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Biomedical subjects

D W Paty

Publications and source records attributed to D W Paty.

At least 91 records · Page 5Linked to original sources
PubMed1989

The lesion of multiple sclerosis: imaging of acute and chronic stages.

Increased blood-brain barrier (BBB) permeability, important in the pathogenesis of MS, may be demonstrated as lesion enhancement with high-volume delayed CT (HVDCT). We studied 40 MS patients with history, neurologic examination, HVDCT, and MRI. In addition, 7 of the patients with enhancing CT lesions were followed with serial MRI for up to 3 years and 7 months. In 3 of these patients we repeated the HVDCT. Patients with enhancing lesions on CT were younger, had shorter duration of disease, and had more frequent clinical relapses than did patients without enhancement. More than half (56%) of the enhancing CT lesions were in the deep white matter, 23% were periventricular, and 21% were at the gray/white matter junction. Half the CT enhancing lesions, when followed by serial MRI, showed significant changes in lesion size. Although the majority (59%) of these lesions faded, some remained actively changing (25%) or became confluent with adjacent lesions (16%). In 48% of the MRI examinations that showed activity, some lesions were increasing in size while others were simultaneously decreasing in size. This study confirms that MS is a dynamic process in which recurrent episodes of BBB disruption and inflammation play a major role. Recurrent episodes of inflammation may well be a prelude to the largely irreversible changes of demyelination and gliosis.

Acute Disease↗
PubMed1988

Natural killer (NK) cells in chronic progressive multiple sclerosis patients treated with lymphoblastoid interferon.

Natural killer (NK) cell functional activity, as defined by the lysis of 51Cr-labelled K-562 cells, and number, defined phenotypically by anti-Leu-11, are significantly decreased in chronic progressive multiple sclerosis (MS) when compared to normal controls. When age- and sex-matched populations are compared, NK cell functional activity is again significantly reduced in MS compared to controls but not when compared to a control group of other medical disease (OMD). The MS group could be differentiated from the OMD group, however, when results of NK cell functional activity are combined with NK cell phenotype. With the administration of lymphoblastoid interferon daily for 6 months, NK cell activity increased significantly at 48 h and at 1 week. By 1 month, activity decreased to a level slightly above placebo treatment values. The results likely reflect interferon's enhancement of mature NK cell activity combined with a variable effect on recruitment of pre-NK cells.

Adult↗
PubMed1988

Magnetic resonance imaging in the assessment of disease activity in multiple sclerosis.

Magnetic resonance imaging (MRI) has been shown to be a good method of visualizing the lesions in MS. We have studied several applications of MRI to the evaluation of patients and experimental models. In diagnosis, MRI is the most sensitive test for the demonstration of dissemination of lesions in space. Pathological correlation studies show that MRI reliably measures the extent of chronic demyelination. Experimental studies show that MRI detects acute inflammatory lesions and measures their evolution. MRI also is a reliable measure of the extent of the MS process, serial MRI scans detect evidence of disease activity in MS not always disclosed by clinical evaluation. MRI will have an enormous future impact on the evaluation of patients in clinical studies and in understanding the evolution of pathological processes.

Humans↗
PubMed1988

Multiple sclerosis: a serial study using MRI in relapsing patients.

Prospective monthly magnetic resonance imaging (MRI) studies were done over 6 months in seven relapsing MS patients. MRI and neurologic evaluations were compared for sensitivity in detecting disease activity. Four patients were clinically stable throughout the study. Three patients had five clinical relapses, two localized to the spinal cord and three to the brainstem. Eighteen new and ten enlarging MRI lesions were seen in five patients. Most lesions were less than 10 mm in diameter. All were clinically silent. Two patients developed major enlarging MRI lesions (seen in three slices) which increased in size over 2 months and then gradually became smaller over 2 months, leaving behind small residual areas of abnormality. There were 36 follow-up scans, 17 of which (47%) showed evidence for increasing activity. Thirteen (36%) of the scans had new lesions, most of them being small. This study shows that MRI evidence for disease activity in MS is much more frequent than is clinical evidence.

Adult↗
PubMed1988

Multiple sclerosis: in relapsing patients, immune functions vary with disease activity as assessed by MRI.

We have serially studied immunoglobulin G secretion in vitro, natural killer cell function, and concanavalin A-induced suppression in a group of seven patients with relapsing-remitting multiple sclerosis. In two patients, the development of a large clinically asymptomatic MRI lesion was accompanied by reductions in natural killer cell function, immunoglobulin G secretion in vitro (after pokeweed mitogen stimulation), and concanavalin A-induced suppression without parallel change in lymphocyte markers. We did not see this type of change in matched controls nor in stable multiple sclerosis studied serially. When clinical attacks appeared, there was no significant change in immune function. We conclude that changes in immune function correlate well with the activity of the disease as recognized by MRI. We suspect that decreased natural killer cell function, immunoglobulin G secretion in vitro, and concanavalin A-induced suppression are secondary to the large lesions recognized by MRI.

Adult↗
PubMed1988

Scales for rating impairment in multiple sclerosis: a critique.

We reviewed scales proposed over the past 35 years for the rating of neurologic impairment in MS. We focused on the Expanded Disability Status Scale (EDSS) which has been recommended as the most useful scale for rating impairment by the International Federation of Multiple Sclerosis Societies in its Minimal Record of Disability for Multiple Sclerosis. We consider that the EDSS has important flaws that seriously limit its usefulness. In light of the widely accepted three-tier classification of dysfunction developed by the World Health Organization, the title is inappropriate. More substantial problems include inadequate precision in defining the degree of impairment in some functional categories of the scale, and the use of a mixture of neurologic signs elicited on examination and subjective information obtained from the patient in defining the overall scale. We suggest guidelines for developing a "Neurologic Impairment Scale" to rate impairment in MS.

Humans↗
PubMed1988

MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT.

We compared the diagnostic capabilities of MRI to CT, evoked potentials (EP), and CSF oligoclonal banding analysis in a prospective evaluation of 200 patients with suspected multiple sclerosis (MS). MRI was the best method for demonstrating dissemination in space. An abnormal appropriate EP in monosymptomatic disease was usually supported by MRI and CSF analysis as being predictive of MS as a clinical diagnosis. A normal appropriate EP study was not satisfactory because MRI and CSF analysis often did not support a diagnosis of non-MS. When there is agreement between three of these paraclinical studies, the diagnosis of MS is probably unequivocal. For use in research studies, laboratory-supported definite MS (LSDMS) could be diagnosed in 85 patients of the total 200 (42.5%), in 19/38 (50%) of optic neuritis (ON) patients, and in 24/52 (46%) of chronic progressive myelopathy (CPM) patients. MRI was 100% successful in identifying patients who qualified for LSDMS in the ON and CPM groups. In a short follow-up (less than 1 year), 19/200 (10%) went on to develop clinically definite MS (CDMS), and MRI predicted that diagnosis in 18/19 (95%). Only long-term follow-up will show how well these studies and the category of LSDMS predict the development of CDMS. The clinical diagnosis of MS (CDMS), even though only 95% accurate, must remain the gold standard.

Adolescent↗
PubMed1988

The retinal nerve fiber layer, neuroretinal rim area, and visual evoked potentials in MS.

In a prospective study of 57 patients with clinically definite, probable, or possible multiple sclerosis (MS), one-half of whom had a history of optic neuritis, retinal nerve fiber layer (RNFL) defects and the neuroretinal rim (NRR) area were quantitatively determined and compared with the visual evoked potential (VEP). There were abnormal VEP latencies in 63% of all patients (definite and probable = 68%, possible = 50%); local or diffuse RNFL defects in 54%, (definite and probable = 54%, possible = 50%); and an abnormally small NRR area in 30% (definite and probable = 32%, possible = 25%). Abnormalities in one or more of the VEP, RNFL, or NRR area occurred in 86% of all patients (definite and probable = 90%, possible = 75%), thus considerably increasing the yield of optic nerve abnormalities over that of the VEP alone. The predominance and extent of the diffuse RNFL defects, which are axonal abnormalities, suggest a more diffuse optic nerve pathology in MS than can be accounted for by a "plaque" pathology and indicate that extensive axonal loss commonly occurs in the optic nerves of MS.

Adult↗
PubMed1987

Temporal lobe involvement in multiple sclerosis patients with psychiatric disorders.

Patients with multiple sclerosis (MS) frequently develop psychiatric disturbances. The clinical histories and magnetic resonance imaging results from eight patients with MS and psychiatric disorders were compared with those from eight control MS patients matched for age, sex, duration and severity of illness, and clinical course. Both groups had widespread lesions on the magnetic resonance imaging scans; however, the psychiatric group had more clinically defined sites of MS involvement, possibly indicating a difference in the biologic activity of the lesions in this group. The total lesion area was not different between the groups. However, the distribution of lesions did differ; the psychiatric group had significantly more temporal lobe involvement than the control group. These results indicate a role for the cerebral lesions themselves, particularly those in the temporal lobes, in the genesis of psychiatric disorders in MS.

Adult↗
PubMed1987

Multiple sclerosis in childhood: clinical profile in 125 patients.

Multiple sclerosis (MS) has its usual onset in early adult life (average age of 30 years), but age at clinical onset varies considerably. The implications of the age of onset on the clinical presentation and course of MS are unclear. This population-based retrospective study presents data from a group of 125 patients with onset of MS before age 16 years and can thus be considered as representative of MS occurring in childhood. It demonstrates that childhood MS is more frequent in girls, that it very often has a relapsing-remitting course, that initial bouts usually involve afferent structures of the central nervous system, that recovery from these is often complete, and that the pace of the disease is slow.

Adolescent↗
PubMed1987

Multiple sclerosis: assessment of disease progression and effects of treatment.

MS could well be a two stage disease. The first stage involves the sequential development of multiple small lesions, mostly inflammatory, that accumulate at a given rate. The second stage could be that of consolidation and confluence of lesions that involves not only demyelination but gliosis. MRI now gives us an opportunity to watch the evolution of these processes and also to monitor treatment effects. It is only after the evolution of this process is understood that we can design rational therapies directed toward the prevention of spasticity in MS.

Anti-Inflammatory Agents↗
PubMed1987

Assessment of multiple sclerosis lesions by magnetic resonance imaging.

Fifty patients clinically suspected to have multiple sclerosis (MS), who were classified by Schumacher's criteria into three clinical categories (definite, probable, or possible MS), underwent complete brain magnetic resonance (MR) scans. The T2-weighted spin echo (SE) pulse sequence was more sensitive than inversion recovery (IR) in detecting MS lesions. Greater than 50% of the lesions demonstrated by SE were missed on the corresponding IR slices. However, lesions in the brainstem were more readily assessed using IR. MS lesions appeared larger on SE than on IR. Fifty-five percent of SE-demonstrated lesions were 1 to 2 cm or larger in size, while only 32% of IR-demonstrated lesions were greater than 1 cm. Axial and coronal planes of study demonstrated the same number, size, and location of lesions.

Adult↗
PubMed1986

A population-based study of multiple sclerosis in twins.

Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.

Canada↗
PubMed1986

Absence of antibody to HTLV I and III in sera of Canadian patients with multiple sclerosis and chronic myelopathy.

Recently, elevated titers of antibody to HTLV I have been demonstrated in patients with tropical spastic paraparesis and multiple sclerosis. We evaluated the possible role of human retroviruses HTLV I and III in Canadian patients with multiple sclerosis and chronic idiopathic myelopathy. Using sensitive enzyme immunoassays, we were unable to find antibody to either HTLV I or III in 201 patients with multiple sclerosis, 29 patients with chronic myelopathy, 51 patients with other neurological disorders, or 29 normal subjects. These data do not support a role for these viruses in the cause of sporadic multiple sclerosis and chronic myelopathy in a regionally based Canadian population, but do not exclude a role for other antigenically distinct retroviruses.

Antibodies, Viral↗
PubMed1986

Fluorescence-activated cell sorter analysis of bulk-isolated porcine oligodendrocytes.

We describe here the methods by which enriched populations of oligodendrocytes were isolated from adult porcine brains using Percoll density gradient centrifugation and their immunological properties analyzed by a fluorescence-activated cell sorter (FACS). The analyses by immunofluorescence microscopy and FACS indicated 95% and 93% purity of oligodendrocytes in the cell preparations when galactocerebroside antibody, an oligodendrocyte-specific marker, was employed. Further FACS analysis indicated that 90% of the cells with the forward angle light scatter characteristics of oligodendrocytes were immunolabelled by the monoclonal antibody HNK-1. The FACS sorting capability was then used to correlate the forward angle light scatter and propidium iodide uptake characteristics of our cell preparations to cell debris, erythrocytes as well as viable and non-viable oligodendrocytes. By gating on a multiparameter basis on both defined forward light scatter and positive galactocerebroside immunolabelling, oligodendrocyte populations exceeding 98% purity were obtained which were suitable for long-term culture and further immunological and neurobiological studies.

Animals↗