All Trans Retinoic Acid: A Cerebral Friend or Foe?
Ryan Pinosky1, Ezekiel Gonzalez-Fernandez, MD, PhD2, Chandra Mannyam, MD2, Maryam Zulfiqar, MD2, Oriana Sanchez, MD2, Shreyas Gangadhara, MD, MS, RPNI2
1University of Mississippi School of Medicine, 2Department of Neurology, University of Mississippi Medical Center
Objective:
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Background:
All-trans retinoic acid (ATRA) is an initial treatment for acute promyelocytic leukemia (APL). Studies suggest that ATRA has neuroprotective effects since it reduces atherosclerosis and neural inflammation. We present a case series of patients that developed acute recurrent ischemic strokes and demonstrated rapid progression of intracranial and extracranial stenosis in the setting of ATRA therapy.
Design/Methods:
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Results:

Case 1: A 47-year-old female with a history of hypertension presented with symptoms concerning for myocardial infarction, deep venous thrombosis, and thrombocytopenia which led to a diagnosis of APL. She was treated with ATRA and two days later developed left gaze deviation, facial droop, and left hemiparesis. Vessel imaging revealed a right middle cerebral artery (MCA) occlusion. Despite successful thrombectomy, the patient continued to decline. Repeat imaging showed re-occlusion of the right MCA as well as a new left MCA infarct. She later developed diffuse cerebral edema and fatal herniation. 

 
Case 2: A 41-year-old female with a history of hypertension and APL treated with ATRA had multiple recent strokes involving bilateral frontal, left occipital and watershed territories. Vessel imaging during the first admission did not show any stenosis. Over the course of the next seven months, she had multiple admissions for recurrent strokes with rapid progression and worsening of her intracranial stenosis despite dual antiplatelet and statin therapy. Cerebrospinal fluid analysis including cell count, protein, cytology and flow cytometry was unremarkable. She subsequently developed extensor posturing with paraparesis due to malignant cerebral edema and died.

Conclusions:

The underlying mechanism of accelerated vessel stenosis in the above cases is unknown. Further research should explore whether ATRA use in APL is indeed associated with the progression and/or poor clinical outcomes in the setting of acute ischemic stroke. Clinicians should remain vigilant about the concomitant use of ATRA in patients with a history of vascular risk factors.

10.1212/WNL.0000000000203309