[What I have learned and accomplished through research on multiple sclerosis (MS)].

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system (CNS). This disease is characterized by so-called "multiplicity in time and space in the CNS". Although the pathomechanisms of MS have been extensively studied for a long time, the etiology is still unknown. It has been pointed out that the prevalence rate of MS is very low, and that the optic spinal form of MS (OSMS), which mainly affects the optic nerves and spinal cord, is common in Japan. There has been a long controversy as to the differences between OSMS and neuromyelitis optica (NMO), and whether NMO or OSMS is a subtype of multiple sclerosis (MS) or a distinct disease. Recently, a highly disease specific autoantibody, NMO-IgG, was found in the sera of patients with NMO as well as OSMS. However, this antibody was not detected in the sera of MS patients. Therefore, we conclude that OSMS is the same as NMO, and speculate that NMO/OSMS may be a distinct disease from MS. Many investigations have revealed several differences clinically and pathologically between MS and NMO/OSMS. The following features such as female predominance, no brain lesions and longitudinally extended spinal cord lesions by MRI study and neuropathologically necrotic or cavitary lesions are commonly seen in NMO/OSMS. The most recent and important discovery that NMO-IgG reacts specifically with aquaporin 4 (AQP4), which is a water channel localized in astrocytes, opened new avenues for understanding the pathogenesis of NMO/OSMS. We immunocytochemically studied the expression of AQP4 in lesions of postmortem NMO/OSMS, and found that AQP4 was completely lost in the acute lesions. In addition, an astrocytic marker, GFAP, was also lost in the NMO/OSMS lesions. However, the myelin basic protein-stained fibers were relatively preserved. These immunocytochemical features are in contrast to those of MS. In MS, there was no loss of either AQP4 or GFAP expression in the lesions. Moreover, the values of GFAP were markedly increased in CSF from patients with NMO/OSMS in the acute phase but were never increased in patients with MS. These results strongly suggest that astrocytic impairment associated with AQP4 antibody may be mainly involved in NMO, and that the pathogenesis of NMO is distinct from MS, which is primarily a demyelinating disease.