Biomedical subjects

S Bonavita

Publications and source records attributed to S Bonavita.

At least 19 recordsLinked to original sources

PubMed2006

Treatment of multiple sclerosis with interferon beta in clinical practice: 2-year follow-up data from the South Italy Mobile MRI Project.

This follow-up study assessed the 2-year clinical and magnetic resonance imaging (MRI) outcomes of patients with multiple sclerosis (MS) originally enrolled in an MRI study conducted at eight centres in south Italy (the South Italy Mobile MRI Project). Of the 597 MS patients recruited at baseline, 391 returned for the follow-up study. Of these, 363 provided 2-year clinical and MRI follow-up data, and 215 were still undergoing treatment with one of four interferon beta regimens: Avonex, 30 mcg intramuscularly once weekly; Betaferon, 250 mcg subcutaneously (sc) every other day; Rebif 22 mcg sc three times weekly (tiw; Rebif 22); or Rebif 44 mcg sc tiw (Rebif 44). Over the 2-year follow-up period, patients receiving the higher dose of Rebif were more likely to remain free from relapses [odds ratio (OR) = 2.23] and from developing both new T2 (OR = 0.15) and new T1 black hole lesions (OR = 0.22), when compared with patients in the Avonex group. Despite some limitations in the trial design, the results from this follow-up study provide helpful clinical and MRI data on the efficacy of interferon beta regimens in MS patients treated in the clinical setting.

Analysis of Variance↗

PubMed2006

Cognitive dysfunction in patients with relapsing-remitting multiple sclerosis.

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients.

Adult↗

PubMed2006

Spectroscopic, diffusion and perfusion magnetic resonance imaging at 3.0 Tesla in the delineation of glioblastomas: preliminary results.

Recent advances in magnetic resonance imaging (MRI) have allowed the evaluation of metabolic, diffusion and hemodynamic features of malignant gliomas. The aim of this study was to evaluate whether such information provided useful, complementary information to conventional MRI for improving the evaluation of glioblastoma extent. Ten patients with glioblastoma multiforme underwent conventional MRI, proton MR spectroscopic imaging (1H-MRSI), perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI). Metabolite signals, including normalized choline, N-acetylaspartate, creatine and lactate/lipids, were obtained by 1H-MRSI; apparent diffusion coefficient (ADC) by DWI; and relative cerebral blood volume (rCBV) by PWI. In edematous-appearing areas, 3 multiparametric patterns were identified: infiltrating tumor, with abnormal metabolite ratios, lower ADC and higher rCBV; pure edema, with normal metabolite ratios, higher ADC and lower rCBV; and tumor-infiltrated edema, with abnormal metabolite ratios and intermediate ADC and rCBV. In normal-appearing areas, 2 multiparametric patterns were identified: tumor-infiltrated tissue, with abnormal metabolite ratios and higher rCBV; and normal tissue, with normal MR parameters. The combination of 1H-MRSI, DWI and PWI features contributed to delineation of glioblastomas, offering information not available with conventional MRI. This approach may enhance the assessment of brain gliomas, providing useful information for guiding stereotactic biopsies, surgical resection and radiation treatment.

Brain Neoplasms↗

PubMed2005

Brain atrophy and lesion load in a large population of patients with multiple sclerosis.

OBJECTIVE: To measure white matter (WM) and gray matter (GM) atrophy and lesion load in a large population of patients with multiple sclerosis (MS) using a fully automated, operator-independent, multiparametric segmentation method. METHODS: The study population consisted of 597 patients with MS and 104 control subjects. The MRI parameters were abnormal WM fraction (AWM-f), global WM-f (gWM-f), and GM fraction (GM-f). RESULTS: Significant differences between patients with MS and control subjects included higher AWM-f and reduced gWM-f and GM-f. MRI data showed significant differences between patients with relapsing-remitting and secondary progressive forms of MS. Significant correlations between MRI parameters and between MRI and clinical data were found. CONCLUSIONS: Patients with multiple sclerosis have significant atrophy of both white matter (WM) and gray matter (GM); secondary progressive patients have significantly more atrophy of both WM and GM than do relapsing-remitting patients and a significantly higher lesion load (abnormal WM fraction); lesion load is related to both WM and even more to GM atrophy; lesion load and WM and GM atrophy are significantly related to Expanded Disability Status Scale score and age at onset (suggesting that the younger the age at disease onset, the worse the lesion load and brain atrophy); and GM atrophy is the most significant MRI variable in determining the final disability.

Adolescent↗

PubMed2004

Gene conversion events in adult-onset spinal muscular atrophy.

OBJECTIVE: To investigate the possible occurrence of a conversion event in three patients with adult-onset spinal muscular atrophy (SMA) type IV, which represents the mildest form within the spectrum of the SMA phenotype. MATERIAL AND METHODS: We observed three patients with adult onset SMA and apparent isolated deletion of telomeric survival motor neuron (SMN1) exon 7. To distinguish between a deletion and a sequence conversion event of exon 7, these patients were analyzed in greater detail by a simple PCR-based assay. RESULTS: Analysis by DdeI digestion showed products for both telomeric and centromeric copies of exon 8. These findings indicated a gene conversion event as the site for primer R111 was retained at least in one of two alleles. CONCLUSIONS: These results provide first evidence that a conversion event may be also associated with adult-onset SMA, and further support the notion that a gene conversion event is usually associated with a milder SMA phenotype and a later onset of disease.

Adult↗

PubMed2003

GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy.

BACKGROUND: Dysfunction of gamma-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE). OBJECTIVE: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE. METHODS: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 +/- 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene. RESULTS: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant. CONCLUSIONS: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.

Age of Onset↗

PubMed2003

High-field proton MRS of human brain.

Proton magnetic resonance spectroscopy (1H-MRS) of the brain reveals specific biochemical information about cerebral metabolites, which may support clinical diagnoses and enhance the understanding of neurological disorders. The advantages of performing 1H-MRS at higher field strengths include better signal to noise ratio (SNR) and increased spectral, spatial and temporal resolution, allowing the acquisition of high quality, easily quantifiable spectra in acceptable imaging times. In addition to improved measurement precision of N-acetylaspartate, choline, creatine and myo-inositol, high-field systems allow the high-resolution measurement of other metabolites, such as glutamate, glutamine, gamma-aminobutyric acid, scyllo-inositol, aspartate, taurine, N-acetylaspartylglutamate, glucose and branched amino acids, thus extending the range of metabolic information. However, these advantages may be hampered by intrinsic field-dependent technical difficulties, such as decreased T2 signal, chemical shift dispersion errors, J-modulation anomalies, increased magnetic susceptibility, eddy current artifacts, limitations in the design of homogeneous and sensitive radiofrequency (RF) coils, magnetic field instability and safety issues. Several studies demonstrated that these limitations could be overcome, suggesting that the appropriate optimization of high-field 1H-MRS would expand the application in the fields of clinical research and diagnostic routine.

Algorithms↗

PubMed2002

Genetic association of alpha2-macroglobulin polymorphisms with AD in southern Italy.

The authors investigated the segregation of two polymorphisms of the alpha2-macroglobulin gene (A2M-I/D and A2M-Ile1000Val) in patients with sporadic AD from southern Italy. The A2M-I and A2M-Val1000 alleles were more frequent in cases than in controls, and this effect was independent from the APOE-epsilon4 status as well as from the age at onset of AD. Moreover, subjects carrying the A2M genotype I/I-Val/Val had a threefold increase of risk for AD. These data support a population-based susceptibility for AD linked to A2M polymorphisms.

Aged↗

PubMed2002

Proton MR spectroscopic imaging in multiple sclerosis.

We studied 24 patients with multiple sclerosis (MS) by proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the neurochemical pathology of the white-matter lesions (WML) and normal-appearing white matter (NAWM). Our 1H-MRSI technique allowed simultaneous measurement of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr) signal intensities from four 15-mm slices divided into 0.84 ml single-volume elements. In WML we found significantly lower NAA/Cr and NAA/Cho ratios and a significantly higher Cho/Cr ratio than in NAWM or control white matter. In NAWM, NAA/Cr and Cho/Cr were significantly lower than in control white matter. 1H-MRSI was compatible with damage to myelin in WML, and with axonal damage and/or dysfunction in WML and NAWM. These findings extend data on involvement of NAWM in MS beyond the abnormalities visible on MRI.

Adult↗

PubMed2002

Anti-GM1 ganglioside antibodies in Parkinson's disease.

OBJECTIVES: To determine whether anti-GM1 antibodies are increased in Parkinson's disease (PD). METHODS: Serum immunoglobulin M (IgM) and IgG anti-GM1 antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 147 patients with PD and in 186 age-matched normal control subjects. Sera were assayed at initial dilution of 1:800 for IgM and 1:200 for IgG and were considered positive at absorbance values exceeding the value of 0.05 for IgM and 0.1 for IgG. RESULTS: Forty patients with PD (27.2%) had sera positive for IgM anti-GM1 antibodies, whereas only five normal controls (2.7%) resulted positive (P < 0.0001). Most of patients (75%) with positive sera had a tremor-dominant form of PD. Only two patients with PD (1.4%) and none of normal controls had sera positive for IgG anti-GM1 antibodies. CONCLUSION: A consistent portion of parkinsonians, mainly with a tremor-dominant form of PD, may have increased circulating IgM anti-GM1 antibodies.

Aged↗

PubMed2001

Evidence for neuroaxonal injury in patients with proteolipid protein gene mutations.

The authors used proton MRS to investigate neuropathologic correlates in nine patients with proteolipid protein (PLP) gene mutations who did not show cerebral atrophy on cranial MRI. When compared with 16 age-matched control participants, patients with PLP mutations had significant and widespread decreased brain N-acetyl aspartate, a neuronal marker. The authors conclude that PLP mutations cause neuroaxonal injury, which in turn contributes to the neurologic deficit observed in these patients.

Adolescent↗

PubMed2000

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients.

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.

Adult↗

PubMed1999

Diffuse central neuronal involvement in Fabry disease: a proton MRS imaging study.

BACKGROUND: The in vivo determination of parenchymal involvement is important to evaluate disease burden. Proton MRS imaging (1H-MRSI) permits simultaneous measurement of N-acetylaspartate (NA), a putative neuron-specific molecule, choline-containing compounds, creatine-phosphocreatine, and lactate from four 15-mm slices divided into 0.84-mL single-volume elements. OBJECTIVE: To assess the cortical and subcortical neuropathology in Fabry disease (FD). METHODS: Regions of interest (ROIs) were selected from several cortical and subcortical locations in nine FD patients. Mean ROI metabolite ratios were compared with control values. RESULTS: FD patients showed a widespread pattern of cortical and subcortical NA reduction. Seven patients showed discrete MRI abnormalities consisting of white matter hyperintensities or basal ganglia infarcts. CONCLUSION: We found diffuse neuronal involvement in FD extending beyond the areas of MRI-visible cerebrovascular abnormalities. 1H-MRSI may become useful in therapeutic trials.

Adult↗

PubMed1999

MR image segmentation and tissue metabolite contrast in 1H spectroscopic imaging of normal and aging brain.

The impact of image segmentation on 0.84-ml nominal voxel volume proton spectroscopic imaging in normal brain and in age-related cortical atrophy was investigated. Segmentation improved the gray matter-white matter (GM-WM) contrast for N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in normal brain, and for NAA/Cho and NAA/Cr in atrophic brain. NAA(GM/WM) (approximately 0.7), Cho(GM/WM) (approximately 0.8), and Cr(GM/WM) (approximately 1.3) in normal brain obtained with segmentation agreed with values obtained with quantitative magnetic resonance spectroscopy. Age-related cortical atrophy led to decreased cortical GM NAA/Cho and NAA/Cr; no changes were evident in WM or in NAA(GM/WM), Cho(GM/WM), or Cr(GM/WM). GM/WM metabolite analysis may be of limited use in conditions in which parallel metabolite changes occur in WM and GM.

Adult↗

PubMed1999

Exploring brain function with magnetic resonance imaging.

Since its invention in the early 1990s, functional magnetic resonance imaging (fMRI) has rapidly assumed a leading role among the techniques used to localize brain activity. The spatial and temporal resolution provided by state-of-the-art MR technology and its non-invasive character, which allows multiple studies of the same subject, are some of the main advantages of fMRI over the other functional neuroimaging modalities that are based on changes in blood flow and cortical metabolism. This paper describes the basic principles and methodology of fMRI and some aspects of its application to functional activation studies. Attention is focused on the physiology of the blood oxygenation level-dependent (BOLD) contrast mechanism and on the acquisition of functional time-series with echo planar imaging (EPI). We also provide an introduction to the current strategies for the correction of signal artefacts and other image processing techniques. In order to convey an idea of the numerous applications of fMRI, we will review some of the recent results in the fields of cognitive and sensorimotor psychology and physiology.

Artifacts↗

PubMed1999

Proton MRS in neurological disorders.

Proton magnetic resonance spectroscopy (1H MRS) permits the acquisition of the signal arising from several brain metabolites. At long echo-time (TE) 1H MRS can detect N-acetyl-aspartate containing compounds, choline containing compounds, creatine + phosphocreatine and lactate. At short TE, lipids, tryglicerides, alanine, glutamate, glutamine, GABA, scyllo-inositol, glucose, myo-inositol, carnosine and histydine are visible. 1H MRS can be performed with single-voxel, multivoxel, single slice and multislice techniques. With single voxel 1H MRS it is possible to measure metabolites relaxation time, which allows the measurement of metabolite concentrations. This technique can be useful in the study of focal lesions in the central nervous system (CNS) such as epilepsy (pre-surgical identification of epileptic focus), brain tumors (evaluation of recurrence and radiation necrosis), stroke, multiple sclerosis, etc. Single slice and multislice 1H MRS imaging (1H MRSI) can be performed only at long TE and permits the mapping of the brain metabolites distribution which makes them particularly useful in studying diffuse diseases and heterogeneous lesions of the CNS. 1H MRS can also be useful in the evaluation of 'ischemic penumbra' of stroke; developmental (myelin and neuronal dysgenesis); head trauma (evaluation of cerebral damage not visible with MRI); degenerative disorders (identification of microscopic pathology not visible with MRI); and metabolic diseases (metabolic disturbances with specific metabolic patterns).

Brain↗

PubMed1998

Proton magnetic resonance spectroscopic imaging in the clinical evaluation of patients with Niemann-Pick type C disease.

OBJECTIVES: 10 patients with Niemann-Pick disease type C (NP-C) were studied by proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess the biochemical pathology of the brain and to determine whether this method can be useful to clinically evaluate these patients. METHODS: 1H-MRSI permits the simultaneous measurement of N-acetyl aspartate (NA), compounds containing choline (Cho), creatine plus phosphocreatine (Cre), and lactate (Lac) signal intensities from four 15 mm slices divided into 0.84 ml single volume elements. Spectroscopic voxels were identified from seven regions of interest. RESULTS: In patients with NP-C, NA/Cre was significantly decreased in the frontal and parietal cortices, centrum semiovale, and caudate nucleus; Cho/Cre was significantly increased in the frontal cortex and centrum semiovale. Significant correlations were found between clinical staging scale scores and 1H-MRSI abnormalities. CONCLUSION: 1H-MRSI showed diffuse brain involvement in patients with NP-C consistent with the pathological features of the disease. 1H-MRSI is an objective and sensitive tool to neurologically evaluate patients with NP-C.

Adolescent↗

PubMed1997

White matter lesion detection in multiple sclerosis: improved interobserver concordance with multispectral MRI display.

An assessment of the detectability of white matter lesions and of concordance between observers with different levels of MRI reading experience was performed with comparative evaluation of spin-echo MRI images and of corresponding "multispectral" maps in 16 patients with definite multiple sclerosis (MS). Multispectral maps were obtained by means of a recently described post-processing technique based on the simultaneous display of MRI parameters and a standardized colour scale with red, green and blue coding for relaxation rates R1 and R2 and proton density, respectively. Spin-echo images on films and multispectral maps displayed on a personal computer were randomly rated at 2-month intervals. Interobserver concordance (k-test) was assessed among three readers with different levels of MRI experience (an experienced neuroradiologist, a radiology resident and a neurologist). For multispectral maps we found increased interobserver concordance with the experienced neuroradiologist (multispectral vs conventional images; k = 0.77 vs 0.66 for the radiology resident and 0.66 vs 0.56 for the neurologist), an increased number of detected lesions and decreased reading time. Multispectral maps permit easy detection of MS lesions and may improve interobserver concordance compared with conventional spinecho studies.

Adult↗