Neuromyelitis optica (NMO): Review

Case Report

A 56-year-old Caucasian woman otherwise in good health until 02/08 presents with sudden painful loss of left eye vision for which she was admitted with a diagnosis of left optic neuritis and improved with steroids. The diagnostic MRI of the head showed an ACM and contrast enhancement of the optic nerve. CSF analysis was unremarkable. She regained vision with mild residual blurriness. She continued with her good state of health until 09/08 when she was hospitalized due to abnormal MRI of the cervical spinal cord showing enhancing lesions surrounded by edema with the working diagnosis of possible MS vs. Devic’s disease.

The MRI was done by outpatient neurology clinic when she presented with complaints of severe pain and numbness in the neck and the right arm that progressed to motor weakness in her right upper extremity. She was treated with a high dose of steroids as outpatient oral steroids did not help her. She improved remarkably.

On 11/6/2008 she was hospitalized due to sudden onset of spasms in the both lower extremities and left upper extremity with severe pain that lasted 30 minutes to 1 hour. There was no associated numbness, headache, neck stiffness, fever, chills, or bowel/bladder incontinence. On examination the vital signs were normal. Residual left eye vision impairment. Other physical examination was unremarkable including neurological examination.

The laboratory data was unremarkable including negative titres of the NPO antibody. MRI of the cervical spine revealed enhancing lesions in the cervical spinal cord. She was treated with IV steroids, clonazepam and neurontin. Her symptoms were refractory to the steroids and on patient request were transferred to higher level care giving facility. Later she was treated with chemotherapy subsequently her symptoms improved and currently she is clinically stable. Finally it was confirmed that she had Devic’s disease.

Introduction

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS) that the majority of targets are generally the optic nerves and spinal cord particularly; NMO is also identified as Devic’s disease. NMO is believed to be an alarming monophasic condition distinguished by bilateral optic neuritis (ON) and myelitis that takes place in rapid progression.

To date, medical point of view has transformed because of a number of advancement. Initially, contrasting to MS, NMO is not linked with brain lesions at disease onset in the majority of patients; however, brain lesions do take place over time in the greater part of patients, and their current description has confirmed information as to the development of the disease. Secondly, a great scientific progression published over the past decade have exposed that most patients with NMO contain longitudinally extensive transverse myelitis (LETM) defined by an MRI lesion which is expanding contiguously over three or more vertebral sections, which is hardly ever occurs in MS (multiple sclerosis) (Ghezzi et al., 2004).

Thirdly, neuropathologic studies exhibit that while the demyelination is present, NMO is differentiated by unique “vasculocentric” pathology with important perivascular immunoglobulin accumulation and evidence of creation in harmonize lytic pathway, to bring up B cell involvement in the disease development ([Lucchinetti et al., 2002] and [Wingerchuk, 2006]). finally, a highly specific serum antibody (NMO-IgG) has been found in patients with NMO but not in patients with “prototypic” MS or in other conditions characterized by optic neuropathy and myelopathy (Lennon et al., 2004). These clinical, radiological, pathological and immunological data provide convincing evidence that NMO spectrum disorders are distinct from MS.

The current breakthrough that NMO-IgG respond specially with aquaporin 4 (AQP4) (Lennon et al., 2005) has release new possibility for the comprehension of the pathogenesis of idiopathic inflammatory demyelinating disease; it is the primary example in which a precise mark for an immune reaction resulting in an inflammatory demyelinating disease in humans has been recognized.

Epidemiology

The occurrences and frequency of NMO has been difficult to evaluate because it is still something not yet already known as illness and diagnostic measures such as spinal MRI and the accessibility of NMO-IgG testing are not readily available in all geographic region.

Relapsing NMO has a female to male ratio of 5:1. Monophasic NMO, by disparity, influences both sexes evenly. The median age of onset in Caucasians is late in the fourth decade, which is noticeably older than that of MS (Wingerchuk et al., 1999). Pediatric cases have been reported and may be both monophasic and relapsing (Arabshahi et al., 2006). Non-Caucasians (African, Hispanic and Asian) are over-represented with NMO patients when measure up to MS patients; on the other hand, Caucasians encompass the greater part in succession from Western countries.

Diagnosis

The diagnosis of Devic’s disease necessitates optic neuritis in addition to transverse myelitis. To make a distinction of Devic’s disease from other demyelinating diseases such as multiple sclerosis (MS), a set of further criteria have been projected:

  1. a spinal cord magnetic resonance imaging (MRI) lesion extending closely over three or more vertebral segments;
  2. a positive NMO-IgG anti body titer; and
  3. a brain MRI that fails to meet diagnostic criteria for MS (Wingerchuk et al, 2006).

Two of these three sustaining criterion must be fulfilled in order to make an analysis of Devic’s disease. As Devic’s disease develop, a number of patients develop brain lesions, for the most part of which are asymptomatic and their MRI features are not usually typical for MS (Pittock et al, 2006).

The MRI distinctiveness of myelitis in MS varies from myelitis seen in Devic’s disease. In MS, spinal cord lesions are naturally small, measuring less than one vertebral fragment, and are asymmetrically situated, frequently in the posterior or lateral portions of the spinal cord. In Devic’s disease, individual spinal cord lesions tend to be proportioned and span multiple vertebral segments. These lesions have been illustrated as longitudinally extensive transverse myelitis (LETM) (Ghezzi et al, 2004). LETM with no confirmation of optic nerve association may signify a restricted form of Devic’s disease (Weinshenker et al, 2006).

Pathology

The characteristic feature of NMO pathology is the occurrence of necrotic spinal cord lesions connecting both gray and white matter, frequently resulting in cavitation, as well as the occurrence of vascular hyalinization (Prineas and McDonald, 1997). Lucchinetti et al (2002) studied that the spinal cord of nine autopsied cases of NMO and discover a noticeable eosinophil infiltration in active NMO lesions in addition to demyelination and necrosis with cavitation.

Lucchinetti (2002) furthermore described perivascular immune complex deposition in a characteristic “rim” and “rosette” outline. The foundation on these findings, the researchers proposed that NMO was a humoral disorder that targets the perivascular region. Moreover, the pathology of cavitary cerebral lesions from two NMO patients was comparable to the discovered in optic nerve and spinal cord NMO lesions, firmly suggesting a common pathogenesis (Jacobs et al., 2006).

Treatment

The suggested treatment is mainly stand on a case series or expert opinion (Wingerchuk and Weinshenker, 2005). The preferred therapy for acute attacks is intravenous corticosteroids, normally 1 g of methylprednisolone for five successive days, starting as soon as possible after relapse onset and exclusion or treatment of bacterial infections (e.g. respiratory or urinary tract).

Treatments intended at relapse prevention should be initiated as soon as the diagnosis of a relapsing NMO is made. It is also reasonable to start therapy after a first episode of LETM in patients seropositive for NMO-IgG, since NMO-IgG has proven to be a potent predictor of future relapse in this context (Weinshenker et al., 2006a). Immunosuppressant, rather than interferon beta or glatiramer acetate, which is used for prototypic MS, is the preferred treatment (Papeix et al., 2005).

The optimal duration of treatment in patients without further relapses with immunosuppressants is uncertain. The long term side effects of medications have to be weighed against the potential risk of relapses. Whether NMO-IgG titers could guide therapy is uncertain and appropriate studies are being pursued.

Conclusion

To make clear of the pathogenesis of NMO could present important insights into the pathobiology of MS and other demyelinating disorders. Reactive or dynamic transfer of the disease, improvement of animal models, identification of probable genetic and environmental susceptibility factors are the current grounds of research. The breakthrough of a possible specific antigenic target, AQP4, may make possible the development of effective antigen-specific therapy.

Reference

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