Nilotinib as an Independent Risk Factor for Stroke by Accelerated Atherosclerosis

Abstract

Nilotinib, a tyrosine kinase inhibitor (TKI) used in patients of chronic myeloid leukemia (CML), has been known to cause atherosclerosis and arterial stenosis as a rare complication of long-term or high-dose therapy. Patients in this group are more likely to have coronary or peripheral artery disease; intracranial involvement is comparatively uncommon. Furthermore, studies on nilotinib-induced ischemia in Indian populations are scarce. Here, we present a case of ischemic stroke in a patient on long-term nilotinib treatment who, prior to treatment, had no risk factors for stroke. He presented with subacute symptoms of ataxia, motor and sensory deficit, and a raised low-density lipoprotein. MRI revealed multifocal arterial stenosis, as well as areas of infarction and hypoperfusion in the left cerebral hemisphere. Nilotinib therapy was immediately stopped; the patient was treated with dual antiplatelets, statins, and physiotherapy, and he had no major focal deficits on discharge. However, this case serves as a good reminder that even for patients considered to be largely safe from cardiovascular adverse events, regular monitoring of cardiovascular parameters is important so that timely preventive action can be initiated if necessary.

Keywords: chronic myeloid leukemia (cml); drug-induced stroke; long term chemotherapy; multifocal intracranial atherosclerosis; nilotinib; vascular adverse effects; young stroke.

Figure 1. MRI showing areas of brain infarcts

Acute left posterior cerebral artery territory infarcts are seen involving the left occipital lobe, left temporal region along para-hippocampal gyrus, left crus of midbrain, and left red nucleus. This is seen in (A) diffusion-weighted imaging, (B) apparent diffusion coefficient,  and (C) fluid-attenuated inversion recovery images.

Figure 2. MRA of intracranial arteries

(A) Focal high-grade stenosis is seen in the left supraclinoid ICA (blue arrow) causing 70-80% narrowing. The right supraclinoid ICA also showing moderate 40-50% narrowing (orange arrow) and focal moderate narrowing in the proximal M1 segment of right MCA (yellow arrow). (B) Focal occlusion of the P1 segment of left PCA (pink arrow). MRA: magnetic resonance angiography; PCA: posterior cerebral artery; ICA: internal carotid artery; MCA: middle cerebral artery