Subclinical peripheral nervous system involvement in multiple sclerosis.
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Adult↗
Biomedical subjects
C Pozzilli
Publications and source records attributed to C Pozzilli.
Human recombinant interferon beta in the treatment of relapsing-remitting multiple sclerosis: preliminary observations.
An open comparative, randomized trial with recombinant human interferon beta (r-hIFN-beta) involving 72 patients with clinically definite and/or laboratory-supported relapsing-remitting MS is in progress at the University 'La Sapienza' and at the S. Camillo Hospital of Rome. After a 6 month period of clinical and magnetic resonance imaging (MRI) observation (baseline findings), patients are randomly assigned to one of two treatment groups receiving 3 or 9 MIU of recombinant human IFN-beta (r-hIFN-beta) self-administered by subcutaneous injection three times a week for 6 months. All patients are examined by MRI with and without gadolinium (Gd-DTPA) every 4 weeks for the entire duration of the study (12 months). The main aim of the study is to test the hypothesis that r-hIFN-beta may halt or slow the progression of the disease by showing a significant reduction in MRI activity. This will be achieved by comparing pre and post-treatment periods. As an additional clinical end point, the exacerbation rate during these two periods will be compared. This study began in June 1993 and the final analysis of MRI data is planned for the spring of 1995.
Adjuvants, Immunologic↗
Psychostimulant drugs increase glucose utilization in the shell of the rat nucleus accumbens.
The nucleus accumbens (NAc) is a heterogeneous area, divided into a 'shell' and a 'core' on the basis of morphological and histochemical criteria. Moreover, the two portions have different anatomical connections. In order to test whether the two portions of NAc are functionally distinct, we measured local cerebral glucose utilization in rats administered intravenously with cocaine (1 mg kg-1) or amphetamine (0.5 mg kg-1). The results of the study show that, at these dosages, both drugs increase glucose utilization in the shell, but not in the core of NAc. This differential effect might reflect functional differences between the two portions of NAc, probably relevant to the abuse liability of psychostimulants.
Amphetamine↗
Factors affecting course and survival in Alzheimer's disease. A 9-year longitudinal study.
OBJECTIVE: To evaluate mean survival and to identify prognostic factors in a cohort of patients with Alzheimer's disease (AD). DESIGN: Multicentric 9-year cohort analytic study. SETTING: Seven neurology departments throughout Italy between April 1982 and January 1984. PATIENTS: We recruited a consecutive sample of 145 patients affected by probable AD (Multicenter Italian Study on Dementia protocol, National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). Five were misdiagnosed, and 21 could not participate in the longitudinal study. The clinicodemographic characteristics of the 119 enrolled patients (49 men, 70 women; mean age, 64.7 years; SD, 4.1 years; mean duration of disease, 3.1 years; SD, 1.8 years) did not differ from those of the 26 excluded patients. All underwent extensive cliniconeuropsychological testing every 6 months for at least 2 years until the patient died or our survey ended (April 30, 1991). Mean follow-up was 5.1 years (SD, 2.5 years). MAIN OUTCOME MEASURES: Death, severe functional impairment (a score > or = 17 on the Blessed Dementia Scale), and severe cognitive impairment (a score of < or = 7 on the Information-Memory-Concentration Test). RESULTS: Survival curves obtained by the Kaplan-Meier method indicated that (1) patients with early- and late-onset disease (ie, before or after age 65 years) showed no difference either in relative survival or in time to reach predetermined functional and cognitive end points; (2) severely aphasic patients became profoundly demented significantly sooner than those with mild to moderate aphasia (P < .0001). Among clinicodemographic variables analyzed by a Cox model, severe language disability and functional loss proved to be the best predictors of death independent of age at onset or degree of dementia. CONCLUSIONS: Age at onset did not influence course and survival in AD. Severe aphasia appears to be the best predictor of death and unfavorable course.
Aged↗
Antiphospholipid antibodies and cerebral artery dissection: two frequent causes of brain ischemia in young adults.
As part of a multicenter study on ischemic stroke in the young, we report the occurrence of high antiphospholipid antibody (aPLs) levels and cerebral dissection in 75 patients. These represent the two most frequent non-thromboembolic causes of cerebral ischemia in our population. Increased aPL titres were found in nine cases (12%); cerebral artery dissection in eleven (14%). Our data stress the need to modify the classical diagnostic approach to cerebral ischemia by including hematological assessments and new neuroimaging techniques as screening tests.
Adult↗
Dynamics of the autoimmune T-cell repertoire in experimental allergic encephalomyelitis and in multiple sclerosis.
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Animals↗
A controlled trial of mitoxantrone in multiple sclerosis: serial MRI evaluation at one year.
We present the results of a randomized double-blinded placebo controlled, multicenter trial, of low-dose mitoxantrone (MX), after one year, in 25 patients with relapsing-remitting multiple sclerosis, who had serial enhanced magnetic resonance imaging (MRI). Treatment groups were balanced for age, gender, duration of illness and neurological disability. Five of the 13 MX patients and 10 of the 12 placebo patients had exacerbations during treatment (p < 0.02). The mean change in the extended disability status scale was not significantly different between the MX and placebo treatment groups. Serial Gadolinium-DTPA enhanced MRI detected no significant difference between the MX treated and placebo groups in the mean total number of new, enlarging, or Gadolinium-DTPA enhancing lesions; there was a trend toward a reduction of new, enlarging and Gadolinium-DTPA enhancing lesions in MX patients. Despite this ameliorating effect, the results indicate that serial Gadolinium-DTPA enhanced MRI, performed over one year in a limited number of patients, could not provide conclusive evidence for a role of MX therapy in relapsing-remitting multiple sclerosis.
Adolescent↗
No differences in corpus callosum size by sex and aging. A quantitative study using magnetic resonance imaging.
To identify normal variations in the magnetic resonance imaging appearances of the corpus callosum with regard to sex and age, a prospective study was performed in 130 normal subjects. Callosal measurements were calculated by morphometric analysis. There were no significant sex differences in corpus callosum area or the callosal subregions. The absolute area did not decrease significantly with aging in normal males or females. However, age-related changes of callosal configuration were shown by a decrease in the ratio of the rostrum and genu to the splenium.
Adolescent↗
Mesial temporal cortex hypoperfusion is associated with depression in subcortical stroke.
BACKGROUND AND PURPOSE: This study was conducted to evaluate local cerebral blood flow changes in patients with depression after a subcortical stroke. METHODS: Clinical and neuropsychological assessments were performed in 15 patients with a single subcortical lesion. Depression was assessed by DSM-III-R. In addition, the Hamilton Rating Scale for depression, the Zung Self-Rating Depression Scale, and the Beck scale were administered to each patient. Single-photon emission-computed tomography study was performed with 99mTc hexamethylpropyleneamine oxime. RESULTS: In all patients cortical regions ipsilateral to subcortical lesions were significantly less perfused than the contralateral cortex. Cerebral blood flow values were significantly lower in depressed patients (n = 8) than in nondepressed patients (n = 7) only in the mesial temporal cortex of the affected hemisphere. Cerebral blood flow values in the mesial temporal cortex of the affected hemisphere significantly correlated with the severity of depression. CONCLUSIONS: Temporal lobe hypoperfusion may reflect a dysfunction of the limbic system, suggesting that this location may be critical for the occurrence of depressive symptoms in patients with subcortical stroke.
Aged↗
Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis.
T lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP-specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant T cell recognitions of distinct MBP regions were present in three patients, all HLA-DR2+, independently of the clinical features of their disease. T cell reactivity was preferentially directed to residues 16-38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86-99 was detected in the two other DR2+ patients. In each of the patients with other HLA-DR haplotypes (DR2-), as well as in three DR2+ non-MS donors, the T cell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2+ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA-DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA-DRB1 gene in individuals with the HLA-DR2 serological specificity is also described. We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA-DR2 gene products alone do not account for the selection of the dominant MBP T cell epitope.
Adolescent↗
Anatomical and functional correlates of cognitive deficit in multiple sclerosis.
This brief article reviews the present state of knowledge concerning the relationship between structural and functional cerebral abnormalities and the cognitive deficits associated with multiple sclerosis. Currently available neuroimaging techniques have substantially contributed to a better understanding of the latter, suggesting that cortical-subcortical disconnection is the most likely cause of the cognitive disturbance. Longitudinal studies are needed to determine the natural history of the cognitive deficit and its relationship to the cerebral changes detected by neuroimaging techniques.
Cognition Disorders↗
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↗
Lack of association between macrocytosis and multiple sclerosis.
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Adult↗
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↗