Blunted perception of breathlessness in three cases of low grade insular-glioma

Better understanding of breathlessness perception addresses an unmet clinical need for more effective treatments for intractable dyspnoea, a prevalent symptom of multiple medical conditions. The insular-cortex is predominantly activated in brain-imaging studies of dyspnoea, but its precise role remains unclear. We measured experimentally-induced hypercapnic air-hunger in three insular-glioma patients before and after surgical resection. Tests involved one-minute increments in inspired CO2, raising end-tidal PCO2 to 7.5 mmHg above baseline (38.5 +/- 5.7 mmHg), whilst ventilation was constrained (10.7 +/- 2.3 L/min). Patients rated air-hunger on a visual analogue scale (VAS). Patients had lower stimulus-response (2.8 +/- 2 vs. 11 +/- 4 %VAS/mmHg; p = 0.004), but similar threshold (40.5 +/- 3.9 vs. 43.2 +/- 5.1 mmHg), compared to healthy individuals. Volunteered comments implicated diminished affective valence. After surgical resection; sensitivity increased in one patient, decreased in another, and other was unable to tolerate the ventilatory limit before any increase in inspired CO2.We suggest that functional insular-cortex is essential to register breathlessness unpleasantness and could be targeted with neuromodulation in chronically-breathless patients. Neurological patients with insula involvement should be monitored for blunted breathlessness to inform clinical management.