Brain, Vol. 125, No. 11, 2460-2468,
November 2002
© 2002 Oxford University Press
Pure optic-spinal form of multiple sclerosis in Japan
1 Department of Neurology, Tohoku University School of Medicine and 2 Department of Neurology, Konan Hospital, Sendai, Japan
Correspondence to: T. Misu, Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan E-mail: misu{at}neurol.med.tohoku.ac.jp
Received March 18, 2002. Revised May 14, 2002. Accepted June 24, 2002.
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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
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. 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.
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Introduction |
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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 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 specific 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 classified as OSMS or CMS. The International Panel on the Diagnosis of Multiple Sclerosis recently presented specific 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 fulfilling 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 lesions—termed pure OSMS—in whom these features were evident for 5 years of follow-up. We evaluated the clinical, MRI and immunological features of pure OSMS.
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Patients
We retrospectively reviewed the medical records of 118 patients with multiple sclerosis who fulfilled the criteria developed by Poser and colleagues of clinically definite multiple sclerosis (Poser et al., 1983
). During 1988–1999, these patients had relapses for which neurological findings 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 manifestations—termed 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 findings; (iii) CSF findings [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 (HLA-A, B, C, DR and DQ locus and DRB1*, DQB1* and DPB1* genotypes). We also examined the visual evoked potential or short T1 inversion recovery for detecting ON.
Disability Status Scale and activities of daily life
The visual disabilities of ON and motor and sensory disabilities of MY at every relapse were clinically graded according to the Neurologic Rating Scale of mild, moderate and severe (Sipe et al., 1984). We used the final scores of functional systems in the Expanded Disability Status Scale (Kurtzke et al., 1983) but also graded ambulation with the Disability Status Scale (DSS) (Kurtzke et al., 1955) and the Barthel Index (Mahoney et al., 1965). This was because we observed discrepant disabilities of ON and MY in some patients, i.e. severe visual impairment and mild spinal involvement for which the Expanded Disability Status Scale is graded based on the severity of ON.
MRI examinations
We examined MRI with 5 mm thick slices using a 0.5 Tesla (Vectra, GE Yokogawa Medical Systems, Tokyo, Japan) or a 1.5 Tesla scanner (Sigma, GE Medical Systems, Milwaukee, WI, USA). The 1.5 Tesla scanner was used for the most recent MRI in every case. Any T2-hyperintense areas in the brain and spinal cord on T2-weighted images with a moderately long repetition time (TR) of 2000–3000 ms and an echo time (TE) of 60–100 ms were considered abnormal. One neurologist among the authors and a blinded neuroradiologist evaluated the scans.
Immunological and HLA studies
We tested OB using isoelectric focusing with the PhastSystemTM (Amersham Pharmacia Biotech, Uppsala, Sweden). Optimal resolution was obtained for the cathodal IgG bands by using isoelectric focusing on PhastGelTM IEF3-9 and expanding the pH gradient in the alkaline region with PharmalyteTM 8–10.5. Immunofixation using rabbit anti-human IgG and silver staining then gave the high sensitivity required for detecting OB in unconcentrated CSF. The 2 bands present in the CSF and not in the serum were defined as OB. ANA were examined using an ANA kit (Fanawell Kit, Japan DPC, Tokyo, Japan). We used enzyme immunoassay (EIA) kits for ANCA (MPO/C-ANC, Nipro, Osaka, Japan), ACLA (Mesacup, MBL, Nagoya, Japan) and ATA (Serodia-ATG/AMC, Fujirebio, Tokyo, Japan). We analysed HLA genotypes using a PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method (Smi test kit, Sumitomokinzoku, Sagamihara, Japan).
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Frequency of pure OSMS compared with CMS and clinical OSMS
Among the 118 Japanese patients, there were 36 patients (30.5%) with clinical OSMS (see Table 1). There was a definite female preponderance in clinical OSMS (female/male = 8.0) compared with CMS (female/male = 2.3). The ages of onset, the duration of the disease and the numbers of neurologic events (onset symptoms and relapses) were similar for CMS and clinical OSMS.
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Among 36 cases of clinical OSMS, 10 cases (8.5% of the 118 cases) had pure OSMS. Nine out of the 10 pure OSMS patients were women. The age of the disease onset ranged from 16 to 62 years. The duration of the disease ranged from 5 to 30 years. Cases 9 and 10 were sisters whose clinical and immunological data are reported elsewhere (Yamakawa et al., 2000
). The follow-up periods of pure OSMS were 5 years and five patients had had the disease for >10 years. On average, the patients with pure OSMS had more relapses than those with CMS or clinical OSMS, though the difference was not statistically significant.
Clinical features of pure OSMS
All the 10 patients had frequent relapses of ON and MY (Fig. 1). The onset symptoms were ON in six patients and MY in four patients (see Table 2). The first ON was often severe (five cases) or moderate (three cases). Bilateral ON at onset was seen in three cases. The interval between the first ON and the first MY ranged from 3 days to 3.5 years. On the other hand, all the four patients with MY at onset developed ON within 6 months.
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Interestingly, the clinical disabilities of the cases could be classified into two groups, mild and severe. Seven patients (Cases 1–7) had a mild disability of ambulation (six out of the seven patients were graded 1 on the DSS and had 100 points in the Barthel Index). In this mild form of pure OSMS, the onset age was 25.6 ± 9.1 years, the symptoms of repeated myelitis were non-transverse and there were often mild sensory disturbances (30 out of 38 episodes, 79%) such as localized paraesthesia and Lhermitte’s sign. These patients also responded well to corticosteroid therapy, although unilateral ON was severe in three cases at the onset of symptoms. The other three patients (Cases 8–10) had severe ON and transverse MY, which was typical in the previously reported OSMS cases. The patients with severe disease were older at onset (52.7 ± 14.5 years) than those with mild pure OSMS. Two patients (Cases 7 and 8) had some episodes of persistent hiccup in association with the symptoms of cervical MY extending to lower medulla. Case 6 had mild hypothyroidism and Case 4 received medication for amenorrhoea at the onset of the disease.
MRI findings in clinical OSMS and pure OSMS
In clinical OSMS (n = 36), 26 patients, i.e. those with clinical but not pure OSMS, had 
4 small cerebral lesions. However, these findings do not fulfil the MRI criteria for brain abnormality in the diagnostic criteria of multiple sclerosis recommended by the International Panel on the Diagnosis of Multiple Sclerosis (McDonald et al., 2001). Cerebellar lesions were not detected in this group of patients. Six patients had a few small lesions in the brainstem or cervical cord lesions extending into the lower medulla oblongata. In the cases of pure OSMS, 3–10 brain MRI examinations had been performed in each case; all were normal, except for some cases with slight Wallerian degeneration of the pyramidal tracts caused by MY.
Spinal MRI revealed focal T2-hyperintense lesions with gadolinium enhancement and cord swelling was often seen during relapses. Eight cases had spinal cord lesions extending over 3 vertebral segments (see Table 3). The mild form of pure OSMS (Cases 1–7) often had lesions of <4 vertebral segments in the relapses (20 out of 28, 71.4%), but some of the lesions in these patients extended over 4 vertebral segments (8 out of 20, 28.6%). Cavity-like longitudinally extending structures were seen in cases with relatively severe disease (Cases 8–10). In Case 10, the cervical cord was atrophied in the chronic stage. Cervical and thoracic cords were affected with similar frequencies (21 cervical lesions and 16 thoracic lesions). All pure OSMS patients showed abnormalities in their visual evoked potential or short T1 inversion recovery findings.
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Immunological data and HLA in pure OSMS
CSF examinations (see Table 4) often revealed mild to moderate pleocytosis (mean 24 cells/µl). IgG indices were normal except in Case 5 (0.81). OB was negative in all cases by repeated examinations, but MBP was detected in six of them. The reported serum autoantibodies (ANA, ACLA and ATA) were detected occasionally in five cases, but ANCA was not detected in any of them (Fukazawa et al., 1993
, 1996; Nakashima et al., 1998; Sakuma et al., 1999). Rheumatoid factors were found in Cases 9 and 10.
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DQ1 (10 out of 10), A2 (five out of 10) and DR2 (five out 10) were relatively common in HLA phenotyping (see Table 5). All five patients with DR2 had mild OSMS. In contrast, all three patients with the severe form of pure OSMS had A33 and B44, which were consistently negative in the mild form of pure OSMS. In HLA genotype analysis, HLA-DPB1*0501 was positive in only six patients. Meanwhile, four patients had DRB1*1501-DQB1*0602, to which CMS is closely linked (Olerup et al., 1991
; Spurkland et al., 1991). These patients had mild disabilities of ambulation and three of them were negative for DPB1*0501. DRB1*1501 and DQB1*0602 were significantly more frequent in pure OSMS than in the Japanese population (P < 0.01 in Fisher’s exact test) (see Table 6).
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Discussion |
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OSMS has been described as a unique feature of multiple sclerosis in Japan. Previous reports emphasized that the characteristic findings of OSMS are a higher female/male ratio, severe involvement of the optic nerves and spinal cord (Kuroiwa et al., 1975
), lower frequency of OB (Kira et al., 1996; Nakashima et al., 1999), and an association with DPB1*0501 (Yamasaki et al., 1999). However, the definitions of OSMS used in these studies were not same and they might have contained heterogeneous groups of patients. Patients with clinical OSMS and asymptomatic brain MRI lesions may develop cerebral, brainstem, or cerebellar symptoms associated with typical brain MRI lesions; this is compatible with the diagnosis of CMS.
To overcome this problem in our study of 118 Japanese patients with clinically definite multiple sclerosis, we used strict criteria for pure OSMS: (i) clinically selective involvement of the optic nerve and spinal cord; (ii) normal brain MRI in repeated examinations; and (iii) 5 years follow-up. Such a study is necessary to delineate the clinical, MRI, and immunological findings specific to pure OSMS. Only 8.5% of the patients had this unique type of multiple sclerosis; a definite female preponderance, extensive spinal involvement and negative OB were found to be the salient features of pure OSMS.
An interesting clinical finding was that pure OSMS was not uniformly severe, i.e. some cases (Cases 8–10) took malignant courses, but others (Cases 1–7) had a mild disease. This finding is in contrast with the general view that the prognosis of OSMS is poor and that patients with pure OSMS have neuropathologically tissue necrosis and cavities in the spinal cord. Spinal MRI lesions in CMS are usually focal and short in length, and lesions extending over 3 vertebral segments are often seen in transverse myelitis or opticomyelitis (Simnad et al., 1997; Bakshi et al., 1998). In the present study, eight patients with pure OSMS had such long MRI lesions, while cavity and atrophy of the spinal cord were seen only in the severe form of pure OSMS (Table 3). Focal lesions were relatively common in the mild form of pure OSMS, but there was no correlation between the total length of the spinal lesions and the clinical severity of MY.
Moreover, HLA genotype in pure OSMS may not be homogenous. Although significantly high frequencies of DPB1*0501 in OSMS (93.1–94.1%) have been reported in Japan (Yamasaki et al., 1999; Fukazawa et al., 2000), this HLA genotype was detected in only 60% of our patients with pure OSMS. The four patients with mild disabilities of ambulation had DRB1*1501-DQB1*0602, which is commonly seen in European patients with CMS (Olerup et al., 1991; Spurkland et al., 1991).
Many investigators have reported that, as in benign and malignant forms of multiple sclerosis, the clinical course and the rate of progression of CMS are highly variable (McAlpine, 1961, 1964; Poser et al., 1979; Thompson et al., 1986; O’Riordan et al., 1998; Hawkins et al., 1999). According to the reports by McAlpine and Poser, benign multiple sclerosis could be defined as grade 3 or less in DSS for >10 years of follow-up, and malignant CMS as grade 7 or more in DSS within 5 years after onset (McAlpine, 1964). With this definition, about 20% of patients had benign CMS (McAlpine, 1961; Thompson et al., 1986). The mild form of pure OSMS in our study was characterized by a female preponderance, early onset and predominantly spinal sensory symptoms. These are similar to the factors described in benign CMS (Hawkins et al., 1999). On the other hand, Kurtzke and colleagues suggested that the DSS at 5 years from diagnosis is predictive of the subsequent course (Kurtzke et al., 1977). All three patients with the severe form of pure OSMS (Cases 8–10) in our study became wheel chair-bound or bed-ridden within three years of onset, in contrast to all the mild form of pure OSMS with grade 1 in the DSS.
The relapsing NMO described in Western countries, which has been classified as a variant of multiple sclerosis (Adams et al., 1997; Matthews, 1998; Miller, 2000), seems to be similar to OSMS. In the same year as Devic (1894) first reported the single case of monophasic NMO with a fatal outcome, he and Gault (1894) also described patients with relapsing NMO (Gault, 1894). Since then, similar cases have been reported and the relationship between this type of NMO and multiple sclerosis has been discussed. Mandler and colleagues studied the clinical and pathological aspects in eight cases of NMO, including five cases of relapsing disease (Mandler et al., 1993). Autopsy examinations in four cases revealed necrotizing and cavitary changes rather than demyelination involving cervico-thoracic cords, which corresponded to severe OSMS in our study. Three of the four patients had no brain lesions, though the follow-up periods were not described. O’Riordan and colleagues reported 12 cases of NMO including nine (eight females and one male) with relapsing disease between 1986 and 1994 (O’Riordan et al., 1996). All had extensive spinal lesions and were OB negative. In three of the nine patients, brain MRI both at baseline and follow-up at unknown intervals was confirmed as normal. These investigators stressed the distinctive features of this condition from typical multiple sclerosis, but the studies also showed that cases of relapsing NMO with normal brain MRI during long-term follow-ups were rare. Recently, Wingerchuk and colleagues presented the results of a large-scale study of relapsing and monophasic NMO cases at the Mayo Clinic (Rochester, MN, USA) (Wingerchuk et al., 1999). They showed that 48 out of 71 patients with NMO had relapsing disease. Most of their patients were white Americans, and those relapsing cases were similar to our cases of pure OSMS with regard to a female preponderance, CSF and MRI features, and variable courses of the disease and prognoses—although only seven out of 16 patients who had more than one brain MRI remained normal. It would be interesting to study HLA class II genotypes in their patients to determine whether they are immunogenetically homogenous. There is also a report on a group of British patients with relapsing NMO, which may be dissimilar to OSMS in some ways (Thorpe et al., 1996). Thorpe and colleagues reported 20 patients with suspected multiple sclerosis and negative brain MRI (clinically isolated syndrome). These patients had neurologic manifestations referable to the spinal cord or optic nerves, which are similar to our cases of pure OSMS. However, the lack of a female preponderance (female/male = 10/10), a primary progressive course in 11 patients and the frequent detection of OB (13 out of 20) in the British study were different features from our patients with pure OSMS. Whether these differences originated from distinct genetic and environmental factors should be elucidated.
Clinical OSMS with asymptomatic brain lesions is an interesting group of patients in terms of future clinical picture. There were 26 such patients in the present study and their MRI findings did not fulfil the MRI criteria of CMS proposed by the International Panel on the Diagnosis of Multiple Sclerosis (McDonald et al., 2001). Although we analysed only well-characterized cases of pure OSMS to delineate the characteristic findings of this type of disease, a fraction or many of the 26 patients with clinical OSMS may have essentially the same disease as those with pure OSMS. The long-term follow-up of the patients with clinical OSMS with brain lesions will clarify if they remain OSMS or are transformed into CMS.
In conclusion, there were 10 cases (8.5%) of pure OSMS in our Japanese series of 118 cases of multiple sclerosis. In contrast to CMS, pure OSMS was associated with a definite female preponderance and negative OB. However, despite these common features, the clinical severity and HLA class II alleles of our patients were not homogenous. Thus, our data does not support the idea that necrotic lesions or specific HLA types are the features distinguishing OSMS from CMS. Similar analyses in larger Japanese or other Asian patient cohorts should be performed to confirm the present findings. Recent immunological studies showed significantly lower levels of interleukin-10 (Nakashima et al., 2000) and matrix metalloproteinase-9 (Mandler et al., 2001) in CSF of OSMS compared with CMS. However, it remains unknown how these findings relate to the specific lesion distribution in OSMS. Further comparative studies are needed to clarify whether there are crucially important differences in the immuno-pathogeneses of OSMS and CMS.
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Acknowledgements |
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We wish to thank Mr Brent Bell for reading the manuscript. This work was supported by grants-in-aid for General Scientific Research (09470150, 13470131, and 13670626) from the Ministry of Education, Culture, Sports, Science and Technology, a grant from the Neuroimmunological Research Committee and a research subsidy from the Japan Foundation for Neuroscience and Mental Health.
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References |
|---|
|
TopSummaryIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
Adams RD, Victor M, Ropper AH. Multiple sclerosis and allied demyelinative diseases. In: Wonsiewicz MJ, Navrozov M, editors. Principles of neurology. 6th ed. New York: McGraw-Hill; 1997. p. 902–27.
Bakshi R, Kinkel PR, Mechtler LL, Bates VE, Lindsay BD, Esposito SE, et al. Magnetic resonance imaging findings in 22 cases of myelitis: comparison between patients with and without multiple sclerosis. Eur J Neurol 1998; 5: 35–48.[Web of Science][Medline]
Devic E. Myélite subaiguë compliquée de névrite optique. Bull Med 1894; 8: 1033–4.
Fukazawa T, Moriwaka F, Mukai M, Hamada T, Koike T, Tashiro K. Anticardiolipin antibodies in Japanese patients with multiple sclerosis. Acta Neurol Scand 1993; 88: 184–9.[Web of Science][Medline]
Fukazawa T, Hamada T, Kikuchi S, Sasaki H, Tashiro K, Maguchi S. Antineutrophil cytoplasmic antibodies and the optic-spinal form of multiple sclerosis in Japan. J Neurol Neurosurg Psychiatry 1996; 61: 203–4.
Fukazawa T, Kikuchi S, Sasaki H, Yabe I, Miyagishi R, Hamada T, et al. Genomic HLA profiles of multiple sclerosis in Hokkaido, Japan: important role of DPB1*0501 allele. J Neurol 2000; 247: 175–8.[Web of Science][Medline]
Gault F. De la neuromyélite optique aiguë [thesis]. Lyon University, Lyon, France: 1894.
Hawkins SA, McDonnell GV. Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychiatry 1999; 67: 148–52.
Ikuta F. Problems in the pathoanatomy of multiple sclerosis. Realities of multiple sclerosis pathology on the US and Japanese cases. In: Kuroiwa Y, editor. Multiple sclerosis in Asia. Tokyo: University of Tokyo Press; 1976. p. 143–53.
Ikuta F, Koga M, Takeda S, Ohama E, Takeshita I, Ogawa H, et al. Comparison of multiple sclerosis pathology between 70 American and 75 Japanese autopsy cases. In: Kuroiwa Y, Kurland LT, editors. Multiple sclerosis East and West. Fukuoka: Kyushu University Press; 1982. p. 297–306.
Ito H, Yamasaki K, Kawano Y, Horiuchi I, Yun C, Nishimura Y, et al. HLA-DP-associated susceptibility to the optico-spinal form of multiple sclerosis in the Japanese. Tissue Antigens 1998; 52: 179–82.[Web of Science][Medline]
Kira J, Kanai T, Nishimura Y, Yamasaki K, Matsushita S, Kawano Y, et al. Western versus Asian types of multiple sclerosis: immunogenetically and clinically distinct disorders. Ann Neurol 1996; 40: 569–74.[Web of Science][Medline]
Kuroiwa Y. Multiple sclerosis in Japan. In: Kuroiwa Y, editor. Multiple sclerosis in Asia. Tokyo: University of Tokyo Press; 1976. p. 109–21.
Kuroiwa Y, Igata A, Itahara K, Koshijima S, Tsubaki T. Nationwide survey of multiple sclerosis in Japan. Clinical analysis of 1,084 cases. Neurology 1975; 25: 845–51.
Kuroiwa Y, Hung TP, Landsborough D, Park CS, Singhal BS. Multiple sclerosis in Asia. Neurology 1977; 27: 188–92.
Kurtzke JF. A new scale for evaluating disability in multiple sclerosis. Neurology 1955; 5: 580–3.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–52.
Kurtzke JF, Beebe GW, Nagler B, Kurland LT, Auth TL. Studies on the natural history of multiple sclerosis—8. Early prognostic features of the later course of the illness. J Chronic Dis 1977; 30: 819–30.[Web of Science][Medline]
Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. MD Med J 1965; 14: 61–5.
Mandler RN, Davis LE, Jeffery DR, Kornfeld M. Devic’s neuromyelitis optica: a clinicopathological study of 8 patients. Ann Neurol 1993; 34: 162–8.[Web of Science][Medline]
Mandler RN, Dencoff JD, Midani F, Ford CC, Ahmed W, Rosenberg GA. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in cerebrospinal fluid differ in multiple sclerosis and Devic’s neuromyelitis optica. Brain 2001; 124: 493–8.
Matthews B. Differential diagnosis of multiple sclerosis and related disorders. In: Compston A, Ebers G, Lassmann H, McDonald I, Matthews B, Wekerle H, editors. McAlpine’s multiple sclerosis. 3rd ed. London: Churchill Livingstone; 1998. p. 223–50.
McAlpine D. The benign form of multiple sclerosis. A study based on 241 cases seen within three years of onset and followed up until the tenth year or more of the disease. Brain 1961; 84: 186–203.
McAlpine D. The benign form of multiple sclerosis: results of a long-term study. Br Med J 1964; 2: 1029–32.
McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50: 121–7.[Web of Science][Medline]
Miller JR. Multiple sclerosis. In: Rowland LP, editor. Merrit’s neurology. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 773–96.
Nakashima I, Fujihara K, Endo M, Seki H, Okita N, Takase S, et al. Clinical and laboratory features of myelitis patients with anti-neutrophil cytoplasmic antibodies. J Neurol Sci 1998; 157: 60–6.[Web of Science][Medline]
Nakashima I, Fujihara K, Itoyama Y. Oligoclonal IgG bands in Japanese multiple sclerosis patients. J Neuroimmunol 1999; 101: 205–6.[Web of Science][Medline]
Nakashima I, Fujihara K, Misu T, Okita N, Takase S, Itoyama Y. Significant correlation between IL-10 levels and IgG indices in the cerebrospinal fluid of patients with multiple sclerosis. J Neuroimmunol 2000; 111: 64–7.[Web of Science][Medline]
Olerup O, Hillert J. HLA class II-associated genetic susceptibility in multiple sclerosis: a critical evaluation. [Review]. Tissue Antigens 1991; 38: 1–15.[Web of Science][Medline]
O’Riordan JI, Gallagher HL, Thompson AJ, Howard RS, Kingsley DP, Thompson EJ, et al. Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica. J Neurol Neurosurg Psychiatry 1996; 60: 382–7.
O’Riordan JI, Thompson AJ, Kingsley DP, MacManus DG, Kendall BE, Rudge P, et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain 1998; 121: 495–503.
Poser S, Wikström J, Bauer HJ. Clinical data and the identification of special forms of multiple sclerosis in 1271 cases studied with a standardized documentation system. J Neurol Sci 1979; 40: 159–68.[Web of Science][Medline]
Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227–31.[Web of Science][Medline]
Sakuma R, Fujihara K, Sato N, Mochizuki H, Itoyama Y. Optic-spinal form of multiple sclerosis and anti-thyroid autoantibodies. J Neurol 1999; 246: 449–53.[Web of Science][Medline]
Shibasaki H, McDonald WI, Kuroiwa Y. Racial modification of clinical picture of multiple sclerosis: comparison between British and Japanese patients. J Neurol Sci 1981; 49: 253–71.[Web of Science][Medline]
Simnad VI, Pisani DE, Rose JW. Multiple sclerosis presenting as transverse myelopathy: clinical and MRI features. Neurology 1997; 48: 65–73.
Sipe JC, Knobler RL, Braheny SL, Rice GP, Panitch HS, Oldstone MB. A Neurologic Rating Scale (NRS) for use in multiple sclerosis. Neurology 1984; 34: 1368–72.
Spurkland A, Ronningen KS, Vandvik B, Thorsby E, Vartdal F. HLA-DQA1 and HLA-DQB1 genes may jointly determine susceptibility to develop multiple sclerosis. Hum Immunol 1991; 30: 69–75.[Web of Science][Medline]
Thompson AJ, Hutchinson M, Brazil J, Feighery C, Martin EA. A clinical and laboratory study of benign multiple sclerosis. Q J Med 1986; 58: 69–80.[Web of Science][Medline]
Thorpe JW, Kidd D, Moseley IF, Thompson AJ, MacManus DG, Compston DA, et al. Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI. Brain 1996; 119: 709–14.
Wingerchuk DM, Hogancamp WF, O‘Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 1999; 53: 1107–14.
Yamakawa K, Kuroda H, Fujihara K, Sato S, Nakashima I, Takeda A, et al. Familial neuromyelitis optica (Devic’s syndrome) with late onset in Japan. Neurology 2000; 55: 318–20.
Yamasaki K, Horiuchi I, Minohara M, Kawano Y, Ohyagi Y, Yamada T, et al. HLA-DPB1*0501-associated opticospinal multiple sclerosis. Clinical, neuroimaging and immunogenetic studies. Brain 1999; 122: 1689–96.
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  M Nakamura, T Misu, K Fujihara, I Miyazawa, I Nakashima, T Takahashi, S Watanabe, and Y Itoyama Occurrence of acute large and edematous callosal lesions in neuromyelitis optica Multiple Sclerosis, June 1, 2009; 15(6): 695 - 700. [Abstract] [PDF]
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 T Misu, R Takano, K Fujihara, T Takahashi, S Sato, and Y Itoyama Marked increase in cerebrospinal fluid glial fibrillar acidic protein in neuromyelitis optica: an astrocytic damage marker J. Neurol. Neurosurg. Psychiatry, May 1, 2009; 80(5): 575 - 577. [Abstract] [Full Text] [PDF]
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H Zephir, I Fajardy, O Outteryck, F Blanc, N Roger, M Fleury, G Rudolf, R Marignier, S Vukusic, C Confavreux, et al. Is neuromyelitis optica associated with human leukocyte antigen? Multiple Sclerosis, May 1, 2009; 15(5): 571 - 579. [Abstract] [PDF]
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 T. Okamoto, M. Ogawa, Youwei Lin, M. Murata, S. Miyake, and T. Yamamura Review: Treatment of neuromyelitis optica: Current debate Therapeutic Advances in Neurological Disorders, July 1, 2008; 1(1): 43 - 52. [Abstract] [PDF]
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M. Tanaka, K. Tanaka, M. Komori, and T. Saida Anti-aquaporin 4 antibody in Japanese multiple sclerosis: the presence of optic spinal multiple sclerosis without long spinal cord lesions and anti-aquaporin 4 antibody J. Neurol. Neurosurg. Psychiatry, September 1, 2007; 78(9): 990 - 992. [Abstract] [Full Text] [PDF]
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S. Watanabe, T. Misu, I. Miyazawa, I. Nakashima, Y. Shiga, K. Fujihara, and Y. Itoyama Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis Multiple Sclerosis, September 1, 2007; 13(8): 968 - 974. [Abstract] [PDF]
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 C. S. Yu, C. Z. Zhu, K. C. Li, Y. Xuan, W. Qin, H. Sun, and P. Chan Relapsing Neuromyelitis Optica and Relapsing-Remitting Multiple Sclerosis: Differentiation at Diffusion-Tensor MR Imaging of Corpus Callosum Radiology, July 1, 2007; 244(1): 249 - 256. [Abstract] [Full Text] [PDF]
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 B. G. Weinshenker Neuromyelitis Optica Is Distinct From Multiple Sclerosis Arch Neurol, June 1, 2007; 64(6): 899 - 901. [Full Text] [PDF]
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 T. Misu, K. Fujihara, A. Kakita, H. Konno, M. Nakamura, S. Watanabe, T. Takahashi, I. Nakashima, H. Takahashi, and Y. Itoyama Loss of aquaporin 4 in lesions of neuromyelitis optica: distinction from multiple sclerosis Brain, May 1, 2007; 130(5): 1224 - 1234. [Abstract] [Full Text] [PDF]
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M. Nakamura, I. Nakashima, S. Sato, I. Miyazawa, K. Fujihara, and Y. Itoyama Clinical and laboratory features of neuromyelitis optica with oligoclonal IgG bands Multiple Sclerosis, April 1, 2007; 13(3): 332 - 335. [Abstract] [PDF]
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T Fukazawa and S Kikuchi A three-dimensional approach for understanding the spectrum of idiopathic inflammatory demyelinating disorders: importance of the 'attack-related severity' axis Multiple Sclerosis, March 1, 2007; 13(2): 199 - 207. [Abstract] [PDF]
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J. A Cabrera-Gomez, L Quevedo-Sotolongo, A Gonzalez-Quevedo, S Lima, Y Real-Gonzalez, M Cristofol-Corominas, K Romero-Garcia, C Ugarte-Sanchez, J Jordan-Gonzalez, J E G. de la Nuez, et al. Brain magnetic resonance imaging findings in relapsing neuromyelitis optica Multiple Sclerosis, March 1, 2007; 13(2): 186 - 192. [Abstract] [PDF]
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S Watanabe, I Nakashima, T Misu, I Miyazawa, Y Shiga, K Fujihara, and Y Itoyama Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica Multiple Sclerosis, January 1, 2007; 13(1): 128 - 132. [Abstract] [PDF]
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I Nakashima, K Fujihara, I Miyazawa, T Misu, K Narikawa, M Nakamura, S Watanabe, T Takahashi, S Nishiyama, Y Shiga, et al. Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG J. Neurol. Neurosurg. Psychiatry, September 1, 2006; 77(9): 1073 - 1075. [Abstract] [Full Text] [PDF]
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T Fukazawa, S Kikuchi, R Miyagishi, Y Miyazaki, I Yabe, T Hamada, and H Sasaki HLA-DPB1*0501 is not uniquely associated with opticospinal multiple sclerosis in Japanese patients. Important role of DPB1*0301 Multiple Sclerosis, February 1, 2006; 12(1): 19 - 23. [Abstract] [PDF]
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M Nakamura, M Endo, K Murakami, H Konno, K Fujihara, and Y Itoyama An autopsied case of neuromyelitis optica with a large cavitary cerebral lesion Multiple Sclerosis, December 1, 2005; 11(6): 735 - 738. [Abstract] [PDF]
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 T. Misu, K. Fujihara, I. Nakashima, S. Sato, and Y. Itoyama Intractable hiccup and nausea with periaqueductal lesions in neuromyelitis optica Neurology, November 8, 2005; 65(9): 1479 - 1482. [Abstract] [Full Text] [PDF]
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 V. A. Lennon, T. J. Kryzer, S. J. Pittock, A.S. Verkman, and S. R. Hinson IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel J. Exp. Med., August 15, 2005; 202(4): 473 - 477. [Abstract] [Full Text] [PDF]
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T. F Scott, S. L Kassab, and S. Singh Acute partial transverse myelitis with normal cerebral magnetic resonance imaging: transition rate to clinically definite multiple sclerosis Multiple Sclerosis, August 1, 2005; 11(4): 373 - 377. [Abstract] [PDF]
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H. Sakuma, K. Kohyama, I.-K. Park, A. Miyakoshi, N. Tanuma, and Y. Matsumoto Clinicopathological study of a myelin oligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1 rats Brain, October 1, 2004; 127(10): 2201 - 2213. [Abstract] [Full Text] [PDF]
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K. Takahashi, T. Aranami, M. Endoh, S. Miyake, and T. Yamamura The regulatory role of natural killer cells in multiple sclerosis Brain, September 1, 2004; 127(9): 1917 - 1927. [Abstract] [Full Text] [PDF]
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S Pradhan and V N Mishra A central demyelinating disease with atypical features Multiple Sclerosis, June 1, 2004; 10(3): 308 - 315. [Abstract] [PDF]
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I. Nakashima, K. Fujihara, J. Fujimori, K. Narikawa, T. Misu, and Y. Itoyama Absence of IgG1 response in the cerebrospinal fluid of relapsing neuromyelitis optica Neurology, January 13, 2004; 62(1): 144 - 146. [Abstract] [Full Text] [PDF]
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K.-k. Kim Idiopathic Recurrent Transverse Myelitis Arch Neurol, September 1, 2003; 60(9): 1290 - 1294. [Abstract] [Full Text] [PDF]
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 Characterizing Pure Opticospinal Multiple Sclerosis Journal Watch Neurology, January 10, 2003; 2003(110): 5 - 5. [Full Text]
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