Refractory Nausea and Vomiting Due to Central Nervous System Injury: A Focused Review

Abstract

The area postrema (AP) is a circumventricular organ (CVO) at the base of the fourth ventricle. It has a crucial role in regulating nausea and vomiting due to its unique blood-brain barrier (BBB)-permeability and extensive neural connectivity. Here, we present two cases of area postrema syndrome (APS), a rare condition of intractable nausea and vomiting resulting from direct AP injury. Our cases each occurred in the context of infratentorial neoplasms or their treatment. Using these cases as a framework, we review the literature on central emetic pathways and propose a treatment algorithm for managing refractory nausea and vomiting of central origin. We also highlight other targets beyond conventional serotonergic, dopaminergic, or histaminergic blockade and their roles in central hyperemesis. Our literature review suggests that APS is due to the disruption of the baseline inhibitory tone of outgoing AP signals. When other options fail, our algorithm culminates in the off-label use of combined serotonergic and neurokinin-1 blockade, which is otherwise used to manage chemotherapy-induced nausea and vomiting (CINV). We believe multimodal CNS receptor blockade is efficacious in APS because it addresses the underlying central neural dysregulation, rather than solely targeting peripheral emetic triggers.

Keywords: area postrema syndrome; chemotherapy; circumventricular organ; nausea; neuromyelitis optica; nucleus tractus solitarius; vomiting.

Figure 1

Pre- and post-operative magnetic resonance imaging (MRI) of two patients with posterior fossa neoplasms. (A) Pre-operative T2 sequence of Patient 1, showing a 1.9 × 1.5 cm ovoid mass in the right cerebellar hemisphere extending into the fourth ventricle. (B) Post-operative T2 FLAIR image showing postsurgical changes with pontine and medullary hyperintensity. (C) Pre-operative T2 from Patient 2 showing an iso-intense mass partially obstructing the fourth ventricle and extending from the cerebellar vermis. (D) Post-operative T2 showing postsurgical volume loss of the inferior vermis.

Figure 2

Proposed step-wise treatment algorithm for refractory nausea and vomiting caused by a lesion to CNS vomiting centers.