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Biomedical subjects

C Pozzilli

Publications and source records attributed to C Pozzilli.

At least 19 recordsLinked to original sources

Relationship between corpus callosum atrophy and cerebral metabolic asymmetries in multiple sclerosis.

Corpus callosum (CC) atrophy by magnetic resonance imaging (MRI) is a common finding in multiple sclerosis (MS). In order to examine the relationship between CC atrophy and cortical brain metabolism, we compared the cerebral metabolic rates for glucose (CMRglc), measured by positron emission tomography (PET), of 8 MS patients with evidence of CC atrophy on midsagittal MRI, 8 MS patients without CC atrophy and 10 healthy controls. Results showed no significant differences in supratentorial CMRglc absolute values between the three groups, although a slight metabolic reduction was observed in both MS groups compared with normal controls. By contrast, only patients with CC atrophy showed greater directional metabolic asymmetry than normals, the left frontal, temporal and parietal association cortices being significantly lower than the right. Predominant left hemispheric metabolic reductions were not accompanied by a corresponding left-sided predominance in the extent of MRI-detected demyelinating lesions. Therefore our data suggest that CC atrophy interfers more with left than with right metabolic function.

Adult

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

Depression in the early phase of MS: influence of functional disability, cognitive impairment and brain abnormalities.

This study investigated the relationship between depression, physical disability, cognitive deficit and brain abnormalities on magnetic resonance imaging (MRI) in patients with early MS. Eighteen relapsing-remitting MS patients were evaluated: depression was diagnosed according to DSM-III R and measured by the MMPI depression subscale, physical disability was assessed by using the Kurtzke Expanded Disability Status Scale (EDSS) and cognitive functions by means of an extensive neuropsychological test battery. A neuroradiologist blinded to clinical findings quantified cerebral lesion on MRI. Weighted brain area lesion score were developed according to number and size of cerebral lesions. On the basis of DSM-III criteria, six patients were classified as having major depression, seven patients had minor depression and five patients were without depressive symptoms. No significant differences were found among the three groups on both neuropsychological performances and weighted MRI lesion scores. However patients with major depression exhibit greater physical disability than the other MS subgroups. A significant correlation was found between MMPI depression subscale and physical disability. This study suggests that at least in the early phase of MS, depression appears more related to the physical disability than to the severity of pathological brain involvement.

Activities of Daily Living

HLA determinants in familial multiple sclerosis.

HLA-A, -B, -C, -DR, -DQ antigens were studied in 11 multiplex MS families, 11 single-case MS families and 100 healthy subjects. The HLA DR4 was the most frequent antigen in all MS patients (p = 0.015). When the antigenic frequency in index familial cases was compared with that in single cases, the DR4 antigen was found to be more frequent (p = 0.01) in familial cases only. Furthermore, when the DR4 antigen was excluded from the analysis, we observed an increase in DR2 (p = 0.11) only in the familial MS cases. These results can be compatible with a multifactorial hypothesis according to which the HLA genes have an important role in MS susceptibility in familial cases.

Gene Frequency

Structural brain correlates of neurologic abnormalities in multiple sclerosis.

We examined the relationship between cerebral magnetic resonance imaging (MRI) findings and urinary dysfunction in 70 consecutive patients with definite multiple sclerosis. MRI-weighted lesion scores for seven different brain regions were recorded according to the number and size of cerebral lesions. Thirty-two subjects (46%) had urinary symptoms and 38 (54%) were asymptomatic. Subjects with urinary symptoms exhibited greater overall functional disability and a higher midbrain MRI-weighted lesion score than asymptomatic patients. No statistically significant group differences were found for the other brain regions.

Adolescent

Cognitive and brain imaging measures of multiple sclerosis.

In this review we will describe the cognitive deficiency in Multiple Sclerosis (MS) and analyze the relationship between the performance on neuropsychological tests and the anatomofunctional findings assessed by neuroimaging techniques. Memory, abstract reasoning, and visuospatial abilities impairments are correlated with lesion extension and with corpus callosum atrophy, quantified on MRI. On the other hand, in MS patients with cognitive disturbance, PET and SPET studies show metabolic alterations and perfusion deficits at the cortical level, particularly in the left hemisphere and in the frontal and temporal lobes.

Cognition Disorders

Anterior corpus callosum atrophy and verbal fluency in multiple sclerosis.

To determine whether different portions of the corpus callosum (CC) are responsible for transferring the information of specific cognitive modalities, eighteen females with relapsing-remitting Multiple Sclerosis (MS) were studied using neuropsychological procedures and Magnetic Resonance Imaging (MRI). Measures of both anterior and posterior CC areas were obtained in patients with MS as well as in eighteen age and sex matched healthy controls. MRI scans were additionally analyzed for each patient in order to evaluate the extent of demyelinating lesions in both periventricular and subcortical areas. Patients with MS exhibited a significant decrease in both the anterior and posterior CC areas compared with normal subjects. The results of statistical analysis showed that, even when the effect of demyelinating lesions was taken into account within a regression equation, the atrophy of anterior CC area strongly affected the performance on verbal fluency task. These data emphasize the importance of the anterior CC area for the interhemispheric transfer of cognitive information associated with verbal fluency.

Adult

Quantitative assessment of cerebral blood flow in partial epilepsy using Xe-133 inhalation and SPECT.

The Xe-133 inhalation method was used to study rCBF in 12 patients with partial epilepsy during the interictal phase. SPECT images evidenced a focal CBF defect in 10 out of 12 patients, while quantitative analysis showed CBF abnormalities in all the patients. The focal CBF defect corresponded to the site of EEG abnormalities in nine patients. Additional low-flow areas beyond the EEG focus were found. Five patients presented a significant CBF decrease in the cerebellar hemisphere contralateral to the EEG focus. In five patients with unilateral EEG abnormalities, a CBF reduction was found in the contralateral cerebral hemisphere, mirror to the EEG focus. Finally, a widespread CBF decrease involving one or both cerebral hemispheres was observed in seven patients. Global and rCBF values were not correlated with age, duration of disease, frequency of seizures, secondary generalization, or specific therapy. SPECT may be useful in evaluating EEG epileptic foci, and quantitative SPECT allows the detection of functional effects of the epileptic focus on anatomically connected remote areas, probably due to the decrease of afferent inputs (diaschisis phenomenon).

Administration, Inhalation

SPECT, MRI and cognitive functions in multiple sclerosis.

Seventeen patients with relapsing remitting multiple sclerosis (MS) and mild physical disability had neuropsychological testing, magnetic resonance imaging (MRI) and single photon emission computerised tomography (SPECT) using technetium 99m (99mTc) hexamethyl-propyleneamine oxime (HMPAO). Performance in verbal fluency, naming and memory testing appeared to be impaired in MS patients compared with 17 age-sex and education matched normal controls. Weighted periventricular and confluent lesion scores and the width of the third ventricle, proved to be the most sensitive MRI measures in differentiating more cognitively impaired patients from those who were relatively unimpaired. Ratios of regional to whole brain activity, measured by SPECT, showed significant reduction in the frontal lobes and in the left temporal lobe of MS patients. A relationship was found between left temporal abnormality in 99mTc-HMPAO uptake and deficit in verbal fluency and verbal memory. Finally, asymmetrical lobar activity indicated a predominant left rather than right temporo-parietal involvement.

Brain

Predictive value of brain perfusion single-photon emission computed tomography in acute ischemic stroke.

We investigated 32 patients with completed ischemic stroke less than or equal to 6 hours after the onset of symptoms by means of computed tomography, cerebral angiography, and technetium-99m-labeled hexamethylpropyleneamine oxime single-photon emission computed tomography to study cerebral blood flow. Follow-up computed tomography and cerebral blood flow studies were performed 1 week and 1 month after admission. Poor outcome at 1 month was evident in 18 (78%) of the 23 patients with severe neurologic deficit on admission and in 11 (92%) of the 12 patients with severe hypoperfusion in the affected hemisphere on admission. All 10 patients with severe impairment of both neurologic status and cerebral blood flow had a poor outcome at 1 month. We detected severe hypoperfusion in patients with large lesions on computed tomograms or cerebral artery occlusions on angiograms. Cerebral blood flow had increased at the 1-week follow-up despite different clinical outcomes. Our data provide evidence that early evaluation of cerebral blood flow with single-photon emission computed tomography is useful to detect subgroups of patients with different clinical outcomes during the acute phase of ischemic stroke.

Brain Ischemia

Serial study of gadolinium-DTPA MRI enhancement in multiple sclerosis.

We performed serial baseline and gadolinium (Gd)-DTPA-enhanced MRI in 4 patients with definite multiple sclerosis. Studies were performed every month for a total of 4 scans. We obtained short TR/short TE sequences at 10 and 60 minutes after Gd-DTPA injection. All patients had multiple hyperintense lesions seen on baseline MRI with long TR/short and long TE. There was Gd-DTPA enhancement in new, enlarging, and preexisting lesions that were unchanged in size. The enhancing lesions were always seen on T2-weighted images. There was no difference in enhancement between the 10- and 60-minute studies. Six of 85 preexisting lesions enhanced whereas all new or enlarging lesions enhanced. Enhancement persisted in only 1/3 of the new or enlarging lesions, suggesting that MR enhancement is a transient phenomenon due to local temporary blood-brain barrier breakdown. Our data indicate that Gd-DTPA enhancement monitoring is more sensitive than unenhanced MRI for detecting disease activity in MS.

Adult

Systemic hypertension as a treatable risk factor for cerebrovascular disease.

It has long been established that hypertension is the major risk factor for stroke. Three Italian studies have been reviewed in order to examine different aspects of the problem. In the first study, the role played by the systolic, diastolic and systodiastolic components of hypertension in causing atherosclerotic damage of extracerebral and intracerebral arteries was examined. At the extracranial level, a significant correlation between systolic hypertension and atherosclerotic lesions was evident. The second study evaluated the risk of major stroke, myocardial infarction and death in patients with transient ischemic attacks and reversible ischemic neurologic deficits. Possible prognostic predictors of these events were thoroughly considered: Cumulative survival with the multivariate Kaplan-Meier analysis was significantly lower in hypertensive than in normotensive subjects, particularly for cerebral deaths and for all deaths. The third study was aimed at assessing the risk factors for transient ischemic attacks and stroke in young adults. Again, hypertension emerged as a fundamental risk factor, significantly more frequent in the subgroup of older patients than in the younger subgroup.

Age Factors

Influence of nimodipine on cerebral blood flow in human cerebral ischaemia.

Cerebral blood flow (CBF) was measured by xenon-133 inhalation and single photon emission computerized tomography (SPECT) in 7 patients with acute cerebral ischaemia prior to and 30 min after intravenous infusion of nimodipine (1 mg). Neurological examination, CT and CBF study were performed no later than 6 h after the onset of symptoms. Regional perfusion abnormalities were seen in all patients when the CT scan was still normal. Follow-up CT revealed low-density areas roughly corresponding to the core of the perfusion defect. Nimodipine infusion significantly decreased the mean arterial blood pressure (P less than 0.01), while PaCO2 and clinical symptoms remained unchanged. A significant CBF improvement (P less than 0.05) after nimodipine was seen in the border zone of the ischaemic infarct but not in the core of the lesion or in the unaffected contralateral hemisphere.

Adult

Acetazolamide effects on cerebral blood flow in acute reversible ischemia.

Cerebral blood flow (CBF) was studied in 4 patients with acute reversible ischemia (RIND). To test the ischemic areas' vasoreactivity, CBF was measured by the Xenon-133 inhalation method, before and after acetazolamide injected intravenously. At the baseline CBF study, 3 patients presented hypoperfused areas while one patient had increased CBF over the affected hemisphere. The acetazolamide test, showed in this latter case a "steal phenomenon" while in the other 3 an increase of perfusion was evidenced, in areas of normal flow, as well as in areas with reduced flow. These results suggest that in the acute phase of patients with RIND, when brain regions of hypoperfusion and neurological signs are still present, the vasomotor response may be preserved.

Acetazolamide

Positron CT imaging of an impending stroke.

We present PET findings of a case of a transient ischemic attack which later progressed to cerebral infarction. Cerebral blood flow at the stroke focus in the right parietal cortex measured after a TIA attack and before stroke was as low as 24 ml/100 g/min with some increase in oxygen extraction fraction and blood volume. The condition was compatible with "misery perfusion". This case may be an example suggestive that the "misery perfusion sign" is a warning of impending stroke and its poor prognosis if left without appropriate treatments.

Aged