Biomedical subjects

V Martinelli

Publications and source records attributed to V Martinelli.

At least 19 recordsLinked to original sources

PubMed2006

Grey matter damage predicts the evolution of primary progressive multiple sclerosis at 5 years.

Reliable prognostic markers of primary progressive (PP) multiple sclerosis evolution are still needed. Diffusion tensor (DT) MRI can quantify normal-appearing white matter (NAWM) and grey matter (GM) damage in multiple sclerosis patients. We investigated whether conventional and DT-MRI-derived measures can predict the long-term clinical evolution of PP multiple sclerosis. In 54 PP multiple sclerosis patients, conventional and DT-MRI scans of the brain and T1-weighted scans of the cervical cord were acquired at baseline and after a median follow-up of 15 months. Another clinical evaluation was performed, 56 months after baseline, in 52 patients. Measures of lesion load, brain and cord atrophy were obtained. Histograms of the mean diffusivity (MD) and fractional anisotropy (FA) values from the NAWM and GM were analysed. At follow-up, 35 patients (65%) experienced a confirmed disability progression. Baseline expanded disability status scale score and average GM MD were independent predictors of subsequent clinical deterioration in a multivariable model (Nagelkerke R2: 0.44; discriminating ability: 81%). A lower level of disability and a more severe GM damage identify PP multiple sclerosis patients with an increased risk of disease progression over the subsequent 5 years. These data may be relevant to select patients for future exploratory phase II trials.

Adult↗

PubMed2006

Grading cervical cord damage in neuromyelitis optica and MS by diffusion tensor MRI.

The authors assessed the ability of diffusion tensor MRI to grade cervical cord damage in 10 patients with neuromyelitis optica, 10 patients with multiple sclerosis, and 10 healthy controls. The three groups differed in terms of average mean diffusivity (p = 0.008) and average fractional anisotropy (p = 0.04). There was a correlation between the Expanded Standard Disability Status Scale score and cord average mean diffusivity (r = 0.52, p = 0.02).

Adult↗

PubMed2006

Multimodal evoked potentials to assess the evolution of multiple sclerosis: a longitudinal study.

BACKGROUND: Evoked potentials are used in the functional assessment of sensory and motor pathways. Their usefulness in monitoring the evolution of multiple sclerosis has not been fully clarified. OBJECTIVE: The aim of this longitudinal study was to examine the usefulness of multimodal evoked potential in predicting paraclinical outcomes of disease severity and as a prognostic marker in multiple sclerosis. METHODS: Eighty four patients with clinically definite multiple sclerosis underwent Expanded Disability Status Scale (EDSS) and functional system scoring at study entry and after a mean (standard deviation) follow-up of 30.5 (11.7) months. Sensory and motor evoked potentials were obtained in all patients at study entry and at follow-up in 64 of them, and quantified according to a conventional score. RESULTS: Cross-sectionally, the severity of each evoked potential score significantly correlated with the corresponding functional system (0.32 < R < 0.60, p < 0.01, for all but follow-up visual evoked potential) and with EDSS (0.34 < R < 0.61; p < 0.001 for all but brain stem evoked potential). EDSS significantly correlated with global evoked potential score severity (baseline R = 0.60, follow-up R = 0.46, p < 0.001). Using longitudinal analysis, only changes in somatosensory evoked potential scores were significantly correlated with changes of sensory functional system (R = 0.34, p = 0.006). However, patients with multiple sclerosis with disability progression at follow-up had more severe baseline evoked potential scores than patients who remained stable. Patients with severe baseline global evoked potential score (higher than the median value) had a risk of 72.5% to progress on disability at follow-up, whereas patients with multiple sclerosis with lower scores had a risk of only 36.3%. CONCLUSIONS: These results suggest that evoked potential is a good marker of the severity of nervous damage in multiple sclerosis and may have a predictive value regarding the evolution of disability.

Adult↗

PubMed2006

Combination therapy.

So far, off-label recommendation of a combination therapy is mainly based on phase II study evidence and on largely accepted expert opinions. Combination therapy represents a new, more global strategy, to increase the possible benefits with the combined use of already available disease-modifying therapies or with other new agents, having an acceptable theoretical rationale and a good safety and efficacy profile. The therapeutic strategies of the near future will try to select among different and individualised combinations of drugs, with distinct mechanisms of action, and possibly with synergistic activity, to maximise benefits and minimise risks. The combination approach is at present particularly recommended for more aggressive forms of multiple sclerosis (MS) and for non-responders to available drugs, although the theoretical rationale and accumulated experience would suggest its use in all MS patients right from the beginning of the disease.

Clinical Trials, Phase II as Topic↗

PubMed2006

Severe reactivation of hepatitis B virus infection in a patient with hairy cell leukemia: Should lamivudine prophylaxis be recommended to HBsAg-negative, anti-HBc-positive patients?

The reverse seroconversion to hepatitis B virus infection has been sporadically described in onco-haematological patients receiving cytotoxic therapy or allogeneic bone marrow transplantation and can be associated with the development of acute icteric hepatitis. We present a male HBsAg-negative, anti-HBc-positive patient with Hairy Cell Leukemia who developed acute B hepatitis more than 1 year after the last course of 2-CdA and 6 months after splenectomy, while the patient was receiving therapy with alphaIFNr. The acute B hepatitis promptly responded to lamivudine therapy followed by viral clearance.

Aged↗

PubMed2005

Axonal injury in early multiple sclerosis is irreversible and independent of the short-term disease evolution.

OBJECTIVE: To define the nature and the temporal evolution of neuronal/axonal injury in patients at the earliest clinical stage of multiple sclerosis (MS), using whole brain N-acetylaspartate (WBNAA) proton MR spectroscopy (1H-MRS). METHODS: Thirty-five patients at presentation with clinically isolated syndromes (CIS) and MRI evidence of disease dissemination in space were studied. The following scans of the brain were acquired within 3 months from the onset of the disease and after 12 months: 1) dual-echo; 2) WBNAA 1H-MRS; 3) pre- and postcontrast T1-weighted. The same scans were obtained in 12 age-matched healthy subjects, without contrast administration. In patients, conventional MRI scans were also repeated 3 months after the first scanning session, to assess the presence of early disease dissemination in time (DIT). RESULTS: Over the study period, 24 patients showed MRI evidence of disease DIT, thus fulfilling the criteria for a diagnosis of MS. The average WBNAA amount was lower in CIS patients than in controls both at baseline (13.7 vs 16.9 mM, p < 0.001) and at 1-year follow-up (12.6 vs 16.2 mM, p < 0.001), but the average yearly percentage change of WBNAA did not differ between the two groups. No MRI or 1H-MRS quantities were significantly associated with the disease DIT over the study period. CONCLUSION: Irreversible brain damage associated with axonal dysfunction occurs at a very early stage in patients with clinically isolated syndromes, but it does not seem to be related with the disease evolution in the subsequent short-term period.

Adult↗

PubMed2005

Movement preparation is affected by tissue damage in multiple sclerosis: evidence from EEG event-related desynchronization.

OBJECTIVE: To investigate the impact of brain tissue damage in Multiple Sclerosis (MS) on the efficiency of programming of voluntary movement, assessed using event-related desynchronization of the EEG. METHODS: The onset latency of mu ERD (percent desyncronization of the mu rhythm preceding movement onset) to hand movement was studied in 34 MS patients. ERD onset was compared with normative data and correlated with T1 and T2 total lesion volume (TLV) at magnetic resonance imaging (MRI). RESULTS: ERD onset latency was significantly correlated with T1-TLV (r = 0.53, P = 0.001) and T2 lesion load (r = 0.5, P = 0.003), even after correcting for disability. Patients with higher T1-TLV had significantly delayed ERD onset compared with normal subjects and with patients with lower T1-TLV; patients with higher T2-TLV had significantly delayed ERD compared with normal subjects only. ERD onset latency was not correlated to clinical disability. CONCLUSIONS: Our finding of delayed ERD onset in patients with more severe measures of brain damage, independently from clinical disability, suggests that functional cortico-cortical and cortico-subcortical connections underlying the expression of ERD during programming of voluntary movement are disrupted by the MS related pathological process. Further, studies are needed to evaluate the role of specific anatomical cortico-subcortical circuits in determining this abnormality. SIGNIFICANCE: The extent of brain lesion load in multiple sclerosis affects cortical changes related to motor preparation, detected by analysis of onset latency of event-related desynchronization (ERD) of the mu rhythm to self-paced movement.

Adult↗

PubMed2005

Induction versus escalation therapy.

Most of the consensus groups in Europe and America support an early decision-making therapeutic approach in patients with a diagnosis of multiple sclerosis (MS), either with interferon-beta or glatiramer acetate, which have been demonstrated to be a reasonable therapeutic strategy because of their benefit. The "treat-early approach" within disease management is based on the assumption, particularly during the early phase of the disease, of the reduction of both relapse rate and of the ongoing inflammatory processes may delay irreversible neurological damages. As soon as the MS diagnosis is certain or even in patients with a first episode suggestive of MS, with negative prognostic factors and a typical presentation, "induction therapy", which is more aggressive on the immune system, seems to have more relevant short- and long-lasting beneficial effects. However, if the disease course is suboptimally controlled, an "escalating strategy", using mitoxantrone, cyclophosphamide, various other immunoactive agents or a combination of different drugs, is suggested. The current challenge in therapeutic strategy is to identify the most effective drug, or combination of drugs, during a specific phase of the disease for each single patient. Anyhow, the decision to adopt a combination therapy in patients with a low response to monotherapy should not be delayed until severe irreversible disability is evident.

Adjuvants, Immunologic↗

PubMed2005

Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study.

OBJECTIVE: Immunomodulatory drugs (IDs) (interferon beta (IFNgamma) and glatiramer acetate (GA)) reduce relapse rate and disease progression in relapsing remitting multiple sclerosis (RRMS) but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. The aim of this study was to evaluate the impact of IFNbeta and GA in MS patients treated before 16 years of age. METHODS: A research group (Immunomodulatory Treatment of Early onset MS (ITEMS)) was promoted in Italy to collect a large series of patients affected by clinically definite and RRMS and treated with IDs before 16 years of age. Fifteen centres recognized subjects suitable for inclusion: 76 patients (52 females) were collected with a mean age at onset of 12.4 (SD 2.5) years, a mean disease duration of 18.6 (SD 14.7) and a relapse rate of 3.1 (SD 2.9). RESULTS: Results were evaluated in 65 (45 females) subjects with a pretreatment and a treatment duration >3 months: 38 were treated with IFNbeta-1a once weekly (Avonex), 18 with IFNbeta three times weekly (16 with Rebif, 2 with Betaferon) and nine with GA (Copaxone). The mean pretreatment period was respectively 20, 18 and 9.2 months. The treatment duration lasted respectively 23.3, 40.7 and 33.3 months. The mean annualized relapse rate decreased dramatically during the treatment: from 2.4 to 0.4 in the Avonex group, from 3.2 to 0.8 in the Rebif-Betaferon group and from 2.8 to 0.25 in the GA group. The mean final EDSS scores were respectively (in brackets the initial scores): 1.3 (1.4), 1.6 (1.8) and 0.6 (1.1). In the whole group, the final score was unchanged or reduced in all subjects except eight. Clinical side effects were recorded in 41/65 subjects (mainly in subjects treated with IFNbeta), abnormal laboratory findings were observed in 13/65 subjects: they were transient in most cases. IFNgamma was stopped in six cases: in four because of inefficacy and in two cases because of side effects. CONCLUSIONS: Sixty-five clinically definite MS subjects were treated during childhood or adolescence with IDs. The treatment reduced the relapse rate and the progression of the disease in most cases. Side effects were common in subjects treated with IFNbeta but were well tolerated in most cases.

Adjuvants, Immunologic↗

PubMed2004

The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study.

In a multicenter cross-sectional study, the authors assessed pain in patients with multiple sclerosis (MS) using a symptom-oriented approach. Out of 2,077 questionnaires, we used 1,672 for data analysis. Pain and frequencies included trigeminal neuralgia 2%, Lhermitte's sign 9%, dysesthetic pain 18.1%, back pain 16.4%, and painful tonic spasms 11%. Comparison between different groups showed significant differences for age, Expanded Disability Status Scale, disease duration, and disease course, but not for sex. This study underlines the relevance of pain in the clinical history of MS.

Adolescent↗

PubMed2004

An MT MRI study of the cervical cord in clinically isolated syndromes suggestive of MS.

Cervical cord magnetization transfer ratio (MTR) histograms were obtained from 45 patients at presentation with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS). The mean values of MTR histogram-derived metrics were not different between CIS patients and healthy control subjects or between patients with and without evidence of disease dissemination in time. Only three patients showed significantly lower cord MTR values than control subjects. These findings suggest the absence of intrinsic structural damage of the cervical cord soon after the onset of CIS suggestive of MS, even in those patients with an early evolution to MS.

Adolescent↗

PubMed2004

Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica.

Using magnetization transfer (MT) and diffusion tensor (DT) MRI, the authors assessed the extent of tissue damage of the brain normal-appearing white and gray matter (NAGM) in patients with neuromyelitis optica (NMO). Compared to healthy controls, patients with NMO showed reduced MT ratio and increased mean diffusivity of the NAGM. This challenges the classic notion of a sparing of the brain tissue in the course of NMO.

Adult↗

PubMed2004

Late onset multiple sclerosis: clinical characteristics, prognostic factors and differential diagnosis.

Late onset multiple sclerosis (LOMS), defined as the first presentation of clinical symptoms in patients over 50, is not a rare phenomenon as previously thought, since the prevalence ranges between 4% and 9.6% in different studies. The course of the disease is often primary progressive and pyramidal or cerebellar involvement is observed in 60%-70% of the patients at presentation. LOMS is usually associated with a faster progression to disability compared to young adult multiple sclerosis (MS) patients. Moreover in patients over 50, MS variants and atypical forms which present a difficult diagnostic problem, may be frequently encountered. The differential diagnosis may be sometimes difficult and includes cerebro-spinal vascular syndromes, hypertension-related disorders, compressive myelopathies, primary or secondary vasculitis, metabolic diseases, degenerative and nutritional syndromes. Clinical characteristics, magnetic resonance imaging (MRI) pattern of abnormalities, evoked potential studies and cerebrospinal fluid (CSF) oligoclonal band analysis are of high diagnostic yield in LOMS patients, but expertise in interpreting their results is strongly required.

Age of Onset↗

PubMed2004

A functional MRI study of movement-associated cortical changes in patients with Devic's neuromyelitis optica.

Movement-associated cortical changes have been shown in several neurological conditions and were found to be associated to the extent of brain and cord damage. Devic's neuromyelitis optica (DNO) is characterized by a severe involvement of the cord and optic nerve, with sparing of the brain. To assess the actual role of cord pathology on the pattern of movement-associated cortical recruitment, we obtained functional magnetic resonance imaging (fMRI) from patients with DNO and investigated whether the extent of brain activation is correlated with the extent of cervical cord damage. We studied 10 right-handed DNO patients and 15 sex- and age-matched healthy controls. The MRI assessment consisted of the following: (a) fMRI during repetitive flexion extension of the last four fingers of the right and left hand, (b) brain and cervical cord conventional MRI, and (c) cervical cord magnetization transfer (MT) MRI. Compared to controls and for both tasks, DNO patients had an increased recruitment of several regions of the sensorimotor network (primary sensorimotor cortex, postcentral gyrus, middle frontal gyrus, rolandic operculum, secondary sensorimotor cortex, precuneus, and cerebellum) and of several other regions mainly in the temporal and occipital lobes, such as MT/V5, the fusiform gyrus, the cuneus, and the parahippocampal gyrus. For both tasks, strong correlations (r values ranging from -0.76 to -0.85) were found between relative activations of cortical sensorimotor areas and the severity of cervical cord damage. This study shows an abnormal pattern of movement-associated cortical activations in patients with DNO, which extends beyond the 'classical' sensorimotor network and also involves visual areas devoted to motion processing. The correlation found between fMRI changes and the extent of cord damage suggests that such functional cortical changes might have an adaptive role in limiting the clinical outcome of DNO structural pathology.

Adult↗

PubMed2003

Cord damage elicits brain functional reorganization after a single episode of myelitis.

OBJECTIVE: To assess, using fMRI, the brain pattern of movement-associated cortical activations in patients with a previous remitting episode of acute cervical myelitis of possible demyelinating origin and to investigate whether the extent of cortical reorganization is associated with the extent of cervical cord pathology measured using magnetization transfer (MT) MRI. METHODS: From 14 right-handed patients in a chronic and stable phase after an isolated myelitis (male/female = 7/7, mean age = 35.3 years, median disease duration = 21.2 months) involving the cervical cord and 15 sex- and age-matched healthy control subjects, we obtained 1) fMRI during repetitive flexion-extension of the last four fingers of the right hand, 2) brain diffusion tensor MRI, and 3) brain and cervical cord conventional and MT MRI. FMRI data were analyzed using Statistical Parametric Mapping software. Brain mean diffusivity, fractional anisotropy, and MT ratio (MTR) histograms of the normal-appearing white and gray matter and cervical cord MTR histograms were produced. RESULTS: Patients with myelitis had lower average cord MTR (p < 0.0001) and cord MTR histogram peak position (p = 0.002) than control subjects. Compared with healthy volunteers, patients with myelitis showed increased recruitment of the ipsilateral hemisphere in the primary sensorimotor cortex (p < 0.0001), supplementary motor area (p = 0.002), and middle frontal gyrus (MFG) (p < 0.0001). Average cervical cord MTR was inversely correlated with relative activations of the ipsilateral MFG (r = -0.80) and of the ipsilateral postcentral gyrus (r = -0.80). The relative activation of the ipsilateral MFG was also correlated with cervical cord MTR peak position (r = -0.92). CONCLUSIONS: An abnormal pattern of movement-associated cortical activations was found in patients with a previous episode of cervical myelitis. These functional cortical changes might have an adaptive role in limiting the clinical outcome of structural cord damage.

Acute Disease↗

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

Attenuated signature-tagged mutagenesis mutants of Brucella melitensis identified during the acute phase of infection in mice.

For this study, we screened 1,152 signature-tagged mutagenesis mutants of Brucella melitensis 16M in a mouse model of infection and found 36 of them to be attenuated in vivo. Molecular characterization of transposon insertion sites showed that for four mutants, the affected genes were only present in Rhizobiaceae. Another mutant contained a disruption in a gene homologous to mosA, which is involved in rhizopine biosynthesis in some strains of Rhizobium, suggesting that this sugar may be involved in Brucella pathogenicity. A mutant was disrupted in a gene homologous to fliF, a gene potentially coding for the MS ring, a basal component of the flagellar system. Surprisingly, a mutant was affected in the rpoA gene, coding for the essential alpha-subunit of the RNA polymerase. This disruption leaves a partially functional protein, impaired for the activation of virB transcription, as demonstrated by the absence of induction of the virB promoter in the Tn5::rpoA background. The results presented here highlight the fact that the ability of Brucella to induce pathogenesis shares similarities with the molecular mechanisms used by both Rhizobium and Agrobacterium to colonize their hosts.

Acute Disease↗

PubMed2003

A post-marketing study on interferon beta 1b and 1a treatment in relapsing-remitting multiple sclerosis: different response in drop-outs and treated patients.

BACKGROUND: Interferon beta 1b (Betaferon) and 1a (Avonex) were licensed in Italy for treating relapsing-remitting multiple sclerosis in February 1996 and August 1997, respectively. OBJECTIVES: To evaluate the effectiveness of these agents on the basis of clinical experience in northern Italian multiple sclerosis centres. DESIGN: Clinical data on patients with relapsing-remitting multiple sclerosis were collected on an appropriate form from 65 centres in northern Italy. Intention to treat analysis was not possible, so patients who discontinued treatment (drop-outs) and who continued treatment (treated) were analysed separately. The main outcome measures were annual relapse frequency, number of relapse-free patients, mean change in extended disability status scale score (EDSS), and number of patients who worsened. RESULTS: 1481 patients were included; 834 were treated with Betaferon and 647 with Avonex for mean periods of 21.4 and 12.0 months, respectively. Basal EDSS was 2.37 and 2.17, respectively, and relapse frequency was 1.62 and 1.45. The annual relapse rate decreased by more than 60% with Betaferon and 55% with Avonex. The proportions of relapse-free, improved, and worsened patients were similar in the two groups. More patients interrupted treatment with Betaferon (41.1%) than with Avonex (15.3%); such patients showed more active disease at baseline and during treatment. The incidence of side effects was higher in Betaferon treated patients. CONCLUSIONS: The effectiveness of Betaferon and Avonex is confirmed. There was a more marked effect than expected from the experimental trial results. This might reflect differences in inclusion criteria, or, more likely, loss of drop-outs, favouring selective retention of responders.

Adjuvants, Immunologic↗