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Eculizumab in aquaporin\4\positive neuromyelitis optica spectrum disorder. the spinal cord. Other lesions described in NMOSD, including linear periventricular peri\ependymal lesions and patch subcortical white matter lesions, may be less specific. The use of advanced MR imaging techniques is usually yielding further useful information regarding focal degeneration of the thalamus and optic radiation in NMOSD and suggests that paramagnetic rim patterns and changes in normal appearing white matter are specific to MS. MR imaging is crucial in the early recognition of NMOSD and in directing testing for AQP4 antibodies and guiding immediate acute treatment decisions. Increasingly, MR imaging is usually playing a role in diagnosing seronegative cases of NMOSD. Keywords: diagnosis, magnetic resonance imaging, multiple sclerosis, neuromyelitis optica This review summarises the clinical and radiological aspects of AQP4 antibody positive NMOSD focusing on the implication for pathophysiology. Common MR imaging features of NMOSD are reviewed in detail and illustrated. The potential future role of advanced MR imaging techniques in diagnosing and characterising NMOSD are discussed. INTRODUCTION Historical perspective A distinct clinical pattern of demyelination affecting optic nerves and spinal cord associated with a characteristically destructive pathological picture was first described more than 150 years ago [1, 2, 3]. What became known as Devics disease or neuromyelitis optica (NMO) remained ambiguous, regarded by some as an extreme variant of multiple sclerosis (MS) and by others as a separate disease state, until 2004 when Lennon and colleagues highlighted an association between cases of longitudinally extensive transverse myelitis with optic neuritis and antibodies with a specific staining pattern on suitably prepared samples of mouse brain and kidney [4]. These NMO immunoglobulin (Ig)G antibodies were subsequently demonstrated to bind to the aquaporin\4 (AQP4) water channel and have become for NMO spectrum disorder (NMOSD) [5]. Interestingly, some of the cases described by Devic, particularly those with simultaneous or sequential transverse myelitis in younger adults, may have had antibodies to myelin oligodendrocyte glycoprotein (MOG) and what is now referred to as MOG antibody\associated disease (MOGAD) [6]. The spectrum of disease associated with AQP4 antibodies has spread MDRTB-IN-1 to encompass area postrema, hypothalamic and diencephalic syndromes, as well as encephalitic presentations [7]. In contrast, MOGAD includes acute disseminated encephalomyelitis (ADEM) presentations (particularly in paediatric populations), focal encephalitic presentations and frequent optic neuritis in a clinical picture that previously would have been difficult MDRTB-IN-1 to MDRTB-IN-1 distinguish from MS, as well as longitudinally extensive transverse myelitis [8]. It will be apparent that these two antibody\mediated central nervous system (CNS) inflammatory diseases share clinical overlap with MS and other disorders that can affect the optic nerves and spinal cord, such as neurosarcoidosis [9] and chronic relapsing idiopathic optic neuritis (CRION) [10]. Isolating antibodies has become essential in diagnosing antibody\mediated CNS inflammatory diseases. However, false\positive and \unfavorable results remain a problem. For example, if used as a screening test in all cases of CNS inflammatory disease, where in populations of European ancestry MS outnumbers antibody\mediated disease by at least 50:1 MDRTB-IN-1 [11], false\positive assessments may lead to inappropriate management and skew epidemiological data. Consequently, clinical features and other ancillary assessments, magnetic resonance imaging (MRI) in particular, remain extremely important in raising suspicion for these diagnoses. For the purposes of this narrative review, we will concern ourselves only with MRI features of AQP4 antibody\positive NMOSD and will refer to this as NMOSD throughout. Clinical features The clinical hallmarks of Col4a3 NMOSD are attacks of optic neuritis (severe, painless, bilateral or sequential with poor recovery), transverse myelitis (severe, bilateral and involving motor, sensory and sphincteric control pathways, sometimes with pain and pruritus), area postrema syndrome (persistent nausea, vomiting and hiccoughs), acute brain stem syndromes (cranial nerve palsies, ataxia and limb weakness), diencephalic syndromes (narcolepsy, hypothermia, daytime somnolence and obesity) and cerebral syndromes (encephalopathy and seizures) [12]. Attacks of optic neuritis tend to occur earlier in the disease course [13]. Acute myelitis (partial or complete) and optic neuritis predominate with other types of attack being less common [13]. The attacks occur more frequently and brain stem/cerebellar presentations are relatively less common compared to MS [14]. Without treatment to prevent further attacks the prognosis in NMOSD is generally worse than it is in MS [14, 15]. Serological markers The discovery of antibodies to AQP4 in NMOSD has been integral to developing a greater understanding of the pathophysiology of NMOSD and also have helped to recognize specific patterns in MR [16] and ocular computed.