Pure optic‐spinal form of multiple sclerosis in Japan

Brain (2002), 125, 2460±2468 Pure optic-spinal form of multiple sclerosis in Japan Tatsuro Misu,1 Kazuo Fujihara,1 Ichiro Nakashima,1 Isabelle Miyazawa,1 Naoshi Okita,2 Sadao Takase2 and Yasuto Itoyama1 1Department of Neurology, Tohoku University School of Medicine and 2Department of Neurology, Konan Hospital, Sendai, Japan Summary We evaluated the clinical and laboratory features of the optic-spinal form of multiple sclerosis (OSMS) with no brain lesions on repeated MRIÐtermed pure OSMS. By reviewing the medical records of 118 Japanese clinically de®nite 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 >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 Correspondence to: T. Misu, Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan E-mail: sclerosis (CMS). MRI often revealed multiple cervicothoracic cord lesions of variable lengths. Oligoclonal IgG bands (OB) were negative in all cases. HLADPB1*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 de®nite female preponderance and negative OB that distinguished it from CMS. Keywords: multiple sclerosis; optic-spinal form; Devic's neuromyelitis optica; demyelinating disease; MRI Abbreviations: ACLA = anti-cardiolipin antibody; ANA = anti-nuclear antigen; ANCA = anti-neutrophil cytoplasmic antibody; ATA = anti-thyroid autoantibody; CMS = classical multiple sclerosis; DSS = Disability Status Scale; HLA = human leukocyte antigen; MBP = myelin basic protein; MY = myelitis; NMO = neuromyelitis optica; OB = oligoclonal IgG band; ON = optic neuritis; OSMS = optic-spinal form of multiple sclerosis. Introduction Optic-spinal form of multiple sclerosis (OSMS) is a unique demyelinating disease characterized by recurrent optic neuritis (ON) and myelitis (MY), and rare or minor involvement of the brain (Kuroiwa et al., 1975, 1977; Ikuta, 1976; Kuroiwa, 1976; Ikuta et al., 1982). OSMS has been relatively common in Japanese, but similar cases in other ethnic groups were reported as relapsing neuromyelitis optica (NMO) or relapsing Devic's syndrome (Kuroiwa et al., 1977; Shibasaki et al., 1981; Ikuta et al., 1982; Mandler et al., 1993; O'Riordan et al., 1996; Wingerchuk et al., 1999). Many investigators in Western countries state that relapsing NMO is a type or variant of multiple sclerosis, and that NMO phenotype may occur in classical multiple sclerosis (CMS) in which demyelinating lesions are disseminated throughout the CNS (O'Riordan et al., 1996; Matthews, 1998). Apart from ã Guarantors of Brain 2002 the characteristic lesion distribution, previous reports have suggested that features that distinguish relapsing NMO from CMS might be neuropathologically necrotic lesions, severe ON and MY (Ikuta et al., 1976, 1982; Shibasaki et al., 1981), a relatively higher female/male ratio, a lower frequency of oligoclonal IgG bands (OB) (Kira et al., 1996; O'Riordan et al., 1996; Nakashima et al., 1999; Sakuma et al., 1999; Yamasaki et al., 1999) and association with a speci®c human leukocyte antigen (HLA) class II allele (DPB1*0501) (Ito et al., 1998; Yamasaki et al., 1999; Fukazawa et al., 2000). However, patients who manifest ON and MY in the early stage of the disease may later develop typical CMS. It is also not easy to determine whether cases of ON and MY with minor brainstem symptoms or several asymptomatic cerebral white matter lesions on MRI should be classi®ed as OSMS or Pure optic-spinal form of multiple sclerosis 2461 Table 1 Comparison of CMS, clinical OSMS and pure OSMS Number of cases (n = 118) Female/male (rate) Age at onset Disease duration Neurological events CMS Clinical OSMS Pure OSMS 82 (69.5%) 57/25 (2.3) 29.0 6 12.0 11.8 6 7.4 4.7 6 2.8 36 (30.5%) 32/4 (8.0)* 32.9 6 13.2 13.3 6 8.4 4.9 6 3.0 10 (8.5%) 9/1 (9.0) 33.7 6 16.5 10.2 6 7.7 6.6 6 3.0 *P < 0.05 (CMS versus clinical or pure OSMS). CMS. The International Panel on the Diagnosis of Multiple Sclerosis recently presented speci®c criteria of brain MRI for the objective demonstration of lesions in multiple sclerosis (McDonald et al., 2001), but the Panel also emphasized the importance of follow-up MRI in cases not ful®lling these criteria. Thus, strict diagnostic criteria and a long-term follow-up are needed to delineate OSMS, but such a study is lacking. In the present study, we collected cases of OSMS having ON and MY clinically and no brain MRI lesionsÐtermed pure OSMSÐin whom these features were evident for >5 years of follow-up. We evaluated the clinical, MRI and immunological features of pure OSMS. Material and methods Patients We retrospectively reviewed the medical records of 118 patients with multiple sclerosis who ful®lled the criteria developed by Poser and colleagues of clinically de®nite multiple sclerosis (Poser et al., 1983). During 1988±1999, these patients had relapses for which neurological ®ndings and brain and spinal cord MRI examinations were made at every neurological event at Department of Neurology, Tohoku University School of Medicine and Department of Neurology, Kohnan Hospital in Sendai City in the north-east of Japan. The diagnosis of multiple sclerosis was also compatible with the diagnostic criteria of multiple sclerosis newly recommended by the International Panel on the Diagnosis of Multiple Sclerosis (McDonald et al., 2001). First, we selected patients who had only recurrent ON and MY as clinical manifestationsÐtermed clinical OSMS. Then, we evaluated the brain MRI of those patients with clinical OSMS and chose the cases of pure OSMS that met the following criteria: (i) clinically selective involvement of the optic nerve and spinal cord; (ii) normal brain MRI except for lesions in the optic nerves and spinal cords in repeated examinations; and (iii) >5 years of follow-up. MRI of the brain and the spinal cord were examined at every relapse. We studied the following items in pure OSMS: (i) clinical manifestations; (ii) spinal and brain MRI ®ndings; (iii) CSF ®ndings [cell counts, IgG index, OB and myelin basic protein (MBP) in relapses]; (iv) serum autoantibodies [anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), anti-cardiolipin antibody (ACLA) and anti-thyroid antibody (ATA)]; and (v) HLA ( (...truncated)