Purpose of Review <p>A subset of patients with headache disorders presents with a dyscapnic state typically clinically symptomatic chronic respiratory alkalosis (CSCRA).</p> <p>CSCRA is well described as an important factor in increased neuromuscular irritability and reduces tissue oxygen delivery through reduction of cerebral blood flow (vasospasm) and left shift of the oxygen-hemoglobin dissociation curve, as well as increasing metabolic tissue oxygen demand all thought to be important factors in headache disorders.</p> Recent Findings <p>Novel testing paradigms that allow assessment of hypoxemia / orthodeoxia-platypnea include hypoxic echocardiography with bubble contrast to diagnose clinically significant right to left shunts (RLS). RLS (commonly through a patent foramen ovale (PFO)) is associated with migraine, particularly migraine with aura.</p> <p>We evaluate patients with an in-depth acid base analysis (including arterial blood gas analysis, comprehensive metabolic profile and urinalysis) and then pursue diagnostic evaluation of potential causative factors. Common causes of CSCRA include sleep disordered breathing, RLS (anatomic and capillary shunting), post-concussive states as well as post-viral or postoperative derangements of acid base status and associated with altered autonomic function.</p> Summary <p>A focused diagnostic approach to discern the root cause for CSCRA may uncover treatable causes such as hypoxemia secondary to RLS or lung disease, sleep disorders and diaphragmatic dysfunction.</p> <p>The time-limited intervention with carbonic anhydrase to normalize acid base status and tissue carbon dioxide stores, as well as rehabilitation measures to normalize breathing patterns serve to normalize the acid base status, reduce neuromuscular irritability and reduce symptoms including headache.</p>