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Maenia Scarpino,1 Giovanni Lanzo,1 Francesco Lolli,2 Antonello Grippo3 1Unit of Neurophysiopathology, Neuromuscolar Department, AOU Careggi, Florence, Italy; 2Neuroscience Department (NEUROFARBA), University of Florence, Florence, Italy; 3Intensive Rehabilitation Unit, IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy Abstract: Cerebral fat embolism (CFE) is an uncommon incomplete type of fat embolism syndrome (FES), characterized by purely cerebral involvement. It usually occurs 12–72 hours after the initial trigger, mainly represented by closed, long-bone multiple fractures of the lower extremities. Neurological manifestations are mainly characterized by headache, confusion, seizures, focal deficit, and alteration of the consciousness state up to coma onset. It represents a diagnostic challenge, above all when secondary to uncommon nontraumatic causes, because neurological signs and symptoms are variable and nonspecific, not satisfying the Gurd and Wilson’s criteria, the diagnostic features most widely used today for FES diagnosis. Neuroimaging (mainly MRI, but in some cases, brain computed tomography too) can hasten the diagnosis, avoiding other unnecessary investigations and treatment. Usually self-limiting, CFE may sometimes be fatal. Treatment is to date mainly supportive and prophylactic strategies are considered an important tool to decrease the development of fat embolism and, consequently, the rate of CFE. Keywords: cerebral fat embolism, neurological deterioration, neuroimaging, prophylactic strategies