Publications by authors named "Paola Naldi"

21 Publications

  • Page 1 of 1

Efficacy of Cannabinoids on Spasticity and Chronic Pain in a Patient with Co-occurrence of Multiple Sclerosis and Neurofibromatosis Type 1.

Eur J Case Rep Intern Med 2021 13;8(5):002424. Epub 2021 May 13.

Neurology Unit, Maggiore della Carità Hospital, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease involving the skin and central nervous system (CNS), and also characterized by skeletal and spinal schwannomas that may cause chronic neurogenic pain. Furthermore, pain in NF1 is underestimated, even though it has an impact on quality of life. Multiple sclerosis (MS) is the most common acquired demyelinating disease that may in later stages present with refractory spasticity, particularly in the lower limbs. Oromucosal cannabinoid sprays are currently available for spasticity treatment in MS, with encouraging results on MS pain, but few data have been reported regarding the use of cannabinoids in NF1. We report the successful treatment of chronic neurogenic pain and spasticity in a patient with co-occurrence of NF1 and MS after a poor response to standard approaches.

Learning Points: Chronic pain is a possible complication of several neurological conditions and may show a poor response to standard drugs, thus affecting quality of life.Oromucosal cannabinoid sprays are routinely used in multiple sclerosis spasticity.Cannabinoids may be also effective against neurogenic pain in neurofibromatosis type 1.
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http://dx.doi.org/10.12890/2021_002424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191353PMC
May 2021

Paraneoplastic neuromyelitis optica spectrum disorders: a case series.

Neurol Sci 2021 Jun 28;42(6):2519-2522. Epub 2021 Jan 28.

Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Novara, Italy.

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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http://dx.doi.org/10.1007/s10072-021-05055-yDOI Listing
June 2021

Cannabinoids in multiple sclerosis: A neurophysiological analysis.

Acta Neurol Scand 2020 Oct 21;142(4):333-338. Epub 2020 Jul 21.

Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.

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.
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http://dx.doi.org/10.1111/ane.13313DOI Listing
October 2020

The Impact of Lifetime Alcohol and Cigarette Smoking Loads on Multiple Sclerosis Severity.

Front Neurol 2019 13;10:866. Epub 2019 Aug 13.

Neurology Unit, Department of Medical Sciences, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

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. We aimed to assess the impact of lifetime alcohol and cigarette smoking load on MS severity. 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. The median MSSS was higher (3.2 vs. 2.3, = 0.002) in ever- vs. never-smokers, but we did not find a difference between ever- and never-drinkers (2.7 vs. 2.8, = 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; < 0.01) if they were never-drinkers, whereas it was only 1.65 (0.89-3.03, = 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; = 0.23) or not (1.49; 0.55-4.04, = 0.43). 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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http://dx.doi.org/10.3389/fneur.2019.00866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700269PMC
August 2019

Holmes tremor caused by a natalizumab-related progressive multifocal leukoencephalopathy: a case report and brief review of the literature.

Neurol Sci 2019 Sep 1;40(9):1943-1945. Epub 2019 Mar 1.

Department of Translational Medicine, Section of Neurology, University of Eastern Piedmont, Novara, Italy.

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http://dx.doi.org/10.1007/s10072-019-03779-6DOI Listing
September 2019

Post-lumbar puncture headache: an adverse effect in multiple sclerosis work-up.

Neurol Sci 2019 Apr 21;40(4):759-762. Epub 2019 Jan 21.

Neurology Unit, Department of Translational Medicine, AOU Maggiore della Carità and University of Piemonte Orientale, Novara, Italy.

Background: 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.

Aims: To describe the occurrence of, and, factors related to PLPH in patients with suspected MS, studied on a daily-basis admission.

Patients And Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1007/s10072-019-3724-zDOI Listing
April 2019

Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy?

J Neurol Sci 2017 Jul 12;378:233-237. Epub 2017 May 12.

Multiple Sclerosis Centre, Spedali Civili di Brescia, Via Ciotti 154, 25018 Montichiari, Brescia, Italy. Electronic address:

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 90days 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.
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http://dx.doi.org/10.1016/j.jns.2017.05.018DOI Listing
July 2017

Combined use of Kappa Free Light Chain Index and Isoelectrofocusing of Cerebro-Spinal Fluid in Diagnosing Multiple Sclerosis: Performances and Costs.

Clin Lab 2017 Mar;63(3):551-559

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.
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http://dx.doi.org/10.7754/Clin.Lab.2016.160930DOI Listing
March 2017

Multiple sclerosis progression is not associated with birth timing in Italy.

J Neurol Sci 2014 Nov 23;346(1-2):194-6. Epub 2014 Aug 23.

MS Centre, SCDU Neurology, Head and Neck Department, AOU "Maggiore della Carità", Corso Mazzini 18, 28100 Novara, Italy; Interdisciplinary Research Center of Autoimmune Diseases IRCAD, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy. Electronic address:

Background: Month of birth has been associated in some studies with the susceptibility to develop Multiple Sclerosis (MS). However, only few studies have evaluated whether birth timing also affects disease progression.

Objectives: To assess whether season and month of birth are associated with disease progression in a large cohort of Italian patients.

Methods: Quantile regression was used to analyze the impact of each month and season of birth with all the others combined on the median Multiple Sclerosis Severity Score of 1866 MS patients.

Results: No significant temporal trend was found after adjustment for multiple comparisons.

Conclusions: Birth timing showed no association with MS progression in Italian patients.
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http://dx.doi.org/10.1016/j.jns.2014.08.021DOI Listing
November 2014

Chronic cerebrospinal venous insufficiency is not associated with multiple sclerosis and its severity: a blind-verified study.

PLoS One 2013 13;8(2):e56031. Epub 2013 Feb 13.

MS Centre, Head and Neck Department, AOU Maggiore della Carità, Novara, Italy.

Background: Chronic 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.

Objective: To 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 Findings: The 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/significance: CCSVI 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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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056031PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572163PMC
August 2013

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Nature 2011 Aug 10;476(7359):214-9. Epub 2011 Aug 10.

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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http://dx.doi.org/10.1038/nature10251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531PMC
August 2011

Association of HLA class I markers with multiple sclerosis in the Italian and UK population: evidence of two independent protective effects.

J Med Genet 2011 Jul 25;48(7):485-92. Epub 2011 Mar 25.

Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy.

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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http://dx.doi.org/10.1136/jmg.2010.080721DOI Listing
July 2011

The expression pattern of inflammatory mediators in cerebrospinal fluid differentiates Guillain-Barré syndrome from chronic inflammatory demyelinating polyneuropathy.

Cytokine 2010 Aug 9;51(2):138-43. Epub 2010 Jun 9.

Clinical Immunology Department and Research Laboratory, Department of Clinical and Experimental Medicine, Università del Piemonte Orientale A. Avogadro, Novara, Italy.

Introduction: 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.

Patients And Methods: 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.

Results: 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 (p<0.002). 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 (p<0.002).

Discussion: 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.
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http://dx.doi.org/10.1016/j.cyto.2010.05.005DOI Listing
August 2010

Elevation of Gas6 protein concentration in cerebrospinal fluid of patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

J Neurol Sci 2008 Jun 14;269(1-2):138-42. Epub 2008 Feb 14.

Laboratorio di Medicina Interna e Immunologia Clinica, Dipartimento di Medicina Clinica e Sperimentale, Università del Piemonte Orientale A. Avogadro, Novara, Italy.

Introduction: 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.

Materials And Methods: 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 CVs <10%, recovery 96%). Variance, Tukey's post-hoc test, regression were calculated with a statistical software (Statsoft).

Results: 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, p<0.005). It was not related to age, CSF total proteins or to CSF/plasma ratio of total proteins (regression, p>0.1).

Conclusions: Gas6 is detectable in CSF and may be involved in chronic autoimmune demyelination or myelin repair.
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http://dx.doi.org/10.1016/j.jns.2008.01.005DOI Listing
June 2008

Candidate gene analysis of SPARCL1 gene in patients with multiple sclerosis.

Neurosci Lett 2007 Oct 17;425(3):173-6. Epub 2007 Aug 17.

Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.

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.
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http://dx.doi.org/10.1016/j.neulet.2007.08.020DOI Listing
October 2007

Cytokines and chemokines in cerebrospinal fluid and serum of adult patients with acute disseminated encephalomyelitis.

J Neurol Sci 2006 Sep 19;247(2):202-7. Epub 2006 Jun 19.

Laboratory of Neuroimmunology, Foundation Neurological Institute C. Mondino, University of Pavia, via Mondino 2, 27100 Pavia, Italy.

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.
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http://dx.doi.org/10.1016/j.jns.2006.05.049DOI Listing
September 2006

Cortico-motoneurone excitability in patients with obstructive sleep apnoea.

J Sleep Res 2004 Jun;13(2):159-63

Section of Neurology, Department of Medical Sciences, Università del Piemonte Orientale A. Avogadro, Novara, Italy.

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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http://dx.doi.org/10.1111/j.1365-2869.2004.00391.xDOI Listing
June 2004

HLA-multiple sclerosis association in continental Italy and correlation with disease prevalence in Europe.

J Neuroimmunol 2004 May;150(1-2):178-85

Dipartimento di Scienze Neurologiche e Psichiatriche, Univ. Firenze, Florence, Italy.

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)<10(-6); Odds Ratio (OR)=3.64) with no dose effect. DRB1*10 was also significantly increased (OR=2.19; p(c)=0.047) and DRB1*07 decreased (OR=0.60; p(c)=1.3 x 10(-3)) independently of DR15 and of each other. We did not detect an influence of the DR phenotype on disease course, age at onset/diagnosis, gender or familiarity. No association with Class I was detected in a random subset of patients and controls. A comparison of the HLA association data in Northern and Southern European populations shows a parallel between disease prevalence and DR15 frequency.
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http://dx.doi.org/10.1016/j.jneuroim.2004.01.015DOI Listing
May 2004

A whole genome screen for linkage disequilibrium in multiple sclerosis performed in a continental Italian population.

J Neuroimmunol 2003 Oct;143(1-2):97-100

Dipartimento di Scienze Neurologiche e Psichiatriche, Univ. Bari, Italy.

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.
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http://dx.doi.org/10.1016/j.jneuroim.2003.08.020DOI Listing
October 2003

Abnormal response to glutamate of T lymphocytes from multiple sclerosis patients.

Neurosci Lett 2003 Apr;340(1):5-8

DISCAFF Department, University of Piemonte Orientale "Amedeo Avogadro", Via Bovio, 6, 28100 Novara, Italy.

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 microM)-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.
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http://dx.doi.org/10.1016/s0304-3940(03)00038-7DOI Listing
April 2003

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.

J Neuroimmunol 2002 May;126(1-2):196-204

Laboratorio di Genetica Umana, Dipartimento Scienze Mediche, Univ. Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy.

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 <0.05, i.e. below the detection limit in the pools. Of these, Arg537Cys was further studied with individually genotyped individuals and was detected in 1/189 patients and 0/85 controls. The frequency of the six remaining SNPs were not significantly different in pools including a total of 1266 patient and 1612 control chromosomes. Considering the statistical power of the experimental design, these results exclude the MAG gene as an MS susceptibility factor with an odds ratio (OR) equal or higher than 1.3.
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http://dx.doi.org/10.1016/s0165-5728(02)00061-9DOI Listing
May 2002
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