Martino D.,University of Bari |
Chiarotti F.,Instituto Superiore Of Sanita |
Buttiglione M.,University of Bari |
Cardona F.,University of Rome La Sapienza |
And 5 more authors.
Developmental Medicine and Child Neurology | Year: 2011
Aim To evaluate the relationship between diagnosis and clinical course of Tourette syndrome and group A Streptococcus (GAS). Method GAS infections, anti-streptococcal, and anti-basal ganglia antibodies (ABGA) were compared between 168 patients (136 males, 32 females) with Tourette syndrome; (median [range] age [25th-75th centile] 10y [8-11y]); median Tourette syndrome duration (25th-75th centile), 3y (1y 3mo-5y 9mo) and a comparison group of 177 patients (117 males, 60 females) with epileptic or sleep disorders median age [25th-75th centile], 10y [8y-1y 6mo]). One hundred and forty-four patients with Tourette syndrome were followed up at 3-month intervals; exacerbations of tics, obsessive-compulsive symptoms, and other psychiatric comorbidities were defined by a bootstrap procedure. The effect of new GAS infections and identification of new ABGA upon risk of exacerbation was assessed using logistic regression analysis. Results Cross-sectionally, patients with Tourette syndrome exhibited a higher frequency of GAS infection (8% vs 2%; p=0.009), higher anti-streptolysin O (ASO) titres (246 [108-432] vs 125 [53-269]; p<0.001), and higher ABGA frequency (25% vs 8%; p<0.001) than the comparison group. On prospective analysis, ASO titres were persistently elevated in 57% of patients with Tourette syndrome; however, new infections or newly identified ABGA did not predict clinical exacerbations (all p>0.05). Interpretation Patients with Tourette syndrome might be more prone to GAS infections and develop stronger antibody responses to GAS, probably as a result of underlying immune dysregulation. New GAS infections are unlikely to exert, years after their onset, a major effect upon the severity of neuropsychiatric symptoms. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.
Bagnardi V.,University of Milan Bicocca |
Bagnardi V.,Italian National Cancer Institute |
Rota M.,University of Milan Bicocca |
Rota M.,Mario Negri Institute for Pharmacological Research |
And 19 more authors.
British Journal of Cancer | Year: 2015
Background:Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial.Methods:We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity.Results:A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated.Conclusions:Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma. © 2015 Cancer Research UK. All rights reserved 0007 - 0920/15.
Bussone G.,Besta Neurological Institute |
Allais G.,University of Turin |
Gabellari I.C.,University of Turin |
Benedetto C.,University of Turin
Expert Opinion on Pharmacotherapy | Year: 2011
Introduction: Approximately 50% of migrainous women associate their headache temporally to menses. Menstrually related migraine (MRM) is a disabling form of migraine characterized by attacks that are generally longer, more severe and less drug-responsive than nonmenstrual ones. Since MRM may be difficult to treat, it is important to find an appropriate treatment option for women suffering from this condition. Areas covered: This paper provides an overview of the clinical features of MRM, with special attention on the use of almotriptan for its treatment. Four studies on almotriptan in the treatment of MRM are present in the medical literature. Two report post hoc analyses of data derived from larger studies on the use of almotriptan for migraine treatment. One reports the results from a study specifically dedicated to MRM and one illustrates a subanalysis on the accompanying symptomatology. Expert opinion: Evidence demonstrates that almotriptan is a molecule with a high efficacy in the treatment of MRM and with an excellent tolerability profile when compared with other triptans. Moreover, it shows a proven ability to control migraine-associated symptoms. All these qualities play a decidedly positive role in making almotriptan a product of choice for the treatment of MRM. © 2011 Informa UK, Ltd.
D'Agata F.,University of Turin |
Caroppo P.,University of Turin |
Caroppo P.,Besta Neurological Institute |
Amianto F.,University of Turin |
And 9 more authors.
Psychiatry and Clinical Neurosciences | Year: 2015
Aims Alexithymia is a personality trait that consists of difficulty in identifying and acknowledging one's own and others' feelings. Recent studies reported that alexithymia is present in both anorexia (AN) and bulimia nervosa (BN). Brain morphological studies on healthy subjects showed that alexithymia correlates with several brain regions involved in emotions processing. The aim of this study was to investigate the anatomical correlates of alexithymia in AN and BN. Methods We performed a voxel-based morphometry study on 21 patients with AN and 18 with BN. Seventeen healthy subjects were used as a control group. Alexithymia, depression and anxiety were assessed with self-administered questionnaires and correlated to gray matter (GM) density in each group. Results In BN, alexithymia was correlated with the GM of the parietal lobe, in particular of the right angular gyrus. The correlation was predominantly linked with Difficulty Describing Feelings. In AN, we did not find correlations between GM and alexithymia. Conclusions In BN, our results support the hypothesis that this trait may represent a relevant pathogenic or maintenance factor that contributes to relational difficulties, present in this pathology. In AN, the lack of correlation between GM volume and alexithymia may be influenced by atrophy in several brain regions that in turn can be, as previously reported, a consequence of caloric restriction. Also, the nature of alexithymia may be different from that of BN and controls and this trait could be secondary to a psychopathologic process specific to AN. © 2015 Japanese Society of Psychiatry and Neurology.
PubMed | Paris-Sorbonne University, University of Coimbra, University of Nantes, University of Milan and 7 more.
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | Year: 2016
Frontotemporal lobar degeneration (FTLD) is a progressive dementia characterized by focal atrophy of frontal and/or temporal lobes caused by mutations in the gene coding for sequestosome 1 (SQSTM1), among other genes. Rare SQSTM1 gene mutations have been associated with Pagets disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD).The aim of the study was to determine whether a characteristic pattern of grey and white matter loss is associated with SQSTM1 dysfunction.We performed a voxel-based morphometry (VBM) study in FTD subjects carrying SQSTM1 pathogenic variants (FTD/SQSTM1 mutation carriers; n=10), compared with FTD subjects not carrying SQSTM1 mutations (Sporadic FTD; n=20) and healthy controls with no SQSTM1 mutations (HC/SQSTM1 noncarriers; n=20). The groups were matched according to current age, disease duration, and gender.After comparing FTD/SQSTM1 carriers with Sporadic FTD, a predominantly right cortical atrophy pattern was localized in the inferior frontal, medial orbitofrontal, precentral gyri, and the anterior insula. White matter atrophy was found in both medial and inferior frontal gyri, pallidum, and putamen. FTD/SQSTM1 carriers compared with HC/SQSTM1 noncarriers showed atrophy at frontal, temporal, and parietal lobes of both hemispheres whereas the MRI pattern found in Sporadic FTD compared with controls was frontal and left temporal lobe atrophy, extending toward parietal and occipital lobes of both hemispheres.These results suggest that fronto-orbito-insular regions including corticospinal projections as described in ALS are probably more susceptible to the damaging effect of SQSTM1 mutations delineatinga specific gene-linked atrophy pattern.
Mantegazza M.,University of Nice Sophia Antipolis |
Mantegazza M.,Besta Neurological Institute
Epilepsia | Year: 2011
Dravet syndrome is caused mainly by mutations of voltage-gated Na + channels (most of them targeting Na V1.1) and in few cases by mutations of γ-aminobutyric acid (GABA) A receptor γ2 subunit. In vitro functional analysis has provided important information about the pathogenic mechanism of these mutations, which is in most cases consistent with reduced GABAergic inhibition and consequent hyperexcitability of neuronal circuits. However, interpretative difficulties have arisen, limiting the exploitation of the data generated with some in vitro experimental systems. I will review the functional studies of Dravet syndrome mutations that have been performed in vitro, highlighting the interpretative difficulties and the possible use of these data in the clinical practice. © Wiley Periodicals, Inc. 2011 International League Against Epilepsy.
PubMed | Besta Neurological Institute
Type: | Journal: Molecular cancer | Year: 2013
The NF-kB family of transcription factors is up-regulated in inflammation and different cancers. Recent data described heterozygous deletions of the NF-kB Inhibitor alpha gene (NFKBIA) in about 20% of glioblastomas (GBM): deletions were mutually exclusive with epidermal growth factor receptor (EGFR) amplification, a frequent event in GBM. We assessed the status of NFKBIA and EGFR in 69 primary GBMs and in corresponding neurospheres (NS). NFKBIA deletion was investigated by the copy number variation assay (CNV); EGFR amplification by CNV ratio with HGF; expression of EGFR and EGFRvIII by quantitative PCR or ReverseTranscriptase PCR. Heterozygous deletions of NFKBIA were present in 3 of 69 primary GBMs and, surprisingly, in 30 of 69 NS. EGFR amplification was detected in 36 GBMs: in corresponding NS, amplification was lost in 13 cases and reduced in 23 (10 vs 47 folds in NS vs primary tumors; p<0.001). The CNV assay was validated investigating HPRT1 on chromosome X in females and males. Results of array-CGH performed on 3 primary GBMs and 1 NS line were compatible with the CNV assay. NS cells with NFKBIA deletion had increased nuclear activity of p65 (RelA) and increased expression of the NF-kB target IL-6. In absence of EGF in the medium, EGFR amplification was more conserved and NFKBIA deletion less frequent point to a low frequency of NFKBIA deletions in GBM and suggest that EGF in the culture medium of NS may affect frequency not only of EGFR amplifications but also of NFKBIA deletions.
PubMed | Flocel Inc., Besta Neurological Institute and French Institute of Health and Medical Research
Type: | Journal: Neuroscience letters | Year: 2017
The cerebral vasculature is a complex tridimensional network of arterial and venous vessels which are anatomically in proximity of and functionally coupled to neurons. Depending on the cellular composition of the vascular wall and its anatomical arrangement, cerebral vessels control regional blood flow, define interstitial homeostasis or cerebrospinal fluid circulation and influence immune cell patrolling. Pathological deviations from these functions promote or are a consequence of brain diseases, directly impacting neuronal firing. We propose that specific cerebrovascular segments are differentially implicated in the pathophysiology of epilepsy, including difference between white and grey matter. We offer plasticity of perivascular mural cells and endothelial-pericyte interactions as emerging players. We outline the potential for MRI vascular biomarkers tailored to the epileptic brain, specifically cerebral blood volume and flow, tissue oxygen saturation and microvessel permeability. Finally, we show the advantages of the guinea pig whole brain preparation to study the link between cerebrovascular permeability, expression of vascular adhesion molecules, inflammation and neuronal excitability.
PubMed | Besta Neurological Institute
Type: Journal Article | Journal: Expert opinion on pharmacotherapy | Year: 2011
Approximately 50% of migrainous women associate their headache temporally to menses. Menstrually related migraine (MRM) is a disabling form of migraine characterized by attacks that are generally longer, more severe and less drug-responsive than nonmenstrual ones. Since MRM may be difficult to treat, it is important to find an appropriate treatment option for women suffering from this condition.This paper provides an overview of the clinical features of MRM, with special attention on the use of almotriptan for its treatment. Four studies on almotriptan in the treatment of MRM are present in the medical literature. Two report post hoc analyses of data derived from larger studies on the use of almotriptan for migraine treatment. One reports the results from a study specifically dedicated to MRM and one illustrates a subanalysis on the accompanying symptomatology.Evidence demonstrates that almotriptan is a molecule with a high efficacy in the treatment of MRM and with an excellent tolerability profile when compared with other triptans. Moreover, it shows a proven ability to control migraine-associated symptoms. All these qualities play a decidedly positive role in making almotriptan a product of choice for the treatment of MRM.
PubMed | Besta Neurological Institute
Type: | Journal: Journal of neuroinflammation | Year: 2013
Autoinflammatory diseases are rare illnesses characterized by apparently unprovoked inflammation without high-titer auto-antibodies or antigen-specific T cells. They may cause neurological manifestations, such as meningitis and hearing loss, but they are also characterized by non-neurological manifestations. In this work we studied a 30-year-old man who had a chronic disease characterized by meningitis, progressive hearing loss, persistently raised inflammatory markers and diffuse leukoencephalopathy on brain MRI. He also suffered from chronic recurrent osteomyelitis of the mandible. The hypothesis of an autoinflammatory disease prompted us to test for the presence of mutations in interleukin-1-pathway genes and to investigate the function of this pathway in the mononuclear cells obtained from the patient. Search for mutations in genes associated with interleukin-1-pathway demonstrated a novel NLRP3 (CIAS1) mutation (p.I288M) and a previously described MEFV mutation (p.R761H), but their combination was found to be non-pathogenic. On the other hand, we uncovered a selective interleukin-6 hypersecretion within the central nervous system as the likely pathogenic mechanism. This is also supported by the response to the anti-interleukin-6-receptor monoclonal antibody tocilizumab, but not to the recombinant interleukin-1-receptor antagonist anakinra. Exome sequencing failed to identify mutations in other genes known to be involved in autoinflammatory diseases. We propose that the disease described in this patient might be a prototype of a novel category of autoinflammatory diseases characterized by prominent neurological involvement.