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\begin{document}

\title{STARS FROM THE BONES - AN UNCOMMON PRESENTATION OF FAT EMBOLISM SYNDROME}



\author[1]{LOKESH KOUMAR Sivanandam}%
\author[2]{Prakash  Gupta}%
\author[3]{Maliha Rahim}%
\author[4]{Vivek Sanker}%
\author[5]{Ashna  Pandita}%
\author[6]{Umang  Gupta}%
\affil[1]{SLIMS}%
\affil[2]{University of Miami Miller School of Medicine}%
\affil[3]{Jinnah Sindh Medical University}%
\affil[4]{Noorul Islam Institute of Medical Science and Research Foundation Medicity}%
\affil[5]{University of Nis Faculty of Medicine}%
\affil[6]{Nepalgunj Medical College}%


\vspace{-1em}



  
  \date{May 28, 2024}


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\selectlanguage{english}
\begin{abstract}
Trauma or surgery to the lower limbs can cause fat from the marrow
within the leg bones to enter the bloodstream and form an embolus.
However, if there is cerebral involvement without any pulmonary or
dermatological manifestations at diagnosis, it could delay identifying
cerebral fat embolism (CFE).%
\end{abstract}%



\sloppy


\textbf{Introduction}

Fat embolism is an abrupt disruption of the circulatory system commonly
caused by orthopedic trauma, which is shown physically by the appearance
of globules of fat in the vessels of the circulatory system. Fat
embolism syndrome is the systemic presentation of fat emboli in the
microcirculation, manifesting with the Gurd's triad of respiratory
distress, neurological deficits, and petechial rashes {[}1,2{]}.~
According to the observations, pulmonary symptoms occur first, typically
24 to 72 hours after the trauma, but symptoms have been reported as
early as 12 hours, usually followed by neurological symptoms {[}2{]}.
The exact occurrence of FES varies from 1\% to 30\%, as there are no
universal standards for diagnosis {[}3{]}.

In 1861, Zenker was the first to conduct a clinical study of FES and
discovered fat droplets in the capillaries of the lungs of a railroad
worker who had died from a traumatic injury. However, despite Gauss'
mechanical explanation of FES in 1924 and Lehman and Moore's biochemical
explanation in 1927, the concept of FES remains obscure {[}4{]}.

Recent studies suggest that FES may have possible connections with
neurocognitive dysfunction and the development of deep vein thrombosis.
Clinical manifestations of FES vary widely and can include restlessness,
dyspnea, delirium, coma, and, in some cases, death. Case studies have
also highlighted the rare occurrence of FES in patients not resulting
from trauma, particularly during bone marrow removal, c-sections,
liposuction, lung transplants, and cosmetic surgeries {[}2{]}.

There are many ways to prevent FES and other long bone fractures from
happening that have been discussed in the literature. Unfortunately,
there is no particular treatment for FES, so the main alternatives are
to give supportive care, although this is not a universal practice.
Damage control orthopedics (DCO) and optimizing reaming approaches have
been the principal management solutions for individuals with long bone
fractures. Although FES can be very dangerous, it is much less common
{[}5{]}.

Here we present a case of a 23-year-old male who suffered a left both
bone closed fracture after an iron rod fell over his left lower limb. He
eventually developed the classic triad of Fat embolism syndrome after
being asymptomatic for 5 days following the trauma.

\textbf{Case Report:}

A 24-year-old male presented to the emergency department with shortness
of breath and altered sensorium of 3 days duration. No symptoms were
seen 5 days back, and no history of expectoration, hemoptysis, chest
pain, palpitations, swollen limbs, or fever. On the night of the
presentation, the sensorium was worsening in the form of decreased
responsiveness, decreased speech output, and eye contact. Medical
consultation was requested for persistent unresponsiveness. On
examination, there was no history of weakness, seizure syncope,
headache, cranial nerve palsies, visual defects, head trauma, or
decreased urine output. No history of childhood epilepsy was revealed.
Further investigations revealed he had a closed long bone fracture of
the tibia and fibula five days back due to an iron rod that fell over
the left lower limb. (Fig.1) He presented to the hospital the same day,
and above-knee (AK) slab was placed, which the patient removed on his
own the next day, and 2 days later, he attended a native treatment for
fracture where manipulation and gross alignment were done.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 1} : Left lower limb X-Ray showing closed long bone
fracture of the tibia and fibula: AP View

General examination at presentation to Emergency Medical Services
revealed mild pallor. He was conscious but not oriented. The pulse rate
was 110 beats/min, the respiratory rate was 30 beats/min, blood pressure
was 100/60 mmHg, and random blood sugar was 74 mg\%. He had tachypnea
and mild tachycardia and developed oxygen desaturation (O2 of 88\%). The
Thoracic Computed tomography (CT) findings showed diffuse bilateral
pulmonary infiltrates comprising consolidations and ground-glass
opacities. (Fig.2) He was sedated and intubated with subsequently
transferred to the intensive care unit.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure.2:} Thoracic computed tomography showing diffuse
bilateral pulmonary infiltrates. Ground-glass opacity of uncertain cause
is present.

There were no abdominal or pelvic abnormalities upon initial imaging
workup, and a plain CT scan of the brain was unremarkable, with no
ischemia or hemorrhage. (Fig.3) On the third day of admission, emergency
magnetic resonance imaging (MRI) Brain revealed extensive bilateral
symmetrical punctate foci of nearly the same size with abnormal signal
intensities. These foci affect the cerebral hemispheres with restricted
diffusion, decreased signals in susceptibility-weighted imaging (SWI)
indicative of microbleeds, and mottled fluid-attenuated inversion
recovery (FLAIR) signals. (Fig.4)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure.3} : The results of the head computed tomography scan
showed that there was no obvious bleeding or abnormality in the skull.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\textbf{Figure.4:} MRI Brain shows extensive bilateral, symmetrical
punctuate foci of nearly the same size and abnormal signal intensities
giving the appearance of a starfield pattern on T2-weighted images with
restricted diffusion.

On the fourth day of admission, bilateral palpebral conjunctival
petechial spots also appeared. His pupils were isochoric, and the light
reflex was bilaterally positive. There were no meningeal signs. The
reflexes and cranial nerves were normal. He could move all 4 limbs. The
Glasgow Coma Scale score was 12: E4V2M6. Cardiac echocardiography also
revealed no evidence of patent foramen ovale.

Treatment:

One dose of hydrocortisone intravenously on day 1 of admission and
subcutaneous heparin was given in view of the pulmonary embolism. His
sensorium improved (GCS 15) with supportive measures. Respiratory
distress was managed conservatively with oxygen by mask. The patient
eventually improved with the same line of management.

Follow-up:

The patient was discharged with a repeat chest X-ray, which was normal,
and hypoxia was quick to resolve with a repeat arterial blood gas (ABG)
analysis showing normal parameters with follow-up at a multidisciplinary
clinic and rehabilitation program.

Discussions:

Fat embolism syndrome (FES) is most frequently associated with trauma
and orthopedic procedures and is characterized by major and minor
findings, as defined by Gurd {[}5{]}. Three major criteria and two minor
criteria marked by (*) in the {[}Table 1{]}, was manifested in our
patient making this a strong case of FES {[}5,6{]}.\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Major criteria & Minor criteria\tabularnewline
\midrule
\endhead
Respiratory insufficiency* Cerebral involvement* Petechial rash &
Tachycardia* \textgreater{} 110 bpm Pyrexia \textgreater{} 38.5 C
Jaundice* Renal Changes Retinal changes Thrombocytopenia Increased ESR
Fat macroglobulinemia\tabularnewline
2 major criteria or one major and criteria and four minor criteria
suggest a diagnosis of FES & 2 major criteria or one major and criteria
and four minor criteria suggest a diagnosis of FES\tabularnewline
\bottomrule
\end{longtable}

Table 1. Gurd's and Wilson criteria for FES

The highest incidence of FES is among closed, long bone fractures of the
lower extremities, especially the femur, and pelvis. Severe burns,
infection, kidney transplant, liposuction, cardiopulmonary bypass, and
transfusions are other possible causes. Males Age: 10--40 years,
multiple fractures, and unstable bone fracture movement are the common
risk factors. In our case, a closed long bone fracture of the tibia and
fibula followed by joint manipulation makes the patient a high-risk
candidate for FES. {[}2,3{]}

The onset of clinical symptoms can occur within 12 hours, but symptoms
mostly present after 24--72 hours. The classic triad of respiratory
manifestations (95 \%), cerebral symptoms (60 \%), and petechiae (33 \%)
are seen among patients with FES and are seen in our case
{[}7,8{]}.~Cerebral emboli cause neurological signs in up to 86 \% of
cases and mainly occur after the onset of respiratory distress, as
observed in our patient's clinical manifestation. Neurological
manifestations of FES can vary from mild cognitive changes to coma, as
evidenced by our patient's Glasgow Coma Scale score of E4V2M6
{[}9{]}.~Petechial rash, as seen in our patient's conjunctiva, is
considered pathognomonic of FES and is reportedly present in up to 60 \%
of patients {[}10{]}. Neurological symptoms are typically accompanied by
respiratory failure and skin eruptions. Several cases of isolated
cerebral fat embolism have also been reported {[}11,12{]}. In our case,
respiratory system, skin, and eye examinations were abnormal. The main
initial symptom was respiratory distress followed by an alteration in
consciousness.

Brain CT showed normal findings in most cases. On the other hand, MRI is
more sensitive and can show small high-signal-intensity lesions
scattered in the cerebral white matter, cerebellum, and brainstem on
T2-weighted or diffusion-weighted images {[}13,14{]}. In our case, CT
Brain was unremarkable, whereas brain MRI showed bilateral symmetrical
punctate foci with restricted diffusion ``star field'' pattern and
mottled fluid-attenuated inversion recovery (FLAIR) signals. Also, a
Chest CT scan of the patient showed diffuse bilateral pulmonary
infiltrates with consolidation and ground glass opacities. A study by
Gupta et al. evaluated 1692 patients with long bone and pelvic fractures
and found that 12 patients met the diagnosis of FES. Three were
diagnosed with CFE, whereas five suffered multiple bone fractures.
Neurological status alterations were seen among all the patients with
CFE with T2 and FLAIR hyperintense lesions in the bilateral cerebral
hemisphere, basal ganglia, thalamus, pons, and cerebellum {[}15{]}.

Despite changes in sensorium and respiratory distress, the symptoms
resolved with supportive care. Although the initial presentation of CFE
may be moderate to severe, most case reports on CFE demonstrate that the
cerebral deterioration associated with CFE is amendable {[}16{]}.

Even though the pathophysiology of FES remains poorly known, mechanical
and biochemical theories are the two main proposed theories to explain
pathology. Gossling et al. {[}17{]} described a mechanical theory, which
states that a rise in intramedullary pressure after an injury forces
marrow to pass into the injured venous sinusoids causing large fat
droplets to be released into the venous system. These fat droplets that
travel to the lungs and occlude pulmonary capillaries and systemic
vasculature may enter the arterial circulation via a patent foramen
ovale or directly through the pulmonary capillary bed, causing the
characteristic neurological and dermatologic findings of FES. Similarly,
Baker et al. {[}18{]} described the biochemical theory, which states
that the clinical manifestations of FES are attributable to a
pro-inflammatory state. The intermediate products, such as glycerol and
toxic-free fatty acids, because of local hydrolysis of triglyceride
emboli by tissue lipase, may lead to an injury to pneumocytes and
pulmonary endothelial cells, causing vasogenic and cytotoxic edema,
leading to the development of acute lung injury or respiratory distress
syndrome.

Prevention, early detection, and appropriate treatment are critical
parameters in FES.~ Intracranial pressure and cerebral tissue
oxygenation monitoring help maintain optimal perfusion, as suggested by
Kumar et al. {[}19{]}. Traumatic patients have improved outcomes with
splinting and fixation of orthopedic fractures in an early phase, and
supportive care remains the mainstay of treatment for FES {[}20,~21{]}.

Adequate supportive treatment and improved care can help the majority of
the patients of FES recover completely. The severity of respiratory
problems is a close indicator of the risk of death, with overall
mortality for this condition 5--15 \% {[}22{]}. Most case reports on CFE
demonstrate that the cerebral deterioration associated with CFE is
amendable {[}23-25,16{]}.

\textbf{Conclusions:}

In summary, a high index of suspicion is required to diagnose FES,
especially in long bone and pelvic fractures, which are clinically not
apparent. CFE should be considered when patients have long bone and
pelvic fractures, multiple bone fractures, or deteriorated neurological
status. Our case highlights the delayed systemic manifestations of FES
and early neurological manifestations that mimic many other diseases
like stroke and meningitis. Patients without an intracardiac shunt may
also suffer CFE. Additionally, the treating physician should be cautious
in excluding pulmonary embolism, which presents similarly but has a
different management line. CFE patients may recover completely with
appropriate treatment.

\textbf{CONFLICTS OF INTEREST:}

None declared.

\textbf{AUTHOR CONTRIBUTION:}

All the authors contributed equally in drafting, editing, revising and
finalizing the case report.

\textbf{ETHICAL APPROVAL:~}

The ethical approval was not required for the case report as per the
country's guidelines.

\textbf{CONSENT:}

Written informed consent was obtained from the patient to publish this
report.

\textbf{DATA AVAILABILITY STATEMENT:}

The data that support the findings of this article are available from
the corresponding author upon reasonable request.

\textbf{Reference:}

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