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Biomedical subjects

F Di Salle

Publications and source records attributed to F Di Salle.

At least 19 recordsLinked to original sources

Subcortical motor plasticity in patients with sporadic ALS: An fMRI study.

OBJECTIVE: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. METHODS: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. RESULTS: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. CONCLUSIONS: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction.

Adult↗

Sudden re-opening of collapsed transverse sinuses and longstanding clinical remission after a single lumbar puncture in a case of idiopathic intracranial hypertension. Pathogenetic implications.

The aetiopathogenetic role of sinus venous obstructions carried by most idiopathic intracranial hypertension (IIH) patients is controversial. We report the case of a young woman diagnosed with IIH with papilloedema and narrowing of transverse sinuses, in which lowering of intracranial pressure by a single 20 ml cerebrospinal fluid (CSF) resulted in a strong dimensional increase of the transverse sinuses. Changes were followed by clinical remission and normalisation of optical nerve calibre, maintained after a 2-month follow-up. Our findings indicate that, although secondary to CSF hypertension, venous sinuses compression may have an important role in hypertensive status maintenance. Pathogenetic implications of venous sinus compression by hypertensive CSF in IIH are discussed.

Adult↗

Perfusion- and BOLD-based fMRI in the study of a human pathological model for task-related flow reductions.

In the present work, an arteriovenous malformation was taken as a pathological model for studying task-related flow decreases during a motor task. Combined Blood Oxygen Level Dependent (BOLD)-perfusion experiments were applied in order to evaluate the relative sensitivity of these techniques to task-related reductions in cerebral blood flow (CBF). Results shows that, by matching the sensitivity of the methods (which exhibit a different contrast-to-noise ratio) in the primary motor cortex, the spatial extent of the regions of decreased perfusion signal is larger than those of the BOLD signal reduction. The above finding suggests that perfusion imaging, that already represents a gold standard method in the detection of vascular phenomena, may estimate task-related flow decreases in a functional time-series better than BOLD.

Adult↗

Issues concerning the construction of a metabolic model for neuronal activation.

The metabolic events underlying neuronal activity still remain the object of intense debate, in spite of the considerable amount of information provided from different experimental techniques. Indeed, several attempts at linking the cellular metabolic phenomena with the macroscopic physiological changes have not yet attained foolproof conclusions. The difficulties in drawing definitive conclusions are due primarily to the heterogeneity of the experimental procedures used in different laboratories, and also given the impossibility of extrapolating the findings obtained under stationary conditions (prolonged stimulation) to dynamic and transient phenomena. Recently, lactate has received much attention, following its proposal by Pellerin and Magistretti (1994; Proc. Natl. Acad. Sci. USA 91:10625-10629), instead of glucose, as the main substrate for neurons during activity. Several challenging aspects suggest the return to a more conventional view of neuronal metabolism, in which neurons are able to metabolize ambient glucose directly as their major substrate, also during activation.

Animals↗

High field functional MRI.

Functional magnetic resonance imaging (fMRI) has become the most widely used approach for studying brain functions in humans. The rapid and widespread diffusion of fMRI has been favoured by the properties this technique presents, and particularly by its sensitivity in analysing brain functional phenomena and by the lack of biological invasiveness, resulting in an unprecedented and unparalleled flexibility of use. These properties of fMRI brought the functional examination of the brain within the reach of the whole neuroscience community and have appreciably stimulated the research on the functional processes of the living brain. Among the main features of fMRI, its spatial and temporal resolution represents clear advantages compared with the other methods of functional neuroimaging. In fact, the high spatial resolution of fMRI permits to produce more precise and better localised information, and its temporal resolution provides the potential of a better understanding of neural dynamics at the level of single functional areas and of the neural constituents of functional patterns. A fundamental possibility of improving spatial and temporal resolution without excessively degrading signal-to-noise ratio consists in the use of high magnetic field intensity fMRI units. Besides, high field units make the use of more demanding fMRI paradigms, like single trial event related studies, much more compatible with the need of a solid statistical evaluation. This has notably promoted the diffusion of high field MRI units for human studies throughout the world, with very high field MRI units, up to 8 T, working in a few research centres, and a larger number of MRI units with field intensity ranging between 3 and 5 T.

Brain↗

The physiology and metabolism of neuronal activation: in vivo studies by NMR and other methods.

In this article, a review is made of the current knowledge concerning the physiology and metabolism of neuronal activity, as provided by the application of NMR approaches in vivo. The evidence furnished by other functional spectroscopic and imaging techniques, such as PET and optical methods, are also discussed. In spite of considerable amounts of studies presented in the literature, several controversies concerning the mechanisms underlying brain function still remain, mainly due to the difficult assessment of the single vascular and metabolic dynamics which generally influence the functional signals. In this framework, methodological and technical improvements are required to provide new and reliable experimental elements, which can support or eventually modify the current models of activation.

Brain↗

The aerobic brain: lactate decrease at the onset of neural activity.

The metabolic events of neuronal energetics during functional activity are still partially unexplained. In particular, lactate (and not glucose) was recently proposed as the main substrate for neurons during activity. By means of proton magnetic resonance spectroscopy, lactate was reported to increase during the first minutes of prolonged stimulation, but the studies reported thus far suffered from low temporal resolution. In the present study we used a time-resolved proton magnetic resonance spectroscopy strategy in order to analyse the evolution of lactate during the early seconds following a brief visual stimulation (event-related design). A significant decrease in lactate concentration was observed 5 s after the stimulation, while a recovering of the baseline was observed at 12 s.

Adult↗

Longitudinal study of vasopressin-cell antibodies and of hypothalamic-pituitary region on magnetic resonance imaging in patients with autoimmune and idiopathic complete central diabetes insipidus.

Diagnosis of autoimmune central diabetes insipidus (CDI) is based on the presence of autoantibodies to AVP-secreting cells (AVPcAb) or the coexistence of other autoimmune polyendocrine syndromes; moreover, it can be also suggested by the presence of lymphocytic infundibulo-neurohypophysitis, evidenced by biopsy of pituitary stalk and/or by pituitary stalk thickening on magnetic resonance imaging (MRI). However, so far, in clinical CDI patients with lymphocytic infundibulo-neurohypophysitis, AVPcAb have not been investigated and in those with or without autoimmune polyendocrine syndromes (APS), longitudinal studies on the behavior of AVPcAb alone, or of both AVPcAb and hypothalamic pituitary imaging on MRI are lacking. Aim of this work was to investigate in these patients the occurrence of AVPcAb (by indirect immunofluorescence) and of pituitary stalk thickening (by MRI) and their longitudinal changes during a follow-up period. We studied 22 patients, aged 29-53, with APS and complete CDI, grouped as follows: 10 with recent onset (< or =1.5 yr) of CDI (group 1a) and 12 with CDI of long-term duration (> or = 7 yr) (group 1b); moreover, a group of 13 patients with apparent idiopathic CDI of recent onset (<1.5 yr) were studied. They were divided, on the basis of the detection of AVPcAb as follows: 5 AVPcAb positive patients (aged 19-26) classified as isolated autoimmune CDI (group 2) and 8 AVPcAb negative patients (aged 21-26), classified as true idiopathic CDI (group 3). All patients were evaluated yearly, along 5 yr, for AVPcAb and for hypothalamic-pituitary region imaging. At study entry, 8/10 (80%) of patients in group 1a and 7/12 (58.3%) in group 1b were positive for AVPcAb and persisted positive subsequently, during all the follow-up period, even if at lower titers. All patients in group 2 were positive and all those in group 3 were negative for AVPcAb and persisted positive and negative, respectively, for all the follow-up study. Among the AVPcAb-positive patients, only 5 in group 1a and 2 in group 2 showed also pituitary stalk thickening at the first observations, which however spontaneously disappeared subsequently indicating a possible lymphocytic infundibulo-neurohypophysitis. All patients in the studied groups showed loss of the hyperintense signal of the neurohypophysis on MRI at entry and during all the follow-up period. Results of this longitudinal study suggest: 1) AVPcAb, frequently present at high titers in recent phases of CDI, persist subsequently, even if at lower titers, several years after the onset of disease. 2) The occurrence of a lymphocytic infundibulo-neurohypophysitis suggested by the pituitary stalk thickening on MRI only in patients positive for AVPcAb confirms a further autoimmune variant of CDI also in these cases. 3) The longitudinal behavior of patients in group 3 suggests that the absence of AVPcAb at the onset of clinical idiopathic CDI is able to exclude a subsequent appearance of these antibodies and consequently an autoimmune involvement in CDI of these patients. Instead the finding of AVPcAb in several patients with only CDI, thought at first clinical observation as idiopathic, indicates that the prevalence of autoimmune CDI must be considered much higher than that so far reported.

Adult↗

Functional fields in human auditory cortex revealed by time-resolved fMRI without interference of EPI noise.

The gradient switching during fast echoplanar functional magnetic resonance imaging (EPI-fMRI) produces loud noises that may interact with the functional activation of the central auditory system induced by experimental acoustic stimuli. This interaction is unpredictable and is likely to confound the interpretation of functional maps of the auditory cortex. In the present study we used an experimental design which does not require the presentation of stimuli during EPI acquisitions and allows for mapping of the auditory cortex without the interference of scanner noise. The design relies on the physiological delays between the onset, or the end, of stimulation and the corresponding hemodynamic response. Owing to these delays and through a time-resolved acquisition protocol it is possible to analyze the decay of the stimulus-specific signal changes after the cessation of the stimulus itself and before the onset of the EPI-acoustic noise related activation (decay-sampling technique). This experimental design, which might permit a more detailed insight in the auditory cortex, has been applied to the study of the cortical responses to pulsed 1000 Hz sine tones. Distinct activation clusters were detected in the Heschl's gyri and the planum temporale, with an increased extension compared to a conventional block-design paradigm. Furthermore, the comparison of the hemodynamic response of the most anterior and the posterior clusters of activation highlighted differential response patterns to the sound stimulation and to the EPI-noise. These differences, attributable to reciprocal saturation effects unevenly distributed over the superior temporal cortex, provided evidence for functionally distinct auditory fields.

Acoustic Stimulation↗

T2 relaxometry of brain in myotonic dystrophy.

We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease.

Adolescent↗

Scintimammography with 99mTc-MIBI versus dynamic MRI for non-invasive characterization of breast masses.

Although mammography remains the technique of choice for the early detection of breast cancer, several imaging techniques, including scintimammography and magnetic resonance imaging (MRI), have recently been proposed as adjuncts for this purpose and included in many diagnostic protocols. This study was undertaken to assess the clinical accuracy of scintimammography with technetium-99m methoxyisobutylisonitrile (MIBI) and contrast-enhanced MRI in the detection of primary breast carcinoma in patients with equivocal mammographic findings. Forty-nine patients with a suspicious breast mass detected either by physical examination or by mammography and ultrasound (US) were studied. All patients underwent scintimammography and dynamic contrast-enhanced MRI 1 week apart. The results of the two techniques were compared and correlated to the final diagnoses. Two independent readers reported the scans using a four-point confidence scale. The areas under the receiver operator characteristic (ROC) curves were obtained. Scintimammography showed an accuracy for tumour detection of 84%, with a sensitivity of 80% and a specificity of 88%. MRI showed an accuracy of 86%, with a sensitivity and specificity of 96% and 75%, respectively. Comparison of the two areas under the ROC curves showed no significant differences between MRI, 0.91+/-0.05 (mean+/-SD), and scintimammography, 0.88+/-0.05 (P=0.9). It is concluded that dynamic MRI and scintimammography possess comparable accuracy in the diagnosis of primary breast carcinoma in patients with equivocal mammographic or US findings.

Biopsy↗

Dilated Virchow-Robin spaces in myotonic dystrophy: frequency, extent and significance.

To study the frequency, extent and significance of dilated Virchow-Robin spaces (VRSs) in dystrophia myotonica (DM), we evaluated the cranial magnetic resonance imaging (MRI) of 41 patients with the adult form of DM and 41 healthy controls. Dilated VRSs and white matter lesions (WMLs) were rated according to semiquantitative methods. Convexity VRSs were more frequent (68 vs. 34%; p < 0.01) and severer (median scores: 4 vs. 0; p < 0.01) in DM patients than in controls, while lenticulostriate VRSs did not show significant differences in frequency (83 vs. 70%; p > 0.05) and severity (median scores: 4 vs. 3; p > 0.05). WMLs were more frequent (66 vs. 22%; p < 0.01) and severer (median scores: 5 vs. 0; p < 0.01) in patients. Disease duration was negatively correlated with convexity VRSs and positively with lobar (centrum semiovale) WML scores. Dilated convexity VRSs might be one of the initial findings in cranial MRI of DM, preceding the appearance of lobar WMLs.

Adolescent↗

Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy.

To evaluate the prevalence of resistance to cabergoline treatment, we studied 120 consecutive de novo patients (56 macroadenoma, 60 microadenoma, 4 nontumoral hyperprolactinemia) treated with cabergoline (CAB) compared with 87 consecutive de novo patients (28 macroadenoma, 44 microadenoma, 15 nontumoral hyperprolactinemia) treated with bromocriptine (BRC) for 24 months. Resistance was evaluated as inability to normalize serum PRL levels (first end point) and to induce tumor shrinkage (second end point). After 24 months, PRL normalization and tumor shrinkage after CAB and BRC treatments, respectively, were obtained in 82.1% and 46.4% of macroprolactinomas (P < 0.001) and in 90% vs. 56.8% of microprolactinomas (P < 0.001). The median doses of CAB and BRC able to fulfill the two criteria of treatment success were 1 mg/wk and 7.5 mg/d in macroprolactinomas, 1 mg/wk and 5 mg/d in microprolactinomas, and 0.5 mg/wk and 3.75 mg/d in nontumoral hyperprolactinemia. Hyperprolactinemia persisted in 17.8% of macroprolactinomas, 10% of microprolactinomas, and after CAB at doses of 5-7 mg/wk and in 53.6% of macroprolactinomas, 43.2% of microprolactinomas, and 20% of nontumoral hyperprolactinemic patients, after BRC at doses of 15-20 mg/d. In these resistant macro- and microprolactinomas, the maximal tumor diameter was reduced by 43.7 +/- 3.6% and 22.1 +/- 3.7% and by 59.3 +/- 7.1% and 4.3 +/- 2.1% after CAB and BRC, respectively (P < 0.001). In conclusion, long-term CAB treatment induced the successful control of hyperprolactinemia associated with tumor shrinkage in a higher proportion of patients than did BRC treatment. In a small number of patients (i.e. 17.8% of macroprolactinomas and 10% of microprolactinomas), however, CAB treatment did not normalize serum PRL levels despite reducing tumor mass, even at very high doses. Therefore, an absence of tumor shrinkage cannot be considered as end point to indicate resistance to CAB, and increasing the dose of CAB higher than 3 mg/wk does not seem to be helpful in controlling PRL hypersecretion.

Adenoma↗

Auditory system: functional magnetic resonance imaging.

Functional MR imaging (fMRI) is being used increasingly to explore the human central auditory system. The considerable background noise produced by echo-planar imaging (EPI) and other fMRI sequences, however, interferes in an unpredictable way with the experimental stimuli. Several approaches exist to overcome this problem. Each has its advantages and disadvantages. These different approaches allow researchers to tailor the experimental designs to specific research questions. Recent studies have yielded significant information about human auditory function. Compared with other sensory systems such as the visual system, the auditory database still is relatively small. It is expected that novel methodologic approaches will stimulate scientific exploration of auditory processing and eventually lead to clinically meaningful applications of auditory fMRI.

Auditory Cortex↗

Atypical Friedreich ataxia phenotype associated with a novel missense mutation in the X25 gene.

We describe two sisters with early onset gait ataxia, rapid disease progression, absent or very mild dysarthria and upper limb dysmetria, retained knee jerks in one, slight to moderate peripheral nerve involvement, and diabetes. Molecular analysis showed that they are compound heterozygotes for GAA expansion and a novel exon 5a missense mutation (R165P). This mutation appears to be associated with an atypical but not milder Friedreich ataxia phenotype.

Adult↗

Traumatic displacement of the globe into the ethmoid sinus.

PURPOSE: To describe displacement of the globe into the ethmoid sinus after an orbital trauma. METHOD: Case report. A 58-year-old man sustained trauma of the left eye and orbit, which resulted in displacement of the globe into the ethmoid sinus. One day after injury, surgery was performed to restore the intact globe into position within the orbit. RESULTS: After operation, the globe held in its anatomical site, and 10 months after surgery the visual acuity was 20/100, slight pallor of the optic disk was present, and there was no limitation of the horizontal and vertical ductions. CONCLUSIONS: To our knowledge, this is the first case of traumatic displacement of the globe into the ethmoid sinus with satisfactory restoration of normal globe position and preservation of vision.

Accidental Falls↗

Matching two imagined clocks: the functional anatomy of spatial analysis in the absence of visual stimulation.

Do spatial operations on mental images and those on visually presented material share the same neural substrate? We used the high spatial resolution of functional magnetic resonance imaging to determine whether areas in the parietal lobe that have been implicated in the spatial transformation of visual percepts are also activated during the generation and spatial analysis of imagined objects. Using a behaviourally controlled mental imagery paradigm, which did not involve any visual stimulation, we found robust activation in posterior parietal cortex in both hemispheres. We could thus identify the subset of spatial analysis-related activity that is involved in spatial operations on mental images in the absence of external visual input. This result clarifies the nature of top-down processes in the dorsal stream of the human cerebral cortex and provides evidence for a specific convergence of the pathways of imagery and visual perception within the parietal lobes.

Adult↗