Multiple sclerosis characteristics in African American patients in the New York State Multiple Sclerosis Consortium.

The objective of this study was to determine the clinical characteristics of multiple sclerosis (MS) in African American (AA) patients in the New York State Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of 18 MS centers throughout New York State organized to prospectively assess clinical characteristics of MS patients. AAs comprise 6% (329) of the total NYSMSC registrants (5602). Demographics, disease course, therapy, and socioeconomic status were compared in AA registrants versus nonAfrican Americans (NAA). There was an increased female preponderance and a significantly younger age at diagnosis in the AA group. AA patients were more likely to have greater disability with increased disease duration. No differences were seen in types of MS and use of disease modifying therapies. Our findings suggest a racial influence in MS. Further genetic studies that consider race differences are warranted to elucidate mechanisms of disease susceptibility.

A profile of multiple sclerosis: the New York State Multiple Sclerosis Consortium.

We have obtained a current profile of multiple sclerosis York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.

Adoptive transfer of experimental allergic encephalomyelitis from immature guinea pig donors.

In immature Strain 13 guinea pigs sensitized to syngeneic spinal cord, a chronic allergic encephalomyelitis is elicited reminiscent of demyelinating diseases of man and which features relapses or progressive downhill course and extensive areas of demyelination in the central nervous system. However, juvenile recipients of syngeneic lymphocytes from similarly sensitized juveniles show only the acute form of experimental allergic encephalomyelitis. Neuropathologically, the CNS of affected animals displayed mild changes only and minimal demyelination. These observations indicate that the age-dependent differences seen between the acute disease of adults and the chronic disease of juveniles may be due to differences in availability of modulating or reparatory factors, rather than differences in the central nervous system organ or in the immune response itself.

Congenital intramedullary spinal dermoid cyst associated with an Arnold-Chiari malformation.

Clinical and neuropathological studies of a case of congenital intramedullary spinal dermoid tumor in a patient with typical Arnold-Chiari malformation have been presented. The bulk of the tumor mass was located at C7 level and extended downward for about 3 cm. Numerous well formed hairs were grossly noted within the lesion. Microscopic examination revealed the presence of keratin squams, hair and hair follicles in chronic inflammatory granulation tissue. These histological features suggest that the dermoid has ruptured and therefore the cyst walls could not be identified as such but the content induced prominent chronic inflammatory granulomatous reaction. The rarity of the lesion, especially at the cervical and upper thoracic level and its unique association with an Arnold-Chiari malformation are discussed.

Attempts to induce chronic experimental allergic neuritis in strain 13 and Hartley guinea pigs.

An attempt has been made to develop a model of chronic experimental allergic neuritis (EAN) using juvenile and adult inbred (Strain 13) and Hartley guinea pigs sensitized with peripheral nerve in complete Freund's adjuvant. Animals were followed clinically for periods ranging from 2 to 44 weeks postinoculation and then sacrificed for light and electron microscopy. Out of a total of 39 animals, 16 showed either clinical signs or had histopathologic changes. The remaining 23 guinea pigs were free of any disease. The animals' age at inoculation and strain did not seem to affect either the clinical course or ultimate histopathologic changes. The 7 animals that had clinical EAN displayed signs ranging from weight loss and soiling to quadriparesis (one animal). The histologic changes consisted of meningeal and perivascular inflammation as well as peripheral nervous system (PNS) and central nervous system demyelination and remyelination. An interesting abnormality seen the nerve roots of several animals was the proliferation of Schwann cells around remyelinated PNS fibers reminiscent of the "onion-bulb" formations seen in human hypertrophic neuropathies. Because of the lack of ongoing demyelination, onion-bulb formation appeared in this case to be a secondary proliferation of Schwann cells after a single primary episode of demyelination. It is concluded from the present study that despite some interesting histopathologic changes, the animals studied were largely resistant both to acute as well as chronic EAN.

Suppression of acute and chronic experimental allergic encephalomyelitis in Strain 13 guinea pigs. A clinical and pathological study.

Adult inbred Strain 13 guinea pigs develop an acute, fatal form of experimental allergic encephalomyelitis (EAE) about 2 weeks after a single injection of isologous spinal cord in complete Freund's adjuvant (CFA), but similarly injected juveniles develop a delayed, rarely fatal chronic form. Thirty-seven sensitised adult Strain 13 animals were separated into 2 groups. One group was permitted to develop acute EAE. The other group was injected intramuscularly with 1 mg of guinea pig or bovine myelin basic protein (MBP) in incomplete Freund's adjuvant (IFA) on day 2, 7 or 10 post-inoculation (PI) followed by 0.2 mg in IFA every third day for a total of 10 doses. Animals in the unsuppressed group succumbed to acute EAE 13-16 days post-sensitisation. No animal in the suppressed group died during this period. Animals treated with MBP beginning 2 days PI showed no clinical signs, but mild clinical manifestations occurred in animals suppressed from days 7 and 10 PI. These signs remitted by 21 days post-sensitisation. One suppressed animal (out of 21) died during the fourth week postsensitisation. The other 20 suppressed animals appeared clinically normal towards the end of the course of MBP injections and remained so for the 6 months of study. Morphological examination revealed that CNS lesions occurred in all animals. In animals suppressed with MBP beginning on day 2 PI, lesions consisted only of a few meningeal inflammatory cells. Animals given MBP beginning on day 7 or 10 PI and sampled 1-2 weeks later, had lesions which could not be distinguished from those occurring in the non-suppressed acute EAE group. In time, the suppressed animals developed lesions which were typical of chronic EAE with remyelination as a predominant feature. Preliminary experiments on the suppression of chronic EAE in 5 juvenile Strain 13 guinea pigs have revealed that 3 MBP-injected animals failed to develop clinical disease over a 28-week period of study although lesions typical of chronic EAE were present. Simultaneously, 2 non-suppressed juvenile animals developed clinical signs by 12 weeks. These were associated with both acute inflammation and demyelination superimposed upon regions of chronic demyelinative activity.

Intranuclear "paramyxovirus-like" material in multiple sclerosis, adreno-leukodystrophy and Kuf's disease.

Detailed comparative ultrastructural examination of multiple sclerosis (MS) plaques, inflammatory CNS lesions from adreno-leukodystrophy(A-LD), tissue from a case of chronic granulomatous meningitis, biopsy samples of necrotic cerebral cortex and CNS tissue from a case of Kuf's disease (adult-type ceroid lipofuscinosis), has revealed that the intranuclear filamentous material previously thought to be related to a viral infection in MS is a non-specific finding. These intranuclear strands were, however, found in greatest frequency in the acute lesions of MS and were absent from chronically demyelinated areas. The macrophages, lymphocytes and fibrocytes containing filamentous material in the nuclei were mainly perivascular. In A-LD, some macrophages in active lesions contained similar nuclei, and in Kuf's disease they were present in some glial cells in the cerebral cortex.

Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomyelitis.

Chronic experimental allergic encephalomyelitis (EAE), produced in inbred guinea pigs given a single inoculation during the juvenile period with isologous spinal cord in complete Freund's adjuvant, has been studied by light and electron microscopy. Most animals showed a delayed onset of nurologic signs from 12 to 68 weeks post-inoculation (PI), while several were asymptomatic up to 74 weeks PI. Two animals showed a relapsing clinical course. Examination of the spinal cords of all animals revealed chronic demyelination, remyelination, and recent demyelination. Marked perivascular inflammation, including plasma cells, was seen within demyelinated plaques. The usual type of central nervous system (CNS) remyelination was documented but in addition, remyelination of CNS axons by invading Schwann cells was noted. This Schwann cell invasion, not previously seen in EAE, was predominantly in the area of the root entry zone, and occasionally involved extensive areas of the dorsal or ventral horns. The extent of Schwann cell invasion, as well as the usual CNS-type remyelination, demonstrates the reparative capacity of the CNS. The recurrent clinical and morphologic changes in these long-term animals provides further evidence that this model of chronic EAE has many features reminiscent of multiple sclerosis. The underlying immunologic mechanisms responsible for the recurrent disease in these animals are unknown. The presence of plasma cells in the inflammatory exudates might suggest a role for B cells in these chronic animals. The possibility of an intermittent release of loculated adjuvant/antigen accounting for the recurrent disease was considered.

Microtubules: evidence for 13 protofilaments.

When microtubules are fixed in glutaraldehyde in the presence of tannic acid and thin sections cut, the subunit structure of the microtubule is readily observed without the need of image reinforcement. Seven types of microtubules were analyzed: those in the heliozoan axoneme, the mitotic apparatus, the contractile axostyle, repolymerized microtubules derived from the chick brain, the central pair in flagella, and the A tubules of flagella and the basal body. In all cases microtubules were composed of 13 equally spaced protofilaments. The B tubules in flagella and the basal body appear to be composed of 11 subunits. The connections of the B to the A and the C to the B are described. A model of a microtubule is presented.