Nontrauma-Associated Cerebral Fat Embolism Syndrome in Sickle Cell-Related Hemoglobinopathies: A Case Series and Systematic Review.

Background: Cerebral fat embolism (CFE) is frequently associated with long bone fractures and orthopedic procedures but can rarely occur without antecedent trauma. Nontrauma-associated CFE has been reported in patients with sickle cell-related hemoglobinopathies during sickle cell crises, presumably due to bone marrow infarction.

Purpose: To characterize the brain MRI features of nontrauma-associated CFE in patients with sickle cell-related hemoglobinopathies during the acute, subacute, and chronic phases after the onset of neurologic symptoms.

Data source: This was a combined case series and systematic review of MEDLINE, EMBASE, and Google Scholar databases up to April 2023. This systematic review was not registered with a review registry.

Study selection: Patients with sickle cell-related hemoglobinopathies who developed nontrauma-associated CFE were selected based on clinicopathologic evidence and brain MRI findings.

Data analysis: Clinical and radiologic data were reviewed.

Data synthesis: The systematic review included 26 studies and our 6 unpublished cases, totaling 33 cases of sickle cell-related hemoglobinopathies presenting with nontrauma-associated CFE (91 MRI examinations). Among the patients reviewed, the predominant hemoglobinopathy associated with nontrauma-associated CFE was hemoglobin SC disease (Hb-SC, 61.3%), followed by hemoglobin S/beta-thalassemia (22.6%), and homozygous sickle cell disease (Hb-SS 12.9%). Head CT scans were normal in 77% of the patients. The most frequently observed MRI feature during the acute phase was punctate foci of microhemorrhage (84.7% of cases), which persisted throughout the subacute (91%) and chronic phases (85.8%). The second most common MRI finding during the acute phase was scattered foci of restricted diffusion in a "starfield pattern" affecting both cerebral and cerebellar hemispheres (65.4% of cases), which typically was not observable after 5 days.

Limitations: The review was based on case reports and small case series, which are subject to reporting bias.

Conclusions: Brain imaging features of nontrauma-associated CFE in the setting of sickle cell-related hemoglobinopathies closely resembled those observed in trauma-related CFE. In patients with complex sickle cell-related hemoglobinopathies (Hb-SC and Hb-S/beta-thalassemia) exhibiting unexplained acute neurologic symptoms, radiologists should maintain a high index of suspicion for nontrauma-associated CFE, even with apparently normal initial head CT.