Labe C. Scheinberg

On the presence of Ia-positive endothelial cells and astrocytes in multiple sclerosis lesions and its relevance to antigen presentation.

Using a monoclonal antibody in combination with the 4-step modified peroxidase-antiperoxidase (PAP) technique, Ia expression was demonstrated on endothelial cells and astrocytes in MS lesions of different ages. On endothelial cells, Ia antigen was found most frequently in grey and white matter parenchyma of acute MS brain and showed lower, comparable numbers in active and silent chronic MS brain tissue. Ia+ astrocytes were most numerous in acute MS lesions. In active chronic MS, Ia+ astrocytes predominated at the lesion edge, where they frequently displayed an atypical, rounded configuration. Positive astrocytes showed somewhat lower numbers within the lesion center and in normal white matter close to the lesion edge. Their frequency was significantly lower in normal white matter remote from the lesion. In silent chronic MS, Ia+ astrocyte processes were detectable only within the lesion center. Grey matter astrocytes displayed no staining with anti-Ia antibody. In normal brain tissue, no Ia antigen could be detected. The presence of Ia molecules on some endothelial cells and astrocytes in MS brain tissue suggests a role in antigen presentation perhaps relevant to the initiation and perpetuation, respectively, of the inflammatory process.

Factors associated with unemployment of patients with multiple sclerosis

As part of a larger study of psychosocial aspects of chronic disease, the employment status of 79 male and 233 female multiple sclerosis patients was evaluated by interview to identify: (1) the relationship between degree of disability and employment status and (2) other determinants of employment status. Seventy-seven per cent of the patients were unemployed. Disability level, age, sex, and level of education accounted for 14% of the differences in employment status, with less disabled, older, more educated males being the most likely to be employed. Employment status was unrelated to marital status or type of occupation. Case histories are presented to illustrate psychosocial and environmental factors which might further account for the differences in employment status.

Adhesion molecules on endothelial cells in the central nervous system: An emerging area in the neuroimmunology of multiple sclerosis

The observation of lymphocyte adhesion/homing molecules with ligands (integrins and vascular addressins) on endothelial cells (EC) within target organs during a number of nonlymphoid chronic inflammatory conditions is occurring with increasing frequency. On the basis of evidence from the literature and pilot data on the localization of the putative vascular addressin for humans, HECA-452, in central nervous system (CNS) tissue, it is suggested that molecular recognition on CNS EC might play a pathogenetic role during immune-mediated demyelination in multiple sclerosis (MS). In one of six cases of MS, a case displaying a particularly malignant course, HECA-452 was specifically and reproducibly demonstrated on postcapillary venules in periplaque white matter beyond the zone of active inflammation. In the same case, CD8+ T cells predominated over CD4+ cells. In no case studied were EC positive for HLA-DR (Ia), in contrast to previous reports. Perivascular Ia positivity was common and was always associated with foamy macrophages or pericytes. In view of the occurrence of semiorganized lymphoid collections in a number of chronic inflammatory conditions, several of which are associated with expression of HEV markers, and in MS, it is concluded that examination of molecular recognition events on lymphocytes and EC within the CNS in MS is an area worthy of further study and an area with considerable therapeutic import.

High‐dose oral baclofen Experience in patients with multiple sclerosis

We reviewed a 10% random sample of charts from an outpatient clinic for multiple sclerosis to determine the frequency with which baclofen was prescribed for spasticity in high doses (>80 mg/d). About 20% of patients had taken high-dose baclofen, and 15% were still receiving a high dose. Taking a high dose was not associated with discontinuing treatment.

Brain AbscessesL: A Review of Ninety‐Nine Cases

THE ADVENT and widespread usage of chemotherapeutic and antibiotic agents have produced favorable changes in the clinical picture and prognosis of most infectious diseases. Since brain abscess is frequently secondary to infections outside the central nervous system, it is reasonable that improvement in therapy of primary infections should be reflected in the outcome of central nervous system suppuration. The purpose of this study is to review the change in mortality of brain abscess coincident with the period of advances in the field of antibacterial therapy. The problem of alteration in the clinical picture of brain abscess by the use of these agents will be investigated and the results compared with those reported during the pre-antibiotic period.

ULTRASTRUCTURAL AND BIOCHEMICAL ANALYSIS IN CEREBRAL EDEMA ASSOCIATED WITH EXPERIMENTAL MOUSE GLIOMAS.

Mouse cerebrum adjacent to implanted ependymoblastoma became edematous, as manifested by an increase in water and sodium content. The affected areas stained with vital dye. The I131 albumin uptake averaged 4.4 per cent as compared to 1.1 per cent for distant brain. S3504 uptake averaged 20.9 per cent as compared to 5.1 per cent in distant brain. However, electron micrographs showed little alteration in extracellular space; the chief morphological change was the swelling of glial cell processes. Therefore, S35O4 uptake does not appear to be a measure of extracellular space. It is suggested that altered membrane or transport processes leads to the accumulation of S35C>4,1131 albumin, and vital dye within the cytoplasm of the edematous glial cell processes.

Cervical spondylosis and dyskinesias

THE ROLE OF TRAUMA, occupational and sporadic, in the production of cervical spondylosis has been alluded to in past studies of this disease entity.l-3 While in the older age groups the importance of this factor may b e disputed, in patients below 50 it seems to have definite significance. By involving the cervical spine in repetitive abnormal movements, the dyskinesias-choreoathetosis, dystonia, and spasmodic torticollis-should give rise to an earlier and higher incidence of spondylosis. This has not been extensively studied. We became interested in this problem through one of our patients, a 38-year-old man with choreoathetosis. In addition, he had severe cervical spondylosis, with progressive neurological disability. Root and cord encroachment had caused bilateral flaccid weakness of the upper extremities with spastic lower extremities. Subsequently, w e reviewed X-rays of the cervical spine in twenty cases of dyskinesia. These suggested a causal relationship between the movement disorder and the development of cervical spondylosis.

Self-Assessment of Neurologic Impairment in Multiple Sclerosis:

The Kurtzke Expanded Disability Status Scale (EDSS) is the standard method for eval uating neurologic impairment in multiple sclerosis. It involves a neurologic exam and ambulation assessment performed by a physician. This study developed and tested a self-assessed EDSS in which MS patients evaluated their own level of disability and selected an overall score akin to that used by the physician. The questionnaire was administered to 50 patients who were independently assessed by a neurologist at a regular clinic visit. Results indicated a high degree of correlation with an average dis crepancy of .55 of a point with 52 percent perfect agreement and 84 percent agree ment within one point. The intraclass correlation was .90. A difference in the dis crepancy was found between low and high EDSS scores. Scores between 0 and 3.5 had an average discrepancy of 1.59, whereas scores in the range from 4.0 to 9.5 had a discrepancy of .26. Thus, although a high degree of agreement was noted overall, agreement was better in the more neurologically impaired range. Key Words: Kurtzke EDSS—Multiple sclerosis—Neurologic impairment—Self-assessment.

Corticosteroid effect on intracerebral melanomata and associated cerebral edema Some unexpected findings

BRAIN TUMORS exert their lethal effect partly because of the edema surrounding them. The other biological properties of such tumors are also important in damaging the patient irreparably, such as recurrence despite surgical extirpation and no immunologic defense reaction. In the present paper, the authors wish to examine the concept that corticosteroids produce relief in patients with brain tumors because of their effect on the surrounding edema. In other diseases manifested by cerebral edema, corticosteroids have been shown to be effective empirically in reducing this edema. Colleagues of the present authors have documented their effectiveness in treating triethyltin (TET) sulfate-induced edema in rabbits.1 The assumption has been made that since corticosteroids reduce cerebrospinal fluid (CSF) pressure in patients with other types of cerebral edema and since patients with brain tumors have associated cerebral edema, the drugs must act to reduce this edema. Clinically, there is no doubt that the patients rapidly become more alert and feel better subjectively.2-5 Nausea, headaches, and visual function are improved, too, and these are commonly ascribed to raised intracranial pressure. The vexed question of cerebral edema necessarily accompanying a raised intracranial pressure will not be further considered in this study. Objective criteria of improvement in patients given corticosteroids have been offered. Angiograms, brain scans, and electroencephalograms all appear more nearly nosmal.24 The possibility that the brain tumors themselves might be inhibited in their growth does not appear to have been generally considered. A priori this idea does not seem to be acceptable, because no other type of tumor is thus inhibited. One important point in favor of such an idea is the prolonged period over which the patients remain more comfortable. Evidence for such improvement has been stated in several articles, but the authors have not drawn this alternative inference from their data.2-5 Edema occurs on a rapid time scale, both in forniing and in dispersing. Hours may suffice for its accumulation, and it very soon reappears after dispersal by osmotic agents.6 The suggestion that steroids continually suppress the formation of edema around brain tumors for several months may be correct, but it requires careful examination. The authors have previously commented on the biochemical criteria for cerebral edema which are acceptable to a11 who work in this field. There is an increase in water content

The cost‐effectiveness of multiple sclerosis rehabilitation: A model

Many patients with multiple sclerosis (MS) who have fixed, chronic neurologic deficits are kept at home with the help of community support systems, which cannot improve the physical independence of the MS patients they serve. We have found that active, intensive, multidisciplinary rehabilitation effectively improves functional performance, even though it cannot alter the underlying disorder. Inpatient rehabilitation with follow-up home care may actually be less expensive than any other current health care alternative.