Autoimmune AQP4 Channelopathy and Bradycardia: Expanding the NMOSD Spectrum (P5.306)

Objectives: To report bradycardia as an accompaniment of “attacks” in Neuromyelitis Optica (NMO) Spectrum Disorder (NMOSD).Background: Attacks of intractable nausea, vomiting and hiccups in NMOSD may be the heralding symptom in up to 12[percnt] of patients. Area postrema (AP) is rich in aquaporin-4(AQP4) and has fenestrated capillaries allowing the free passage of peripheral IgG. Binding of AQP4-IgG causes inflammatory non-destructive lesions, potentially disrupting the AP’s connections with brainstem/hypothalamic areas involved in autonomic and endocrine regulation.Design: We searched our clinical database of 728 seropositive NMOSD patients for history of bradycardia concurrent with a clinical “attack”.Results: Thirteen (1.8[percnt]) NMOSD patients (10 females, 3 males) reported bradycardia occurring in the context of an “attack”. Clinical information pertaining to attack type at time of bradycardia was available in 11 patients. A majority of patients (7) developed bradycardia in the setting of an attack of nausea, vomiting or hiccups: alone in 2 or in combination with other manifestations in 5 [at least 1 of longitudinally extensive transverse myelitis (LETM, 3), optic neuritis (ON, 2), SIADH (1), ataxia/diplopia (1) or amenorrhea (1)]. The remaining 4 patients developed bradycardia in the context of ON (2), LETM (1) or LETM with hypophagia (1). Bradycardia developed during the onset attack in 5 patients (45[percnt]). Bradycardia was complicated by hypotension in 3 patients (all with nausea, vomiting or hiccups), severe enough to warrant ICU admission in 1.Conclusions: Bradycardia encountered in nearly 1 in 50 NMOSD patients mostly occurred concurrent with symptoms reflecting AP involvement. Astrocytes at the level of the nucleus tractus solitarius (NTS) may play a role in modulating baroreflex function. We suspect that binding of IgG to AQP4 leads to disruption of astrocyte function including glutamate buffering, thereby contributing to the high prevalence of bradycardia via excitatory effects of the NTS on caudovagal neurons. Disclosure: Dr. Majed has nothing to disclose. Dr. Lucchinetti stands to receive royalty payments for commercial assays. Dr. Benarroch has received personal compensation in an editorial capacity for being a section editor for Neurology. Dr. Sagen has nothing to disclose. Dr. Pittock has received (royalty or license fee or contractual rights) payments from Peripherin-Specific Autoantibodies as a Marker for Neurological and Endocrinological Disease.