Chapter 26 - Neuromyelitis optica (Devic’s syndrome)
Introduction
Neuromyelitis optica (NMO), also known as Devic’s syndrome or Devic’s disease, after the French physician who is most credited with bringing this entity to clinical attention, was first reported in the 19th century (Cree et al., 2002, de Seze, 2003, Wingerchuk and Weinshenker, 2003a). For the next hundred years, standard neurology references contained the oft-repeated definition of NMO as a severe, monophasic disorder simultaneously affecting the spinal cord and both optic nerves but sparing the remainder of the central nervous system (CNS). The position of NMO within the nosologic schema of CNS demyelinating diseases has been long debated (Cree et al., 2002, de Seze et al., 2003). Many investigators have considered it simply a severe variant of multiple sclerosis (MS), with a disproportionate burden of white-matter lesions affecting optic nerve and spinal cord; others have maintained that it represents a distinct disease (Wingerchuk and Weinshenker, 2003a). Some clinicians espouse an intermediate position, suggesting that NMO is a form of acute disseminated encephalomyelitis peculiarly restricted to expression in optic nerve and spinal cord (Modi et al., 2001). In this chapter, we review the features of NMO that distinguish it from typical forms of MS, and recent advances in immunology and immunopathology that further support the distinctness of NMO. These advances support the importance of antibodies in the pathogenesis of NMO and current beliefs that optimal treatment of NMO differs from that for MS.
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History and nomenclature
Although Albutt’s (1870) account of a patient with a “sympathetic disorder of the eye” that came on “twelve or thirteen weeks at least” after an acute myelitis was often credited as the first description of a syndrome compatible with NMO, recent reports suggest case descriptions from the 19th century as early as 1804 (Albutt, 1870, Jarius and Wildemann, 2011, Jarius and Wildemann, 2012a, Jarius and Wildemann, 2012b). Erb, however, provided the first detailed description of NMO in 1880. He
Prevalence and incidence relative to MS
Studies of prevalence and incidence of NMO are difficult to interpret because of the evolving nature of diagnostic criteria, and the indistinct separation between “optic spinal” presentations of MS and NMO in published literature. Some patients with ON and myelitis episodes, even those without clinical or radiologic evidence for brain involvement, follow a typical course of MS in follow-up. Such patients usually have attacks of myelitis that are not accompanied by the relatively specific
Current diagnostic criteria
A variety of NMO definitions or diagnostic criteria have been put forth but the criteria that we proposed in 1999 based on a large retrospective case series were widely used until the discovery of NMO-IgG (Table 26.1). These criteria require both ON and myelitis and absence of clinical symptoms or signs implicating other CNS structures. Attainment of certain major or minor supportive criteria, including characteristics of the attacks (bilateral ON, attack severity and recovery), brain and
Natural history and prognosis
Once the “index events” of ON and myelitis have occurred, establishing a diagnosis of NMO, the disease may seemingly remit permanently (monophasic course) or additional relapses of ON or myelitis may occur (relapsing course) (Wingerchuk et al., 1999, Wingerchuk and Weinshenker, 2003b). It is difficult to be completely certain that the course is monophasic because NMO, like MS, can remit clinically for years, and occasionally decades, before attacks re-emerge. Over 80% of patients have relapsing
Pathology
Recent studies have reported a consistent set of distinctive findings that may permit a specific pathologic diagnosis when an adequate sample of active inflammatory tissue is examined, although the results are based on limited data. Several groups had described necrotic central spinal cord lesions, affecting gray and white matter with macrophage infiltration that ultimately result in atrophic, gliotic, and cavitary lesions in some cases (Cloys and Netsky, 1970, Mandler et al., 1993, Prineas and
Immunology
One or more organ-specific and nonspecific immunoglobulins are encountered in approximately 50% of patients with NMO, often in high titer; about 25% have clinical evidence of nonneurologic autoimmunity (Wingerchuk et al., 1999). However, the only autoantibody specific for NMO is one detected by Lennon and colleagues (2004), which has been called NMO-IgG. NMO-IgG was originally detected by immunofluorescence on a substrate of mouse tissues with a protocol used to test for organ-specific
Therapy
Interest in NMO is increasing but the relative rarity of the disorder in most developed world regions has hindered the development of concerted efforts to perform large-scale treatment trials. Recommendations for treatment of attacks and long-term therapy to prevent them rely entirely on case series and individual clinical experience (Wingerchuk and Weinshenker, 2008).
Future research directions
Future research will clarify the boundaries of NMO. NMO-IgG and its antigen target, AQP4, undoubtedly will be major clues to the pathogenesis of this condition. However, it remains to be established whether NMO-IgG is a marker of the disease or a pathogen. Preliminary evidence, outlined above, is compatible with its pathogenicity, but active immunization and passive transfer experiments, among other studies, will be required to confirm this hypothesis. If pathogenic, it will be necessary to
Conclusion
A growing body of clinical, neuroimaging, immunologic, and immunopathologic evidence demonstrates that NMO is a distinct disease. The NMO disease spectrum has widened to encompass as many as half of patients previously diagnosed with “idiopathic recurrent transverse myelitis,” most patients with Japanese opticospinal MS, and some patients with silent or clinically manifest brain and brainstem lesions. The combination of a longitudinally extensive spinal cord lesion and normal or nonspecific
References (138)
- et al.
‘Noteomielite’ accompanied by acute amaurosis (1844). On an early case of neuromyelitis optica
J Neurol Sci
(2012) - et al.
Treatment of neuromyelitis optica: review and recommendations
Mult Scler Relat Disord
(2012) - et al.
Anti-aquaporin-4 antibody induces astrocytic cytotoxicity in the absence of CNS antigen-specific T cells
Biochem Biophys Res Commun
(2010) Multiple sclerosis in the Japanese population
Lancet Neurol
(2003)- et al.
Changes in the clinical phenotypes of multiple sclerosis during the past 50 years in Japan
J Neurol Sci
(1999) - et al.
A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis
Lancet
(2004) The pattern of neurological illness in tropical Africa Experience at Ibadan, Nigeria
J Neurol Sci
(1971)- et al.
Sur un cas de myelite aigue diffuse avec double nevrite optique
Arch Med Exp Anat Pathol
(1889) - et al.
Reappraisal of Lhermitte's sign in multiple sclerosis
Mult Scler
(2005) On the ophthalmoscopic signs of spinal disease
Lancet
(1870)
The molecular basis of water transport in the brain
Nat Rev Neurosci
A population-based study of neuromyelitis optica in Caucasians
Neurology
Devic's neuromyelitis optica treated with intravenous gamma globulin (IVIG)
Can J Neurol Sci
Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis
Brain
A case of diffuse myelitis associated with optic neuritis
Brain
Glatiramer acetate treatment in Devic's neuromyelitis optica
Brain
Lack of response to pulse cyclophosphamide in neuromyelitis optica: evaluation of 7 patients
Arch Neurol
Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution
J Neurol
Plasma exchange in severe spinal attacks associated with neuromyelitis optica spectrum disorder
Mult Scler
Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination
Neurology
Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo
Ann Neurol
Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate
Ann Neurol
HLA-DRB association in neuromyelitis optica is different from that observed in multiple sclerosis
Mult Scler
MS and neuromyelitis optica in Martinique (French West Indies)
Neurology
An epidemiological study of neuromyelitis optica in Cuba
J Neurol
Neuromyelitis optica (Devic's syndrome) in two sisters
Clin Electroencephalogr
Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica
Proc Natl Acad Sci U S A
The marvellous harmony of the nervous parts: The origins of multiple sclerosis
Clin Med
Azathioprine: Tolerability, efficacy, and predictors of benefit in neuromyelitis optica
Neurology
Neuromyelitis optica
Semin Neurol
An open label study of the effects of rituximab in neuromyelitis optica
Neurology
A retrospective review of patients with clinically definite multiple sclerosis
Ann Acad Med Singapore
Neuromyelitis optica
Arch Neurol
Is Devic's neuromyelitis optica a separate disease? A comparative study with multiple sclerosis
Mult Scler
Myelite aigue compliquee de nevrite optique, autopsie
Bull Med (Paris)
CSF electrophoresis in one thousand patients
Can J Neurol Sci
Uber das Zusammenkommen von Neuritis optika und Myelitis subacuta
Arch Psychiatr Nervenkr
Devic's neuromyelitis optica: study of nine cases
Acta Neurol Scand
Primary demyelinating processes of the central nervous system: an attempt at unification and classification
Arch Neurol Psychiat (Chic)
Long-term follow-up of acute partial transverse myelopathy
Neurology
Genomic HLA profiles of MS in Hokkaido, Japan: important role of DPB1*0501 allele
J Neurol
Clinical profile of multiple sclerosis in Bengal
Neurol India
De la neuromyelite optique aigue
Clinical characteristics, course and prognosis of relapsing Devic's neuromyelitis optica
J Neurol
Devic's disease: bridging the gap between laboratory and clinic
Brain
Optic neuritis and myelitis
Ophthal Rev
Neuroptic myelitis versus multiple sclerosis: a pathologic study
Arch Neurol Psychiat (Chic)
Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients
Arch Neurol
Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients
Arch Neurol
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2021, The Lancet NeurologyCitation Excerpt :Because presence of aquaporin-4 IgG is so strongly predictive of a future relapse, treatment efforts have focused on preventive therapies that could help avoid severely disabling attacks in people with neuromyelitis optica spectrum disorder.5,6 Conventional immunosuppressive therapies have been used for prevention of relapses out of license because of their effectiveness in other antibody-mediated conditions and because they appear to provide some benefit to people with neuromyelitis optica spectrum disorder; these include rituximab, mycophenolate mofetil, azathioprine, and prednisone.7,8 Consensus treatment recommendations9 have been based on a few observational clinical studies that lacked masking or control groups; yet these studies all suggested that immune suppression in general prevents relapses compared with no immunosuppressive treatment.
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2020, Archivos de la Sociedad Espanola de OftalmologiaAnti-HSV-2 antibody in patients with MS and NMO
2019, Multiple Sclerosis and Related DisordersCitation Excerpt :Neuromyelitis optica spectrum disorder (NMOSD) is yet another demyelinating disorder of the CNS which used to be considered as a subtype of MS. This disease almost always involves the optic nerve and the spinal cord and its course is often relapsing. NMOSD is distinctive from MS in that it is associated with antibodies against the aquaporin-4 channels (AQP-4) in the astrocytes of the CNS (Wingerchuk and Weinshenker, 2014). Studies have provided evidence that reactivation and active replication of EBV may be causative in NMOSD (Masuda et al., 2015; Mori, 2015).