Robert M. Herndon

MULTICENTRE DOUBLE-BLIND STUDY OF EFFECT OF INTRATHECALLY ADMINISTERED NATURAL HUMAN FIBROBLAST INTERFERON ON EXACERBATIONS OF MULTIPLE SCLEROSIS☆

n Abstractn n In this randomised, double-blind, placebo-controlled, 2-year multicentre study intrathecally administered natural human fibroblast interferon (IFN-B) was effective in reducing exacerbations of multiple sclerosis (MS) in patients with exacerbating/remitting disease. The mean reduction in exacerbation rate of 34 patients who received IFN-B (recipients) was significantly greater during the study than that of 35 patients who received placebo (p <0.04). The prestudy exacerbation rates were comparable in recipients and controls, but the rate at the end of the study was significantly lower in recipients than in controls (p <0.001). IFN-B was given by nine or ten lumbar punctures over the first 6 months of the study, and patient observations continued for 2 years. IFN-B was well tolerated in 95% of the recipients, and the side-effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin reduced the toxicity of IFN-B and played an important role in successful double-blinding.n n

Ultrastructural evidence for phagocytosis by oligodendroglia

Although the phagocytic ability of brain macrophages and astrocytes is well established, the question of whether oligodendrocytes may become phagocytic remains controversial. Observations reported here indicate that oligodendroglia may become activated and ingest degenerating or foreign material in vivo following experimental injury to the central nervous system.

Is Alexander's disease a nosologic entity or a common pathologic pattern of diverse etiology?

Address correspondence to Dr Robert M. Herndon, G.V. (Sonny) Montgomery VA Medical Center, Department of Neurology. 1500 E. Woodrow Wilson, Jackson, MS 39216. Tel: 601-36-1-1280; fax: 601-364-1257; e-mail: herndon.robert@:jackson.va.gov. Since the original description by Alexander, which he titled &dquo;Progressive fibrinoid degeneration of fibrillary astrocytes associated with mental retardation in a hydrocephalic infant,&dquo;1 cases of what has come to be known as Alexan-

Multiple Sclerosis and Autoimmunity

Dr Herndon is Professor, Department of Neurology, University of Rochester Medical Center, Rochester, New York. With the introduction of the polio vaccine in the mid-1950s, multiple sclerosis (MS) replaced polio as the most common crippling neurological disease of young adults in North America and Europe. Unlike polio, which remains an infantile disease in undeveloped countries, MS has always been rare in infancy,’ and diagnosis in infants and small children requires caution. A healthy skepticism and continued reevaluation of the diagnosis in cases with an onset before 10 years of age is warranted. A century and a half after the pathological descriptions of MS,2, ’ and more than a century after Charcot’s classic description of the clinical and pathological features,4 the etiology remains unknown. Etiologic theories have included infections, toxins, and autoimmunity.5 At least ten viral isolations have

MULTIPLE SCLEROSIS: CLINICAL TRIALS WITH INTERFERONS

The rationale for the use of the interferons as treatment for multiple sclerosis (MS) is based upon a large body of evidence which documents a variety of immunological aberrations as well as various types of viral association in patients with this disease. Among the immunological abnormalities in MS are decreased numbers of suppressor T lymphocytes during exacerbations (1, 2), defective NK cell activity and defective in vitro interferon production (3). A possible viral etiology of MS has been proposed (4). Elevated serum and cerebrospinal fluid (CSF) levels of antibodies against viruses, particularly measles virus (5, 6), have been reported, as well as the isolation of a viral agent, termed the IM virus, from the CSF of several patients with MS (7, 8). Recently, evidence of a human T-lymphotropic virus type I (HTLV-I) type of virus has been found in patients with MS (9). A T-cell clone with some morphologic and histochemical properties of HTLV-I-infected cells has been established from an MS patient’s CSF. This clone grew independently of exogenous interleukin 2 (IL-2). It was postulated that this lymphotropic virus or its products play a role in the pathophysiology of MS by altering immune regulation (10).