinelli, Chiara R., De Rossi, Nicola, Lugaresi, Alessandra, Capobianco, Marco, Moiola, Lucia, Naldi, Paola, Imberti, Luisa, Gerevini, Simonetta, and Capra, Ruggero
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0301 basic medicine ,Oncology ,Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Immune reconstitution inflammatory syndrome ,Maraviroc ,Natalizumab ,Progressive multifocal leukoencephalopathy ,Brain ,Cyclohexanes ,Female ,Humans ,Immune Reconstitution Inflammatory Syndrome ,Immunologic Factors ,Leukoencephalopathy, Progressive Multifocal ,Longitudinal Studies ,Middle Aged ,Treatment Failure ,Triazoles ,Viral Fusion Protein Inhibitors ,viruses ,Context (language use) ,Progressive Multifocal ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Leukoencephalopathy ,Internal medicine ,medicine ,Adverse effect ,business.industry ,Multiple sclerosis ,Clinical course ,medicine.disease ,Virology ,030104 developmental biology ,chemistry ,Neurology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Despite the recent advances in the understanding of natalizumab (NTZ) related progressive multifocal leukoencephalopathy (PML) and its associated immune reconstitution inflammatory syndrome (PML-IRIS), the therapeutic options are still under investigated. In this context, the beneficial use of maraviroc is still an anecdotal observation. Objective To evaluate the impact of maraviroc in modifying the course of PML preventing IRIS or blunting IRIS manifestations. Methods Three patients with NTZ PML included in the Italian dataset of PML were treated with maraviroc. Their longitudinal clinical and radiological course was described in detail. Results The three patients were characterized by a steady clinical worsening not controlled by maraviroc. All the three patients manifested PML-IRIS, which emerged, respectively, at 62, 64 and 90 days post NTZ withdrawal. This is in accordance with the data of the Italian dataset. Clinical and radiological stabilization of PML-IRIS occurred only after corticosteroids administration. Conclusion In these three cases, maraviroc did not show any clear effect in modulating the clinical course of PML preventing IRIS. Moreover, once PML-IRIS emerged, the clinical stabilization was achieved only with the use of corticosteroids. Thus, the use of maraviroc should be regarded with extreme caution due the potential adverse events associated with its use.
- Published
- 2017
19. Growth Arrest Specific Gene 6 Protein Concentration in Cerebrospinal Fluid Correlates with Relapse Severity in Multiple Sclerosis
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Federica Alciato, Daniele Sola, G.C. Avanzi, Paola Naldi, E. Ranza, Maurizio Leone, Mario Pirisi, Pier Paolo Sainaghi, Rossella Molinari, Francesco Monaco, and Laura Collimedaglia
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Adult ,Male ,Schumacher criteria ,medicine.medical_specialty ,Spinal tap ,Multiple Sclerosis ,Article Subject ,Immunology ,Disease ,medicine.disease_cause ,Gastroenterology ,Autoimmunity ,Cerebrospinal fluid ,Text mining ,Recurrence ,Internal medicine ,lcsh:Pathology ,medicine ,Humans ,business.industry ,Multiple sclerosis ,Cell Biology ,Middle Aged ,medicine.disease ,film.actor ,film ,Clinical Study ,Intercellular Signaling Peptides and Proteins ,Biomarker (medicine) ,Female ,business ,lcsh:RB1-214 - Abstract
Background. Growth arrest specific gene 6 (Gas6) protein enhances survival of oligodendrocytes and neurons, and it is involved in autoimmunity. Therefore, we aimed to verify whether cerebrospinal-fluid (CSF) Gas6 concentration may represent a biomarker of disease activity in multiple sclerosis.Methods. Sixty-five patients who underwent a spinal tap during relapse of relapsing/remitting multiple sclerosis (RR-MS)(McDonald-criteria) were studied. Forty patients affected by noninflammatory/nonautoimmune neurological diseases served as controls. Relapse was defined according to Schumacher criteria. Symptoms were grouped according to Kurtzke-Functional System (FS). Clinical characteristics of the relapse, duration, Expanded-Disability-Status Scale (EDSS) change, number of FS involved, completeness of recovery, age, steroid therapy, were categorised. Patients were followed at 6-month intervals to assess relapse rate and EDSS progression. Gas6 was measured (CSF, plasma) by in-house-enzyme-linked immunoassay (ELISA).Results. Higher CSF Gas6 concentrations were observed in relapses lasting ≤60 days (8.7 ± 3.9 ng/mL) versus >60 days (6.5 ± 2.6) or controls (6.5 ± 2.4;P=0.05), with ≤2 FS involved (8.5 ± 3.8) versus >2 FS (5.6 ± 2.5) (P<0.05) and EDSS change ≤2.5 points (8.8 ± 3.7) versus >2.5 (6.5 ± 3.5) (P=0.04). Conversely, CSF Gas6 was not predictive of the completeness of recovery. Plasma and CSF concentrations were not related (R2=0.0003), and neither were predictive of relapse rate or EDSS progression after first relapse.Conclusions. CSF concentration of Gas6 is inversely correlated with the severity of relapse in RR-MS patients but does not predict the subsequent course of the disease.
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- 2013
20. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
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Per Hall, Simon C. Potter, Richard Reynolds, Robert Heard, Gil McVean, An Goris, Joseph T. Glessner, Pamela Whittaker, Niall Tubridy, Olivier Gout, Ann-Christine Syvaenen, Leena Peltonen, Bénédicte Dubois, Anders Hamsten, Alastair Compston, Hugh S. Markus, Mariaemma Rodegher, Lisa F. Barcellos, Wendy Cozen, Rosetta M. Chiavacci, Jenefer M. Blackwell, William M. Carroll, Patricia P. Ramsay, Amie Baker, Krzysztof Selmaj, Serge Dronov, Zhan Su, C. Smestad, Stanley Hawkins, Janna Saarela, Matti Pirinen, Sabine Cepok, Gavin Band, Norman Klopp, Simon Heath, Sandra D'Alfonso, Peter Donnelly, Ina-Maria Rueckert, Deborah F. Mason, Alagurevathi Jayakumar, Hakon Hakonarson, Cecilia Kim, Colin Freeman, Jeannette Lechner-Scott, Marc Debouverie, Neil Robertson, Inger-Lise Mero, Paola Cavalla, Sabine Roesner, H-Erich Wichmann, Daniele Cusi, Wendy Ingram, Sarah Edkins, Tania Mihalova, Mark J. Daly, Mark Marriott, Roland Martin, Adrian J. Ivinson, Hong L. Quach, Jeremy Hobart, Filippo Martinelli Boneschi, Carmen Infante-Duarte, Catherine Schaefer, Irina Elovaara, Jonathan L. Haines, John Zajicek, Michelle Ricketts, Ananth C. Viswanathan, Colin A. Graham, Allan G. Kermode, Helmut Butzkueven, Kai Wang, John Mottershead, Francesca Taddeo, Stefan Schreiber, Aarno Palotie, Trevor Pickersgill, Naomi Hammond, David A. Hafler, Robert Plomin, Robin R. Lincoln, David Sexton, Jianjun Liu, Finn Sellebjerg, Françoise Clerget-Darpoux, David Brassat, Sarah E. Hunt, Per Soelberg Sørensen, Vittorio Martinelli, Eleni Giannoulatou, Paul I.W. de Bakker, Alexander T. Dilthey, Stephen Leslie, Ulrika Liljedahl, Hanne F. Harbo, Alison Page, Keijo Koivisto, Ingrid Kockum, Stephen L. Hauser, Ewa Tronczynska, Ayman Tourbah, K Baker, Panos Deloukas, Hannah Blackburn, Janusz Jankowski, Mauri Reunanen, Trevor J. Kilpatrick, Sheila Skidmore, Sergio E. Baranzini, Nicholas W. Wood, Fredrik Piehl, Lars Alfredsson, Daniela Galimberti, Federica Esposito, Marco Salvetti, Jennifer Liddle, Jenny Link, Helle Bach Søndergaard, Suzannah Bumpstead, Jonathan P. Bradfield, Richard C. Strange, Céline Bellenguez, David R. Booth, Refujia Gomez, Michael Wittig, Matthew A. Brown, Laura Bergamaschi, Elisabeth Gulowsen Celius, William E R Ollier, Juan P. Casas, Ling Shen, Loukas Moutsianas, Fabio Macciardi, Anne H. Cross, Maja Jagodic, Marie B. D'hooghe, Tomas Olsson, Mark D. Cossburn, O. T. McCann, Justin P. Rubio, Isabelle Cournu-Rebeix, Struan F.A. Grant, Colin N. A. Palmer, Matthew W. Gillman, John D. Rioux, Christopher G. Mathew, Maria Ban, Anna-Maija Sulonen, Garrett Hellenthal, Dorothea Buck, Jorge R. Oksenberg, Frauke Zipp, James Wason, Stephen Sawcer, Franca Rosa Guerini, Clive Hawkins, Cristin Aubin, Elvira Bramon, Paul A. Weston, Andre Franke, Laura Piccio, Jane Vickery, Nikolaos A. Patsopoulos, Jacob L. McCauley, Kristin G. Ardlie, A. Strange, Marcin P. Mycko, Richard C. Trembath, Giancarlo Comi, Gillian Ingram, Graeme J. Stewart, Allan L. Bernstein, Emilie Sundqvist, Xavier Montalban, Juliane Winkelmann, Rhian Gwilliam, Ruggero Capra, Bruce V. Taylor, Maurizio Leone, Brigid Simms-Acuna, Emma J. Davis, Bertrand Fontaine, Chris C. A. Spencer, Malin Larsson, Hans-Peter Hartung, Emma Gray, Virpi M. Leppä, Pablo Villoslada, Audrey Duncanson, Åslaug R. Lorentzen, Rathi Ravindrarajah, Izaura Lima Bomfim, Christian Schulze, Talat Islam, Manuel Comabella, Rita Dobosi, Simon Broadley, Bernhard Hemmer, Margaret A. Pericak-Vance, Jan Hillert, Michael Kabesch, J. Yaouanq, Mark Lathrop, Angelo Ghezzi, Rodney J. Scott, K Dixon, Jean Pelletier, Annette Bang Oturai, Mike Boggild, Philip L. De Jager, Anne Spurkland, M. Perez, Roby Abraham, Pentti J. Tienari, Matthew Waller, Katleen Clysters, Adam Santaniello, David Ellinghaus, Cordelia Langford, Anna Rautanen, Frank D. Mentch, Achim Berthele, Kjell-Morten Myhr, Simon J. Foote, Thomas M. Mack, Bruce A.C. Cree, Susan Pobywajlo, Ernest Willoughby, Haitao Zhang, M. B. Cox, Anu Kemppinen, Muna Hoshi, Sara Widaa, Claire Fontenille, Erika Salvi, Sara Lupoli, Aiden Corvin, Roberto Bergamaschi, Jim Stankovich, Rebecca L. Zuvich, Paola Naldi, Patrick M. A. Sleiman, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, and Faculty of Psychology and Educational Sciences
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Immunity, Cellular/genetics ,Cellular immunity ,Multiple Sclerosis ,Genome-wide association study ,CLEC16A ,Biology ,Polymorphism, Single Nucleotide ,Cell Differentiation/immunology ,Europe/ethnology ,Major Histocompatibility Complex/genetics ,Major Histocompatibility Complex ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,HLA-A Antigens/genetics ,Alleles ,030304 developmental biology ,Genetic association ,Genetics ,0303 health sciences ,Immunity, Cellular ,Multidisciplinary ,HLA-A Antigens ,Genome, Human ,Multiple sclerosis ,Genetic Predisposition to Disease/genetics ,HLA-DR Antigens/genetics ,Lymphocyte differentiation ,Cell Differentiation ,HLA-DR Antigens ,T-Lymphocytes, Helper-Inducer ,RC346 ,medicine.disease ,Polymorphism, Single Nucleotide/genetics ,Genetic architecture ,3. Good health ,Europe ,Sample Size ,Immunology ,Genome, Human/genetics ,Multiple Sclerosis/genetics ,030217 neurology & neurosurgery ,T-Lymphocytes, Helper-Inducer/cytology ,Genome-Wide Association Study ,HLA-DRB1 Chains - Abstract
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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- 2016
21. Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry
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Prosperini, Luca, De Rossi, Nicola, Scarpazza, Cristina, Moiola, Lucia, Cosottini, Mirco, Gerevini, Simonetta, Capra, Ruggero, the Italian PML study group, Maria Pia Amato, Artusi, Carlo Alberto, Fabio, Bandini, Antonio, Bertolotto, Vincenzo, Bresciamorra, Guido, Cavaletti, Paolacavalla, Marco, Capobianco, Clerico, Marinella, Eleonora, Cocco, Giangaetano, D'Aleo, Marilena de Riz, Luciano, Deotto, Durelli, Luca, Mario, Falcini, Eugenio, Ferrari, Maria Luisa Fusco, Claudio, Gasperini, Simonetta, Gerevini, Angelo, Ghezzi, Luigi, Grimaldi, Mario, Guidotti, Alessandra, Lugaresi, Maria Giovanna Marrosu, Lucia, Moiola, Paola, Naldi, Patrizia, Perrone, Matteo, Pizzorno, Carlo, Pozzilli, Monica, Rezzonico, Marco, Rovaris, Giuseppe, Salemi, Marco, Salvetti, Giuseppe, Santuccio, Elio, Scarpini, Edoardo, Sessa, Claudio, Solaro, Giulia, Tabiadon, Carla, Tortorella, Maria, Trojano, and Paola, Valentino
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Male ,Central Nervous System ,Genetics and Molecular Biology (all) ,0301 basic medicine ,Pathology ,Physiology ,viruses ,JC virus ,lcsh:Medicine ,Medicine (all) ,Biochemistry, Genetics and Molecular Biology (all) ,Agricultural and Biological Sciences (all) ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Nervous System ,Biochemistry ,Diagnostic Radiology ,Leukoencephalopathy ,0302 clinical medicine ,Natalizumab ,Medicine and Health Sciences ,Ethnicities ,lcsh:Science ,Immune Response ,Cerebrospinal Fluid ,Multidisciplinary ,Cognitive Neurology ,Radiology and Imaging ,Progressive multifocal leukoencephalopathy ,Leukoencephalopathy, Progressive Multifocal ,Middle Aged ,JC Virus ,Magnetic Resonance Imaging ,Body Fluids ,Italian People ,Survival Rate ,Neurology ,Female ,Anatomy ,medicine.symptom ,Research Article ,medicine.drug ,Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Imaging Techniques ,Cognitive Neuroscience ,Immunology ,Progressive Multifocal ,Research and Analysis Methods ,Asymptomatic ,Disease-Free Survival ,Humans ,Retrospective Studies ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Internal medicine ,medicine ,Survival rate ,Inflammation ,Expanded Disability Status Scale ,business.industry ,Multiple sclerosis ,lcsh:R ,Biology and Life Sciences ,medicine.disease ,030104 developmental biology ,People and Places ,Lesions ,Cognitive Science ,Population Groupings ,lcsh:Q ,business ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Background The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV). Objective To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions. Methods An Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated. Results Ten patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values
- Published
- 2016
22. Association of HLA class I markers with multiple sclerosis in the Italian and UK population: evidence of two independent protective effects
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Valeria Bargiggia, Patricia Momigliano-Richiardi, Maurizio Leone, Rosella Mechelli, Marco Salvetti, Susanna Cordera, Maria Edvige Fasano, Daniela Ferrante, Domenico Caputo, Sandra D'Alfonso, Elio Scarpini, Daniela Galimberti, Lucia Corrado, Paola Naldi, Ennia Dametto, Cristina Agliardi, Paola Cavalla, Franca Rosa Guerini, Laura Bergamaschi, Maria Ban, Francesco Monaco, and Nadia Barizzone
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Adult ,Male ,Linkage disequilibrium ,Multiple Sclerosis ,Population ,Human leukocyte antigen ,Biology ,Young Adult ,Gene Order ,Genetics ,Humans ,Genetic Predisposition to Disease ,Allele ,education ,Alleles ,Genetic Association Studies ,Genetics (clinical) ,Genetic association ,education.field_of_study ,Histocompatibility Antigens Class I ,HLA-DR Antigens ,Middle Aged ,United Kingdom ,HLA-B ,HLA-A ,Gene Expression Regulation ,Haplotypes ,Italy ,Case-Control Studies ,Immunology ,Cohort ,Female - Abstract
Background The association of HLA A*02 with multiple sclerosis (MS) was recently confirmed by the authors, and it was observed that the combined presence of HLA Cw*05 significantly enhanced (threefold) the protective effect of HLA A*02 . Objectives and methods Since A*02 - Cw*05 is carried by two HLA extended haplotypes characterised by the B*4402 and B*1801 alleles, respectively, the association analysis was extended to HLA B*44 and B*18 in an Italian sample (1445 MS cases and 973 controls) and these associations were verified in a UK cohort (721 MS cases, 408 controls and 480 family trios). Results A strong protective effect, independent of DR15 , of the A*02 - Cw*05 combination carrying B*44 (OR 0.27, p=3.3×10 -5 ) was seen in the Italian samples and confirmed in UK family trios (OR 0.33, p=5.5×10 -4 ) and in a combined cohort of UK families and case–controls (OR 0.53, p=0.044). This protective effect was significantly stronger than that mediated by A*02 alone. Logistic regression showed that A*02 - Cw*05 maintained a significant protection when adjusted for B alleles (Italy: OR 0.38, p=6.5×10 -7 ; UK: OR 0.60, p=0.0029), indicating that it was not secondary to linkage disequilibrium with B*44 . Different from A*02 , the other HLA class I tested markers individually showed no significant ( Cw*05 , B*18) or a modest (B*44) protection when adjusted for the remaining markers. Conclusions This study identified at least two independent protective effects which are tagged by A*02–Cw*05 and A*02 , respectively. Further studies are needed to elucidate whether this protective effect is due to the presence of an unanalysed factor characterising the HLA extended haplotype(s) carrying A*02 and Cw*05 or to a direct interaction between these alleles.
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- 2011
23. HLA-class I markers and multiple sclerosis susceptibility in the Italian population
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Nadia Barizzone, Laura Bergamaschi, Daniela Ferrante, Roberto Bergamaschi, Patricia Momigliano-Richiardi, Cristina Agliardi, Sandra D'Alfonso, Marco Vercellino, Elisabetta Bolognesi, Maurizio Leone, Maria Edvige Fasano, Franca Rosa Guerini, Lucia Corrado, Paola Naldi, Andrea Visconti, Ennia Dametto, Elio Scarpini, Daniela Galimberti, Francesco Monaco, Domenico Caputo, and Marco Salvetti
- Subjects
Genetic Markers ,Linkage disequilibrium ,medicine.medical_specialty ,extended hla haplotypes ,genetic association ,Immunology ,myelin oligodendrocyte glycoprotein ,Biology ,multiple sclerosis ,Gastroenterology ,Linkage Disequilibrium ,Population Groups ,Risk Factors ,Internal medicine ,Odds Ratio ,Genetics ,medicine ,Humans ,Allele ,Risk factor ,Alleles ,Genetics (clinical) ,Genetic association ,HLA-A Antigens ,Multiple sclerosis ,Haplotype ,hla-class i markers ,Original Articles ,Odds ratio ,medicine.disease ,Confidence interval ,Myelin-Associated Glycoprotein ,Haplotypes ,Italy ,Myelin-Oligodendrocyte Glycoprotein ,Disease Susceptibility ,Myelin Proteins - Abstract
Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51-0.72, P10(-9)), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI=0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI=0.58-0.83) with a significant (P=4.94 x 10(-5)) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR=3.89, P=0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.
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- 2009
24. Cortico-motoneurone excitability in patients with obstructive sleep apnoea
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Carlo Civardi, Paola Naldi, and Roberto Cantello
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Adult ,Male ,Cognitive Neuroscience ,medicine.medical_treatment ,Body Mass Index ,Pharyngeal muscles ,Magnetics ,Behavioral Neuroscience ,medicine ,Humans ,Latency (engineering) ,Hypoxia ,Cerebral Cortex ,Motor Neurons ,Sleep Apnea, Obstructive ,musculoskeletal, neural, and ocular physiology ,Snoring ,Eye movement ,Electroencephalography ,General Medicine ,Evoked Potentials, Motor ,Sleep in non-human animals ,Cortex (botany) ,Oxygen ,Transcranial magnetic stimulation ,medicine.anatomical_structure ,Anesthesia ,Pharynx ,Female ,Silent period ,Abnormality ,Arousal ,Psychology - Abstract
A disordered neuromotor control of pharynx muscles may play a role in the genesis of obstructive sleep apnoea syndrome (OSAS). This raises the possibility of a dysfunction of projections descending from the cortex to segmental nuclei. With single pulse transcranial magnetic stimulation (TMS) we studied the physiology of the corticospinal projection to hand muscles in seven OSAS patients. At first, we compared them with nine age- and sex-matched normal controls in the wake state. The only abnormality was a lengthening of the central silent period (P < 0.001). This supports a steady imbalance of motor cortical interneurone activities towards a state of enhanced inhibition. Then we looked at changes of the motor-evoked potential (MEP) size and latency, according to whether patients were awake, or in a non-rapid eye movement (REM) 2 sleep stage, or during a typical apnoea. During non-REM 2 sleep, the average MEP amplitude was significantly (P < 0.05) smaller than in the awake state. The MEP latency was, in turn, significantly longer (P < 0.05). During apnoeas, the MEP size decreased, and the latency increased further (P < 0.05), indicating an extra depression of the cortico-motoneuronal activity. All TMS changes were detected outside the pharyngeal district, suggesting a widespread dysfunction of the cortico-motoneuronal system in the OSAS, which is more evident during apnoeas.
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- 2004
25. Identification of single nucleotide variations in the coding and regulatory regions of the myelin-associated glycoprotein gene and study of their association with multiple sclerosis
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Patricia Momigliano-Richiardi, Sandra D'Alfonso, Domenico Caputo, Mara Giordano, Maria Liguori, Paola Naldi, Alessandro Pastore, Giovanni Savettieri, Stefania Cannoni, Giulia Malferrari, Clara Milanese, Anna Maria Repice, and Marta Mellai
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Adult ,Male ,Heterozygote ,Multiple Sclerosis ,5' Flanking Region ,Immunology ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Denaturing high performance liquid chromatography ,Gene Frequency ,medicine ,Humans ,Immunology and Allergy ,SNP ,Gene ,Chromatography, High Pressure Liquid ,Genetic association ,Genetics ,Myelin-associated glycoprotein ,Multiple sclerosis ,Middle Aged ,medicine.disease ,Molecular biology ,Myelin-Associated Glycoprotein ,Neurology ,Regulatory sequence ,Female ,Neurology (clinical) ,Chromosomes, Human, Pair 19 - Abstract
The myelin-associated glycoprotein (MAG) gene is an appealing candidate in the 19q13 Multiple Sclerosis (MS) candidate region. Using denaturing high performance liquid chromatography (DHPLC), we identified 14 single nucleotide polymorphisms (SNPs) in MAG coding and regulatory regions, and we tested their possible association with MS in Italian patient and control DNA pools. Eight variations had a frequency
- Published
- 2002
26. Corrigendum to 'Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy?' [J. Neurol. Sci. 378 (2017) 233–237]
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Luisa Imberti, L. Prosperini, Lucia Moiola, Alessandra Lugaresi, Cristina Scarpazza, Paola Naldi, N. De Rossi, Ruggero Capra, Chiara Rosa Mancinelli, Marco Capobianco, and Simonetta Gerevini
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medicine.medical_specialty ,business.industry ,Multiple sclerosis ,Progressive multifocal leukoencephalopathy ,medicine.disease ,Dermatology ,chemistry.chemical_compound ,Natalizumab ,Neurology ,chemistry ,Medicine ,Neurology (clinical) ,business ,Maraviroc ,medicine.drug - Published
- 2017
27. Network-based multiple sclerosis pathway analysis with GWAS data from 15,000 cases and 30,000 controls
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Bertrand Fontaine, Safa Saker-Delye, Malin Larsson, Kjell-Morten Myhr, Lena Guillot-Noel, Frauke Zipp, Graeme J. Stewart, Pouya Khankhanian, Bernhard Hemmer, Anders Hamsten, Per Hall, Finn Sellebjerg, Isabelle Cournu-Rebeix, Juliane Winkelmann, Nadia Barizzone, Bénédicte Dubois, Adrian J. Ivinson, David A. Hafler, An Goris, Lennox Din, Philip DeJager, Alastair Compston, Vincent Damotte, Stephen Sawcer, Janna Saarela, Giancarlo Comi, Stephen L. Hauser, Bruce V. Taylor, Maurizio Leone, Christina M. Lill, Anne Spurkland, Anu Kemppinen, David R. Booth, Keijo Koivisto, Maria Ban, Sandra D'Alfonso, Paola Naldi, Jorge R. Oksenberg, Fabio Macciardi, Helle Bach Søndergaard, Per Soelberg Sørensen, Jonathan L. Haines, Dorothea Buck, Tomas Olsson, Annette Bang Oturai, Andre Franke, Ingrid Kockum, F. Martinelli-Boneschi, Pentti J. Tienari, Vittorio Martinelli, Margaret A. Pericak-Vance, Jan Hillert, Federica Esposito, Laura Bergamaschi, Elisabeth Gulowsen Celius, Jim Stankovich, Roland Martin, Marco Salvetti, Pierre-Antoine Gourraud, Manuel Comabella, Mark Lathrop, Franco Perla, Chris Cotsapas, Hakon Hakonarson, Christiane Graetz, Nikolaos A. Patsopoulos, Mauri Reunanen, Michael Li, Paola Cavalla, Sergio E. Baranzini, Jacob L. McCauley, Franca Rosa Guerini, Irina Elovaara, Hanne F. Harbo, Zipp, F, Ivinson, A. J, Haines, J. L, Sawcer, S, Dejager, P, Hauser, S. L, Oksenberg, J. R, and Comi, Giancarlo
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TRAF3 ,Risk ,Linkage disequilibrium ,Multiple Sclerosis ,network-based multiple sclerosis pathway ,gwas ,genome-wide association ,disease genes ,Genome-wide association study ,Human leukocyte antigen ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,SNP ,Humans ,Genetic Predisposition to Disease ,Protein Interaction Maps ,Gene ,Genetics (clinical) ,030304 developmental biology ,Genetic association ,0303 health sciences ,Models, Genetic ,Multiple sclerosis ,Epistasis, Genetic ,medicine.disease ,Genetic Loci ,Case-Control Studies ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Multiple sclerosis (MS) is an inflammatory CNS disease with a substantial genetic component, originally mapped to only the human leukocyte antigen (HLA) region. In the last 5 years, a total of seven genome-wide association studies and one meta-analysis successfully identified 57 non-HLA susceptibility loci. Here, we merged nominal statistical evidence of association and physical evidence of interaction to conduct a protein-interaction-network-based pathway analysis (PINBPA) on two large genetic MS studies comprising a total of 15,317 cases and 29,529 controls. The distribution of nominally significant loci at the gene level matched the patterns of extended linkage disequilibrium in regions of interest. We found that products of genome-wide significantly associated genes are more likely to interact physically and belong to the same or related pathways. We next searched for subnetworks (modules) of genes (and their encoded proteins) enriched with nominally associated loci within each study and identified those modules in common between the two studies. We demonstrate that these modules are more likely to contain genes with bona fide susceptibility variants and, in addition, identify several high-confidence candidates (including BCL10, CD48, REL, TRAF3, and TEC). PINBPA is a powerful approach to gaining further insights into the biology of associated genes and to prioritizing candidates for subsequent genetic studies of complex traits.
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- 2013
28. Predictors of attack severity and duration in multiple sclerosis: a prospective study
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Alessandro Stecco, F Perl, M. G. Rosso, Laura Collimedaglia, Maurizio Leone, Francesco Monaco, Paola Naldi, and Domizia Vecchio
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Pediatrics ,medicine.medical_specialty ,Multivariate analysis ,Season of birth ,macromolecular substances ,Article ,Multiple sclerosis ,Recovery ,medicine ,Relapse ,Prospective cohort study ,Severity ,business.industry ,Odds ratio ,Attack ,medicine.disease ,Prognosis ,Functional system ,Confidence interval ,Psychiatry and Mental health ,Duration ,Neurology ,Duration (music) ,Neurology (clinical) ,Course ,business - Abstract
Objective: To evaluate predictors of severity and duration of early Multiple Sclerosis (MS) attacks. Methods: We analyzed 248 attacks in 95 patients in a prospective study. Severity: the difference between the EDSS score at the day of maximum worsening and the EDSS score before the onset of the attack. Duration: the time between the date of onset of the first symptom and the date of maximum improvement of the last symptom. Results: The number of involved Functional Systems (FS), FS type (brainstem and pyramidal), and total attack duration were linked to severity. Number of FS involved, FS type (sphincteric and sensory), and severity of the attack were related to duration. Neither severity nor duration were correlated to other predictors: gender, age and season at attack onset, speed of onset, infections in the preceding month, age at first attack, season of birth and first attack, CSF examination, first brain MRI, recovery from the first attack. In the multivariate analysis, the Odds Ratio (OR) and Confidence Intervals (CI) for severe attacks was 3.6, 1.7-7.7 for involvement of pyramidal FS, 2.6, 1.2-6.0 for brainstem and 2.5, 1.2-5.3 for long attack duration. Sphincteric (4.4; 1.7-11.0) and sensory FS (1.8; 1.0-3.2) were the only variables explaining duration. The prob- ability of a second moderate/severe or long attack was not influenced by severity or duration of the first. Conclusions: FS are predictive of severity and duration of early MS attacks. Severity and duration of the first attack do not predict severity and duration of the second.
- Published
- 2011
29. Severe rebound of spinal cord multiple sclerosis activity after fingolimod withdrawal
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Maurizio Leone, Alessandro Stecco, Domizia Vecchio, Paola Naldi, and Roberto Cantello
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business.industry ,Multiple sclerosis ,Immunology ,Neuroscience (miscellaneous) ,medicine.disease ,Spinal cord ,Fingolimod ,medicine.anatomical_structure ,Immunology and Microbiology (miscellaneous) ,Anesthesia ,medicine ,Neurology (clinical) ,business ,medicine.drug - Published
- 2014
30. The expression pattern of inflammatory mediators in cerebrospinal fluid differentiates Guillain-Barré syndrome from chronic inflammatory demyelinating polyneuropathy
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Pier Paolo Sainaghi, Federica Alciato, Laura Collimedaglia, Paola Naldi, Rossella Molinari, Maurizio Leone, Gian Carlo Avanzi, and Francesco Monaco
- Subjects
Adult ,Immunology ,Chronic inflammatory demyelinating polyneuropathy ,CCL2 ,Guillain-Barre Syndrome ,Hematopoietic Cell Growth Factors ,Biochemistry ,Cerebrospinal fluid ,Immunology and Allergy ,Medicine ,Humans ,Molecular Biology ,Guillain-Barre syndrome ,business.industry ,Hepatocyte Growth Factor ,Interleukin-8 ,Polyradiculoneuropathy ,Hematology ,medicine.disease ,CXCL1 ,Interleukin 1 Receptor Antagonist Protein ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,CXCL9 ,CCL27 ,Inflammation Mediators ,business - Abstract
Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) share histopathological features but display different disease courses; we measured the concentration of 50 inflammatory mediators in the cerebrospinal fluid (CSF) of patients with either of these diseases.CSF samples were collected during a diagnostic lumbar puncture and stored at -30 degrees C. We analyzed the CSF of nine subjects with GBS; eight with CIDP; eight with diabetic polyneuropathy (DP) and seven with headache (controls). Fifty inflammatory mediators were simultaneously measured with a multiplex bead-based ELISA on a Suspension Array System. After Bonferroni's correction for repeated measures, non-parametric variance and post hoc test were calculated.Thirty-two inflammatory mediators were expressed. The median concentration of IL-6, IL-9, IL-15, IL-18, CCL4, CXCL1, LIF, MIF, PDGFbb, IFN-gamma2, IL-2ra, IL-12(p40), IL-16, SCGF-b, TRAIL, FGF, G-CSF, GM-CSF, and M-CSF was not different among groups (variance: n.s.). The median concentration of CCL2, CCL7, CCL27, CXCL9, CXCL10, CXCL12, ICAM-1, VCAM1 and VEGF was higher in CIDP and GBS compared with controls (p0.002). The median concentration of IL-8 and IL-1ra was higher in GBS than CIDP or DP or controls, whereas stem cell factor (SCF) and hepatocyte growth factor (HGF) were higher in CIDP than GBS or DP or controls (p0.002).Mediators of the recruitment and activation of lymphocytes and monocytes are expressed in the CSF of CIDP and GBS. IL-8 and IL-1ra are characteristic of GBS, whereas growth factors (SCF, HGF) of CIDP are possibly related to chronicity or to the survival/repair processes of neurons.
- Published
- 2009
31. Responsiveness of patient reported outcome measures in multiple sclerosis relapses: the REMS study
- Author
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Eugenio Pucci, Laura Mendozzi, Loredana La Mantia, Giorgio Giuliani, Alessandra Solari, Clara Milanese, Federica Tronci, Maurizio Leone, Andrea Giordano, N. Mascoli, and Paola Naldi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Longitudinal study ,Multiple Sclerosis ,Exacerbation ,Adolescent ,Health Status ,Emotions ,Anti-Inflammatory Agents ,Disability Evaluation ,Young Adult ,Cohen's kappa ,Quality of life ,Recurrence ,medicine ,Humans ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Expanded Disability Status Scale ,Receiver operating characteristic ,business.industry ,Middle Aged ,Psychiatry and Mental health ,Mental Health ,Treatment Outcome ,ROC Curve ,Injections, Intravenous ,Physical therapy ,Quality of Life ,Surgery ,Patient-reported outcome ,Female ,Steroids ,Neurology (clinical) ,business ,Follow-Up Studies - Abstract
Objectives: To assess the responsiveness of the three most used patient reported multiple sclerosis (MS) specific questionnaires: the Functional Assessment of MS (FAMS), the MS Impact Scale (MSIS-29) and the 54 item MS Quality of Life (MSQOL-54). Design: Prospective multicentre longitudinal study on 104 MS patients treated with intravenous steroids for clinical exacerbation. Methods: Patient reported data, Expanded Disability Status Scale (EDSS) score and clinical information were collected at admission and 8 weeks later. “Internal” (distribution based) responsiveness was assessed by standardised response means (SRM). “External” (anchor based) responsiveness was assessed by receiver operating characteristic (ROC) curves in relation to corresponding changes in a pre-specified reference measure (anchor). The pre-specified anchor was patients’ self-reported recovery assessed on a 5 point Likert scale. Results: SRM was 0.39 for FAMS, 0.58 for MSIS-29 physical scale, 0.45 for MSIS-29 psychological scale, 0.71 for MSQOL-54 physical health composite and 0.57 for MSQOL-54 mental health composite. Seventy-three patients (70%) reported they had improved; physicians agreed substantially with patient assessments (kappa statistic 0.70, 95% CI 0.54 to 0.85). Areas under ROC curves differed significantly from 0.50 only for the MSIS-29 and MSQOL-54 scales where areas ranged from 0.65 (95% CI 0.53 to 0.76) for the MSIS-29 psychological scale to 0.70 (95% CI 0.58 to 0.81) for the MSQOL-54 mental health composite. Areas under ROC curves assessed using a physician based anchor were similar to the patient based areas. Conclusions: The responsiveness of the MS specific instruments was less than ideal. The MSIS-29 and MSQOL-54 were significantly more responsive, using both distribution based and anchor based approaches, than FAMS, and should be preferred in longitudinal studies.
- Published
- 2009
32. Factors predicting incomplete recovery from relapses in multiple sclerosis: a prospective study
- Author
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Fabiana Tesser, Laura Collimedaglia, Francesco Monaco, Maurizio Leone, S. Calzoni, Sara Bonissoni, Alessandro Stecco, and Paola Naldi
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Every Six Months ,Season of birth ,Severity of Illness Index ,Central nervous system disease ,Degenerative disease ,Multiple Sclerosis, Relapsing-Remitting ,Predictive Value of Tests ,Recurrence ,Risk Factors ,medicine ,Humans ,Prospective Studies ,Age of Onset ,Sex Distribution ,Prospective cohort study ,Clinically isolated syndrome ,business.industry ,Multiple sclerosis ,Oligoclonal Bands ,Recovery of Function ,medicine.disease ,Magnetic Resonance Imaging ,Surgery ,Logistic Models ,Neurology ,Cohort ,Female ,Neurology (clinical) ,Seasons ,business ,Follow-Up Studies - Abstract
Objective To prospectively evaluate predictors of incomplete recovery after the first attacks in a cohort of patients with clinically isolated syndrome or relapsing—remitting multiple sclerosis. Methods Seventy-two consecutive patients recruited from January 2001 to December 2003, evaluated every six months or at any relapse up to 31 July 2005. Relapse intervals were calculated from the date of onset, nadir, onset of improvement and maximum improvement. Predictive factors analysed were relapse-related (age at relapse onset, season and severity of the relapse, type of symptoms, speed of onset, plateau and total duration, number of affected Functional systems, preceding infections) and individual-related (gender, age at first attack, season of birth and first attack, characteristics of first brain MRI and cerebrospinal fluid oligoclonal bands, Link Index, IgG). Results We counted 209 attacks: 44 (21%) left mild sequelae, and 27 (13%) severe. The highest probability of sequelae was associated with sphincteric symptoms (9/20; 45%), followed by sensitive (38/113; 34%), motor (20/84; 24%), visual (13/61; 21%), cerebellar (4/24; 17%), brainstem (5/44; 11%) and others (0/6) ( P 0.005). Four variables were still relevant to predict sequelae after multivariate analysis: mild, moderate or severe relapses versus very mild (Odds ratio = 17.2, 95% confidence limits = 2.2—136.4), intermediate or long relapses versus short (3.2, 1.5—6.9), age ≥ 30 at relapse onset (2.9, 1.5—5.7) and bi-polysymptomatic versus monosymptomatic (2.2, 1.1—4.3). Conclusions Factors predicting incomplete recovery are more closely linked to the characteristics of the single relapse (extension and duration of tissue damage) than to the patient's genetic and environmental background. Multiple Sclerosis 2008; 14: 485—493. http://msj.sagepub.com
- Published
- 2008
33. Elevation of Gas6 protein concentration in cerebrospinal fluid of patients with chronic inflammatory demyelinating polyneuropathy (CIDP)
- Author
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Maurizio Leone, Gian Carlo Avanzi, Laura Collimedaglia, Pier Paolo Sainaghi, Paola Naldi, Erinda Puta, Francesco Monaco, Luigi Mario Castello, and Federica Alciato
- Subjects
Adult ,Male ,medicine.medical_specialty ,Chronic inflammatory demyelinating polyneuropathy ,Enzyme-Linked Immunosorbent Assay ,medicine.disease_cause ,Guillain-Barre Syndrome ,Gastroenterology ,Autoimmunity ,Myelin ,Cerebrospinal fluid ,Internal medicine ,medicine ,Humans ,Stroke ,Aged ,Retrospective Studies ,Aged, 80 and over ,Guillain-Barre syndrome ,business.industry ,Reproducibility of Results ,Polyradiculoneuropathy ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Neurology ,Gene Expression Regulation ,Polyradiculoneuropathy, Chronic Inflammatory Demyelinating ,Immunology ,Intercellular Signaling Peptides and Proteins ,Regression Analysis ,Female ,Neurology (clinical) ,business ,Polyneuropathy - Abstract
Gas6 enhances survival of Schwann cells and neurons in vitro and participates in autoimmunity in animal models. Since its concentration in human cerebrospinal fluid (CSF) is unknown, we measured it in samples from patients with non-inflammatory/non-autoimmune neurological diseases (NINAD) and autoimmune polyneuropathies.Samples collected after informed consent during diagnostic lumbar puncture in the period 1999-2006 were stored at -30 degrees C. We considered subjects with NINAD (stroke, ALS, headache, psychiatric conditions simulating neurological diseases, otologic dizziness) or with Guillain-Barré syndrome (GBS) or CIDP. CSF and plasma total protein and age were obtained from clinical records. Gas6 was measured with an ELISA developed and validated in our laboratory (inter-, intra-assay CVs10%, recovery 96%). Variance, Tukey's post-hoc test, regression were calculated with a statistical software (Statsoft).Mean Gas6 concentration in patients with NINAD was 6.5+/-2.4 ng/ml, 7.2+/-2.6 ng/ml in GBS and significantly higher (11.5+/-1.7 ng/ml) in CIDP than in the other conditions (post-hoc, p0.005). It was not related to age, CSF total proteins or to CSF/plasma ratio of total proteins (regression, p0.1).Gas6 is detectable in CSF and may be involved in chronic autoimmune demyelination or myelin repair.
- Published
- 2007
34. A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy
- Author
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Domenico Caputo, Cristina Agliardi, Daniela Ferrante, Maurizio Leone, Sandra D'Alfonso, Luca Massacesi, Marco Salvetti, S Bocca, Elisabetta Bolognesi, Franca Rosa Guerini, Maria Trojano, Patricia Momigliano-Richiardi, Laura Bergamaschi, Daniela Galimberti, Luca Castelli, Paola Naldi, Nadia Barizzone, Pasquale Ferrante, and Clara Ballerini
- Subjects
Genetic Markers ,Male ,Candidate gene ,Multiple Sclerosis ,Immunology ,Single-nucleotide polymorphism ,Human leukocyte antigen ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Myelin oligodendrocyte glycoprotein ,Gene Frequency ,HLA Antigens ,Genetics ,Humans ,Family ,Genetic Predisposition to Disease ,Allele ,Indel ,Genetics (clinical) ,Alleles ,biology ,Genetic Variation ,Transmission disequilibrium test ,Genotype frequency ,Pedigree ,Myelin-Associated Glycoprotein ,Logistic Models ,Italy ,Case-Control Studies ,biology.protein ,Female ,Myelin-Oligodendrocyte Glycoprotein ,Myelin Proteins ,Microsatellite Repeats - Abstract
Several studies suggest that the histocompatibility complex (HLA) class I region harbours genes modulating multiple sclerosis (MS) susceptibility independently from the effect of class II alleles. A candidate gene in this region is MOG, encoding the myelin oligodendrocyte glycoprotein. A significant association with the missense variation V142L (rs2857766) was previously reported in a small sample of 50 Italian MS patients. We confirmed this result in two independent Italian sample sets consisting of 878 MS patients and 890 matched controls (P=6.6 x 10(-4)) and 246 trio families (P=1.5 x 10(-3)). The comparison of genotype frequencies suggested a dominant-protective effect of L142. In the combined sample sets L142 conferred an odds ratio (OR)=0.70 (95% confidence interval (CI): 0.60-0.82) that remained similar after accounting for HLA-DRB1(*)15 carrier status. The association with MOG V142L was still significant after conditioning for all DRB1 alleles (P=0.035). Eleven additional single nucleotide polymorphisms in the MOG gene (namely -1077T/C, -910T/C, -875A/G, -93T/C, S5S, Indel L22, V145I, +814C/T, +900A/G, +1024A/T, +1059C/T), two microsatellites in the MOG 5' flanking (MOGCA) and 3' untranslated (MOGTAAA) regions and four microsatellites in the HLA-class I region, from HLA-B to HFE, (namely MIB, D6S265, D6S1683 and D6S2239) were tested by transmission disequilibrium test in 199 trio families. None of these polymorphisms or of their haplotypic combinations showed a significant transmission distortion, in the absence of V142L. In conclusion, MOG V142L, or an untested variant in tight-linkage disequilibrium with it, is an independent MS susceptibility-modulating factor in the HLA class I region.
- Published
- 2007
35. Candidate gene analysis of SPARCL1 gene in patients with multiple sclerosis
- Author
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Cristoforo Comi, Francesca Cortini, Francesco Monaco, Mirko Piola, Chiara Villa, Diego Scalabrini, Daniela Galimberti, Paola Naldi, Eliana Venturelli, Chiara Fenoglio, Nereo Bresolin, Milena De Riz, Elio Scarpini, Scalabrini, D, Fenoglio, C, Scarpini, E, De Riz, M, Comi, C, Venturelli, E, Cortini, F, Piola, M, Villa, C, Naldi, P, Monaco, F, Bresolin, N, and Galimberti, D
- Subjects
Adult ,Genetic Markers ,Male ,Multiple Sclerosis ,Genotype ,SPARCL1 ,Population ,DNA Mutational Analysis ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,DNA Mutational Analysi ,Exon ,Sex Factors ,Gene Frequency ,Single nucleotide polymorphism (SNP) ,Polymorphism (computer science) ,Genetic Marker ,Multiple Sclerosi ,Haplotype ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Sex Distribution ,education ,Allele frequency ,Calcium-Binding Protein ,education.field_of_study ,Extracellular Matrix Proteins ,Base Sequence ,General Neuroscience ,Calcium-Binding Proteins ,Extracellular Matrix Protein ,Middle Aged ,Multiple sclerosis (MS) ,Molecular biology ,Genotype frequency ,Amino Acid Substitution ,Haplotypes ,Female ,Human - Abstract
Recently, proteomic analysis in cerebrospinal fluid (CSF) from patients with MS identified four proteins which are present in MS but not in normal human CSF, including SPARCL1, an extracellular matrix-associated protein member of the SPARC family. One hundred eighty-six patients with MS and 185 age-matched controls were genotyped for A/G single nucleotide polymorphism (SNP) in exon 1 (rs1049539), C/G SNP in exon 4 (rs1049544), resulting in a substitution of an aspartate with an histidine, and A/G substitution in the exon 5 (rs1130643), leading to the substitution of alanine with threonine. No significant differences in either allelic or genotypic frequency of the three SNPs were found (P > 0.05), even in stratifying MS patients according to the course of the disease. Stratifying according to gender, a trend towards a decreased frequency of the C/C genotype of the rs1049544 was observed in male patients as compared with male controls (30.2% versus 44.0%; P = 0.217). Despite proteomic studies in CSF from MS patients suggested an important role for SPARCL1 in the development of the disease, SPARCL1 gene does not appear to act as susceptibility factor for MS in the population investigated here. However, the frequency of the C/C genotype of rs1049544 was decreased in male patients, possibly conferring a lower risk of developing MS in male population. Further studies are needed to clarify this issue. © 2007 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2007
36. Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis
- Author
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Eleonora Tavazzi, Giovanni Piccolo, Elisabetta Zardini, Mauro Ceroni, Sabrina Ravaglia, Alfredo Romani, Paola Naldi, Laura Andreoni, Diego Franciotta, Roberto Bergamaschi, and Enrico Marchioni
- Subjects
Adult ,Male ,Chemokine ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Encephalomyelitis ,Blotting, Western ,CCL1 ,Statistics, Nonparametric ,Cerebrospinal fluid ,CSF pleocytosis ,Medicine ,CCL17 ,Humans ,Aged ,biology ,business.industry ,Encephalomyelitis, Acute Disseminated ,respiratory system ,Middle Aged ,medicine.disease ,Cytokine ,Neurology ,Acute disseminated encephalomyelitis ,Immunology ,biology.protein ,Cytokines ,Female ,Neurology (clinical) ,Chemokines ,business - Abstract
Cytokines and chemokines contribute to the pathogenesis of acute disseminated encephalomyelitis (ADEM). Using a multiplex immunochemiluminescence ELISA, we measured 8 Th1/Th2 cytokines and 18 chemokines in the cerebrospinal fluid (CSF) and serum of 17 ADEM patients, 14 multiple sclerosis (MS) patients, and 7 healthy controls (HCs). Relative to HCs, ADEM patients had significantly high mean CSF concentrations of chemokines with attractant/activating properties towards neutrophils (CXCL1 and CXCL7), monocytes/T cells (CCL3 and CCL5), Th1 cells (CXCL10), and Th2 cells (CCL1, CCL22, and CCL17). Mean CSF concentrations of CXCL7, CCL1, CCL22, and CCL17 were higher in ADEM than in MS, whereas those of CCL11 were lower in MS than in ADEM and HCs. CSF pleocytosis correlated with CSF concentrations of CXCL1, CXCL10, CCL1, CCL17, and CCL22. Most of the functionally homologous chemokines correlated with each other. CSF Th1/Th2 cytokines were not detectable in most samples. Their mean concentrations did not differ in the three groups, and the same held for serum cytokines and chemokines. Our data suggest that the upregulation of chemokines active on neutrophils and Th2 cells differentiates ADEM from MS inflammation, and that both Th1 and Th2 chemokines might be produced in ADEM. Chemokines upregulated in ADEM could become CSF biomarkers after a posteriori evaluations in unselected case series.
- Published
- 2006
37. Progression of MRI abnormalities in herpes simplex encephalitis despite clinical improvement: natural history or disease progression?
- Author
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E. Macchiarulo, Paola Gaviani, Marco Mula, Paola Naldi, D. Brustia, Maurizio Leone, and Francesco Monaco
- Subjects
Pediatrics ,medicine.medical_specialty ,Neurology ,Acyclovir ,Dermatology ,Herpesvirus 1, Human ,Neuropsychological Tests ,Antiviral Agents ,Cerebrospinal fluid ,Cognition ,medicine ,Humans ,Neuroradiology ,Aged ,Cerebral Cortex ,medicine.diagnostic_test ,business.industry ,Mortality rate ,Magnetic resonance imaging ,General Medicine ,medicine.disease ,Virology ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,Cohort ,DNA, Viral ,Nerve Degeneration ,Disease Progression ,Female ,Neurology (clinical) ,Neurosurgery ,Encephalitis, Herpes Simplex ,business ,Encephalitis - Abstract
Herpes simplex virus encephalitis (HSVE) is associated with a high mortality rate and a high probability of neurological sequelae. Good results are obtained when HSVE is promptly diagnosed and treated with acyclovir. We present a 71-year-old woman with clinically diagnosed HSVE, confirmed by PCR detection of HSV-1 DNA in the cerebrospinal fluid. She was treated with acyclovir (30 mg/kg day) for two weeks. Clinical and neuropsychological assessments 6 months after admission were normal; however MRI at 2, 6 and 12 months showed progressive deterioration with extensive white matter and cortical damage. Imaging studies of a cohort of patients surviving PCR-confirmed HSVE are needed to determine whether this pattern is occasional or a frequent form of progression.
- Published
- 2004
38. Churg-Strauss syndrome associated with the leukotriene antagonist montelukast
- Author
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S. Colombi, Fabiana Tesser, Paola Naldi, C. Boccagni, Francesco Monaco, E. Zoppis, Daniela Mittino, and Emanuela Terazzi
- Subjects
Cyclopropanes ,medicine.medical_specialty ,Neurology ,Pain ,Dermatology ,Acetates ,Churg-Strauss Syndrome ,Sulfides ,Gastroenterology ,immune system diseases ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Eosinophilia ,Humans ,Montelukast ,Asthma ,Aged ,Leukotriene ,business.industry ,Peripheral Nervous System Diseases ,General Medicine ,medicine.disease ,respiratory tract diseases ,Electrophysiology ,Psychiatry and Mental health ,surgical procedures, operative ,Peripheral neuropathy ,Quinolines ,Leukotriene Antagonists ,Female ,Neurology (clinical) ,medicine.symptom ,Vasculitis ,business ,Polyneuropathy ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Churg-Strauss syndrome (CSS) is a disseminated small vessel vasculitis characterized by late-onset asthma, upper airways disease, eosinophilia and late neurological manifestations such as peripheral neuropathy. Recently, several cases of CSS have been reported in patients treated with leukotriene antagonists after weaning corticosteroids. We describe a case of CSS developed while the patient was receiving montelukast for asthma treatment, after corticosteroids withdrawal. A causal relationship between montelukast therapy and CSS is hypothesized.
- Published
- 2003
39. HLA-multiple sclerosis association in continental Italy and correlation with disease prevalence in Europe
- Author
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Giovanni Rombolà, Pasquale Ferrante, Maria Liguori, Paola Naldi, Lorenzo Figà Talamanca, Patricia Momigliano-Richiardi, Luca Massacesi, Sandra D'Alfonso, Mehdi Alizadeh, Clara Ballerini, Franca Rosa Guerini, Eleonora Rosati, and Domenico Caputo
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Multiple Sclerosis ,Immunology ,Prevalence ,Human leukocyte antigen ,Gastroenterology ,Correlation ,HLA Antigens ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Genetic Predisposition to Disease ,Allele ,Sex Distribution ,Association (psychology) ,Alleles ,HLA-DR Serological Subtypes ,business.industry ,Multiple sclerosis ,Histocompatibility Testing ,Histocompatibility Antigens Class I ,Odds ratio ,HLA-DR Antigens ,medicine.disease ,Europe ,Phenotype ,Neurology ,Italy ,Female ,Neurology (clinical) ,business ,HLA-DRB1 Chains - Abstract
The association with HLA-DRB1 alleles was tested in 609 Continental Italian MS patients and 836 controls. The phenotype frequency of DRB1*15 in the patients was significantly higher (0.316 vs. 0.112; p(c)
- Published
- 2003
40. Abnormal response to glutamate of T lymphocytes from multiple sclerosis patients
- Author
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Pier Luigi Canonico, Gianluca Miglio, Grazia Lombardi, Cristoforo Comi, Paola Naldi, and Francesco Monaco
- Subjects
Adult ,Male ,medicine.medical_specialty ,Multiple Sclerosis ,Lymphocyte ,T-Lymphocytes ,Proliferation ,Central nervous system ,Excitotoxicity ,Glutamic Acid ,Biology ,medicine.disease_cause ,Statistics, Nonparametric ,Internal medicine ,medicine ,Demyelinating disease ,Humans ,General Neuroscience ,Multiple sclerosis ,Glutamate receptor ,Long-term potentiation ,T lymphocyte ,medicine.disease ,Endocrinology ,medicine.anatomical_structure ,Glutamate ,Intracellular Ca2+ ,Female - Abstract
Multiple sclerosis (MS) is an immune-mediate, inflammatory and demyelinating disease of the central nervous system (CNS). Since glutamate (Glu) is a modulator of T lymphocyte function and Glu excitotoxicity has been proposed as one of the mechanisms of the demyelination, we studied the responses of T lymphocytes from normal controls (NC), MS or other non-inflammatory neurological disease (ONND) patients to Glu, by measuring phytohemagglutinin-induced intracellular Ca 2+ ([Ca 2+ ] i ) rise (Fura-2 method) and cell proliferation (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetric assay). No differences in the Glu (1 μM)-induced potentiation of the [Ca 2+ ] i rise were measured in T lymphocytes from all groups of subjects, while a significant decrease in the Glu (1 mM)-induced inhibition of cell proliferation was observed in T lymphocytes from MS patients. These data demonstrate that MS T lymphocytes abnormally respond to Glu.
- Published
- 2003
41. A whole genome screen for linkage disequilibrium in multiple sclerosis performed in a continental Italian population
- Author
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Marta Mellai, Giuseppe Salemi, Anna Maria Repice, Efrosini Setakis, Giovanni Ristori, Franca Rosa Guerini, Domenico Caputo, Francesca De Robertis, Ida Biunno, Maurizio Leone, Isabella Ferro, Stephen Sawcer, Maria Liguori, Paola Naldi, Giancarlo Comi, Stefania Cannoni, Giovanni Savettieri, Luigi M.E. Grimaldi, Giulia Malferrari, Tiziana Biagioli, Roberto Bomprezzi, Maria Trojano, Luca Massacesi, Patricia Momigliano-Richiardi, Marco Salvetti, Paolo Aridon, Sandra D'Alfonso, Alastair Compston, Paolo Livrea, Cinzia Gellera, La Mantia Loredana, Pasquale Ferrante, Clara Ballerini, Clara Milanese, Mara Giordano, Liguori, M., Sawcer, S., Setakis, E., Compston, A., Giordano, M., D'Alfonso, S., Mellai, M., Malferrari, G., Trojano, M., Livrea, P., De Robertis, F., Massacesi, L., Repice, A., Ballerini, C., Biagioli, T., Bomprezzi, R., Cannoni, S., Ristori, G., Salvetti, M., Grimaldi, L., Biunno, I., Comi, G., Leone, M., Ferro, I., Naldi, P., Milanese, C., Gellera, C., Loredana, L., Savettieri, G., Salemi, G., Aridon, P., Caputo, D., Guerini, F., Ferrante, P., and Momigliano-Richiardi, P.
- Subjects
Male ,Linkage disequilibrium ,Multiple Sclerosis ,Genotype ,International Cooperation ,Immunology ,Biology ,Genome ,Linkage Disequilibrium ,Whole genome linkage disequilibrium ,Gene Frequency ,medicine ,Humans ,Immunology and Allergy ,Genetic Predisposition to Disease ,Multiple sclerosi ,Genetic Testing ,Genotyping ,Allele frequency ,Alleles ,Genetic testing ,Genetics ,medicine.diagnostic_test ,Genome, Human ,Racial Groups ,DNA pool ,Microsatellite ,Settore BIO/18 - Genetica ,Italy ,Neurology ,Case-Control Studies ,Human genome ,Female ,Settore MED/26 - Neurologia ,Neurology (clinical) ,Microsatellite Repeats - Abstract
We have systematically screened the genome for evidence of linkage disequilibrium (LD) with multiple sclerosis (MS) by typing 6000 microsatellite markers in case-control and family based (AFBAC) cohorts from the Italian population. DNA pooling was used to reduce the genotyping effort involved. Four DNA pools were considered: cases (224 Italian MS patients), controls (231 healthy Italians), index (185 index cases from trio families) and parents (the 370 parents of the patient included in the Index pool), respectively. After refining analysis of the most promising 14 markers to emerge from this screening process, only marker D2S367 retained evidence for association. © 2003 Elsevier B.V. All rights reserved.
- Published
- 2003
42. Hemispheric asymmetries of cortico-cortical connections in human hand motor areas
- Author
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A Cavalli, Paola Naldi, Roberto Cantello, Claudia Varrasi, and Carlo Civardi
- Subjects
Adult ,Male ,medicine.medical_treatment ,Central nervous system ,Stimulation ,Lateralization of brain function ,Functional Laterality ,Magnetics ,Physiology (medical) ,medicine ,Humans ,Motor Cortex ,Motor control ,Neural Inhibition ,Hand ,Sensory Systems ,Electric Stimulation ,Transcranial magnetic stimulation ,medicine.anatomical_structure ,Neurology ,Laterality ,Facilitation ,Female ,Neurology (clinical) ,Psychology ,Neuroscience ,Motor cortex - Abstract
Objective : To evaluate possible functional asymmetries of the motor cortex on the hand-dominant versus the non-dominant hemisphere. Methods : We assessed the handedness of 15 consenting volunteers using the Edinburgh Inventory. They were divided in two groups: 9 right-handers and 6 left-handers. We used single- and paired-transcranial magnetic stimulation (TMS) to measure the relaxed and active motor threshold and the ipsilateral cortico-cortical inhibition and facilitation curve for both hand motor areas. We looked for hemispheric asymmetries of variables related to the side of stimulation (dominant versus non-dominant) and to handedness. Results : We found no significant intra- or intergroup hemispheric asymmetry for the relaxed and active thresholds. Among the right-handers, the cortico-cortical inhibition and facilitation curve showed an increased amount of facilitation in the dominant as compared with the non-dominant hand area. No such changes were seen among the left-handers. Both the dominant and the non-dominant hand areas of the right-handers showed more inhibition and less facilitation on the cortico-cortical inhibition and facilitation curve than the corresponding areas of left-handers. Conclusion : In the right-handers, paired TMS studies showed a functional asymmetry of the motor cortex between the dominant and the non-dominant hand. The left-handers did not show this lateralization. Under TMS investigation their motor cortex function appeared different from that of right-handers.
- Published
- 2000
43. Idiopathic generalized epilepsy: magnetic stimulation of motor cortex time-locked and unlocked to 3-Hz spike-and-wave discharges
- Author
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Roberto Cantello, Diego Bettucci, Carlo Civardi, M. Gianelli, M. Pia Schiavella, Paola Naldi, and Roberto Mutani
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pyramidal Tracts ,Electromyography ,Stimulus (physiology) ,Electroencephalography ,Audiology ,Functional Laterality ,Idiopathic generalized epilepsy ,Epilepsy ,medicine ,Humans ,Evoked potential ,Evoked Potentials ,medicine.diagnostic_test ,Motor Cortex ,Spike-and-wave ,medicine.disease ,medicine.anatomical_structure ,Neurology ,Epilepsy, Absence ,Anesthesia ,Anticonvulsants ,Female ,Neurology (clinical) ,Psychology ,Electromagnetic Phenomena ,Motor cortex - Abstract
In 20 patients with idiopathic generalized epilepsy who showed typical 3-Hz spike-and-wave (SW) EEG complexes, we studied the corticospinal motor output with a transcranial electromagnetic stimulator. First we measured the corticospinal discharge threshold for both hemispheres in the patient group and compared it with that of 10 age- and sex-matched volunteers. Threshold was significantly higher in the patient group, regardless of whether subjects were treated with antiepileptic drugs (AEDs). In 4 patients with very frequent SW paroxysms, we were able to study motor evoked potential (MEP) changes time-locked to epileptic EEG transients. The EEG signal was recorded bipolarly (C3-P3, C4-P4) by scalp needle-electrodes. For a given stimulus intensity, we collected and measured MEPs occurring during the spike or the wave portion of the SW complexes. Data were compared with those of MEPs obtained time-locked to normal EEG segments. MEP size was significantly decreased when the cortical stimulus was time-locked to the wave component, and was decreased or unchanged when the stimulus was time-locked to the spike. Magnetic stimulation never produced remarkable side effects.
- Published
- 1994
44. Menstrual migraine without aura: cortical excitability to magnetic stimulation
- Author
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Roberto Mutani, M. Gianelli, D. Bettucci, Roberto Cantello, and Paola Naldi
- Subjects
Adult ,Time Factors ,Aura ,media_common.quotation_subject ,Migraine Disorders ,Brain ,Menstrual migraine ,Stimulation ,Middle Aged ,medicine.disease ,Magnetics ,Neurology ,Migraine ,Anesthesia ,medicine ,Humans ,Ictal ,Female ,Neurology (clinical) ,Patient group ,Psychology ,Conduction time ,Menstrual cycle ,Menstrual Cycle ,media_common - Abstract
SYNOPSIS The purpose of the present study was the evaluation of the excitability threshold and the central motor conduction time (CCT) studied by means of electromagnetic cortical stimulation in tan subjects affected by menstrual migraine without aura, both in the ictal end the interictal period. The patients were chosen from among a group of 254 outpatients affected by migraine, diagnosed according to the International Headache Society criteria.1 The control group consisted of ten healthy female subjects. As far as CCTs were concerned no differences emerged between patients and controls. However In the patient group we found a significant increase in the excitability threshold values, both in the ictal and the interictal period, and in both hemispheres. If confirmed, the Increased excitability threshold may be a useful neurophysiological correlate of migraine without aura.
- Published
- 1992
45. Crowned dens syndrome in an elderly man
- Author
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Francesco Monaco, Paola Gaviani, Marco Mula, G. Bordin, Maurizio Leone, and Paola Naldi
- Subjects
Aged, 80 and over ,Skull Base ,Neck pain ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Chondrocalcinosis ,Syndrome ,Fibrinogen ,X ray computed ,Erythrocyte sedimentation rate ,medicine ,Humans ,Neurology (clinical) ,Radiology ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Neck stiffness ,Aged ,medicine.drug - Abstract
An 89-year-old man presented to the emergency room with neck pain and fever (37.5°). Neurologic examination showed neck stiffness; general examination was normal. Erythrocyte sedimentation rate was 97 mm/1st h, fibrinogen 681 mg/dL, …
- Published
- 2001
46. Refining genetic associations in multiple sclerosis
- Author
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Åslaug R. Lorentzen, Bertram Müller-Myhsok, David R. Booth, Jonathan L. Haines, Françoise Clerget-Darpoux, Anne Spurkland, David A. Hafler, P. Villoslada, Bertrand Fontaine, Graeme J. Stewart, An Goris, Stephen Sawcer, Virpi M. Leppä, Tania Mihalova, Daniela Galimberti, Alastair Compston, Xavier Montalban, Margaret A. Pericak-Vance, Hanne F. Harbo, Antje Kroner, Colin M. Graham, A. Oturai, Janna Saarela, Sandra D'Alfonso, A Ivinson, Paola Naldi, Stephen L. Hauser, Tomas Olsson, C M van Duijn, Manuel Comabella, R Q Hintzen, Rita Dobosi, Ingrid Kockum, John D. Rioux, Amie Walton, J. Hoksenberg, P. L. De Jager, L. F. Barcellos, Francesco Cucca, Bénédicte Dubois, Maria Ban, Mark J. Daly, Koen Vandenbroeck, Helle Bach Søndergaard, Laura Bergamaschi, Peter Rieckmann, Neil Robertson, Elisabeth Gulowsen Celius, David Sexton, Robert Heard, Florian Holsboer, Finn Sellebjerg, Marie-Claude Babron, Frank Weber, Leena Peltonen, Stanley Hawkins, Jacob L. McCauley, Isabelle Cournu-Rebeix, J. Hillert, Maria Giovanna Marrosu, Marco Salvetti, A. Palotie, Gillian Ingram, Franca Rosa Guerini, and Clive Hawkins
- Subjects
Empirical data ,medicine.medical_specialty ,Multiple Sclerosis ,Genetic Linkage ,Reflection and Reaction ,Bayesian probability ,Complex disease ,03 medical and health sciences ,0302 clinical medicine ,medicine ,False positive paradox ,Humans ,Genetic Predisposition to Disease ,Psychiatry ,030304 developmental biology ,Genetic association ,0303 health sciences ,business.industry ,Multiple sclerosis ,Chromosome Mapping ,medicine.disease ,3. Good health ,Neurology (clinical) ,business ,True positive rate ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Genome-wide association studies involve several hundred thousand markers and, even when quality control is scrupulous, are invariably confounded by residual uncorrected errors that can falsely inflate the apparent difference between cases and controls (so-called genomic inflation). As a consequence such studies inevitably generate false positives alongside genuine associations. By use of Bayesian logic and empirical data, the Wellcome Trust Case Control Consortium suggested that association studies in complex disease should involve at least 2000 cases and 2000 controls, at which level they predicted that p values of less than 5×10 −7 would more commonly signify true positives than false positives.
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