Central Dysregulation of Heart Rate and Blood Pressure in Autoimmune AQP4 Channelopathy: Expanding the neuromyelitis optica spectrum disorder (NMOSD). (S20.008)

Objective: To report heart-rate and blood-pressure dysregulation as novel accompaniment of the NMOSD-attack. Background: Since the discovery of AQP4-IgG as the pathogenic biomarker of NMO, there has been an expansion of the clinical spectrum of NMOSD. Design/Methods: Case reports Results: Patient #1 presented with symptoms of an area-postrema (nausea, vomiting and hiccups [NVH]) and cervical-cord attack, as well as a single episode of syncope. MRI revealed areas of signal abnormality in area-postrema and posterior cervical-cord. During hospitalization, she had marked lability of blood-pressure (monitored over 15 days) with hypotensive events requiring fluid replacement. Patient #2 also presented with area-postrema symptoms (NVH) as well as symptomatic bradycardia and hypotension requiring ICU admission for cardiac monitoring. MRI-head also demonstrated signal abnormality in the area-postrema. In contrast, patient #3, presented with a severe cervicothoracic LETM without NVH or area-postrema lesions on MRI. She had severe tachycardia and labile blood-pressure requiring 14 days of cardiac monitoring. In contrast to the first two patients, she had urinary incontinence during the attack, reflecting involvement of descending autonomic pathways in the lateral spinal cord. In all cases both heart-rate and blood-pressure normalized after the acute episode. Conclusions: We hypothesize that in patients #1 and #2, area-postrema lesions could have extended to the surrounding NTS, which has a critical role in baroreflex control of blood-pressure and heart-rate via its projections to the nucleus ambiguus and ventrolateral medulla. Hyperactivity of baroreceptive NTS neurons due to inflammatory mediators, impaired synaptic homeostasis, or both, would have triggered cardiovagally mediated bradycardia and sympathoinhibition resulting in hypotension. In contrast, bilateral involvements of the descending autonomic pathways in patient #3, would have interrupted the descending modulation of preganglionic sympathoexcitatory cardiovascular neurons resulting in labile blood-pressure and tachycardia. Cardiovascular dysregulation may therefore be a prominent manifestation of an NMO-attack. Disclosure: Dr. Majed has nothing to disclose. Dr. Benarroch has received personal compensation in an editorial capacity for being a section editor for Neurology. Dr. Lucchinetti has received royalty payments for aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica. Dr. Krecke has nothing to disclose. Dr. Sagen has nothing to disclose. Dr. Guo has nothing to disclose. Dr. Costanzi has nothing to disclose. Dr. Pittock9s institution has received compensation for Dr. Pittock9s activities with Alexion Pharmaceuticals, Medimmune and Chugai Pharma USA. Dr. Pittock and Dr. Pittock9s institution stand to receive patent payments that relate to patents for functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker. Dr. Pittock has received research support from NIH, Alexion Pharmaceuticals and Medimmune related to autoimmune NMO/AQP4 channelopathy.