Biomedical subjects

M Rovaris

Publications and source records attributed to M Rovaris.

At least 19 recordsLinked to original sources

PubMed2003

The effect of interferon beta-1b on quantities derived from MT MRI in secondary progressive MS.

BACKGROUND: Magnetization transfer (MT) MRI can provide in vivo markers reflecting the severity of irreversible, MS-related brain damage occurring within and outside T2-visible lesions. OBJECTIVE: To assess the effect of interferon (IFN) beta-1b treatment on the accumulation of brain damage in patients with secondary progressive (SP) MS, measured using MT MRI. METHODS: Eighty-two patients with SPMS from five centers participating in a European, multicenter, double-blind, placebo-controlled trial of IFNbeta-1b in SPMS underwent brain T2-weighted and MT MRI at baseline. Evaluable follow-up data were available for 75 patients at 12 months, 54 at 24 months, and 47 at 36 months. MT MRI scans were postprocessed and analyzed to obtain histograms of MT ratio (MTR) values from the whole brain. A region of interest-based analysis of MTR values from the normal-appearing white matter (NAWM) was also performed. RESULTS: In both the treatment arms, there was a decrease of average brain MTR values from baseline to month 24 (mean change -4.9%) and month 36 (mean change -4.3%). These changes were significant for the placebo group at both timepoints and for the IFNbeta-1b group at month 24 only, with no significant treatment effect. A decrease of NAWM MTR was also observed, with no significant difference between the two treatment arms. CONCLUSION: In this cohort of patients with secondary progressive MS, interferon beta-1b did not show an overall effect on the worsening of magnetization transfer MRI measures, when compared with placebo. The data show that change in magnetization transfer ratio is a promising tool for monitoring disease evolution in secondary progressive MS and that the information obtained from magnetization transfer MRI complements that obtained from MRI measures of lesion load and inflammation.

Adult↗

PubMed2003

Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis.

Although axonal pathology is recognized as one of the major pathological features of multiple sclerosis, it is less clear how early in its course it occurs and how it correlates with MRI-visible lesion loads. To assess this early axonal pathology, we quantified the concentration of whole-brain N-acetylaspartate (WBNAA) in a group of patients at the earliest clinical stage of the disease and compared the results with those from healthy controls. Conventional brain MRI and WBNAA using unlocalized proton magnetic resonance spectroscopy were obtained from 31 patients at presentation with clinically isolated syndromes suggestive of multiple sclerosis and paraclinical evidence of dissemination in space, and from 16 matched controls. An additional conventional MRI scan was obtained in all patients 4-6 months later to detect dissemination of lesions in time. The mean WBNAA concentration was significantly lower in patients compared with the controls (P < 0.0001). It was not significantly different between patients with and without enhancing lesions at the baseline MRI or between patients with and without lesion dissemination in time. No correlation was found between WBNAA concentrations and lesion volumes. Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis. This finding lessens the validity of the current concept that the axonal pathology of multiple sclerosis is the end-stage result of repeated inflammatory events, and argues strongly in favour of early neuroprotective intervention.

Adult↗

PubMed2003

Beta endorphin concentrations in PBMC of patients with different clinical phenotypes of multiple sclerosis.

The possible link between the opioid peptide beta endorphin and the heterogeneity of the clinical course of multiple sclerosis (MS) was investigated. Peripheral blood mononuclear cells (PBMC) concentrations of beta endorphin were measured in 50 patients in different phases of MS. Thirty nine patients also underwent post-contrast magnetic resonance imaging of the brain. Among MS forms, the highest beta endorphin concentrations were found in PBMC from patients with relapsing remitting MS and the lowest in patients with the progressive forms. Average beta endorphin concentrations were lower, although not significantly, in patients with than in those without magnetic resonance imaging enhanced lesions. These data suggest that beta endorphin may have a role in the downregulation of the inflammatory process.

Adult↗

PubMed2002

Effect of glatiramer acetate on MS lesions enhancing at different gadolinium doses.

This baseline-vs-treatment study of 20 patients with relapsing-remitting MS investigated whether glatiramer acetate (GA) has a graduated effect on MS inflammatory activity, which was measured using monthly, standard, and triple dose gadolinium (Gd)-enhanced MRI. GA significantly reduced the mean numbers of enhancing lesions/patient/month on both standard dose and triple dose scans, without interactions with the Gd dose. GA is effective in reducing MS activity, independent of the severity of the MRI-detectable inflammatory process.

Adolescent↗

PubMed2002

Contribution of cervical cord MRI and brain magnetization transfer imaging to the assessment of individual patients with multiple sclerosis: a preliminary study.

This study was performed to assess how established diagnostic criteria for brain magnetic resonance imaging (MRI) interpretation in cases of suspected multiple sclerosis (MS) (Barkhofs criteria) would perform in the distinction of MS from other diseases and whether other MR techniques (cervical cord imaging and brain magnetization transfer imaging [MTI]), might help in the diagnostic work-up of these patients. We retrospectively identified 64 MS and 59 non-MS patients. The latter group included patients with systemic immune-mediated disorders (SID; n=44) and migraine (n=15). All patients had undergone MRI scans of the brain (dual echo and MTI) and of the cervical cord (fast short-tau inversion recovery). The number and location of brain T2-hyperintense lesions and the number and size of cervical cord lesions were assessed. Brain images were also postprocessed to quantify the total lesion volumes (TLV) and to create histograms of magnetization transfer ratio (MTR) values from the whole of the brain tissue. Barkhofs criteria correctly classified 108/123 patients, thus showing an accuracy of 87.8%. "False negative" MS patients were 13, while 2 patients with systemic lupus erythematosus (SLE) were considered as "false positives". Using brain T2 TLV, nine of the "false negative" patients were correctly classified. Correct classification of 10 MS patients and both the SLE patients was possible based upon the presence or absence of one cervical cord lesion. Two MS patients with negative Barkhofs criteria and no cervical cord lesions were correctly classified based on their brain MTR values. Overall, only one MS patient could not be correctly classified by any of the assessed MR quantities. These preliminary data support a more extensive use of cervical cord MRI and brain MTI to differentiate between MS and other disorders in case of incondusive findings on T2-weighted MRI scans of the brain.

Adolescent↗

PubMed2002

Two-year follow-up study of primary and transitional progressive multiple sclerosis.

This study documents changes in clinical and magnetic resonance imaging (MRI) characteristics in a large cohort of patients with primary and transitional progressive multiple sclerosis (PP and TPMS) over 2 years. Patients with PPMS and TPMS were recruited from six European centres and underwent clinical and MRI examination at three time points: baseline, year one and year two. Of the 190 patients recruited clinical data were available on 125 patients (66%, five centres) and MRI data were available on 113 patients (59%, four centres) at 2 years. Significant increases were seen in T2 load and T1 hypointensity, while brain and cord volume decreased. In PPMS significantly higher lesion loads were found in those who presented with non-cord syndromes when compared to cord presentation and there was a trend to greater brain atrophy in those who deteriorated clinically over the course of the study compared to those who remained stable. Significant cord atrophy was only seen in those with a cord presentation. Measurable changes in MRI parameters can be detected in PPMS patients over a relatively short period of time. MRI quantification is likely to be useful in elucidating disease mechanisms in PPMS and in the execution of clinical trials.

Adult↗

PubMed2001

Sample size estimations for MRI-monitored trials of MS comparing new vs standard treatments.

The authors estimated the sample sizes needed for exploratory trials of MS assessing the efficacy of new treatments in reducing the number of new enhancing lesions vs those of interferon-beta or glatiramer acetate. The sample sizes per arm ranged from 868 (effect: 20%) to 94 (effect: 50%) for patients with relapsing-remitting MS and from 2,484 (effect: 20%) to 361 (effect: 50%) for patients with secondary progressive MS. In MS, exploratory trials of new vs available therapies require large numbers of patients, even when MR end-points are used.

Adjuvants, Immunologic↗

PubMed2001

Glatiramer acetate reduces the proportion of new MS lesions evolving into "black holes".

The authors evaluated whether glatiramer acetate (GA) modifies the severity of tissue damage in 1,722 new lesions from 239 patients with MS enrolled in a placebo-controlled trial monitored with monthly cerebral MRI. The percentage of new lesions that evolved into "black holes" was lower in GA-treated than in placebo patients on scans at 7 (18.9 and 26.3%; p = 0.04) and 8 (15.6 and 31.4%; p = 0.002) months after lesion appearance. GA has a favorable effect on tissue disruption in MS lesions once they are formed.

Adolescent↗

PubMed2001

Magnetization transfer and diffusion tensor MR imaging of the optic radiations and calcarine cortex from patients with Leber's hereditary optic neuropathy.

Optic nerve abnormalities are easily detectable in patients with Leber's hereditary optic neuropathy (LHON), using magnetic resonance imaging (MRI). However, the presence of structural changes in the optic radiations and calcarine cortex of these patients is still an unresolved issue. In this study, we obtained magnetization transfer (MT) and diffusion tensor (DT) MRI to investigate the integrity of these structures in patients with LHON. Dual echo, MT- and DT-MRI scans of the brain were obtained from 10 men with LHON and 10 healthy sex- and age-matched controls. After image co-registration, we obtained MT ratio (MTR), average diffusivity (D) and fractional anisotropy (FA) maps. MTR, D and FA values for the white matter of the optic radiations and MTR and D values for the calcarine cortex were obtained using a region of interest (ROI) analysis. No macroscopic abnormalities were detected in any of the scans from LHON patients and controls. No statistically significant differences of MTR, D or FA values were found for any of the regions studied in LHON patients and healthy controls. Our results suggest that, in patients with LHON, the optic radiations and the calcarine cortex are spared from structural damage, both at a macroscopic and a microscopic level.

Adult↗

PubMed2001

Delivery to the central nervous system of a nonreplicative herpes simplex type 1 vector engineered with the interleukin 4 gene protects rhesus monkeys from hyperacute autoimmune encephalomyelitis.

Systemic administration of antiinflammatory molecules to patients affected by immune-mediated inflammatory demyelinating diseases of the central nervous system (CNS) has limited therapeutic efficacy due to the presence of the blood-brain barrier (BBB). We found that three of five rhesus monkeys injected intrathecally with a replication-defective herpes simplex virus (HSV) type 1-derived vector engineered with the human interleukin 4 (IL-4) gene were protected from an hyperacute and lethal form of experimental autoimmune encephalomyelitis induced by whole myelin. The intrathecally injected vector consistently diffused within the CNS via the cerebrospinal fluid and infected ependymal cells, which in turn sustained in situ production of IL-4 without overt immunological or toxic side effects. In EAE-protected monkeys, IL-4-gene therapy significantly decreased the number of brain as well as spinal cord inflammatory perivenular infiltrates and the extent of demyelination, necrosis, and axonal loss. The protective effect was associated with in situ downregulation of inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP-1), upregulation of transforming growth factor beta (TGF-beta), and preservation of BBB integrity. Our results indicate that intrathecal delivery of HSV-1-derived vectors containing antiinflammatory cytokine genes may play a major role in the future therapeutic armamentarium of inflammatory CNS-confined demyelinating diseases and, in particular, in the most fulminant forms where conventional therapeutic approaches have, so far, failed to achieve a satisfactory control of the disease evolution.

Animals↗

PubMed2001

Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study.

BACKGROUND: Interferon beta reduces activity in multiple sclerosis as measured clinically and by magnetic resonance imaging (MRI). We assessed the effect of interferon beta-1a on the occurrence of relapses in patients after first presentation with neurological events, who are at high risk of conversion to clinically definite multiple sclerosis. METHODS: Eligible patients had had a first episode of neurological dysfunction suggesting multiple sclerosis within the previous 3 months and had strongly suggestive brain MRI findings. Patients were randomly assigned interferon beta-1a 22 microg or placebo subcutaneously once weekly for 2 years. Neurological and clinical assessments were done every 6 months and brain MRI every 12 months. Analyses excluded one patient assigned placebo who received no study injections. FINDINGS: 241 (78%) of 308 randomised patients received study treatment for 2 years; 278 (90%) remained in the study until termination. 57 (85%) of 67 who stopped therapy did so after conversion to clinically definite multiple sclerosis. Fewer patients developed clinically definite multiple sclerosis in the interferon group than in the placebo group (52/154 [34%] vs 69/154 [45%]; p=0.047). The time at which 30% of patients had converted to clinically definite multiple sclerosis was 569 days in the interferon group and 252 in the placebo group (p=0.034). The annual relapse rates were 0.33 and 0.43 (p=0.045). The number of new T2-weighted MRI lesions and the increase in lesion burden were significantly lower with active treatment. INTERPRETATION: Interferon beta-1a treatment at an early stage of multiple sclerosis had significant positive effects on clinical and MRI outcomes.

Adolescent↗

PubMed2001

The role of non-conventional MR techniques to study multiple sclerosis patients.

Conventional magnetic resonance imaging (MRI) lacks pathological specificity to the heterogeneous substrates of multiple sclerosis (MS) lesions and is not able to detect subtle, disease-related changes in the normal-appearing white matter (NAWM). As a consequence, the correlation between MRI findings and the long-term evolution of MS is moderate at best. To overcome the limitations of conventional MRI, new quantitative magnetic resonance (MR) techniques, such as cell-specific imaging, magnetization transfer imaging (MTI), proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and functional MR imaging (fMRI) have all been recently applied to the study of MS. These techniques should provide more accurate and pathologically specific estimates of the MS lesion burden than conventional MR and should improve our understanding of the mechanisms leading to MS-related irreversible disability.

Humans↗

PubMed2001

An MR study of tissue damage in the cervical cord of patients with migraine.

Hyperintense abnormalities on T2-weighted magnetic resonance (MR) scans of the brain from patients with migraine are a relatively frequent finding and may represent a diagnostic challenge. We studied the cervical cord of patients with migraine using T2-weighted and magnetization transfer (MT) scans to assess whether the study of macro- and microscopic tissue damage in the cervical cord of these patients may have some diagnostic utility. T2-weighted and MT scans of the cervical cord and dual-echo scans of the brain were acquired from 16 patients with migraine and 17 sex- and age-matched healthy volunteers. Cervical cord MT ratio (MTR) histograms were obtained from all subjects and the relative peak height, the peak position, and the average MTR measured. Five migraine patients (31%) had hyperintense lesions in the brain. Neither healthy controls nor patients with migraine had any abnormalities on cervical cord MR scans. There was no difference for any of the cord MTR histogram-derived metrics between patients with migraine and healthy controls. No MTR histogram-derived measures from migraine patients were 2 standard deviations below the mean values from controls. Patients with migraine do not have MR or MT abnormalities in the cervical cord. MR scanning of the cervical cord in patients with migraine and hyperintense brain lesions of unknown etiology may be a useful investigation to facilitate the diagnostic workout.

Adolescent↗

PubMed2001

Differential diagnosis of posterior fossa multiple sclerosis lesions--neuroradiological aspects.

Various infratentorial pathological conditions can mimic multiple sclerosis (MS) both clinically and radiologically. We review the inflammatory, vascular, neoplastic and metabolic conditions which show features similar to those of MS on magnetic resonance imaging (MRI). Behcet's disease, Lyme disease, progressive multifocal leukoencephalopathy, neurosarcoidosis, Whipple's disease, listeria rhombencephalitis, Bickerstaff's brainstem encephalitis, vasculitis due to systemic lupus erythematosus, and acute disseminated encephalomyelitis produce inflammatory lesions similar to those of MS in the brainstem and cerebellum. Neoplastic diseases, in particular pontine gliomas and lymphomas, can mimic MS. Vascular ischaemic lesions, either due to infarction produced by occlusion of a major posterior circulation artery or due to small vessel vasculopathy, can lead to posterior fossa lesions. The MRI changes of central pontine myelinolysis can also mimic MS. Diffuse axonal injury, radiation and chemotherapy induce lesions that resemble MS, however the clinical history will exclude these possibilities. Finally, we discuss a few conditions which are similar to MS in clinical presentation but have different MRI appearances, such as brainstem cavernomas, posterior fossa tumoural lesions, aneurysms and vascular loops producing neurovascular conflicts. Analysis of the MRI findings with clinical history and laboratory data helps to narrow down the diagnosis of the infratentorial pathology.

Brain↗

PubMed2001

Clinical and MRI assessment of brain damage in MS.

Cognitive impairment in multiple sclerosis (MS), generally in the form of the so-called subcortical dementia, results predominantly by the disruption of communication among cortical and subcortical areas, consequent to white matter damage. Studies with conventional magnetic resonance imaging (MRI) demonstrated that cognitive impairment in MS patients is related to lesion burden, although the strength of this correlation is weak. This can be partially explained by the poor pathological specificity of conventional MRI techniques and by damage in the normal-appearing white matter (NAWM). This interpretation is supported by studies using non-conventional MRI techniques, more specific to the heterogeneous substrates of MS pathology, such as the assessment of hypointense lesion load on T1-weighted scans and the measurement of the magnetization transfer ratio (MTR) of whole brain, MS lesions and NAWM. Other factors, such as the site of MS lesions and the presence of active inflammation, also seem to play an important role.

Brain↗

PubMed2001

Neuroimaging techniques in the diagnostic work-up of patients with the antiphospholipid syndrome.

The detection of multisystemic involvement often leads to a correct diagnosis of the antiphospholipid syndrome (APS), even in cases with predominant neurologic manifestations. However, when central nervous system deficits are isolated and have a relapsing-remitting or a progressive course, other conditions must be carefully considered. In this context, the diagnostic accuracy of conventional magnetic resonance imaging (MRI) is hampered by its limited pathologic specificity, which is one of the reasons why no or only modest correlations have been found between the burden of MRI-visible lesions and other clinical or laboratory measures of disease severity in patients with APS. Neuroimaging techniques with a higher pathologic specificity than conventional MRI show promise in achieving diagnostic confidence earlier in the course of APS and in better monitoring the efficacy of therapeutic interventions.

Antibodies, Antiphospholipid↗

PubMed2001

In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis.

In patients with primary progressive (PP) multiple sclerosis, brain MRI lesion activity and burden are low, despite the presence of severe neurological impairment. On the contrary, the degree of cord atrophy and diffuse tissue damage in the brain and cervical cord have been found to be associated with clinical disability. Against this background, this study aimed at providing an in vivo indirect assessment of brain and cervical cord pathology in a large cohort of PP multiple sclerosis patients, using conventional MRI and magnetization transfer imaging (MTI). Ninety-one PP multiple sclerosis patients, 36 secondary progressive (SP) multiple sclerosis patients and 30 healthy controls underwent brain and cervical cord MRI scans, using dual echo (brain) or fast short-tau inversion recovery (cervical cord) MTI and T(1)-weighted sequences. For the brain, T(2) hyperintense and T(1) hypointense lesion volumes were calculated and the volume of the whole of the brain tissue measured. For the cervical cord, the number and burden of lesions and the cross-sectional area were assessed. MTI scans were post-processed and analysed to obtain magnetization transfer ratio (MTR) histograms from the whole of the brain and cervical cord tissue and from the normal-appearing brain tissue in isolation. In PP multiple sclerosis patients, brain, normal-appearing brain tissue and cervical cord MTR histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP multiple sclerosis patients, even though SP multiple sclerosis patients had higher MRI-visible lesion burdens. None of the correlations between MRI or MTI measures obtained from the brain and the cord were significant. PP multiple sclerosis patients' disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of cervical cord tissue. Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SP multiple sclerosis patients with similar levels of disability. They also suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PP multiple sclerosis.

Adult↗

PubMed2001

Short-term brain volume change in relapsing-remitting multiple sclerosis: effect of glatiramer acetate and implications.

The assessment of brain volume change with serial MRI provides an objective measure of an important component of the pathology of multiple sclerosis. Glatiramer acetate (GA) has a beneficial effect on clinical and MRI measures of disease activity and burden in patients with relapsing-remitting (RR) multiple sclerosis. This study investigated the impact of GA treatment on the development of brain atrophy in RR multiple sclerosis patients. The study consisted of a 9-month, double-blind, placebo-controlled phase followed by a 9-month open-label phase. Patients were randomized to receive either 20 mg GA or placebo by daily subcutaneous injections and underwent brain MRI scans every month during the first phase, and every 3 months during the second phase of the study. Using a semi-automated segmentation technique based on local thresholding, brain volume was measured from seven contiguous periventricular slices from the scans obtained at baseline, the end of the double-blind phase and the end of the study. From the original trial cohort, image sets from 113 out of 119 patients randomized to GA, and 114 out of 120 randomized to placebo treatment were evaluated. Brain volume was significantly correlated with patients' disability at each time-point. No significant differences between placebo- and GA-treated patients were found for baseline brain volume and rate of brain volume change over the study, even though a possible late trend for treatment with GA to retard the loss of brain volume was observed. There was a significant, but modest, correlation between MRI activity during the double-blind phase, and brain volume change over the entire study among patients originally treated with placebo. The modest correlation between enhancement frequency and brain atrophy loss indicates that the suppression of inflammatory activity in RR multiple sclerosis patients is not fully and rapidly associated with a similar effect on the global neurodegenerative processes. This study also suggests that any effect of GA in preventing brain volume decrease is not evident early following institution of treatment.

Adult↗