Sildenafil-Induced Cervical Spinal Cord Infarction

Discussion

Infarction of the cervical spinal cord is exceptionally rare due to its rich anastomotic arterial network.⁴ In the upper cervical spine, blood cord supply is from the vertebral arteries and the posterior inferior cerebellar arteries. Below the upper cervical levels, the anterior and posterior spinal arteries become narrow in caliber and form an anastomotic network with radicular arteries. These radicular arteries arise from the subclavian artery via the ascending cervical branch of the thyrocervical trunk or via the deep cervical branch of the costocervical trunk.¹ This anastomotic network contributes to the vascularization of the lower cervical and upper thoracic cords.¹ The blood supply of the anterior spinal artery is at its most marginal in the upper thoracic region, T2-T4; thus, this watershed zone is vulnerable to hypotension.^1,6 Additionally, the pattern of cervical radicular arteries suggests a minor watershed zone at C4.¹ The pattern of our patient's spinal cord infarct corresponded to these watershed zones, with his cord infarct spanning C4-T1.

After other etiologies were excluded as the source of our patient's cord infarct, we concluded that the cause was the combined simultaneous use of sildenafil citrate and hydrochlorothiazide. This drug combination likely led to systemic hypotension, resulting in cord infarction in the watershed zones of the cervical and upper thoracic cord. Reported cardiovascular side effects of sildenafil citrate are usually minor and associated with vasodilation, leading to small decreases in systolic and diastolic blood pressures.⁷ Sildenafil typically produces a transient 8- to 10-mm Hg reduction in systolic blood pressure and a 5- to 6-mm Hg reduction in diastolic blood pressure. This transient reduction in blood pressure generally returns to baseline 4 hours later. Sildenafil may be hazardous to patients on multidrug antihypertensive drug regimens. Although the significant risk of potentially life-threatening hypotension with coadministration of nitrates and sildenafil is well-known, to our knowledge, no formal drug-drug interaction studies have been conducted with sildenafil and hydrochlorothiazide. The effects of sildenafil may be augmented by hypotension caused by nitrates, drugs that inhibit its metabolism, and comorbidities that increase its levels such as kidney/liver diseases.⁸ Transient ischemic attacks, transient global amnesia, and ischemic optic neuritis have been reported to occur after sildenafil use.^9⇓⇓–12 The addition of other drugs, such as hypoglycemic agents, to sildenafil may result in diffuse cerebral anoxia.¹³ Intracerebral and subarachnoid hemorrhages and seizures have been reported with sildenafil.⁸

In conclusion, the possibility that rarely sildenafil, particularly in combination with other drugs, may cause significant neurologic abnormalities, including spinal cord infarction, must be kept in mind.