Relapsing neuromyelitis optica responsive to glatiramer acetate treatment

Neuromyelitis optica (NMO; Devic’s syndrome) is a severe inflammatory disease affecting selectively the optic nerves and spinal cord [1]. Due to some similarities of NMO and relapsing–remitting multiple sclerosis, immunomodulating agents like interferon-beta (IFN-b) and glatiramer acetate (GA) are potential therapeutic options, but so far treatment response was mostly insufficient and immunosuppressive agents are preferred (e.g. cyclophosphamide or mitoxantrone) [2]. Here, we report the case of a female suffering from relapsing NMO who experienced relapses despite regular cyclophosphamide and steroid therapy but who responded to treatment with GA. This previously healthy 48-year-old female presented with subacute onset of hypaesthesia of the right trunk, arm and leg extending to the left side and consecutive pyramidal weakness of the lower extremities. Also, she developed blurred vision beginning on the right eye, later on progressing to the left eye with marked reduction of visual acuity. An magnetic resonance imaging (MRI) of the brain was normal. The MRI of the cervical spine demonstrated a T2-hyperintensive lesion extending from C1 to Th7 with a maximum at C3/4 and gadolinium enhancement (Fig. 1) indicating an inflammatory process. NMO was diagnosed and steroid treatment was initiated. Nevertheless her symptoms deteriorated, thus we induced an immunosuppressive therapy with cyclophosphamide (initially 600 mg/m) which led to marked clinical improvement. Despite monthly cycles of cyclophosphamide (1000 mg/m, cumulative dose: 19.4 g) she experienced three exacerbations within the next 11 months. Thereafter the patient refused any further immunosuppressive treatment. We initiated a new treatment regimen with GA (20 mg s.c. daily) in combination with monthly steroid pulses. Since then no more relapses occurred until today (38-month therapy duration). After a year, steroid pulses were discontinued. A follow-up MRI of the spinal cord after 12 months of treatment with GA showed that all cervical lesions were in remission and no new lesions or gadolinium positive lesions have occurred. Until today no established therapeutic concept for NMO exists. The use of parenteral steroids in acute attacks is based on anecdotal evidence and has been reported to fail frequently [2]. Concerning immunosuppressive long-term therapy few clinical observation series are reported, but data suggest efficacy of mitoxantrone and cyclophosphamide. Immunmodulatory agents have not been formally evaluated for the treatment of NMO. Few reports indicate that IFN-b may be ineffective for attack prevention in NMO [2]. With regard to GA, a reduction of the annual relapse rate from 0.93 to 0.29 in a single patient with NMO within the first 6 years after treatment initiation was recently reported [3]. Thus, GA was considered the preferable option after cyclophosphamide had failed and further immunosuppression was denied in this case. The pathogenesis of NMO is largely unknown. However, there is some evidence that B-cell autoimmunity and activation of eosinophiles play an important role [1], which could explain the efficacy of B-cell modulating agents such as mitoxantrone and rituximab [2]. Eosinophiles cause a Th1 to Th2 shift, and Th2 cells again attract eosinophiles. Therefore, activated Th2 cells seem to maintain the inflammatory process in NMO [1]. The potential mode of action of GA includes an inhibition of myelin reactive T-cell clones and the induction of immunomodulatory Th2-like T-cell populations [4]. But as the whole mode of action is still not fully understood this does not necessarily contradict effectiveness in NMO. Although the long remission of the reported patient during treatment with GA is remarkable, it is not definitely attributable to the treatment with GA. Long quiescent courses of NMO have been described [2]. In the initial phase of GA treatment, also the regular steroid pulses might have contributed to clinical stabilization. Our case and one other case suggest that GA might be considered as a