To report a less known association of a frequently used medication with posterior reversible encephalopathy syndrome (PRES). 

Hypomagnesemia is a well-known complication of proton pump inhibitor (PPI). Magnesium exerts effects on vasculature by stabilization of smooth muscle membrane potential. Hypomagnesaemia can cause destabilization of these potentials, resulting in vasospasm, endothelial dysfunction, cerebral edema, and as proposed here, PRES. Hypomagnesemia can present with a variety of symptoms including seizure, cardiac arrhythmias, and neurological deficits.

A 42 year-old male presented with severe headache, dizziness, anorexia, dyspepsia and nausea. His medication list was notable for chronic use of PPI, omeprazole 40 mg daily. Laboratory studies revealed a calcium of 6.5 mg/dl, magnesium 0.4mg/dl and phosphorus of 3.8 mg/dl. A repeat calcium was 5.5 mg/dl, urinary calcium <5.0 mg/dl. Fractional urinary excretion of magnesium was 0.2%. A PTH level was normal. Brain MRI showed bilateral cerebellar vasogenic edema. The differential diagnosis included PRES versus acute cerebellitis. EBV, Bartonella and Lyme serology were negative. ANA was negative. Patient was diagnosed with PPI induced hypomagnesemia and omeprazole was discontinued. Magnesium was replaced to optimal levels and calcium level rapidly normalized. His symptoms quickly resolved. A repeat MRI showed significant improvement in the cerebellar edema.

PPIs can cause hypomagnesemia. Impaired active absorption of magnesium by intestinal epithelial cells is caused by inhibition of transient receptor potential melastatin TRPM6 and TRPM7 channels. In addition, hypomagnesemia impairs release of PTH and decreases peripheral tissue sensitivity to PTH leading to secondary hypoparathyroidism. Our patient’s presentation and MRI findings of cerebellar vasogenic edema rapidly responding to magnesium repletion are compatible reversible cerebellar findings due to PPI induced hypomagnesemia. Severe hypomagnesemia is an easily identifiable and treatable cause of PRES with potential life threatening consequences. Thus, early magnesium level check is recommended in patients with chronic PPI use and neurological symptoms.