Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are immune-mediated inflammatory conditions of the central nervous system that frequently involve the optic nerves and the spinal cord. Because of their similar clinical manifestations and habitual relapsing course they are frequently confounded with multiple sclerosis (MS). Early and accurate diagnosis of these distinct conditions is relevant as they have different treatments. Some agents used for MS treatment may be deleterious to NMOSD. NMOSD is frequently associated with antibodies which target aquaporin-4 (AQP4), the most abundant water channel in the CNS, located in the astrocytic processes at the blood-brain barrier (BBB). On the other hand, anti-MOG syndromes result from damage to myelin oligodendrocyte glycoprotein (MOG), expressed on surfaces of oligodendrocytes and myelin sheaths. Acute transverse myelitis with longitudinally extensive lesion on spinal MRI is the most frequent inaugural manifestation of NMOSD, usually followed by optic neuritis. Other core clinical characteristics include area postrema syndrome, brainstem, diencephalic and cerebral symptoms that may be associated with typical MRI abnormalities. Acute disseminated encephalomyelitis and bilateral or recurrent optic neuritis are the most frequent anti-MOG syndromes in children and adults, respectively. Attacks are usually treated with steroids, and relapses prevention with immunosuppressive drugs. Promising emerging therapies for NMOSD include monoclonal antibodies and tolerization.

The relationship between Sjögren’s syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.

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.