Stroke in Middle Eastern children with cancer: prevalence and risk factors

Abstract

Objective To determine the prevalence and to characterize the different types of strokes in children with cancer at the Children’s Cancer Center of Lebanon (CCCL), in addition to assess the factors and clinical findings leading to stroke in children. Methods We retrospectively reviewed the medical records and brain images (MRIs and CTs) of children admitted to the CCCL and diagnosed with cancer between years 2008 and 2017. Brain images were reviewed for the strokes’ onset, size, location, possible origin, its recurrence and type: intracranial hemorrhage (ICH), acute arterial ischemic stroke, and cerebral sinus venous thrombosis (CSVT) with and without venous infarct. Medical charts of the patients were reviewed for age, sex, their type of cancer, the treatment protocol they followed, and abnormal findings on their laboratory studies and neurological exams. Results Out of the 905 charts reviewed, twenty-seven children with variable types of cancer had strokes, with a prevalence of 2.9%. Their median age at cancer diagnosis was 9.4 (4.8-13.7) years and the median age at stroke onset was 10.6 (6.7-15.5) years. The median time between the cancer diagnosis and the stroke episode was 6 months. CSVT cases were the most common (60%) followed by acute arterial ischemic (22%) and hemorrhagic strokes (18%), with CSVT being the latest to occur. We observed that the different types of strokes were related to some types of cancer. Of the children that had acute arterial ischemic stroke in this cohort, 83% had brain tumors, of the children who had CSVT, 87.5% had leukemia, and of the children who had hemorrhagic stroke, 40% had leukemia. Neurological abnormalities were more prevalent in acute arterial ischemic stroke (80%). Patients with CSVT recovered better than those with other types of strokes. Strokes recurred in 60% of ischemic strokes. L-Asparaginase was significantly associated with CSVT. Conclusions The prevalence of strokes was 2.9% in children with cancer. We were able to identify factors related to the types of the stroke that occurred in children including the type and location of the cancer the type of treatment received, and stroke recurrence.

Stroke in Pediatric Cancer Patients: A Systematic Review

“…In Sun et al, 12 a prothrombotic state was the most frequently identified risk factor in patients with CSVT, especially after asparaginase treatment. In the study by Zadeh et al, 15 half of the patients had coagulation abnormalities, with a history of asparaginase use in all the patients with CSVT. Other potential risk factors proposed were high initial white blood cell (WBC) count (median in ICH group of 374,925/mm 3 ), high peripheral blast cell count (median of 96%), and high initial lactate dehydrogenase level (median of 4140 mg/dL) 10 .…”

“…Three studies (Santoro et al, 13 Kuskonmaz et al, 11 and Intusoma et al 10 ) focused their research on stroke only in ALL patients. The other 3 studies included a mixed oncology population: Kyrnetskiy et al 14 (ALL, lymphoma, chronic myeloid leukemia, and brain tumors), Zadeh et al 15 (brain tumors, lung tumors, ALL, and lymphoma), and Noje et al 5 (ALL, lymphoma, and brain tumors). Campen et al 9 only analyzed patients with brain tumors, and Sun et al 12 did not report incidence.…”

“…Both had AIS, and the recurrence episode was new AIS in 1, and ICH in the other. Zadeh et al 15 described a stroke recurrence rate of 19% (1 patient with hemorrhagic stroke and 3 patients with CSVT).…”

“…This is particularly expected in these patients because of an overproduction of inflammatory cytokines, high WBC count, high blast counts, hyperviscosity, and higher probability of coagulopathy. l -asparaginase plays a major role as well in the occurrence of stroke in leukemia patients, especially in those with CSVT 15,17 . Asparaginase depletes asparagine, inhibiting protein synthesis of many plasma proteins including anticoagulation factors 18 .…”

“…Santoro et al 13 Noje et al 5 Kuskonmaz et al 11 Intusoma et al 10 Sun et al 12 Campen et al 9 Zadeh et al 15 Kyrnetskiy et al…”