Optic-spinal Form Of Multiple Sclerosis Research Articles

Multiple sclerosis and neuromyelitis optica spectrum disorders: some similarities in two distinct diseases.

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory disorder of the central nervous system that particularly involves the optic nerve and spinal cord. It is pathologically characterized by astrocytopathy, followed by tissue destruction (Fujihara, 2011). Historically, NMOSD has been considered to be an Asian optic-spinal form of multiple sclerosis (MS), as patients with NMOSD were distributed predominantly in Asian rather than in Western countries.

Multiple sclerosis: clinical features and MRI findings in Northern China.

BackgroundReports in Asian populations suggest that ethnic and geographical differences may influence susceptibility to multiple sclerosis (MS) and its clinical behaviors. Here, we sought to retrospectively survey clinical characteristics and MRI data in Chinese subjects with MS.MethodsWe conducted a retrospective analysis in 117 patients with MS. The patients were divided into subgroups with optic-spinal form of multiple sclerosis (OSMS; n = 42) and classical multiple sclerosis (CMS; n = 75). Clinical characteristics, MRI finding and expanded disability status scale (EDSS) score were compared between the two groups.ResultsIn 117 MS patients, 64.1% patients were classified as having CMS and 35.9% OSMS forms. White blood cell counts of OSMS patients were significantly higher than those of CMS patients (P <0.05). The longitudinal fusion lesions of spinal cord on MRI were statistically significant between groups (P <0.05). Spinal cord MRI showed that MS lesions were longer, and revealed spinal cord swelling in patients with CMS, but atrophy in patients with OSMS. The EDSS score at five years was significantly higher in patients with OSMS than in those with CMS (P <0.05). Relapse rates of patients with OSMS were also higher than those of patients with CMS (P <0.01) within one to three years.ConclusionsOSMS accounts for a higher proportion of MS populations in Northern China than in Western countries. MRI showed a longitudinally extensive spinal cord lesion in patients with OSMS and spinal cord swelling at onset.

Effect of geranylgeranylacetone on optic neuritis in experimental autoimmune encephalomyelitis

Optic neuritis is an acute inflammatory demyelinating syndrome of the central nervous system (CNS) that often occurs in multiple sclerosis (MS). Since it can cause irreversible visual loss, especially in the optic-spinal form of MS or neuromyelitis optica (NMO), the present study was conducted to assess the effects of geranylgeranylacetone (GGA) on optic neuritis in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Myelin oligodendrocyte glycoprotein-induced EAE mice received oral administration of GGA at 500mg/kg or vehicle once daily for 22 days. The effects of GGA on the severity of optic neuritis were examined by morphological analysis on day 22. Visual functions were measured by the multifocal electroretinograms (mfERG). In addition, the effects of GGA on severity of myelitis were monitored both on clinical signs and morphological aspects. The visual function, as assessed by the second-kernel of mfERG, was significantly improved in GGA-treated mice compared with vehicle-treated mice. GGA treatment decreased the number of degenerating axons in the optic nerve and prevented cell loss in the retinal ganglion cell layer. However, the severity of demyelination in the spinal cord remained unaffected with the treatment of GGA. These results suggest that oral GGA administration has beneficial effect on the treatment for optic neuritis in the EAE mouse model of MS.

Association of HLA-DRB1 and -DPB1 allele polymorphism with multiple sclerosis in Chinese Han population from Southern areas

To examine the correlation between multiple sclerosis (MS) in Chinese Southern Han population and the polymorphism of HLA-DRB1 and -DPB1 alleles, and compare it to the reports of Western, Japanese and Northern Chinese populations. The HLA-DRB1 and -DPB1 alleles of 26 patients with conventional MS (C-MS), 13 patients with optic-spinal form of MS (OS-MS), and 50 normal controls were determined by sequence-based typing (SBT) method. The frequency of the HLA alleles was compared between the 2 MS subtypes and the MS subtypes and the controls by chi(2) or Fisher exact probability test. The P values were corrected according to Bonferroni's method to calculate corrected the P values (Pc). A total of 27 HLA-DRB1 alleles and 13 HLA-DPB1 alleles were identified in the 39 MS patients and 50 controls. The frequencies of DRB1(*)0406 (P = 0.014, OR = 2.09) and DRB1(*)1302 alleles (P = 0.007, OR = 2.84) were higher in the OS-MS patients than in the controls. In addition, the DRB1(*)120201 allele was more frequent in the C-MS patients than in the controls, and the frequency of DPB1(*)2101 was higher in the OS-MS patients than in the controls. However, all the differences were of no significance since the corrected P values (Pc) were all > 0.1. There was no correlation between the MS subtypes and the HLA-DRB1(*)1501 or DPB1(*)0501 as reported in Western and Japanese populations (all P > 0.1). The correlation between HLA-DRB1 and -DPB1 in Southern Han MS population is different from that in the Western, Japanese, and Northern Chinese populations. Southern Han MS patients may be linked to the HLA-DRB1(*)0406, DRB1(*)1302, DRB1(*)120201 and DPB1(*)2101, but not to the HLA-DRB1(*)1501 or DPB1(*)0501 alleles as reported in the above populations.

Two subtypes of optic-spinal form of multiple sclerosis in Japan: clinical and laboratory features

Seventy-seven cases of the optic-spinal form of multiple sclerosis (OSMS) were collected from 6 institutes in 3 cities of Japan, and the clinical and MRI features were analyzed. Two-thirds of the OSMS patients had longitudinally extensive spinal cord MRI lesions (LESL), and had clinical features similar to those of relapsing neuromyelitis optica which often causes severe disability. In contrast, OSMS patients without LESL tended to have milder disease and had some feature commonly seen in the conventional form of MS. The percentage of OSMS without LESL in total OSMS has recently been increasing. The present study suggests that LESL is crucially important for distinguishing the two subtypes of OSMS.

Oligoclonal IgG bands in Japanese patients with multiple sclerosis. A comparative study between isoelectric focusing with IgG immunofixation and high-resolution agarose gel electrophoresis

A low prevalence of oligoclonal IgG bands (OB) has been reported as a unique feature of Japanese multiple sclerosis (MS) as compared with Western MS. We compared the frequency of OB between isoelectric focusing (IEF) and agarose gel electrophoresis (AGE) in 59 Japanese patients with clinically definite MS [39 with conventional form of MS (CMS) and 20 with optic-spinal form of MS (OSMS)]. The frequency of IEF-OB in total MS was 54%, whereas that of AGE-OB was only 17%. When OSMS was excluded, the frequency increased to 77% by IEF, whereas it remained 23% by AGE. Our study strongly suggests that IEF is highly effective for detecting OB in Japanese MS 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.

Significant correlation between IL-10 levels and IgG indices in the cerebrospinal fluid of patients with multiple sclerosis

We measured the interleukin (IL)-6 and IL-10 levels in the plasma and the cerebrospinal fluid (CSF) of a total of 23 relapsing multiple sclerosis (MS) patients [18 with conventional form of MS (C-MS) and 5 with optic-spinal form of MS (OS-MS)] using ELISA and correlated them with the IgG indices and oligoclonal IgG bands (OB) to determine whether these cytokines play a role in the intrathecal immunoglobulin production. IL-10 values in the CSF significantly correlated with the IgG indices and tended to be higher in OB-positive patients. In contrast, IL-10 values in the plasma and IL-6 values in the CSF and the plasma did not correlate with the IgG indices or OB. The CSF-IL-10 value in OS-MS were much lower than those of C-MS, but those of CSF IL-6 did not differ between C-MS and OS-MS. The results remained unchanged even when OS-MS patients were excluded. Our results may suggest a role of IL-10 in upregulating the intrathecal IgG synthesis in relapsing MS.

Optic-spinal form of multiple sclerosis and immune-mediated myelopathy in Japan.

Optic-spinal form of multiple sclerosis (OS-MS) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) are two immune-mediated myelopathy relatively common in Japan. (1) Transverse myelitis, once seen in 60% of MS, mostly OS-MS, 30 years ago, drastically decreased (5%) recently in Japan. In contrast, frequency of conventional form of MS (C-MS) increased during this period of time. But unlike C-MS in white patients, cerebellar hemispheric lesions are uncommon in Japanese C-MS. These findings emphasize influence of changes in exogenous factors on manifestations of MS and distinct genetic factors related to MS in Japanese and white patients. (2) To clarify the reason of high HTLV-I proviral load in HAM/TSP, we studied cellular immune surveillance against HTLV-I and found that significant cytotoxic T lymphocyte activity, and suppressed natural killer activity and antibody-dependent cell-mediated cytotoxicity in the patients. These altered immune surveillance may be associated with the spread of HTLV-I infection and the pathogenesis of HAM/TSP.

The significance of oligoclonal bands in multiple sclerosis in Japan: relevance of immunogenetic backgrounds.

We compared clinical and demographic features, MRI findings, and HLA profiles of 57 Japanese patients with multiple sclerosis (MS) between groups with and without oligoclonal IgG bands (OCB) in the cerebrospinal fluid (CSF). Patients with the optic-spinal form of MS (OpS-MS) or acute transverse myelopathy (ATM), which are distinctive and relatively common in Japanese MS, were excluded in this study. The OCB-positive rate was only 56.1% (32/57) among these 57 'conventional' MS patients, of whom clinical features were similar to those of Western MS patients. The demographic features, clinical course, disability, and cerebral abnormalities seen on MRI were similar in the OCB-negative and OCB-positive patient groups. HLA-DR2 antigen, which has been confirmed to be associated with MS in many populations, was more common in the OCB-positive than in the OCB-negative and control groups. Furthermore, DR4 antigen was statistically more common in the OCB-negative patient group. These results raise the possibility that the presence of OCB is related to the immunogenetic background of the patient, and that there may be at least two subpopulations in Japanese patients with 'conventional' MS from the viewpoint of immunogenetics. In one subpopulations, MS is associated with the DR2 antigen, and shows a stronger humoral immune response in the CSF, while in the other MS is associated with DR4, which has a milder humoral response. Further investigations involving more patients are warranted.

Anti-nuclear antibodies and the optic-spinal form of multiple sclerosis.

We found anti-nuclear antibodies (ANA) (1:20 or higher) in sera from 11 of 16 patients with a diagnosis of the optic-spinal form of multiple sclerosis (OpS-MS) and 13 of 59 patients with other forms of MS (other MS), both rates being significant (P = 0.0004). Six of the OpS-MS patients had a high level of ANA (1:80 or higher), while levels were high in only three of the other MS patients, showing a significant difference (P = 0.0022). Titres of ANA were significantly higher in OpS-MS patients than in other MS patients (P < 0.0001). There was no relationship between the presence of ANA and age in OpS-MS patients, while patients with were older than those without high ANA levels among other MS patients. ANA-positive rate and titres were significantly higher in OpS-MS patients than in sex- and age-matched other MS patients. These results support the concept that OpS-MS constitutes a distinct subgroup among patients with a clinical diagnosis of MS and may indicate that systemic dysregulation of the inflammatory or immune response is more common in OpS-MS patients; the possible pathogenetic relevance of ANA-associated vasculopathy to some patients with a clinical diagnosis of OpS-MS should be considered.