Glucocorticoid-associated worsening in reversible cerebral vasoconstriction syndrome

Abstract

Objective: Factors predicting poor outcome in patients with the reversible cerebral vasoconstriction syndrome (RCVS) have not been identified.

Methods: In this single-center retrospective study, we analyzed the clinical, brain imaging, and angiography data in 162 patients with RCVS. Univariable and multivariable regression analysis were performed to identify predictors of persistent (nontransient) clinical worsening, radiologic worsening, early angiographic progression, and poor discharge outcome (modified Rankin Scale score 4-6).

Results: The mean age was 44 ± 13 years; 78% of patients were women. Persistent clinical worsening occurred in 14% at 6.6 ± 4.1 days after symptom onset, radiologic worsening in 27% (mainly new infarcts), and angiographic progression in 15%. Clinical worsening correlated with angiographic progression and new nonhemorrhagic lesions. Age and sex did not independently predict any type of worsening. Infarction on baseline imaging predicted poor outcome. Prior serotonergic antidepressant use predicted clinical and angiographic worsening but not poor outcome. Intra-arterial vasodilator therapy independently predicted clinical worsening and poor discharge outcome but was offered to more severe cases. Glucocorticoid treatment proved to be an independent predictor of clinical, imaging, and angiographic worsening and poor outcome. Of the 23 patients with clinical worsening, 17 received glucocorticoids (15 within the preceding 2 days). There were no significant differences in baseline brain lesions and angiographic abnormalities between glucocorticoid-treated and untreated patients.

Conclusion: Patients with RCVS at risk for worsening can be identified on basis of baseline features. Iatrogenic factors such as glucocorticoid exposure may contribute to worsening.

Figure 1. Clinical, radiologic, and angiographic worsening in reversible cerebral vasoconstriction syndrome (RCVS)

A 43-year-old woman with malabsorption syndrome, on parental nutrition, was hospitalized for treatment of port-a-cath infection. On day 2, she developed a thunderclap headache. Head CT and CSF examination were normal. Hydrocortisone 100 mg three times daily was administered for suspected adrenal insufficiency and sepsis. On day 4, brain MRI fluid-attenuated inversion recovery (FLAIR) images showed multiple dot and linear shaped sulcal hyperintensities suggesting dilated cortical surface arteries (A.a) and subtle bilateral white matter vasogenic edematous lesions (A.b) consistent with posterior reversible encephalopathy syndrome (PRES). Headaches recurred, and on day 7 she developed cortical blindness. Head CT angiography (A.c) showed segmental narrowing of multiple intracranial arteries. Brain MRI showed new PRES lesions and progression of prior PRES lesions (B.a, B.b). She was transferred to our hospital. Neurologic examination showed features of the Balint syndrome and aphasia. Repeat CT angiography showed worsening cerebral vasoconstriction (B.c). Hydrocortisone was tapered to 25 mg twice daily; nimodipine and magnesium were administered for suspected RCVS. Repeat MRI on day 9 showed new bilateral ischemic lesions on diffusion-weighted images (C.a), persistent PRES (C.b), and stable cerebral vasoconstriction (C.c). The port-a-cath infection was successfully treated. She was discharged on day 19 on oral prednisone 5 mg daily and nimodipine. Follow-up imaging on day 42 showed established infarctions on FLAIR images (D.a), reversal of PRES lesions (D.b), and resolution of vasoconstriction (D.c). Neurologic examination showed no residual deficits.

Figure 2. Relationship between clinical worsening and glucocorticoid treatment (± intra-arterial [IA] therapy)

Cumulative event rate curves show the time of clinical progression with or without glucocorticoid and IA vasodilator treatment. Circles along the curves depict individual patients. Circles are colored according to the patient's eventual discharge modified Rankin Scale scores (mRS) as follows: white, mRS 0–3; gray, mRS 4–5; black, mRS 6 (death). White arrowheads reflect the day after reversible cerebral vasoconstriction syndrome (RCVS) onset when glucocorticoids were initiated. Gray arrowheads reflect the day after RCVS onset when IA vasodilator treatment was administered. The length of the dotted lines connecting arrowheads to circles reflects the interval between treatment and worsening.