although fat embolization may occur in almost all patients with pelvic or long bone fractures ; in most cases it is sub - clinical.12 the reported incidence of fat embolism syndrome in long bone fractures is 0.5 - 11% and up to 30% in bilateral femoral fractures.345 cerebral fat embolism syndrome where the clinical manifestation is dominated by neurological dysfunction is rare and only scarcely reported .
6 reported two cases with prolonged coma due to cerebral fat embolism which required ventilatory support for 2 and 3 weeks duration .
we report two such cases which recovered completely despite rapid initial deterioration and prolonged coma .
although clinical pictures are well reported , our cases are unique that both presented with normal neurology to the hospital and had neurological worsening due to cerebral fat embolism phenomenon 24 - 48 h prior to surgery without associated respiratory distress . both needed ventilation for a prolonged period and had poor mentation at the time of discharge .
furthermore , during the followup they showed complete recovery to normal and social life ; highlighting the fact that prolonged intensive care and good rehabilitation can lead to normal neurology despite poor clinical picture initially .
a 20-year - old male presented 7 h following a road traffic accident ( rta ) with closed fracture of mid - shaft tibia and fibula involving both his legs . on arrival patient was conscious and oriented with a glasgow coma scale ( gcs ) - 15/15 .
blood investigations were normal except for raised serum lactate ( 5.7 mmol / l ) .
two hours after admission ( 9 h since injury ) , patient became drowsy with a blood pressure of 116/74 mmhg , oxygen saturation 
further 4 h later patient became lethargic and comatose with the gcs falling to 8/15 .
patient was intubated and ventilated and was on supportive treatment with neuro - monitoring . magnetic resonance imaging ( mri ) of the brain revealed multiple well defined tiny hyperintense lesions on t2 and fluid - attenuated inversion - recovery sequences with restricted diffusion bilaterally scattered in the subcortical white matter , centrum semiovale , basal ganglia , thalami and cerebellum suggestive of multiple tiny infarcts due to fat embolism [ figure 1 ] .
chest x - ray which was initially clear , revealed minimal bilateral diffuse haziness only after 3 days [ figure 2 ] .
fractures of both bones of both legs were stabilized by external fixation on 4th day after injury .
patient regained consciousness only after 2 weeks , but had poor higher mental functions such as slurred speech , poor cognition and disturbed memory .
gcs had improved to 13/15 and ventilator support was gradually weaned and withdrawn at 3 weeks . later at 4 weeks ( since injury ) , external fixator removal and interlocking nailing was carried out for fractures of both the tibiae . at 10 weeks
postinjury , patient was conscious and oriented , but with poor cognition . at 5 months ,
patient had regained full neurological recovery and fractures of both bones of both the legs united [ figure 3 ] .
neurological recovery was evaluated by glasgow outcome scale ( gos)7 and mini - mental state examination ( mmse),8 which showed good recovery and normal cognition respectively .
mri of the brain repeated at 10 months postinjury revealed resolution of previously visualized hyperintense lesions except in the periventricular region without any diffusion restriction pattern [ figure 3 ] .
( a ) radiograph of leg bones with ankle joint ( anteroposterior views ) showing fractures in both legs ( b and c ) t2w magnetic resonance imaging of the brain ( arrow ) showing multiple well defined tiny hyperintense lesions suggestive of cerebral fat embolism ( arrow ) ( a ) radiograph of chest , which was normal initially ; ( b ) bilateral diffuse haziness after 3 days ( arrow ) ( a ) radiograph of leg bones ( anteroposterior views ) showing well united fractures of both legs ; ( b and c ) t2w magnetic resonance imaging of brain repeated 10 months postinjury shows incomplete , but significant resolution of previous hyperintense lesions ( arrow ) a 28 year old male presented with rta and sustained closed fracture of the right femur .
he was admitted in the evening at 6 pm and was planned for interlocking nailing the following day .
next day morning at 7 am , patient was found to be drowsy and ct of the brain was carried out , which was reported to be normal .
the pulse rate was 114/min , blood pressure was 122/84 mmhg with an oxygen saturation of 86% at room air . within 3 h ,
consciousness of patient rapidly deteriorated with the gcs falling to 7/15 and he required intubation and ventilation to maintain oxygen saturation .
clinically , a diagnosis of fat embolism syndrome was made after ruling out head injury , hypotension , electrolyte and metabolic disturbances .
the fracture was then stabilized by an external fixator on the 2 day after injury .
chest x - ray , was initially normal and showed bilateral diffuse haziness after 2 days [ figure 4 ] . since consciousness did not improve even after 6 days , mri of the brain was done , which confirmed cerebral fat embolism [ figure 4 ] .
as there was continued requirement of mechanical ventilation with positive end expiratory pressure , tracheostomy was done .
mechanical ventilation was continued for 5 weeks until he regained consciousness with the gcs improving to 11/15 .
gradual weaning was carried out with t - piece and ventilation support was discontinued at 6 weeks .
external fixator removal and interlocking nailing was carried out for fracture femur at 8 weeks since injury .
neurologically , patient had poor cognition and spasticity initially , which gradually improved and the patient returned to his original job . at 6 months ,
postinjury the patient had good neurological recovery ( gos ) and normal cognition ( mmse ) .
( a ) initial radiograph of chest ; ( b ) radiograph of chest repeated after 2 days reveals diffuse haziness ( arrow ) compared to initial radiograph ; ( arrow ) ( c ) magnetic resonance imaging of brain shows features of cerebral fat embolism ( arrow )
a 20-year - old male presented 7 h following a road traffic accident ( rta ) with closed fracture of mid - shaft tibia and fibula involving both his legs . on arrival patient was conscious and oriented with a glasgow coma scale ( gcs ) - 15/15 .
blood investigations were normal except for raised serum lactate ( 5.7 mmol / l ) .
two hours after admission ( 9 h since injury ) , patient became drowsy with a blood pressure of 116/74 mmhg , oxygen saturation 
further 4 h later patient became lethargic and comatose with the gcs falling to 8/15 .
patient was intubated and ventilated and was on supportive treatment with neuro - monitoring . magnetic resonance imaging ( mri ) of the brain revealed multiple well defined tiny hyperintense lesions on t2 and fluid - attenuated inversion - recovery sequences with restricted diffusion bilaterally scattered in the subcortical white matter , centrum semiovale , basal ganglia , thalami and cerebellum suggestive of multiple tiny infarcts due to fat embolism [ figure 1 ] .
chest x - ray which was initially clear , revealed minimal bilateral diffuse haziness only after 3 days [ figure 2 ] .
fractures of both bones of both legs were stabilized by external fixation on 4th day after injury .
patient regained consciousness only after 2 weeks , but had poor higher mental functions such as slurred speech , poor cognition and disturbed memory .
gcs had improved to 13/15 and ventilator support was gradually weaned and withdrawn at 3 weeks . later at 4 weeks ( since injury ) , external fixator removal and interlocking nailing was carried out for fractures of both the tibiae . at 10 weeks
postinjury , patient was conscious and oriented , but with poor cognition . at 5 months ,
patient had regained full neurological recovery and fractures of both bones of both the legs united [ figure 3 ] .
neurological recovery was evaluated by glasgow outcome scale ( gos)7 and mini - mental state examination ( mmse),8 which showed good recovery and normal cognition respectively .
mri of the brain repeated at 10 months postinjury revealed resolution of previously visualized hyperintense lesions except in the periventricular region without any diffusion restriction pattern [ figure 3 ] .
( a ) radiograph of leg bones with ankle joint ( anteroposterior views ) showing fractures in both legs ( b and c ) t2w magnetic resonance imaging of the brain ( arrow ) showing multiple well defined tiny hyperintense lesions suggestive of cerebral fat embolism ( arrow ) ( a ) radiograph of chest , which was normal initially ; ( b ) bilateral diffuse haziness after 3 days ( arrow ) ( a ) radiograph of leg bones ( anteroposterior views ) showing well united fractures of both legs ; ( b and c ) t2w magnetic resonance imaging of brain repeated 10 months postinjury shows incomplete , but significant resolution of previous hyperintense lesions ( arrow )
a 28 year old male presented with rta and sustained closed fracture of the right femur . he was admitted in the evening at 6 pm and was planned for interlocking nailing the following day . he had no other injuries and was fully conscious at admission .
next day morning at 7 am , patient was found to be drowsy and ct of the brain was carried out , which was reported to be normal .
the pulse rate was 114/min , blood pressure was 122/84 mmhg with an oxygen saturation of 86% at room air . within 3 h ,
consciousness of patient rapidly deteriorated with the gcs falling to 7/15 and he required intubation and ventilation to maintain oxygen saturation .
clinically , a diagnosis of fat embolism syndrome was made after ruling out head injury , hypotension , electrolyte and metabolic disturbances .
the fracture was then stabilized by an external fixator on the 2 day after injury .
chest x - ray , was initially normal and showed bilateral diffuse haziness after 2 days [ figure 4 ] . since consciousness did not improve even after 6 days , mri of the brain was done , which confirmed cerebral fat embolism [ figure 4 ] .
as there was continued requirement of mechanical ventilation with positive end expiratory pressure , tracheostomy was done .
mechanical ventilation was continued for 5 weeks until he regained consciousness with the gcs improving to 11/15 .
gradual weaning was carried out with t - piece and ventilation support was discontinued at 6 weeks . external fixator removal and interlocking nailing
neurologically , patient had poor cognition and spasticity initially , which gradually improved and the patient returned to his original job .
at 6 months , postinjury the patient had good neurological recovery ( gos ) and normal cognition ( mmse ) .
( a ) initial radiograph of chest ; ( b ) radiograph of chest repeated after 2 days reveals diffuse haziness ( arrow ) compared to initial radiograph ; ( arrow ) ( c ) magnetic resonance imaging of brain shows features of cerebral fat embolism ( arrow )
gurd and wilson9 reported that fat embolism syndrome typically develops between 12 h and 72 h after the injury in young adults .
this was seen in our cases also where they were completely normal neurologically at presentation and rapidly deteriorated in the next 9 - 12 h. diagnosis of fat embolism syndrome is by and large clinical and is characterized by the classical triad of petechial rash , respiratory distress and neurological dysfunction.9 however , this triad may not be present in all patients and poses a diagnostic challenge.10 both our cases had profound neurological dysfunction at presentation , but had no petechial rash . although they had no respiratory distress at presentation , dysfunction was manifested by worsening hypoxia detected by pulse oxymetry .
cases where the neurological manifestations are predominant are referred to as cerebral fat embolism syndrome.511 cerebral manifestations are highly variable and nonspecific .
this includes headache , lethargy , irritability , delirium , stupor , convulsions , focal deficits or coma.11 these features may be seen even with head injury , substance abuse , polytrauma and sedative medication , making the diagnosis of cerebral fat embolism difficult.12 cerebral fat embolism has been reported in young adults between 18 and 39 years.561012131415161718192021 the two patients , we report here are also in the same age group .
although , neurological deterioration in many reported patients was postoperative following intramedullary nailing for long bone fractures;561013141516 onset prior to surgery has also been reported as seen in our patients.101217181920 mri is helpful in diagnosis of cerebral fat embolism and also to exclude other causes of deterioration.121721 parizel et al.19 reported that diffusion weighted mri characterized by 
bright spots on a dark background helps in early diagnosis . in the cases reported in literature , the duration of ventilatory support ranged up to a maximum of 3 weeks , but our patients required prolonged ventilation support for 3 and 6 weeks respectively .
butteriss et al.13 emphasized the role of neurotoxicity and metting et al.21 highlighted the occurrence of delayed coma due to cerebral fat embolism in association with head injury .
complete neurological recovery has been reported in many case reports at 3 weeks to 4 months after the initial insult .
our two patients also had delayed , but complete recovery after 5 and 6 months respectively .
manousakis et al.20 studied the cognitive outcome in cerebral fat embolism and reported that neuropsychological evaluation was normal except for borderline frontal dysfunction at the end of 4 months .
pfeffer and heran14 although reported poor outcome in cerebral fat embolism associated with restricted diffusion in mri , there was clear evidence of intraoperative hypoxia and hypotension in their cases , which might have contributed to the poor outcome .
metting et al.21 reported persistent cognitive dysfunction in patient with cerebral fat embolism associated with head injury .
mueller et al.15 reported poor outcome in fulminant cerebral fat embolism associated with atrial septal defect
. early suspicion of fat embolism syndrome should be raised when there are subtle changes in consciousness , tachycardia , tachypnea and evidence of hypoxemia picked up by pulse oxymetry for early suspicion .
cytological examination of urine for fat globules is not sensitive and its absence does not rule out fat embolism syndrome as was seen in our patients.22 dongfeng et al.,23 in a retrospective multicenter study , emphasized early diagnosis for good outcome in cerebral fat embolism .
treatment of cerebral fat embolism syndrome is essentially supportive.16 cerebral edema plays a major part in neurological deterioration in fulminant type of cerebral fat embolism syndrome.6 neurological manifestations in fat embolism syndrome can be worsened by associated primary head injury or secondary brain damage due to cerebral hypoxia , which may occur due to acute respiratory distress syndrome or low gcs .
meyer et al.5 has reported that any intention to withdraw supportive measures must be tempered until the patient is at least 1 month from the date of injury and the brain magnetic resonance image shows no sign of improvement .
however in one of our patient , ventilation was required for 42 days and finally the patient recovered completely .
this proves that there is no limit for supportive treatment in cerebral fat embolism syndrome considering the excellent prognosis .
the cognitive dysfunction following cerebral fat embolism is reported to be similar to hypoxic brain injury,2024 which if avoided during management has excellent outcome .
cerebral fat embolism syndrome has to be strongly considered in young adults with long bone and pelvic fractures presenting with rapid deterioration of neurological status in the absence of head injury .
magnetic resonance imaging of the brain is helpful for early diagnosis in isolated cerebral fat embolism .
importance of its early recognition lies in the fact that despite grave presentation , rapid worsening and late neurological recovery ; the prognosis is very good with intensive care and rehabilitation . prevention of secondary brain damage due to hypoxia is essential to avoid permanent neurological sequelae .
 fat embolism syndrome presenting primarily with cerebral manifestations is rarely reported . 
 we report here two such patients who showed complete recovery following initial deterioration . 
 the aim of these reports is to highlight that prolonged intensive care and good rehabilitation can lead to normal neurologic recovery despite poor clinical picture initially . 
 the importance of adequate oxygenation to prevent secondary brain damage is emphasized during prolonged recovery . 
I
C
Case 1
Case 2
D