Common and Rare Manifestations of Neuromyelitis Optica Spectrum Disorder

Abstract

The discovery of a highly specific biomarker of neuromyelitis optica (NMO)-the anti-aquaporin-4 (AQP4) antibody-has opened new paths to understanding disease pathogenesis and afforded a way to confirm the diagnosis in clinical practice. An important consequence of the discovery is the broadening of the spectrum of syndromes seen in the context of AQP4 autoimmunity. These syndromes have been subsumed under the rubric of NMO spectrum disorder (NMOSD). The current classification recognizes not only optic neuritis and myelitis as core syndromes of NMOSD but also cerebral, diencephalic, brainstem, and area postrema syndromes. These neurologic syndromes are the focus of our review. AQP4 is also expressed in many organs outside of the central nervous system, and this may explain some of the unusual, non-neurologic features that have been occasionally reported in NMOSD. Our review catalogues non-neurologic manifestations seen in NMOSD and concludes with a discussion of frequently associated autoimmune and neoplastic comorbidities of NMOSD.

Neuroimmunological Implications of AQP4 in Astrocytes

“…Another AQP4-autoimmunity disease, NMO-spectrum disorder (NMOSD), classifies, not only optic neuritis and myelitis as NMO, but also cerebral, diencephalic, brainstem, and area postrema syndromes [52,53]. Furthermore, non-neurologic features involving other AQP4-positive organs outside of the CNS have also been reported for NMOSD.…”

Complexity and wide range of neuromyelitis optica spectrum disorders: more than typical manifestations

“… 103 It is a well-established fact that AQP4 is not only mainly expressed in astrocytes within the CNS, but also in diverse organs such as the stomach, skeletal muscle, inner ear, and kidneys. 17 , 104 Thus, AQP4-IgG may inhibit the production of intrinsic factor and gastric acid secretion by parietal cells with resultant vitamin B12 malabsorption. In summary, the presence of AQP4 receptors outside the CNS may help explain some of the unusual features of NMOSD.…”

“…In this vein, we have begun to recognize several rare but possible manifestations and overlapping autoimmune diseases in patients with NMOSD. 17 However, these symptoms and comorbid conditions in patients with NMOSD have not aroused much concern among clinical neurologists. This review attempts to present a new message and summarize the present state of knowledge on these significant atypical presentations and comorbid conditions in patients with NMOSD.…”

Area postrema lesion as a cause of intractable nausea, vomiting and hiccups in neuromyelitis optica spectrum disorders

“…Клинические проявления у пациентов с антителами к аквапорину-4 могут быть представлены не только признаками поражения спинного мозга (продольно-распространенный миелит) и зрительных нервов (оптический неврит), но и признаками поражения дна IV желудочка и area postrema (неукротимая икота, тошнота, рвота), ствола головного мозга (глазодвигательные нарушения, снижение слуха и головокружение), диэнцефальной области (нарколепсия, гиперсомния, гипотермия, снижение массы тела и другие эндокринные нарушения). Для всех указанных синдромов характерна высокая экспрессия аквапорина-4 [8].…”

“…Синдром поражения area postrema и дна IV желудочка в виде неукротимой икоты, тошноты и рвоты является третьим по частоте клиническим проявлением спектра оптикомиелит-ассоциированных расстройств после миелита и оптического неврита [9]. В 2015 г. были опубликованы диагностические критерии заболеваний спектра оптикомиелита, согласно которым поражение зоны area postrema является основным клиническим проявлением.…”