European Journal of Cardiovascular Medicine

Fat embolism syndrome (FES) is a well-recognized yet underdiagnosed complication of trauma, occurring in 0.9–2.2% of long bone fractures【1】. The classic triad of respiratory distress, neurological dysfunction, and petechial rash is seen in only a fraction of cases, making diagnosis challenging【2】. Cerebral fat embolism (CFE) represents a severe but often overlooked form of FES, with neurological manifestations ranging from mild confusion to seizures, coma, and even brain death【3】

The pathophysiology of CFE is explained by two primary mechanisms:

1. Mechanical theory – Fat droplets from disrupted bone marrow enter the systemic circulation and embolize cerebral capillaries【4】.
2. Biochemical theory – Free fatty acids released into the bloodstream cause endothelial damage, triggering an inflammatory cascade and leading to cerebral edema and ischemia【5】

Despite advances in neuroimaging, CFE remains difficult to diagnose early, as non-contrast CT (NCCT) scans are often normal in initial stages【6】. MRI brain is the gold standard, with T2/FLAIR hyperintensities and the "star field" pattern being characteristic findings【7】.

This case series describes five patients diagnosed with cerebral fat embolism, each presenting with distinct challenges in recognition and management. The cases highlight the importance of early MRI screening, even in trauma patients without long bone fractures, and emphasize the role of supportive care in improving neurological outcomes.

CASE 1

An 18-year-old female was brought to the emergency department following a road traffic accident. She sustained a closed sacral fracture and an open grade 3b Lisfranc injury. On admission, she was conscious and hemodynamically stable, with no history of head trauma or neurological deficits. Contrast-enhanced CT (CECT) abdomen revealed moderate hemoperitoneum and an inframuscular hematoma of the right iliacus muscle, while HRCT chest was normal.

On day 2 of admission, the patient developed respiratory distress, requiring oxygen supplementation. HRCT chest revealed bilateral consolidation with pleural effusion, suggestive of pulmonary fat embolism syndrome (FES). She was intubated and mechanically ventilated in the intensive care unit (ICU). After 48 hours of supportive care, she showed improvement in oxygenation and was extubated.

On day 8, the patient had three episodes of generalized seizures within 24 hours. She was loaded with intravenous phenytoin (20 mg/kg) and levetiracetam, but continued to have breakthrough seizures.

• NCCT head showed no abnormalities.
• MRI brain revealed bilateral fronto-occipito-parietal hyperintensities, suggestive of subacute cerebral fat embolism (Figure 1).

She remained seizure-free under dual antiepileptic therapy, and her neurological status gradually improved. She was discharged on day 12, fully alert and without any residual neurological deficits.

CASE 2

A 22-year-old male sustained multiple long bone fractures, including a closed fracture of the right humerus, tibia-fibula, and left calcaneum, following a high-speed road traffic accident. He was initially managed at a private hospital, where he developed respiratory distress 18 hours post-injury. HRCT chest showed diffuse alveolitis with bilateral hazy infiltrates, suggestive of pulmonary fat embolism syndrome (FES).

He was intubated, sedated, and paralyzed with morphine and vecuronium infusions before being transferred to our hospital 24 hours post-injury. Due to deep sedation and neuromuscular blockade, neurological assessment was delayed.

Six hours after stopping the muscle relaxant infusion, his Glasgow Coma Scale (GCS) was E2VtM5 (8/15). The patient had no history of head trauma, and NCCT head was normal. However, he showed no significant neurological improvement over the next 12 hours, prompting further evaluation.

• MRI brain revealed discrete and confluent T2/FLAIR hyperintensities in the periventricular and deep white matter, with restricted diffusion on DWI, suggestive of confluent cytotoxic edema of white matter (Figure 2).
• Differential diagnoses included fat embolism, toxic leukoencephalopathy, and septic leukoencephalopathy.

The patient was tracheostomized and underwent gradual ventilator weaning. Over the next two weeks, his neurological status improved, and his GCS increased to E4VtM5. He was transferred to the ward and later discharged in a neurologically intact state. At his three-month follow-up, he had fully recovered, with no cognitive or motor deficits.

CASE 3

A 28-year-old male was admitted following a fall from a height, resulting in pelvic fractures without any long bone fractures. He was conscious and hemodynamically stable at presentation, with no respiratory distress or neurological deficits. HRCT chest and NCCT head were normal, and he was admitted for conservative orthopedic management.

On day 6 post-injury, the patient developed progressive confusion and agitation, followed by disorientation to time and place. His oxygen saturation remained normal, and he had no fever, metabolic derangements, or infection markers to suggest an alternative cause.

• NCCT head was normal.
• MRI brain revealed multiple scattered microemboli in the frontal and temporal lobes, consistent with cerebral fat embolism.

He was managed conservatively with oxygen therapy, hydration, and neuroprotective measures. His neurological symptoms gradually improved, and by day 10, he was fully alert and oriented. He was discharged without residual neurological deficits and remained neurologically intact at follow-up.

CASE 4

A 34-year-old female was admitted after a motorcycle accident, sustaining bilateral femur fractures. She was conscious at presentation, with no signs of head injury or neurological deficits. She underwent surgical fixation of both femurs on day 2 post-injury and was recovering uneventfully.

On day 4 post-surgery, she developed sudden onset right-sided weakness and slurred speech, with a Glasgow Coma Scale (GCS) of E4V4M5 (13/15). There was no history of seizure activity, fever, or hemodynamic instability.

• NCCT head was unremarkable.
• MRI brain revealed multiple small infarcts in the left hemisphere, consistent with cerebral fat embolism.

She was managed with oxygen therapy, supportive care, and physiotherapy. Anticoagulation was not initiated, as there was no evidence of deep vein thrombosis (DVT) or cardiac embolism. Over the next two weeks, her neurological symptoms gradually improved, and she regained full motor function. At her three-month follow-up, she was walking independently without residual deficits.

CASE 5

A 45-year-old male was admitted following a high-impact road traffic accident, sustaining polytrauma with rib fractures, right femur fracture, and right humerus fracture. He was initially hemodynamically stable and underwent surgical fixation of his femur and humerus on day 2 post-injury.

On day 3 post-surgery, he developed acute confusion followed by generalized tonic-clonic seizures. His oxygen saturation remained normal, and there was no metabolic disturbance, fever, or signs of infection.

• NCCT head showed no abnormalities.
• MRI brain demonstrated the "star field" pattern of multiple microinfarcts, characteristic of cerebral fat embolism (CFE).

He was managed with oxygen therapy, seizure control (levetiracetam and phenytoin), and neuroprotective care. Over the following week, his neurological symptoms resolved, and he was weaned off antiepileptics before discharge. At his three-month follow-up, he remained neurologically intact, with no cognitive deficits or recurrent seizures.

Cerebral fat embolism (CFE) remains an underdiagnosed complication of trauma, often presenting with delayed or nonspecific neurological symptoms. The classic triad of fat embolism syndrome (FES)—respiratory distress, neurological dysfunction, and petechial rash—is seen in only a subset of patients, making clinical recognition challenging【1】. Isolated CFE, without pulmonary or dermatological manifestations, has been increasingly reported, requiring a high index of suspicion for timely diagnosis【2】. The pathophysiology of CFE is attributed to two major theories. The mechanical theory suggests that fat globules from fractured bone marrow enter the venous circulation and embolize the brain via a patent foramen ovale or pulmonary arteriovenous shunts【4】. The biochemical theory proposes that free fatty acids and cytokine-mediated endothelial injury lead to blood-brain barrier disruption, resulting in vasogenic and cytotoxic edema【5】. MRI studies have supported the role of diffuse microvascular ischemia, as seen in the “star field” pattern on diffusion-weighted imaging (DWI). Scarpino et al. reviewed 31 cases of cerebral fat embolism and found that respiratory symptoms preceded neurological deterioration in 85% of cases, similar to Cases 1 and 2 in this series, where pulmonary manifestations developed before cerebral involvement【6】. However, Case 3 demonstrated an atypical presentation, with isolated neurological symptoms without respiratory distress, highlighting that CFE can occur in the absence of pulmonary involvement, as reported in other case series【7】. Zhou et al. described five patients with CFE who presented with confusion, agitation, and seizures, findings that were mirrored in Cases 3 and 5 in this study【8】. The diagnostic challenge in CFE lies in its variable presentation and normal initial imaging findings. NCCT head scans are often unremarkable, delaying diagnosis in sedated or ventilated patients, as seen in Case 2. MRI brain remains the gold standard, with T2/FLAIR hyperintensities and restricted diffusion on DWI, reflecting microvascular embolization and cytotoxic edema【9】. Kuo et al. found that 92% of patients with CFE had abnormalities on MRI, reinforcing its superior diagnostic accuracy【10】.Management of CFE remains supportive, focusing on oxygen therapy, seizure control, and hemodynamic stabilization. The role of corticosteroids in FES is controversial. Schonfeld et al. demonstrated that early steroid administration reduced the severity of symptoms, but more recent studies have questioned their efficacy due to potential immunosuppressive risks【11】. In this series, none of the patients received corticosteroids, yet all recovered fully, suggesting that early supportive care plays the most crucial role in prognosis. A unique aspect of this series was the diverse neurological presentations. While Cases 1 and 2 followed the classic pulmonary-first pattern, Case 3 mimicked metabolic encephalopathy, Case 4 presented with stroke-like symptoms, and Case 5 had seizures as the primary manifestation. These variations align with previous reports describing CFE as a "neurological chameleon," capable of mimicking acute ischemic stroke, encephalitis, and toxic leukoencephalopathy【12】. Prognosis in CFE is generally favorable with early recognition, but long-term neurocognitive impairment remains underreported. Habashi et al. suggested that subtle cognitive dysfunction may persist even after clinical recovery, warranting neuropsychological follow-up in patients with prolonged ICU stays【13】. All five patients in this series had complete neurological recovery at three months, but further research is needed to assess potential subclinical cognitive deficits. In summary, this case series highlights the heterogeneous presentation of CFE and the need for early MRI screening in trauma patients with unexplained neurological symptoms. Clinicians should maintain a high index of suspicion, particularly in polytrauma cases, sedated ICU patients, and those with delayed neurological deterioration. With timely supportive management, outcomes remain favorable, reinforcing the importance of early recognition and intervention.

TABLE 1: Clinical and Radiological Findings of Patients with Cerebral Fat Embolism

FIGURES

Figure 1: MRI of Case 1 shows white matter signal changes in the bilateral cerebral hemispheres, predominantly in the bilateral fronto-occipito-parietal lobes, suggestive of subacute cerebral fat embolism.

Figure 2: MRI of Case 2 shows discrete and confluent T2/FLAIR hyperintensities in the periventricular and deep white matter of the bilateral cerebral hemispheres, with restricted diffusion on DWI, suggestive of confluent cytotoxic edema of the white matter. Differential diagnoses include fat embolism, toxic leukoencephalopathy, and septic leukoencephalopathy.

Cerebral fat embolism (CFE) is a rare but potentially serious complication of trauma that requires early recognition and intervention to prevent long-term neurological sequelae. While fat embolism syndrome (FES) typically presents with respiratory symptoms followed by neurological dysfunction, some cases—such as those described in this series—demonstrate isolated or delayed neurological manifestations, leading to diagnostic challenges. MRI brain remains the gold standard for diagnosis, as initial NCCT head findings are often normal. The cases presented in this series highlight the heterogeneous clinical spectrum of CFE, including patients with seizures, stroke-like symptoms, confusion, and agitation. This underscores the need for high clinical suspicion, particularly in polytrauma patients, ventilated ICU patients, and those with unexplained neurological deterioration. The absence of long bone fractures does not exclude CFE, as seen in Case 3, further emphasizing the importance of early neuroimaging in high-risk trauma patients. Management remains supportive, focusing on oxygen therapy, seizure control, and hemodynamic stabilization. The role of corticosteroids remains controversial, but timely ICU care, early diagnosis, and aggressive supportive management significantly improve outcomes. All patients in this series had full neurological recovery, consistent with previous reports that early recognition and supportive care lead to favorable prognoses. In conclusion, CFE should always be considered in trauma patients with unexplained neurological symptoms, even in the absence of respiratory involvement or classic FES features. Routine MRI screening in suspected cases can aid early diagnosis, prevent mismanagement, and improve patient outcomes. With prompt supportive care, the long-term prognosis remains excellent.

1. Scarpino M, Lanzo G, Lolli F, Grippo A. From the diagnosis to the therapeutic management: cerebral fat embolism, a clinical challenge. Int J Gen Med. 2019;12:39-48.
2. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970 Nov;52(4):732-7.
3. Fabian TC, Hoots AV. Fat embolism syndrome: a review of the pathophysiology and treatment. Trauma Surg Acute Care Open. 2020 Feb;5(1):e000448.
4. Habashi NM, Andrews PL, Scalea TM. Therapeutic aspects of fat embolism syndrome. Injury. 2006 Dec;37 Suppl 4:S68-73.
5. Parizel PM, Demey HE, Veeckmans G, Verstreken J, Cras P, Jorens PG, De Schepper AM. Early diagnosis of cerebral fat embolism syndrome by diffusion-weighted MRI (star field pattern). Stroke. 2001 Dec;32(12):2942-4.
6. Kuo KH, Pan YJ, Lai YJ, Cheung WK, Chang FC, Jarosz J. Dynamic MR imaging patterns of cerebral fat embolism: a systematic review with illustrative cases. AJNR Am J Neuroradiol. 2014 Jun;35(6):1052-7.
7. Zhou Y, Yuan Y, Huang C, Hu L, Cheng X. Pathogenesis, diagnosis, and treatment of cerebral fat embolism. Chin J Traumatol. 2015 Apr;18(2):120-3.
8. Sullivan R, Kazanjian R, Cooper H, Barron A. Neurological manifestations of fat embolism syndrome: a case report and review of the literature. J Clin Neurosci. 2013 Nov;20(11):1541-3.
9. Mishra AK, Sinha A, Singh S, Tiwary BK. Cerebral fat embolism: a diagnostic dilemma. J Clin Neurosci. 2016 Apr;24:95-8.
10. Schonfeld SA, Ploysongsang Y, DiLisio R, Crissman JD, Miller E, Hammerschmidt DE. Fat embolism prophylaxis with corticosteroids: a prospective study in high-risk patients. Ann Intern Med. 1983 Oct;99(4):438-43.
11. Sostman HD, Matthay RA, Putman CE. Fat embolism syndrome: current concepts and pathophysiology. Radiology. 1983 Nov;149(2):219-26.
12. Filomeno LT, Carelli CR, Silva N. Fat embolism: a review for current orthopedic practice. Acta Ortop Bras. 2005;13(4):196-208.
13. Habashi NM, Andrews PL, Manaker S. Fat embolism syndrome: pathophysiology, diagnosis, and management. Am J Respir Crit Care Med. 2003;168(12):1416-9.