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M Fiorelli

Publications and source records attributed to M Fiorelli.

At least 55 records · Page 3Linked to original sources
PubMed1995

A controlled study of potential risk factors preceding exacerbation in multiple sclerosis.

A wide variety of potential risk factors for acute exacerbations in multiple sclerosis were evaluated in a one year case-control study. Eighty nine consecutive patients with clinically definite multiple sclerosis and relapsing remitting course presenting with a relapse between January and December 1992 were compared with patients matched for age, sex, and degree of disability, who did not experience clinical exacerbations during the same period. Only potential risk factors occurring in the three months preceding the interview were considered patients. Relapsing patients reported no significant increase in the frequency of any risk factor in the three month period before exacerbation compared with the control group. These results suggest that most relapses are not preceded by the conditions commonly considered as risk factors.

Adolescent↗
PubMed1995

Clinical and prognostic correlates of stroke subtype misdiagnosis within 12 hours from onset.

BACKGROUND AND PURPOSE: Pure motor hemiparesis and sensorimotor stroke syndromes are not accurate predictors of lacunar infarct when described in the first 12 hours of stroke onset. We evaluate here whether this inaccuracy of clinical diagnosis might have influenced the planning of patient management either in routine practice or in therapeutic trials. METHODS: A consecutive hospital series of 517 first-ever ischemic hemispheric stroke patients presented lacunar or nonlacunar syndromes at the first examination within 12 hours of the event. A distinction was subsequently made, by means of a CT scan or autopsy performed within 15 +/- 2 days of stroke, between patients affected by lacunar or nonlacunar infarcts. We compared stroke risk factors, considered to be indicative of potential pathogenetic mechanisms, and the clinical outcome of lacunar infarct versus nonlacunar infarct patients and those of lacunar syndrome versus nonlacunar syndrome patients. RESULTS: Two hundred nineteen patients (42%) presented a lacunar syndrome and 298 (58%) a nonlacunar syndrome, while 170 (33%) had lacunar infarcts and 347 (67%) nonlacunar infarcts. Lacunar infarct patients were more frequently associated with hypertension and a previous transient ischemic attack and less frequently with atrial fibrillation when compared with their nonlacunar infarct counterparts, whereas no differences were apparent between lacunar syndrome and nonlacunar syndrome patients. Logistic regression analysis showed that hypertension and a previous transient ischemic attack on the one hand and atrial fibrillation on the other were strongly correlated with the diagnosis of lacunar infarct and nonlacunar infarct, respectively, while no risk factor was correlated with the diagnosis of lacunar syndrome. Twenty-two percent of lacunar infarct patients and 68% of nonlacunar infarct subjects had a poor outcome (death plus disability of survivors) as opposed to 40% of lacunar syndrome and 63% of nonlacunar syndrome patients. Logistic regression selected age, severity of neurological deficit at entry, cardiopathies, diabetes, and lacunar infarct, but not lacunar syndrome, as predictors of outcome. CONCLUSIONS: The inaccurate clinical diagnosis of lacunar infarct made in the first 12 hours of stroke might lead to no distinction being made between stroke subgroups with potentially different pathogenetic mechanisms and prognostic estimates, thus negatively influencing the planning of patient management.

Age Factors↗
PubMed1994

Influence of hyperglycaemia on infarct size and clinical outcome of acute ischemic stroke patients with intracranial arterial occlusion.

We investigated the effects of hyperglycaemia on infarct size of 82 acute ischaemic stroke patients with angiographically diagnosed intracranial occlusion in middle cerebral artery territory. There were 9 diabetics, 40 non-diabetic hyperglycaemics and 33 non-diabetic normoglycaemics (mean age 67 +/- 8 SD years, male/female ratio 1:1). For each patient the infarct at CT was compared to that predicted from the location of the arterial occlusion. The extent of the infarct was then classified as equal to, smaller than and larger than estimated, taking a standard anatomical template of arterial territories as reference. The results were analysed separately according to the presence or absence of a collateral blood supply (CBS) at angiography. The clinical outcome at 30 days was also evaluated. The 35 patients lacking CBS had a high frequency of equal to estimated lesions (75%), without substantial differences among the three subgroups (72% of hyperglycaemics, 82% of normoglycaemics and 67% of diabetics; Fisher's exact test not significant for any of the pairwise comparisons). On the contrary, the 47 patients with CBS exhibited an overall predominance of smaller than estimated lesions (66%) but with a very uneven distribution among hyperglycaemics, normoglycaemics and diabetics (82%, 64% and 0%, respectively; p < 0.05 at Fisher's exact test for diabetics vs hyperglycaemics). Finally, the clinical outcome was bad (death and neurological impairment) in 89% of diabetics, 72% of hyperglycaemics and 54% of normoglycaemics (p < 0.05). These results suggest that in patients with intracranial arterial occlusion associated with CBS the effects of hyperglycaemia might be beneficial in non-diabetics and harmful in diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Correlation between decreased myocardial glucose phosphorylation and the DNA mutation size in myotonic dystrophy.

BACKGROUND: Myotonic dystrophy, the most common form of adult dystrophy, has been shown to be caused by amplification of CTG triplet repeat in the 3' untranslated region of a protein kinase gene located on chromosome 19. Impaired glucose metabolism has been suggested as a possible explanation of brain and skeletal muscle involvement in this multisystem disease. We investigated whether myocardial glucose metabolism is impaired in myotonic dystrophy and whether this impairment is related to the size of the mutation. METHODS AND RESULTS: The myocardial metabolic rate for glucose (MMRGlu, mumol.min-1.g-1), K1 (blood-to-tissue transfer constant), k2 (tissue-to-blood transfer constant), and k3 (phosphorylation rate constant) were determined in 7 control subjects and 12 patients with myotonic dystrophy by using parametric images generated from dynamic cardiac positron emission tomography (PET) and 18F-fluoro-2-deoxy-glucose studies. The expansion of the CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. Nonparametric tests were used to compare quantitative variables between control subjects and patients. The correlations between the size of the mutation and PET parameters were studied by linear regression. MMRGlu and k3 were significantly decreased in patients compared with control subjects (0.39 +/- 0.20 versus 0.64 +/- 0.25, P = .03, and 0.09 +/- 0.07 versus 0.24 +/- 0.21, P = .03, respectively), whereas K1 and k2 were not statistically different between control subjects and patients. MMRGlu and k3 correlate inversely with the length of the CTG triplet repeat (r = -.65 and P = .03 for MMRGlu, and r = -.85 and P = .001 for k3, respectively). CONCLUSIONS: In myotonic dystrophy, the observed reductions in MMRGlu and phosphorylation are inversely linked to the length of the mutation. This observation suggests that impaired modulation of a protein kinase involved in myocardial hexokinase activation may give a pathophysiological schema to relate the molecular defect and the abnormal myocardial metabolism in myotonic dystrophy.

Adult↗
PubMed1994

Pure motor hemiparesis and sensorimotor stroke. Accuracy of very early clinical diagnosis of lacunar strokes.

BACKGROUND AND PURPOSE: Clinical differentiation of lacunar from nonlacunar strokes in the very early phase could help to exclude patients with lacunar stroke from pharmacologic trials designed for nonlacunar strokes, namely, those with thrombolytic agents. In a continuous series of acute ischemic stroke patients, we evaluated how accurately a clinical diagnosis of pure motor hemiparesis or sensorimotor stroke formulated in the first hours from onset predicts a lacunar stroke documented by cerebral computed tomography or by autopsy. METHODS: We examined 517 patients (299 men, 218 women; mean +/- SD age, 67 +/- 10 years) within 12 hours (mean +/- SD, 6.1 +/- 3.2 hours) of the event. At hospital admission, we observed 151 (29%) patients with pure motor hemiparesis and 68 (13%) patients with sensorimotor stroke. RESULTS: Computed tomography or autopsy was compatible with a lacunar stroke (ie, detection of a lacune or permanently negative computed tomography) in 170 (33%) patients, of whom 123 (72%) had pure motor hemiparesis and 47 (28%) had sensorimotor stroke. This led to a sensitivity of 72%, a specificity of 72%, a positive predictive value of 56%, and a negative predictive value of 84%. Overall positive predictive value of pure motor hemiparesis was 58% (60% for two areas and 58% for three areas involved), and that of sensorimotor stroke was 51% (87% for two areas and 40% for three areas involved). By separately evaluating the sides of lesions, we found a positive predictive value of 46% for right-side infarcts and of 72% for left-side infarcts. Right-side lesions constituted 51% of lesions in lacunar syndrome patients with lacunar stroke, 76% in those with nonlacunar stroke, 19% in nonlacunar syndrome patients with lacunar stroke, and 31% in those with nonlacunar stroke (P < .0001). During the first days of hospital stay we observed a deterioration of 21% of lacunar syndrome patients with nonlacunar stroke and an improvement of 49% of nonlacunar syndrome patients with lacunar stroke, with appearance and disappearance of symptoms of cortical involvement, respectively. The examination of these patients after the occurrence of these clinical changes would have led to a daily increase of the positive predictive value up to a maximum of 66% at day 7. CONCLUSIONS: Pure motor hemiparesis and sensorimotor stroke diagnosed within 12 hours of the event are poorly predictive of lacunar strokes. Hence, the very early identification of these syndromes cannot be used for patient selection in therapeutic trials.

Aged↗
PubMed1993

PET study of changes in local brain hemodynamics and oxygen metabolism after unilateral middle cerebral artery occlusion in baboons.

Local cerebral hemodynamics and oxygen metabolism were measured by positron emission tomography (PET) with the oxygen-15 (15O) steady-state method in baboons, immediately before (T0), 1 (T1), and 3-4 (T2) h after permanent middle cerebral artery occlusion (MCAO). At T1, there was a marked fall in both cerebral blood flow (CBF) and the CBF/cerebral blood volume (CBV) ratio in the occluded territory; these changes were sustained at T2, indicating stable reduction in cerebral perfusion pressure and lack of spontaneous reperfusion within this time range. Compared with preocclusion conditions, the oxygen extraction fraction (OEF) in the occluded territory was elevated at both T1 and T2, indicative of a persistent oligemia/ischemia for up to 3 h after MCAO. At T2, however, this OEF increase had lessened, concomitantly with a decline in cerebral metabolic rate of oxygen (CMRO2). This impairment of oxidative metabolism occurred earlier in the deep, compared with the cortical, MCA territories; in the latter, the CMRO2 was essentially preserved at T1 and only moderately reduced at T2, possibly suggesting prolonged viability. Finally, no significant changes in CBF or CMRO2 were observed in the contralateral MCA territory in this time range after MCAO. Despite methodological limitations (mainly partial volume effects related to PET imaging, which may have resulted in an underestimation of true changes and an overlooking of heterogeneous changes) our study demonstrates the feasibility of the combined PET-MCAO paradigm in baboons; this experimental approach should be valuable in investigating the pathophysiology and therapy of acute stroke.

Animals↗
PubMed1993

Loss of brain 5-HT2 receptors in Alzheimer's disease. In vivo assessment with positron emission tomography and [18F]setoperone.

Using [18F]setoperone and positron emission tomography (PET), alterations in serotonergic 5-HT2 receptor binding were studied in cerebral cortex of nine unmedicated patients with probable Alzheimer's disease and 37 healthy controls. The kinetics of unchanged radioligand in plasma and 18F-radioactivity in blood and brain were obtained for 90 min following tracer injection. The specific binding of [18F]setoperone to 5-HT2 receptors in the cerebral cortex was quantitated by subtraction using cerebellum as reference. In controls, a significant reduction in specific binding was associated with age and similar linear regression slopes were obtained in all the cortical regions studied. No significant difference was observed between patients with Alzheimer's disease and age-matched controls in the injected mass of setoperone, percentage of unmetabolized [18F]setoperone in plasma, 18F-radioactivity in blood fractions and cerebellar 18F-radioactivity concentration, indicating similar non-specific brain kinetics and metabolism of the radioligand. In contrast, there was a significant reduction in specific [18F]setoperone binding in the cerebral cortex in patients with Alzheimer's disease relative to control values (temporal, 69%; frontal, 69%; parietal, 55%; temporo-parietal, 54%; occipital cortex, 35%). The results demonstrate that the loss in 5-HT2 receptor binding in the cerebral cortex of patients with Alzheimer's disease, long documented by post-mortem studies, can now be assessed in vivo using PET.

Aged↗
PubMed1992

Right motor neglect associated with dynamic aphasia, loss of drive and amnesia: case report and cerebral blood flow study.

A 30-year-old right-handed man had right motor neglect, amnesia, aphasia and loss of drive following bilateral thalamic and subthalamic infarctions. Serial resting cerebral blood flow (CBF) measurements with either Xenon 133 inhalation or positron emission tomography at 1, 8 and 10 months post-onset showed a widespread and long-lasting low CBF in the cortex. An additional CBF measurement, during motor tasks, showed a marked interhemispheric asymmetry in the pattern of activation: whereas left hand movement resulted in a CBF increase in contralateral superior rolandic and prerolandic areas, no significant regional CBF changes were seen during right hand movement, despite recovery from motor neglect. This loss of CBF increase in cortical motor and premotor areas during voluntary movement of the previously neglected side points to a disruption of cortico-subcortical pathways subserving motor activation. The pathophysiology of aphasia, loss of drive and amnesia as well as their relationships to motor neglect, may also be discussed on the basis of thalamo-cortical disconnections.

Adult↗
PubMed1992

T-lymphocyte reactivity to the recombinant mycobacterial 65- and 70-kDa heat shock proteins in multiple sclerosis.

Owing to their conservation and immunogenicity, heat shock proteins (hsps) represent a class of potential autoantigens. Moreover, they could be targets for gamma delta T lymphocytes, which are prominent in various immune disorders. We studied the T cell proliferative primary responses to recombinant M. bovis 65 kDa hsp (hsp65) and M. tuberculosis 70 kDa hsp (hsp70) in 31 patients with multiple sclerosis (MS), 19 patients with other neurological diseases (OND) and 19 healthy individuals. Positive responses to hsp70, but not to hsp65 were significantly more frequent in patients with MS than in patients with OND or in healthy individuals. In order to verify and refine these results and to characterize the hsp reactive T lymphocytes, we screened 147 PPD-specific long-term T cell lines (76 from 10 patients with MS and 71 from 12 healthy donors) for their proliferative response to hsp65 and hsp70. hsp70-reactive T lines were significantly more common in patients with MS than in healthy controls. The number of T lines responding to hsp65 increased in the MS group only slightly. In 19 T lymphocyte lines from patients with MS and healthy donors, a cytofluorometric analysis was performed with special attention paid to distinct T cell receptor gamma delta determinants. With one exception, in each line the population of gamma delta T cells remained a minority. We conclude that an increased T cell response to mycobacterial hsp70 may be present in patients with multiple sclerosis.

Adolescent↗
PubMed1992

Cortical metabolism in posterolateral thalamic stroke: PET study.

In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the 18F-fluorodeoxyglucose or the 15O-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the "non-specific" thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain.

Aged↗
PubMed1992

Decreased cerebral glucose utilization in myotonic dystrophy.

To test the hypothesis that cerebral metabolism is altered in myotonic dystrophy (MyD), we investigated cerebral glucose kinetics and utilization in 11 adult patients with MyD and 14 healthy controls, using 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) and dynamic positron emission tomography. Estimation of rate constants in MyD revealed a reduction of FDG delivery to the brain. Cortical glucose utilization rate was reduced by about 20% in MyD. These findings may be related to the presence of neurologic impairment in MyD and prompt further investigations on the metabolic and clinical features of brain dysfunction in this disease.

Adult↗
PubMed1991

Intracranial arachnoid cysts in myotonic dystrophy.

Clinically apparent brain dysfunction is common in myotonic dystrophy. In a sample of fourteen adult patients with the definite form of this disease, brain magnetic resonance imaging detected frequent white matter abnormalities and ventriculomegaly. In addition, two patients exhibited an intracranial arachnoid cyst, a condition of neurosurgical interest that could be related to the generalized dysmaturational process present in this disease. Patients with myotonic dystrophy deserve a careful screening for brain involvement. Further MRI studies should ascertain the actual prevalence of brain anomalies in myotonic dystrophy and define the role of this procedure in the workup of this disease.

Adult↗
PubMed1991

PET studies of cortical diaschisis in patients with motor hemi-neglect.

Six patients presenting with multimodal, predominantly motor hemi-neglect, were investigated by 15O2 or 18F-DG and PET to study the local cerebral metabolism in intact regions. All had suffered from an acute right-sided (n = 5) or left-sided (n = 1) focal hemispheric lesion (cortico-subcortical and purely subcortical in three patients each). Frontal and parietal cortices on the side of the lesion were significantly hypometabolic relative to the other side in each case, presumably as a result of diaschisis, whereas thalamic hypometabolism was significant in only 4 patients. Compared to absolute metabolic rates for controls, the uninjured hemisphere showed a trend towards hypometabolism. Hence, true hyperactivity of the contralateral hemisphere with respect to the ipsilateral cerebral cortex was not associated with motor hemineglect in this series. On the contrary, hemineglect was associated with a widespread hypometabolism of the entire ipsilateral cerebral cortex in the context of a moderately reduced metabolism of the ipsilateral thalamus and contralateral cerebral cortex. These findings are consistent with the implication of a cortico-subcortical network serving attention.

Aged↗
PubMed1990

A method for the in vivo investigation of the serotonergic 5-HT2 receptors in the human cerebral cortex using positron emission tomography and 18F-labeled setoperone.

Following previous validation in baboons, we have studied the characteristics of [18F]setoperone as a radioligand for investigating serotonergic 5-hydroxytryptamine2 (5-HT2) receptors in the normal, unmedicated human brain with positron emission tomography (PET); subjects orally pretreated with therapeutic amounts of ketanserin, sulpiride, or prazosin were also studied to evaluate the specificity and sensitivity of [18F]setoperone brain specific binding. In controls (n = 10), the tracer showed a clear-cut retention in both frontal cortex and striatum (known to contain a high density of 5-HT2 receptors) relative to cerebellum (known to be devoid of 5-HT2 receptors). In the seven young controls (20-39 years old), the frontal cortex/cerebellum and striatum/cerebellum ratios increased during the first hour to reach similar values of 2.53 +/- 0.12 and 2.38 +/- 0.11 (mean +/- SEM), respectively, and were essentially stable during the second hour. Pretreatment with ketanserin (a 5-HT2 blocker) significantly reduced the frontal cortex/cerebellum ratio to 0.7-1.0 at 65 min, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. During sulpiride treatment (a D2 blocker), the frontal cortex/cerebellum ratio was not altered, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. With prazosin pretreatment (an alpha 1-adrenergic blocker), neither the frontal cortex/cerebellum nor the striatum/cerebellum ratio was modified. These data in humans with PET demonstrate that [18F]setoperone labels with high sensitivity and selectivity 5-HT2 receptors in the frontal cortex; in striata, however, binding is to both 5-HT2 and D2 receptors. The deproteinated-to-whole plasma radio-activity concentration ratio increased with time following injection. The mean percentage of intact [18F]setoperone, in deproteinated plasma, was 82, 74, 53, 45, 30, and 22% at 5, 10, 20, 30, 60, and 110 min following injection, respectively. These data indicate that [18F]setoperone (a) is significantly bound to plasma proteins and (b) is significantly metabolized into several labeled metabolites that are much more hydrophilic than setoperone and, hence, presumably do not cross the blood-brain barrier. These results suggest the suitability of [18F]setoperone data for modeling of 5-HT2 receptor binding in brain.

Adult↗
PubMed1990

Cerebrotendinous xanthomatosis: clinical and MRI study (a case report).

We report a patient with cerebrotendinous xanthomatosis (CTX) presenting with dementia, spastic tetraparesis and an unreported akinetic-rigid syndrome. Computed tomography (CT) showed only cerebellar abnormalities while magnetic resonance imaging (MRI) detected additional pallidal and mesencephalic focal alterations. MRI findings, but not CT, correlated with the clinical picture.

Achilles Tendon↗
PubMed1988

Changing prognosis of primary intracerebral hemorrhage: results of a clinical and computed tomographic follow-up study of 104 patients.

One hundred four consecutive cases of primary intracerebral hemorrhage hospitalized at the time of stroke were followed until death or for 1 year. All were treated nonsurgically. The 30-day mortality rate was 30%. Good clinical outcome and complete resolution of the lesion on computed tomography were observed in 49 and 13% of patients, respectively. Age, state of consciousness, and size of the hemorrhage on computed tomography scan were reliable prognostic indicators. The long-term survival rate, 66%, was higher than that previously reported and should be considered in future trials evaluating medical and surgical treatment of intracerebral hemorrhage.

Adult↗