Classical Multiple Sclerosis Research Articles

Interferon beta-1b is effective in Japanese RRMS patients

To assess the efficacy of interferon beta-1b (IFNB-1b) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS). The effects of IFNB in RRMS have been assessed in study populations comprised predominantly of white patients. MS in Japanese patients is different from that in white patients in that there are two different presentations--classic MS (C-MS) and optic-spinal MS (OS-MS)--and chronic progressive forms are infrequent. A total of 205 Japanese patients with RRMS were randomized to receive 50 microg or 250 microg (1.6 or 8.0 MIU) IFNB-1b administered SC every other day for up to 2 years. The primary endpoint was annual relapse rate. Secondary endpoints included further relapse-related and MRI outcome measures, as well as changes in Expanded Disability Status Scale and Neurologic Rating Scale. Efficacy was assessed in 188 patients, and safety was assessed in 192 patients. Supplemental ad hoc subgroup analyses were also performed for patients with OS-MS and those with C-MS. Annual relapse rates were 0.763 in the 250 microg group and 1.069 in the 50 microg group, a relative reduction of 28.6% (p = 0.047). Results for all secondary endpoints favored 250 microg IFNB-1b. Subgroup analyses suggested that the magnitude and direction of treatment effect in patients with OS-MS and C-MS was similar, albeit not significant due to small sample size. Interferon beta-1b (IFNB-1b) 250 microg significantly reduced relapse rates and change in MRI lesion area in Japanese patients with relapsing-remitting multiple sclerosis, and seemed to be comparably effective in optic-spinal multiple sclerosis (MS) and classic MS. The response to treatment with IFNB-1b in Japanese patients with MS suggests that a common pathogenesis and underlying genetic characteristics are shared with white patients.

Pure optic-spinal form of multiple sclerosis in Japan.

We evaluated the clinical and laboratory features of the optic-spinal form of multiple sclerosis (OSMS) with no brain lesions on repeated MRI--termed pure OSMS. By reviewing the medical records of 118 Japanese clinically definite multiple sclerosis patients seen between 1988-1999, we found 10 patients (8.5%), nine of whom were women, with only relapsing optic neuritis (ON) and myelitis (MY) clinically and consistently normal brain MRI during follow-ups of >or=5 years. Three patients suffered severe ON and MY, but the other seven had mild disease (six were graded 1 in the Disability Status Scale). Despite frequent relapses, mild pure OSMS was characterized by younger onset and mild spinal symptoms as in 'benign' classical multiple sclerosis (CMS). MRI often revealed multiple cervico-thoracic cord lesions of variable lengths. Oligoclonal IgG bands (OB) were negative in all cases. HLA-DPB1*0501, whose association with OSMS has been reported, was positive only in six patients (including three patients with severe pure OSMS). Four patients with DRB1*1501-DQB1*0602, to which CMS is closely linked, had mild disease. Though pure OSMS was heterogeneous with regard to clinical severity and human leukocyte antigen (HLA) class II alleles, this form of multiple sclerosis was characterized by a definite female preponderance and negative OB that distinguished it from CMS.

Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology.

Multiple sclerosis is a chronic inflammatory disease characterized by perivenous inflammation and focal destruction of myelin. Many attempts have been undertaken previously to create animal models of chronic inflammatory demyelinating diseases through autoimmunity or virus infection. Recently, however, a new model of myelin oligodendrocyte glycoprotein (MOG) induced autoimmune encephalomyelitis became available, which, in a very standardized and predictable way, leads to chronic (relapsing or progressive) disease and widespread CNS demyelination. In the present study we actively induced MOG-experimental autoimmune encephalomyelitis (EAE) in different inbred rat strains using different immunization protocols. The pathology found in our models closely reflects the spectrum of multiple sclerosis (MS) pathology: Classical MS as well as variants such as optic neuritis, Devic's disease and Marburg's type of acute MS are mimicked in rats immunized with MOG antigen. Furthermore we demonstrate, that by using the proper strain/sensitization regime, subforms of MS such as for instance neuromyelitis optica can be reproducibly induced. Our study further supports the notion, that incidence and expression of the disease in this model, alike the situation in multiple sclerosis, is determined by genetic and environmental factors.

Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS.

Brain cells from a patient with classic multiple sclerosis were inoculated intracerebrally into the frontal lobe of a newborn chimpanzee. The animal developed acute quadriplegia three years, two months later and was killed four days after the onset of symptoms. Central nervous system lesions were primarily localized in the spinal cord at root entry zones; these were characterized by demyelination and regeneration of myelin by Schwann cells.

Clinical studies of multiple sclerosis in Japan: Classical multiple sclerosis and Devic's disease

Eleven representative cases were selected from our 69 consecutive Japanese patients with probable multiple sclerosis (MS) seen in Kyushu University Hospitals, Fukuoka, Japan, so that these 11 cases demonstrated a spectrum of clinical presentations, ranging from that of classical MS to that of classical Devic's disease. Clinical analysis of the present series of cases revealed the existence of “intermediate” or “transitional” forms between classical MS and Devic's disease. These “intermediate” or “transitional” forms include: cases with bilateral visual impairment of severe degree at the onset followed by multifocal and multiphasic CNS lesions to give later a chronic, typical variety of MS; cases with frequent exacerbations and remissions of optic and spinal symptoms leading to severe disability within a relatively short period; cases with a rapidly-occurring, severe, extensive, transverse myelopathy associated with other CNS symptoms of mild degree; cases with classical Devic's disease showing remissions and exacerbations; and finally cases with Devic's disease followed by severe brain-stem symptomatology. These clinical observations suggest that the classical forms of MS and Devic's disease are the two extremes of a spectrum of the same disease, and that the opticospinal form of MS, which is most frequently encountered in Japan, might essentially be the same disease as MS seen in Western countries.

Multiple Sclerosis and Allied Diseases in Japan: Epidemiological and Clinical Aspects

Publisher Summary This chapter discusses epidemiological and clinical aspects of multiple sclerosis and allied diseases in Japan. Demyelinating encephalomyelitis, especially multiple sclerosis and allied disorders, are known to show characteristic geographical distributions and are most prevalent in the temperate zones of the world, and have low rates in the tropical and subtropical areas. It is found that cases which showed affectation of both predominantly optic nerves and spinal cord were most common and these included 4 cases of Devic's disease and 7 cases of multiple sclerosis. A second feature was the relatively high ratio of optic spinal vulnerability. There was a gradual transition from Devic's disease to multiple sclerosis. Some of the autopsied cases showed necrotic optic chiasma and necrosis in the spinal cord, which were clinically more compatible with multiple sclerosis than with Devic's disease. This may indicate that the Japanese cases were different from classical multiple sclerosis or there may be some constitutional factors which modify the demyelinating processes of the Japanese.