The expanded spectrum of neuromyelitis optica: evidences for a new definition

Abstract

Neuromyelitis optica (NMO) has been traditionally described as the association of recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM). Identification of aquaporin-4 antibody (AQP4-IgG) has deeply changed the concept of NMO. A spectrum of NMO disorders (NMOSD) has been formulated comprising conditions which include both AQP4-IgG seropositivity and one of the index events of the disease (recurrent or bilateral optic neuritis and LETM). Most NMO patients harbor asymptomatic brain MRI lesions, some of them considered as typical of NMO. Some patients with aquaporin-4 autoimmunity present brainstem, hypothalamic or encephalopathy symptoms either preceding an index event or occurring isolatedly with no evidence of optic nerve or spinal involvement. On the opposite way, other patients have optic neuritis or LETM in association with typical lesions of NMO on brain MRI and yet are AQP4-IgG seronegative. An expanded spectrum of NMO disorders is proposed to include these cases.

Review of the Etiological Causes and Diagnosis of Myelitis and Its Medical Orientation Protocol

“…1: Lesions present in up to 60% of patients [9]; 2: Lesions located periventricular zone and brainstem a (involving more frequently its central and dorsal aspects [28]). 3: Lesions localized at sites of high AQP4 expression such as in hypothalamus a [28] .…”

“…3: Lesions localized at sites of high AQP4 expression such as in hypothalamus a [28] . 4: Corticospinal tract lesions frequently bilateral involving the posterior limb of the internal capsule and the cerebral peduncle a [28]. 5: Lesions lining the ependymal surface of the lateral ventricles a [28].…”

“…4: Corticospinal tract lesions frequently bilateral involving the posterior limb of the internal capsule and the cerebral peduncle a [28]. 5: Lesions lining the ependymal surface of the lateral ventricles a [28]. 6: Acute phaselarge edematous and heterogeneous lesions in the corpus callosum; Chronic phase -reduction in their size and intensity or even its disappearance a [28].…”

“…5: Lesions lining the ependymal surface of the lateral ventricles a [28]. 6: Acute phaselarge edematous and heterogeneous lesions in the corpus callosum; Chronic phase -reduction in their size and intensity or even its disappearance a [28].…”

Seronegative Neuromyelitis Optica Spectrum - The challenges on disease definition and pathogenesis

“…Currently, the diagnosis of NMOSD is usually suspected in patients with the following phenotypes: monophasic or recurrent NMO, monophasic or recurrent longitudinally extensive transverse myelitis (LETM) that extends over three or more vertebral segments, and bilateral simultaneous or recurrent ON 6 . Although many patients have no lesions outside the optic nerve and spinal cord, several reports confirmed that NMOSD patients might also have some characteristic brain or brainstem lesions for NMO 7,8,9,10 , resulting in proposed diagnostic criteria that includes more features now considered typical for NMOSD 11 . Serum antibodies against aquaporin-4 (AQP4) are present in the majority of NMOSD patients and its discovery clearly segregated NMOSD from multiple sclerosis (MS) 12 .…”