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To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA). Data of all pregnancies occurring between 2009 and 2015... more
To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA). Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. Rates of SA and CA were also compared with those reported in the Italian population. Multivariable logistic and linear regression models were performed. A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with SA (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.9-8.5,< 0.001). However, the rate of SA (17.4%) was within the estimates for the general population, as well as the rate of major CA (3.7%). Moreover, exposure to natalizumab and interferon-β (IFN-β) ...
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Cognitive impairment (CI) affects 40-65% of multiple sclerosis (MS) patients. This study attempted evaluating the effects of fingolimod and interferon beta-1b (IFN β-1b) on CI progression, magnetic resonance imaging (MRI) and clinical... more
Cognitive impairment (CI) affects 40-65% of multiple sclerosis (MS) patients. This study attempted evaluating the effects of fingolimod and interferon beta-1b (IFN β-1b) on CI progression, magnetic resonance imaging (MRI) and clinical outcomes in relapsing-remitting MS (RRMS) patients over 18 months. The GOLDEN study was a pilot study including RRMS patients with CI randomised (2:1) to fingolimod (0.5 mg daily)/IFN β-1b (250 µg every other day). CI was assessed via Rao's Brief Repeatable Battery and Delis-Kaplan Executive Function System test. MRI parameters, Expanded Disability Status Scale scores and relapses were measured. Overall, 157 patients were randomised, of whom 30 discontinued the study (fingolimod, 8.49%; IFN β-1b, 41.18%; p ≤ 0.0001). Patients randomised to fingolimod had more severe clinical and MRI disease characteristics at baseline compared with IFN β-1b. At Month (M) 18, both treatment groups showed improvements in all cognitive parameters. At M18, relapse rate...
Research Interests: Neurology, Multiple sclerosis, Depression, Magnetic Resonance Imaging, Adolescent, and 15 moreMedicine, Executive Function, Electrocardiography, Humans, Internal Medicine, Female, Male, Clinical Sciences, Middle Aged, Longitudinal Studies, Adult, Glatiramer acetate, Cognition disorders, Neuropsychological Tests, and Disability Evaluation
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Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our... more
Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset. 50 clinically isolated syndromes/early relapse-onset MS (CIS/eRRMS) with mean disease duration of 4.0±3.5 months, 28 MRI healthy controls (HC) and 31 OCT-HC were studied. Ten patients had optic neuritis at presentation (MSON+), 40 presented with other symptoms (MSON-). MRI examination included 3D-T1, 3D-FLAIR and 3D-DIR sequences. Global cortical thickness (gCTh), pericalcarin CTh (pCTh) and white matter volume (WMV) were analysed by means of Freesurfer on 3D-T1 scans. Optic radiation morphology (OR) and volume (ORV) were reconstructed on the base of the Jülich's ...
Research Interests: Ophthalmology, Multiple sclerosis, Magnetic Resonance Imaging, Optical coherence tomography, Adolescent, and 15 moreMedicine, Multidisciplinary, Humans, Optic Nerve, Female, Male, Retina, Young Adult, PLoS one, Middle Aged, Optic Neuritis, Optic Radiation, White matter, Adult, and Demyelinating diseases
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Cortical lesions (CLs) and atrophy are pivotal in multiple sclerosis (MS) pathology. This study determined the effect of disease modifying drugs (DMDs) on CL development and cortical atrophy progression in patients with... more
Cortical lesions (CLs) and atrophy are pivotal in multiple sclerosis (MS) pathology. This study determined the effect of disease modifying drugs (DMDs) on CL development and cortical atrophy progression in patients with relapsing-remitting MS (RRMS) over 48 months. Patients (n=165) were randomized to sc IFNβ-1a 44 μg, im IFNβ-1a 30 μg, or glatiramer acetate 20 mg. The reference population comprised 50 DMD-untreated patients with RRMS. After 24 months, 43 of the untreated patients switched to DMDs. The four groups of patients were followed up for an additional 24 months. At 48 months the mean standard deviation number of new CLs was significantly lower in patients treated with sc IFNβ-1a (1.4 ± 1.0, range 0–5) compared with im IFNβ-1a (2.3 ± 1.3, range 0–6,P=0.004) and glatiramer acetate (2.2 ± 1.5, range 0–7,P=0.03). Significant reductions in CL accumulation and new white matter and gadolinium-enhancing lesions were also observed in the 43 patients who switched to DMDs after 24 mont...
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We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) ( n=544).... more
We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) ( n=544). We observed an opposite relationship in the two disease courses: a higher weighted genetic risk score was associated with an earlier age at onset in BOMS (rho= −0.1; p=5 × 10−3) and a later age at onset in PrMS cases (rho=0.07; p=0.15) ( p of difference of regression=1.4 × 10−2). These findings suggest that established MS risk variants anticipate the onset of the inflammatory phase, while they have no impact on, or even delay, the onset of the progressive phase.
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Research Interests: Multiple sclerosis, Clinical Trial, Magnetic Resonance Imaging, Medicine, Multidisciplinary, and 15 moreHumans, Cerebral Cortex, Regression Analysis, Research article, Sample Size, PLoS one, Longitudinal Studies, Randomized Controlled Trial, Longitudinal Study, Akaike Information Criterion, Randomized Clinical Trial, Binomial Distribution, Poisson Distribution, Clinical Trials as Topic, and Outcome measure
Research Interests: Cognitive Science, Neurology, Multiple sclerosis, Nonparametric Statistics, Incidence Geometry, and 15 moreMedicine, Italy, Acute Myeloid Leukemia, Humans, Internal Medicine, Female, Male, Follow-up studies, Clinical Sciences, Aged, Retrospective Studies, Neurosciences, Acute Myelocytic Leukemia, Analgesics, and Cumulative Incidence
The objective was to evaluate the safety, tolerability and effectiveness of intramuscular (IM) interferon beta-1a (IFNbeta-1a; Avonex, Biogen) 30 mg once a week in patients with onset of symptoms of multiple sclerosis (MS) in childhood or... more
The objective was to evaluate the safety, tolerability and effectiveness of intramuscular (IM) interferon beta-1a (IFNbeta-1a; Avonex, Biogen) 30 mg once a week in patients with onset of symptoms of multiple sclerosis (MS) in childhood or adolescence. Patients with a diagnosis of definite MS according to McDonald&#39;s criteria, relapsing course according to Lublin&#39;s criteria, onset of symptoms of MS before 16 years of age, and who had received IM IFNbeta-1a therapy before 16 years of age were eligible for the study if they had a pretreatment and treatment duration of at least 6 months. Clinical and laboratory evaluations were performed every 3 months. A total of 52 patients were identified as receiving treatment with IM IFNbeta-1a 30 mg once a week before 16 years of age. Mean age at onset of symptoms of MS was 11.7+/-2.7 years, mean disease duration was 25.9+/-30.3 months, mean annualised relapse rate was 1.9+/-1.1 and mean Expanded Disability Status Scale (EDSS) score was 1.5+/-1.1. After a mean (+/-SD) treatment duration of 42.9+/-19.9 months, annualised relapse rate decreased to 0.4+/-0.5. Final EDSS score was 1.3+/-1.1. Adverse events were recorded for 35 (67%) patients (flulike syndrome, 33%; headache, 29%; myalgia, 21%; fever, 11%; fatigue, 6%; nausea and vomiting, 6%; and skin reaction, 4%); most were transient. IM IFNbeta-1a was effective and well tolerated in these paediatric patients with MS.
Research Interests: Multiple sclerosis, Adolescent, Medicine, Humans, Child, and 15 moreFemale, Male, Clinical Sciences, Neurological, Adult, Adverse Event, Neuropediatrics, Neurosciences, SECONDARY PREVENTION, Translation for Neurological Sciences, Age of Onset, Age at Onset, Neurological Sciences, Disability Evaluation, and Paediatrics and reproductive medicine
Research Interests: Multiple sclerosis, Magnetic Resonance Imaging, Medicine, Italy, Brain, and 15 moreHumans, Female, Spinal Cord, Disease, Male, Neurofibromatosis, Rare Event, Prevalence, Adult, North East, Disease Progression, immunoglobulin G, Brain stem, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Research Interests: Neurology, Multiple sclerosis, Magnetic Resonance Imaging, Adolescent, Medicine, and 15 moreHumans, Child, Female, Male, Differential Diagnosis, Clinical Sciences, Aged, Middle Aged, Adult, Age Factors, Chi Square Distribution, Age at Onset, Diagnostic Criteria, Disability Evaluation, and High protein
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In this study, dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) was used to quantify the cerebral blood flow (CBF), the cerebral blood volume (CBV), and the mean transit time (MTT) and to analyze the changes in... more
In this study, dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) was used to quantify the cerebral blood flow (CBF), the cerebral blood volume (CBV), and the mean transit time (MTT) and to analyze the changes in cerebral perfusion associated with the cortical lesions in 44 patients with relapsing-remitting multiple sclerosis. The cortical lesions showed a statistically significant reduction in CBF and CBV compared with the normal-appearing gray matter, whereas there were no significant changes in the MTT. The reduced perfusion suggests a reduction of metabolism because of the loss of cortical neurons. A small population of outliers showing an increased CBF and/or CBV has also been detected. The presence of hyperperfused outliers may imply that perfusion could evolve during inflammation. These findings show that perfusion is altered in cortical lesions and that DSC-MRI can be a useful tool to investigate more deeply the evolution of cortical lesions in multiple scl...
Research Interests: Neuroscience, Cognitive Science, Neurology, Multiple sclerosis, Magnetic Resonance Imaging, and 15 moreInflammation, Medicine, Humans, Cerebral Cortex, Brain Circulation, Female, Male, Clinical Sciences, Middle Aged, Adult, Cerebral Blood Flow, Blood Flow Velocity, Magnetic resonance angiography, Cerebral Blood Volume, and Cardiovascular medicine and haematology
Research Interests: Magnetic Resonance Imaging, Medicine, Action observation, Brain Mapping, Humans, and 15 moreCerebral Cortex, Female, Mirror Neuron System, Functional Imaging, Male, Mirror Neuron, Action Understanding, Clinical Sciences, Experimental, Adult, Group Interaction, Hand, Experimental Neurology, Cortical Reorganization, and Functional Laterality
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Research Interests: Multiple sclerosis, Magnetic Resonance Imaging, Medicine, Brain, Prospective studies, and 13 moreHumans, Natural Killer cells, Female, Male, CD, Immune system, Longitudinal Studies, Adult, Prognosis, Immunophenotyping, Psychology and Cognitive Sciences, Medical and Health Sciences, and leukocyte Count
Research Interests: Cognitive Science, Multiple sclerosis, Magnetic Resonance Imaging, Archives, Inflammation, and 15 moreAdolescent, Medicine, Humans, Internal Medicine, Cerebral Cortex, Female, Male, Clinical Sciences, Middle Aged, Adult, Lesion, Neurosciences, immunoglobulin G, Magnetic resonance image, and Disability Evaluation
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Research Interests: Cognitive Science, Multiple sclerosis, Magnetic Resonance Imaging, Archives, Adolescent, and 15 moreMedicine, Comorbidity, Brain Mapping, Humans, Cerebral Cortex, Female, Male, Clinical Sciences, Middle Aged, Cognitive impairment, Atrophy, Adult, Disease Progression, Cross Sectional Studies, and Cognition disorders
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The clinical significance of Virchow Robin spaces (VRS) in inflammatory brain disorders, especially in multiple sclerosis (MS), is still undefined. We analysed enlarged VRS (eVRS) by means of phase sensitive inversion recovery (PSIR) MRI... more
The clinical significance of Virchow Robin spaces (VRS) in inflammatory brain disorders, especially in multiple sclerosis (MS), is still undefined. We analysed enlarged VRS (eVRS) by means of phase sensitive inversion recovery (PSIR) MRI sequence and investigated their association with inflammation or brain atrophy, and to clinical or physical disability. Forty-three MS patients (21 clinically isolated syndrome suggestive of MS [CIS], 15 RRMS, 7 progressive [PMS]) and 10 healthy controls (HC) were studied. 3DT1, 3DFLAIR and 2DPSIR images were obtained with a 3T MRI scanner. eVRS number and volume were calculated by manual segmentation (ITK-SNAP). Freesurfer was used to assess brain parenchymal fraction (BPF). All patients underwent clinical (EDSS) and cognitive (Rao's BRB and DKEFS) evaluation. eVRS number and volume resulted significantly higher on 2D-PSIR compared to both 3D-T1 (p<0.001) and 3D-FLAIR (p<0.001) and were significantly increased in CIS compared to HC (p<...
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Combined central and peripheral demyelination (CCPD) is a rare chronic inflammatory disorder of the nervous system. We describe the case of a patient with a history of recurrent myelitis that acutely and simultaneously developed a brain... more
Combined central and peripheral demyelination (CCPD) is a rare chronic inflammatory disorder of the nervous system. We describe the case of a patient with a history of recurrent myelitis that acutely and simultaneously developed a brain tumour-like lesion and a sensitive-motor demyelinating polyneuropathy. The diagnosis of CCPD was supported by a detailed diagnostic workup. Up to date, no similar cases have been reported in the literature.
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There is limited and inconsistent information on the clinical determinants of cognitive impairment (CI) in multiple sclerosis (MS). The aim of this study was to compare the prevalence and profile of CI across MS disease subtypes and... more
There is limited and inconsistent information on the clinical determinants of cognitive impairment (CI) in multiple sclerosis (MS). The aim of this study was to compare the prevalence and profile of CI across MS disease subtypes and assess its clinical determinants. Cognitive performance was assessed through the Brief Repeatable Battery and the Stroop test in consecutive patients with MS referred to six Italian centers. CI was defined as impairment in ⩾ 2 cognitive domains. A total of 1040 patients were included, 167 with clinically isolated syndrome (CIS), 759 with relapsing remitting (RR), 74 with secondary progressive (SP), and 40 with primary progressive (PP) disease course. The overall prevalence of CI was 46.3%; 34.5% in CIS, 44.5% in RR, 79.4% in SP, and 91.3% in PP. The severity of impairment and the number of involved domains were significantly higher in SP and primary progressive multiple sclerosis (PPMS) than in CIS and RR. In multivariable logistic regression analysis, t...
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To identify immunological markers that could be used to monitor relapsing-remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b (IFNβ1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T... more
To identify immunological markers that could be used to monitor relapsing-remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b (IFNβ1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T lymphocytes in 15 IFNβ1b-treated RRMS patients. Peripheral blood T cell subsets were analysed before therapy (T0), and after 1 (T1), 2 (T2), 3 (T3), 6 (T4) and 12 (T5) months after therapy initiation. HLADR expression and the CD3+HLA-DR+ T cell number showed a peculiar trend in almost all (14/15) the patients: a significant decrease at T1 and T2 followed by a return to pre-treatment levels from T3 to T5. At T1 and T2, eight patients showed an up-regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number. However, a marked, significant reduction of this T cell subset was observed in all the patients at T3, followed by the progressive return to pre-treatment values from T4 to T5. All the patients developed anti-IFNβ1b `binding&#39; antibodies within the first three months of therapy. Our findings demonstrate that: (1) the expression of HLA-DR and CD25 on T cells, as well as the number of circulating CD3+HLA-DR+ and CD4+CD25+ cells, are only transiently reduced in vivo in IFNβ1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T lymphocytes cannot be used to monitor MS course/activity during IFNβ1b therapy, (3) the long-lasting beneficial effect of IFNβ1b on RRMS reported in the literature cannot be explained by the down-regulation of MHC class II antigens and/or interleukin-2 receptor expression induced by this cytokine.
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Natalizumab is a promising option for pediatric multiple sclerosis (MS) patients with active evolution and a poor response to Interferon-beta or Glatiramer Acetate. However, no data are available in large cohorts of patients and after a... more
Natalizumab is a promising option for pediatric multiple sclerosis (MS) patients with active evolution and a poor response to Interferon-beta or Glatiramer Acetate. However, no data are available in large cohorts of patients and after a long-term follow up. Our study was planned to shed lights on this topic. A registry was established in 2007 in Italy to collect MS cases treated with Natalizumab (NA) before 18 years of age. 101 patients were included (69 females), mean age of MS onset 12.9 ± 2.7 years, mean age at NA initiation 14.7 ± 2.4 years. Mean treatment duration was 34.2 ± 18.3 months. During NA treatment, a total of 15 relapses were recorded in 9 patients, annualized relapse rate was 2.3 ± 1.0 in the year prior to NA and decreased to 0.1 ± 0.3 (p < 0.001) at last NA infusion. Mean Expanded Disability Status Scale (EDSS) decreased from 2.6 ± 1.3 at initiation of NA to 1.8 ± 1.2 at the time of last visit (p < 0.001). At brain MRI, new T2 or Gd enhancing lesions were obse...
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Background: The demonstration of cortical lesions (CL) in the cerebellum by magnetic resonance imaging (MRI) is hampered by technical and anatomical constraints. Objective: To investigate the occurrence of cerebellar CL and their... more
Background: The demonstration of cortical lesions (CL) in the cerebellum by magnetic resonance imaging (MRI) is hampered by technical and anatomical constraints. Objective: To investigate the occurrence of cerebellar CL and their correlation with cerebellar-related disability by combining Double Inversion Recovery (DIR) and Phase Sensitive Inversion Recovery (PSIR) MRI images in multiple sclerosis (MS) patients. Material and methods: 40 MS patients (10 CIS/eRRMS, 24 RRMS, 6 SPMS), having a wide range of disability and disease duration, were enrolled. DIR and PSIR images were obtained with a 3T-MRI. Results: Cerebellar white matter lesions (WML) and/or CL were observed in 33/40 patients (82.5%) among which 14/40 had only CL. CL were demonstrated in 26/40 patients by DIR and in 31/40 by PSIR, and their number increased from CIS/eRRMS to SPMS. PSIR disclosed a significantly higher number of CL compared to DIR (RRMS: p=0.0008; SPMS: p=0.002). CL number correlates with the cerebellar Exp...
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In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery (DIR) sequences have improved MRI... more
In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery (DIR) sequences have improved MRI sensitivity in the detection of cortical lesions (CLs) in patients with relapsing-onset MS. This 2-year longitudinal study was designed to assess the frequency, extent, and rate of formation of CLs in PPMS and their relationship with T2 lesion volume (LV), gray matter (GM) atrophy, and disability. Forty-eight patients with PPMS underwent clinical and magnetic resonance examinations at baseline and after 2 years. The number and volume of CLs, WM T2 LV, and GM fraction (GMf) were assessed at baseline and at follow-up. At baseline, CLs were detected in 81.2% of patients with PPMS. At least one new CL was found in 28 patients during the follow-up. In patients with PPMS, CL and T2 WM LVs increased over the follow-up. At baseline, CL number and volumes were significantly correlated with T2 WM LV, GMf, disease duration, and Expanded Disability Status Scale score, as well as with increasing GM atrophy and disability during the follow-up. A multivariate analysis showed that CL volume at baseline was an independent predictor of percentage GM volume change and disability accumulation during the subsequent 2-year period. Cortical lesions are a frequent finding in primary progressive multiple sclerosis. The extent of such abnormalities is associated with the extent of cortical atrophy and clinical disability, and is able to predict their changes over a medium time period.
Research Interests: Cognitive Science, Neurology, Magnetic Resonance Imaging, Adolescent, Multivariate Analysis, and 12 moreHumans, Cerebral Cortex, Female, Male, Young Adult, Clinical Sciences, Middle Aged, Longitudinal Studies, Adult, Disease Progression, Neurosciences, and Primary Progressive Multiple Sclerosis Market
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Among the diagnostic procedures aimed at defining the etiology and the pathogenesis of inflammatory myelopathies, the examination of the cerebrospinal fluid (CSF) plays a central role. Indeed, for several autoimmune and inflammatory... more
Among the diagnostic procedures aimed at defining the etiology and the pathogenesis of inflammatory myelopathies, the examination of the cerebrospinal fluid (CSF) plays a central role. Indeed, for several autoimmune and inflammatory syndromes and diseases involving the spinal cord, in addition to immunological screening of the blood, a detailed analysis of the CSF may allow the achievement of the diagnosis. Routine CSF analysis should include a detailed cytology, the evaluation of the blood-brain barrier dysfunction, quantitative and qualitative analysis of the intrathecal IgG synthesis (i.e. calculation of the IgG index and demonstration of oligoclonal IgG bands), and immunological and virological tests based on immunoenzymatic (ELISA, RIA) and molecular biology techniques (PCR, nested PCR). A more advanced step includes fluorescence-activated cell sorting (FACS) analysis of CSF lymphocytes, and, when possible, virological and immunological tests on cell culture supernatants.
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The demonstration of intrathecally synthesized IgG constitutes one of the most important aids in the diagnosis of multiple sclerosis (MS). This can be done either by the application of empirical formulae or by analytical electrophoretic... more
The demonstration of intrathecally synthesized IgG constitutes one of the most important aids in the diagnosis of multiple sclerosis (MS). This can be done either by the application of empirical formulae or by analytical electrophoretic migration of IgG. However, all methods are influenced by the presence of blood-brain barrier (BBB) damage, as confirmed by the present study. We compared the results achieved by the application of 3 formulae (IgG index, intra-BBB IgG synthesis rate, IgG hyperbolic function) to those by isoelectric focusing (IEF) of unconcentrated cerebrospinal fluid (CSF). The most reliable method to detect intrathecal IgG production was IEF followed by specific immunofixation; even so, this method was subjected to pitfalls due to BBB damage. All formulae gave incorrect and misleading results, especially in case of BBB damage. Therefore, this limiting factor should be considered when formulae are used for clinical purposes.
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ABSTRACT
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Research Interests: Adolescent, HIV, Humans, Female, Male, and 15 moreThe, Brain Ischemia, Antiphospholipid antibodies, Clinical Sciences, Middle Aged, Adult, Cerebrovascular Disorders, Neurosciences, Enzyme Linked Immunosorbent Assay, Nervous System Diseases, immunoglobulin G, Neurosyphilis, immunoglobulin M, HIV infections, and Migraine disorders
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Using an immunocytochemical method we demonstrated the presence of TfR on adult rat neurons, particularly in the cerebral cortex and brain stem. The monoclonal antibody (mab) against rat TfR (clone OX 26) stained neurons of all cortical... more
Using an immunocytochemical method we demonstrated the presence of TfR on adult rat neurons, particularly in the cerebral cortex and brain stem. The monoclonal antibody (mab) against rat TfR (clone OX 26) stained neurons of all cortical layers and in the brain stem where the reaction was most evident. Purkinje cells in the cerebellum and scattered neurons in the gray matter of the cervical spinal cord were weakly stained. Choroid plexus cells also reacted with the mab against TfR whereas oligodendrocytes in the cerebral white matter were faintly outlined by the mab. The presence of TfR on endothelial cells of brain capillaries was here confirmed.
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Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to... more
Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated. 115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed. We found a significant global cortical thinning in p-MS (2.22 +/- 0.09 mm), RR-MS (2.16 +/- 0.10 mm) and SP-MS (1.98 +/- 0.11 mm) compared to CIS (2.51 +/- 0.11 mm) and HV (2.48 +/- 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = -0.393, p = 0.03) and absent in p-MS (r = -0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas. Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology.
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ABSTRACT