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Biomedical subjects

A Falini

Publications and source records attributed to A Falini.

At least 19 recordsLinked to original sources
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↗
PubMed2002

Evidence for widespread movement-associated functional MRI changes in patients with PPMS.

BACKGROUND: Previous work has suggested that functional reorganization of cortical motor areas might have a role in limiting the motor deficits in patients with MS. OBJECTIVE: To test whether movement-associated cortical changes in MS might extend beyond the "classic" motor areas and involve sites for multimodal integration. METHODS: fMRI was used to assess patterns of brain activations associated with 3 different motor tasks in 30 right-handed patients with primary progressive MS (PPMS) and variable degrees of motor impairment, which were compared with those from 15 right-handed, sex- and age-matched control subjects. RESULTS: Compared with control subjects, patients with MS showed increased activation of brain regions within both traditional motor planning and execution regions (including the supplementary motor area and the cingulate motor area), the insula (a region implicated in sensory processing), and several multimodal cortical regions in the temporal, parietal, and occipital lobes. In patients, the extent of the fMRI activations was strongly correlated with MR lesion burden (r ranging from 0.70 to 0.86, p < 0.001). CONCLUSIONS: This study shows that movement-associated cortical activation in patients with PPMS is widely distributed and also involves multimodal "nonmotor" cortical networks. It also suggests that adaptive cortical reorganization might be one of the mechanisms limiting the clinical impact of MS in the progressive phases of the disease.

Adult↗
PubMed2002

Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis.

Although fatigue is a common and troublesome symptom of multiple sclerosis (MS), its pathogenesis is poorly understood. In this study, we used functional magnetic resonance imaging (fMRI) to test whether a different pattern of movement-associated cortical and subcortical activations might contribute to the development of fatigue in patients with MS. We obtained fMRI during the execution of a simple motor task with completely normally functioning hands from 15 MS patients with fatigue (F), 14 MS patients without fatigue (NF), and 15 sex- and age-matched healthy volunteers. F and NF MS patients were also matched for major clinical and MRI variables. FMRI data were analyzed using statistical parametric mapping. In all patients, severity of fatigue was rated using the Fatigue Severity Scale (FSS). Compared to healthy subjects, MS patients showed more significant activations of the contralateral primary somatomotor cortex, the contralateral ascending limb of the Sylvian fissure, the contralateral intraparietal sulcus (IPS), the contralateral supplementary motor area, and the ipsilateral and contralateral cingulate motor area (CMA). Compared to F MS patients, NF patients showed more significant activations of the ipsilateral cerebellar hemisphere, the ipsilateral rolandic operculum, the ipsilateral precuneus, the contralateral thalamus, and the contralateral middle frontal gyrus. In contrast, F MS patients had a more significant activation of the contralateral CMA. Significant inverse correlations were found between FSS scores and relative activations of the contralateral IPS (r = -0.63), ipsilateral rolandic operculum (r = -0.61), and thalamus (r = -0.62). This study provides additional evidence that fatigue in MS is related to impaired interactions between functionally related cortical and subcortical areas. It also suggests that fMRI might be a valuable tool to monitor the efficacy of treatment aimed at reducing MS-related fatigue.

Adult↗
PubMed2002

Correlations between structural CNS damage and functional MRI changes in primary progressive MS.

In patients with primary progressive multiple sclerosis (PPMS), we investigated whether brain and cervical cord structural changes in lesions and normal-appearing brain tissue (NABT), measured using conventional, magnetization transfer (MT), and diffusion tensor (DT) MRI, are correlated with movement-associated cortical activations measured using functional magnetic resonance imaging (fMRI). From 26 right-handed PPMS patients and 15 right-handed, sex- and age-matched healthy controls, we obtained: (a) brain and cervical cord dual-echo scans and MT ratio (MTR) maps; (b) brain mean diffusivity (D(-)) maps, and (c) f-MRI (flexion-extension of the last four fingers of the right hand). All PPMS patients had no previous symptoms affecting their right upper limbs, which were functionally normal. Healthy volunteers showed more significant activation in the ipsilateral cerebellar hemisphere than PPMS patients. PPMS patients showed greater activation bilaterally in the superior temporal gyrus, ipsilaterally in the middle frontal gyrus, and, contralaterally in the insula/claustrum. In PPMS patients, moderate to strong correlations (r values ranging from 0.59 to 0.68) were found between relative activations of cortical areas located in a widespread network for sensory-motor and multimodal integration and the severity of structural changes of the NABT (as measured using MT and DT MRI) and the severity of cervical cord damage (as measured using MT MRI). This study shows that the pattern of cortical activation of PPMS patients is different from that of normal controls even when performing a motor task with clinically unaffected limbs. It also suggests that cortical reorganization might be able to limit the consequences of MS injury in the brain and cervical cord.

Adult↗
PubMed2002

White matter damage in Alzheimer's disease assessed in vivo using diffusion tensor magnetic resonance imaging.

OBJECTIVE: To investigate the extent and the nature of white matter tissue damage of patients with Alzheimer's disease using diffusion tensor magnetic resonance imaging (DT-MRI). BACKGROUND: Although Alzheimer's disease pathology mainly affects cortical grey matter, previous pathological and MRI studies showed that also the brain white matter of patients is damaged. However, the nature of Alzheimer's disease associated white matter damage is still unclear. METHODS: Conventional and DT-MRI scans were obtained from 16 patients with Alzheimer's disease and 10 sex and age matched healthy volunteers. The mean diffusivity (D), fractional anisotropy (FA), and inter-voxel coherence (C) of several white matter regions were measured. RESULTS: D was higher and FA lower in the corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimer's disease than in the corresponding regions from healthy controls. D and FA of the white matter of the occipital lobe and internal capsule were not different between patients and controls. C values were also not different between patients and controls for any of the regions studied. Strong correlations were found between the mini mental state examination score and the average overall white matter D (r=0.92, p<0.001) and FA (r=0.78; p<0.001). CONCLUSIONS: White matter changes in patients with Alzheimer's disease are likely to be secondary to wallerian degeneration of fibre tracts due to neuronal loss in cortical associative areas.

Aged↗
PubMed2001

Quantification of tissue damage in AD using diffusion tensor and magnetization transfer MRI.

The authors measured mean diffusivity (D) and magnetization transfer ratio (MTR) of the brain from 18 patients with AD and 16 healthy control subjects. The peak heights of cortical gray matter (cGM) D (p < 0.001) and MTR (p < 0.001) histograms were lower and average cGM D (p < 0.01) higher in patients with AD than in control subjects. A composite MR score based on brain volume and cGM MTR peak height was correlated with patient cognitive impairment (r = 0.65, p = 0.003). This preliminary study presents a novel approach to quantify AD-related tissue damage in-vivo.

Aged↗
PubMed2001

Anatomical and biochemical investigation of primary brain tumours.

Cancerous transformation entails major biochemical changes including modifications of the energy metabolism of the cell, e.g. utilisation of glucose and other substrates, protein synthesis, and expression of receptors and antigens. Tumour growth also leads to heterogeneity in blood flow owing to focal necrosis, angiogenesis and metabolic demands, as well as disruption of transport mechanisms of substrates across cell membranes and other physiological boundaries such as the blood-brain barrier. All these biochemical, histological and anatomical changes can be assessed with emission tomography, X-ray computed tomography (CT), magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Whereas anatomical imaging is aimed at the diagnosis of brain tumours, biochemical imaging is better suited for tissue characterisation. The identification of a tumoural mass and the assessment of its size and vascularisation are best achieved with X-ray CT and MRI, while biochemical imaging can provide additional information that is crucial for tumour classification, differential diagnosis and follow-up. As the assessment of variables such as water content, appearance of cystic lesions and location of the tumour are largely irrelevant for tissue characterisation, a number of probes have been employed for the assessment of the biochemical features of tumours. Since biochemical changes may be related to the growth rate of cancer cells, they can be thought of as markers of tumour cell proliferation. Biochemical imaging with radionuclides of processes that occur at a cellular level provides information that complements findings obtained by anatomical imaging aimed at depicting structural, vascular and histological changes. This review focusses on the clinical application of anatomical brain imaging and biochemical assessment with positron emission tomography, single-photon emission tomography and MRS in the diagnosis of primary brain tumours, as well as in follow-up.

Brain↗
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↗
PubMed1998

Benign versus secondary-progressive multiple sclerosis: the potential role of proton MR spectroscopy in defining the nature of disability.

PURPOSE: We determined the clinical utility of proton MR spectroscopy in defining the extent of disability in benign versus secondary-progressive multiple sclerosis (MS). METHODS: Thirty patients with clinically definite MS, including 16 patients with benign MS and 14 with secondary-progressive MS, and a group of 13 healthy volunteers were studied with combined stimulated-echo acquisition mode proton MR spectroscopy and MR imaging (all patients received contrast material). RESULTS: Acute enhancing lesions of benign and secondary-progressive MS were characterized by a reduction in N-acetylaspartate (NAA)/choline and NAA/creatine and an increase in inositol compounds/creatine as compared with normal white matter. Such variations were also detected in chronic unenhancing lesions in patients with secondary-progressive MS, although they were not found in chronic unenhancing lesions in patients with benign MS. Chronic lesions of the two forms of the disease have significative differences in NAA and inositol signals. CONCLUSION: Proton MR spectroscopy is able to show metabolic changes occurring in the white matter of patients with MS. Such changes differ according to the phase (acute versus chronic) and the clinical form (benign versus secondary-progressive) of the disease.

Adult↗
PubMed1998

Progressive brain failure after diffuse hypoxic ischemic brain injury: a serial MR and proton MR spectroscopic study.

The findings at sequential MR imaging and proton MR spectroscopy of a patient with profound hypoxic-ischemic brain injury are reported. The pattern of structural and biochemical changes observed closely reflected the known evolution of postasphyxic brain degeneration. Particularly noteworthy were the sharp decrease of cortical N-acetylaspartate in the acute phase, suggesting the severity of the neuronal insult, and the subsequent progressive increase of choline, paralleling the delayed degeneration of white matter.

Adult↗
PubMed1998

The use of magnetic resonance spectroscopy in the evaluation of the natural history of multiple sclerosis.

Magnetic resonance spectroscopic imaging (MRSI) can be used to define specific chemical-pathological changes in the brain of patients with multiple sclerosis. Magnetic resonance spectroscopy offers promise for improved definition of the nature of individual lesions, the dynamics of their evolution, their effects on normal appearing white matter, and their relation to clinical disability. Combined multimodal MRSI studies of the brains of patients with multiple sclerosis therefore soon may provide efficient, specific, and quantitative new approaches to assessment of drug effects in therapeutic trials.

Axons↗
PubMed1997

Cerebral involvement in celiac disease: a serial MRI study in a patient with brainstem and cerebellar symptoms.

A patient with celiac disease and relapsing-progressive symptoms suggesting brainstem and cerebellar involvement underwent serial MRIs. The first examination revealed multiple enhancing and nonenhancing lesions. Thereafter, a large enhancing cerebellar lesion appeared, followed by severe cerebellar atrophy. The presence of structural neuronal damage was confirmed by proton MR spectroscopy and magnetization transfer imaging. MRI results and CSF findings suggested that neurologic complications were more likely due to an inflammatory process.

Adult↗
PubMed1996

Proton magnetic resonance spectroscopy and intracranial tumours: clinical perspectives.

Proton magnetic resonance spectroscopy (1H-MRS) was applied to characterize intracranial tumours of different hystological types. Seventy patients with intracranial neoplasms were studied before receiving surgery, radiotherapy or chemotherapy. All tumours were characterized by reduced or absent N-acetylasparate and increased signal from choline-containing compounds. Distinctive patterns were observed only for primitive brain neoplasms; high-grade gliomas were differentiated from low-grade ones by higher levels of choline-containing compounds. The metabolic aspects of metastatic lesions were similar to high-grade gliomas. These results, together with the limitations of 1H-MRS and future applications are reviewed.

Adenoma↗
PubMed1996

Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study.

The authors represent a cooperative group of 15 institutions that examined the feasibility of using metabolic features observed in vivo with 1H-magnetic resonance (MR) spectroscopy to characterize brain tumors of the glial type. The institutions provided blinded, centralized MR spectroscopy data processing long with independent central review of MR spectroscopy voxel placement, composition and contamination by brain, histopathological typing using current World Health Organization criteria, and clinical data. Proton 1H-MR spectroscopy was performed using a spin-echo technique to obtain spectra from 8-cc voxels in the tumor and when feasible in the contralateral brain. Eighty-six cases were assessable, 41 of which had contralateral brain spectra. Glial tumors had significantly elevated intensities of choline signals, decreased intensities of creatine signals, and decreased intensities of N-acetylaspartate compared to brain. Choline signal intensities were highest in astrocytomas and anaplastic astrocytomas, and creatine signal intensities were lowest in glioblastomas. However, whether expressed relative to brain or as intratumoral ratios, these metabolic characteristics exhibited large variations within each subtype of glial tumor. The resulting overlaps precluded diagnostic accuracy in the distinction of low-and high-grade tumors. Although the extent of contamination of the 1H-MR spectroscopy voxel by brain had a marked effect on metabolite concentrations and ratios, selection of cases with minimal contamination did not reduce these overlaps. Thus, each type and grade of tumor is a metabolically hetero-geneous group. Lactate occurred infrequently and in all grades. Mobile lipids, on the other hand, occurred in 41% of high-grade tumors with higher mean amounts found in glioblastomas. This result, coupled with the recent demonstration that intratumoral mobile lipids correlate with microscopic tumor cell necrosis, leads to the hypothesis that mobile lipids observed in vivo in 1H-MR spectroscopy may correlate independently with prognosis of individual patients.

Adolescent↗
PubMed1992

Imaging of tumors of the central nervous system.

Research in diagnosing and understanding brain tumors in neuroradiology is influenced by the investigative tools available to neuroradiologists. CT has represented the gold standard for the past two decades. The role of angiography has become complementary; relevant in the therapeutic phase of embolization of meningiomas or base of the skull tumors or in intra-arterial chemotherapy for gliomas. In 1991, the MR imaging revolution continues to provide new insights in the diagnosis, classification, and understanding of the biology of brain tumors. Interest has been focused mainly on information provided by MR imaging and MR spectroscopy. Spectroscopy is being used in a more systematic way and in large series with different histologic tumor types. Spectra from tumors are definitely different from those of normal brain, although no specific patterns for histologic types were found, with the possible exception of meningiomas. Comparison with positron emission tomography is considered to be useful. Analysis of rare tumors using MR imaging allows better understanding, classification, diagnosis, and surgical therapy of lesions such as central neurocytomas, hamartomatous tumors, and lymphomas. An attempt at a better classification for brain tumors was proposed and may prove to be very useful for systematization and communication.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Human fetal brain beta-nerve growth factor cDNA: molecular cloning of 5' and 3' untranslated regions.

The mRNA of beta-nerve growth factor (beta-NGF) has been demonstrated to be present in the human brain, both in adult and fetal stages of development. However, its complete nucleotide sequence is unknown since a full-length cDNA has yet to be isolated. We report here the cloning and complete analysis of the human fetal brain beta-NGF transcript. cDNA synthesis was performed from total brain RNA and overlapping regions of beta-NGF cDNA were enzymatically amplified and sequenced. The central portion of the cDNA was amplified using primers designed on the known genomic DNA sequence. The 5' and 3' unknown regions were amplified by the anchored polymerase chain reaction (PCR) and by complementary DNA Ends-PCR respectively. The latter method is an original variation of Inverted PCR. The sequenced transcript is very similar to the most common form of beta-NGF mRNA present in the mouse central nervous system. In addition, both the 5' and 3' untranslated regions show a high degree of homology to the corresponding murine sequences.

Base Sequence↗
PubMed1991

Beta-nerve growth factor (beta-NGF) mRNA expression in the parkinsonian adrenal gland.

The adrenal gland is a well-demonstrated source for different neurotrophic factors. The presence of the beta-nerve growth factor (beta-NGF) mRNA in the adrenal tissue used for grafting in a Parkinsonian patient is reported here. Adrenal samples were obtained on the day of implantation, and a specific cDNA was synthesized after the extraction of total RNA using a synthetic oligonucleotide as a reverse transcription primer. A 168-bp portion of the cDNA was amplified using two other oligonucleotides as Taq polymerase primers in a polymerase chain reaction. Thirty-two cycles of amplification were performed. The amplification products were identified by agarose gel electrophoresis and Southern blot analysis as a single DNA band hybridizing with a third beta-NGF specific oligonucleotide. The identity of the fragment was confirmed by DNA sequencing. Quantitative analysis demonstrated a beta-NGF mRNA concentration exceeding 5 fg/micrograms of total adrenal RNA. These findings add NGF to the other neurotrophic factors produced by the gland (i.e., basic fibroblast growth factor) and demonstrate the retained functional capacity of the Parkinsonian adrenal to express the beta-NGF mRNA. All these data may assume relevant meaning for neurotransplantation research.

Adrenal Glands↗