DHE and ketamine are both known to be safe and effective abortive treatments for migraine pain. While DHE exhibits strong vasoconstrictive effect, ketamine increases sympathetic activity by inhibiting the neuronal reuptake of catecholamines. It is possible that ketamine and DHE together elicit a synergistic effect increasing the possibility of vasospasm causing RCVS/PRES.

We present a 63 year-old woman with a history of remote, small, cortical non-traumatic, non-aneurysmal subarachnoid hemorrhage, chronic migraine and medication overuse headache who used amitriptyline, duloxetine, and erenumab as migraine preventives along with oral morphine and ketamine nasal spray as home migraine abortives. In previous migraine inpatient treatments she received lidocaine infusion, intravenous DHE, neuroleptics, valproate, and steroid with no adverse effect. During this third admission, she received five days of subanesthetic ketamine infusion (up to 45 mg/hr) with adjunctive intravenous DHE, promethazine, methylpredinisone, and valproate. Following her 4^th dose of intravenous DHE (0.25mg) and first dose of valproate (500mg), she developed acute bilateral decreased visual acuity, optic ataxia, and unsteady gait. BP was 130/70mmHg. Brain MRI showed confluent bilateral T2 hyperintensities with punctate restricted diffusion in the occipital lobes consistent with PRES. Brain MRA showed multi-segmental narrowing involving anterior, middle, posterior cerebral, and basilar arteries consistent with RCVS. Verapamil was given and all ergots, neuroleptics, and serotonergic agents were stopped. Though she continued to have constant, non-thunderclap migrainous headache, her visual symptoms otherwise resolved in 24 hours and her exam returned to normal.

Concomitant use of ketamine infusion and DHE may result in RCVS/PRES especially in the setting of polypharmacy with medications that cause enzyme inhibition and protein binding displacement.