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\begin{document}

\title{Multilevel Percutaneous Vertebroplasty with the Spine Jack\selectlanguage{ngerman}® system in a
patient with Cushing disease\selectlanguage{english}}



\author[1]{Cuauhtemoc Gil-Ortiz}%
\author[1]{Dulce Bonifacio-Delgadillo}%
\author[1]{Alberto Ramírez-Romero}%
\author[1]{Javier Alfredo Lagos-Servellon}%
\affil[1]{Centro Medico Nacional 20 de Noviembre}%


\vspace{-1em}



  
  \date{May 30, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
A 55-year-old male with lumbago, with Imaging studies that showed
osteoporotic fractures at T5,T8,T11,T12 and L1-L5 vertebrae secondary to
Cushing disease. PV was performed with a Spine Jack\selectlanguage{ngerman}® intracorporal
implant device. Post-operative course demonstrated improvement of pain,
height, correction of the kyphotic angle and Oswestry score, without any
neurological deficit.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{COVER LETTER}

\textbf{Authors:}

Cuauhtemoc Gil-Ortiz\textsuperscript{1,4},

Alberto Ram\selectlanguage{ngerman}írez-Romero\textsuperscript{1,4}

Javier Lagos-Servellon\textsuperscript{2,4}

Dulce Bonifacio-Delgadillo\textsuperscript{3,4}

\textbf{Title: Multilevel Percutaneous Vertebroplasty with the Spine
Jack® system in a patient with Cushing disease}

\textbf{Authors and Affiliations:}

Cuauhtemoc Gil-Ortiz\textsuperscript{1},

Alberto Ramírez-Romero\textsuperscript{1}

Dulce Bonifacio-Delgadillo\textsuperscript{1}

Javier Lagos-Servellon\textsuperscript{1}

Department of Neuroscience. Centro Médico Nacional ''20 de Noviembre'',
Mexico City, Mexico

\textbf{Attached files:}

4 figures

1 table

\textbf{Status:} new

\textbf{Multilevel Percutaneous Vertebroplasty with the Spine}

\textbf{Jack® system in a patient with Cushing disease}

\textbf{Cuauhtemoc Gil-Ortiz\textsuperscript{1}, Alberto
Ramírez-Romero\textsuperscript{1},Dulce
Bonifacio-Delgadillo\textsuperscript{1 ,}Javier Lagos
Servellon\textsuperscript{1}}

Department of Neuroscience. Centro Médico Nacional ''20 de Noviembre'',
Mexico City, Mexico

\textbf{Corresponding author:}

\textbf{Dulce Bonifacio-Delgadillo, Centro Médico Nacional ``20 de
Noviembre''}

Félix Cuevas 540, Col del Valle Sur, Benito Juárez, 03229 Ciudad de
México, México.

Email: drabonifacio@yahoo.com.mx

\textbf{ABSTRACT}

\textbf{Background:} Percutaneous vertebroplasty (PV) is a minimally
invasive procedure that requires the injection of cement into a
fractured vertebral body. Spine Jack® is a vertebroplasty system with an
intracorporal implant designed to restore the height of the vertebral
body in osteoporotic vertebral fractures. There are no reported cases of
PV with Spine Jack® system as treatment for multilevel compression
fractures in patients with vertebral osteoporosis due to Cushing
disease.

\textbf{Case presentation} : A 55-year-old male with lumbago, impaired
deambulation six weeks prior to presentation, with Oswestry score of
72\% and a visual analogue scale (VAS) score of 9 points. Imaging
studies showed osteoporotic fractures at T5, T8, T11, T12 and L1-L5
vertebrae secondary to Cushing disease. PV was performed with a Spine
Jack® intracorporal implant device, in three sessions, and multiple
levels were operated at each intervention. Post-operative course
demonstrated improvement of pain, height, correction of the kyphotic
angle and Oswestry score, without any neurological deficits despite
having nine vertebral fractures.

\textbf{Conclusion:} PV with the Spine Jack® system is a safe and
effective procedure to treat multilevel vertebral fractures due to
Cushing disease, improving the quality of life and allowing the patient
to remain pain-free while avoiding major surgery.

Keywords: Percutaneous vertebroplasty, Cushing Disease, Spine Jack
system,

Vertebral compression fractures, case report.

\textbf{BACKGROUND}

Percutaneous vertebroplasty (PV) is a minimally invasive procedure in
which liquid polymethylmethacrylate cement is injected into a fractured
vertebral body to relieve pain, reinforce the bone, and prevent further
vertebral compression {[}1{]}. Spine Jack® is a vertebroplasty system
with an intracorporal implant designed to restore the height of the
vertebral body in osteoporotic vertebral fractures, primary or secondary
bone tumors, or traumatic fractures {[}2{]}. It is an effective,
low-risk procedure for patients with a significant reduction in pain and
analgesic use immediately after surgery that is maintained over time
{[}3{]}. Patients treated with Spine Jack® had more efficient height
restoration and kyphosis correction and a lower recurrent fracture rate
than patients treated with vertebroplasty without increased risk of
adjacent or nonadjacent fractures {[}4{]}.

In patients with endogenous or exogenous hypercortisolism, bone loss is
more severe in trabecular bone than in cortical bone {[}5{]}. Fractures
affect about 70\% patients with Cushing syndrome. Most of them are
vertebral fractures, so patients suffer from back pain and kyphosis
together with height loss. The fracture risk is related to the age at
onset, disease duration and severity of the disease, even in cured
patients {[}6{]}. The majority of~vertebral fractures~referred
for~vertebroplasty~are secondary to vertebral insufficiency caused
by~osteoporosis {[}1{]}. We report the case of a patient with multiple
vertebral compression fractures (VCFs) secondary to osteoporosis due to
Cushing disease treated with PV with a Spine Jack® system. We did not
find case reports of this type in the literature.

\textbf{CASE PRESENTATION}

This is a 55-year-old man, with central obesity, non-smoker, auto
mechanic technician. In December 2014, he attended the emergency
department complaining of serious low back pain without neurological
deficit associated to impaired deambulation of six weeks secondary to
pain. Low back pain started after lifting a heavy object. Five months
earlier, he was treated symptomatically for back pain related to
domestic activities. On admission, the physical examination demonstrated
localized tenderness and percussion pain at lower thoracic and lumbar
level, with no restriction of the waist motion. Mild dorsal kyphosis was
seen. Muscular tone of the lower limb was normal, and no hypoesthesia
nor paresis of the lower limb was observed. There was no evidence of
bladder or bowel dysfunction. Physiological reflexes were existent
without any pathological ones. We apply the Oswestry score of 72\% and a
visual analogue scale (VAS) score of 9 points. Initially, plain X-rays
showed a biconcave fracture of L1 with a height loss of 90\%, biconcave
fracture of L4 and subchondral sclerosis in the endplate of L5 and the
superior plates of L3 and L2 (Figure 1 (A)). The computed tomography
(CT) scan showed new fractures in T12, T11, T8, and T5 (Figure 1 (B)).
Subsequently, we performed a magnetic resonance image (MRI) that
confirmed vertebral compression fractures (VCFs) in T5, T8, T11, T12,
L1, L2, L3, L4, and L5 (Figure 1 (C)). Patient was elected to undergo
surgical repair with ambulatory pre-surgical work-up.

In the next months, the patient was diagnosed with difficult-to-control
systemic arterial hypertension. Even though the patient never had
exogenous steroid exposure, impaired fasting glucose was found. A bone
mineral density measurement was performed which revealed a T-score of
\selectlanguage{english}-2.5 in total hip and a T-score of \selectlanguage{english}-3.2 in the left femoral neck,
confirming suspicion of osteoporosis. His base morning cortisol and
adrenocorticotropic hormone~(ACTH) were found to be 1,625 (normal range
126--662) nmol/L and 62.2 (normal range 0--35) pmol/L, respectively.
Cortisol was suppressed to 86\% with high-dose dexamethasone. A brain
MRI was performed that showed a mass in the sellar region measuring 29
mm with invasion of both cavernous sinuses, suggestive of pituitary
macroadenoma (Figure 2 (A)). Finally, we concluded that it was Cushing
disease caused by an ACTH-secreting pituitary adenoma. Multiple
osteoporotic VCFs were found to be secondary to this disease.

With diagnosis of nine VCFs we decided PV as treatment which was
performed with a Spine Jack(r) intracorporal implant device. In May 2016,
a 3-steps staged repair was decided at multiple levels, as follows: 1)
T8, T11, L1 and L4; volumes of cement used were 4 ml, 4 ml, 4 ml, and 3
ml, respectively; 2) L2, L3, and L5; volumes of cement used were 3 ml, 4
ml, and 4 ml, respectively; and 3) T5 and T12; volumes of cement used
were 3.8 ml and 4 ml, respectively. The patient had minor leakage of
cement from T5 without motor weakness, and he was treated with a
laminectomy and remotion of the leaked cement. Spine CT and MRI (Figure
3 (A, B)) were performed after the last Spine-Jack(r) procedure.

The post-operative outcome after the treatment of nine chronic VCFs
showed an improvement of 30 points for the Oswestry score, a VAS score
of 0 and the patient achieved autonomous ambulation (Figure 4). A
partial restoration of vertebral height with craniocaudal expansion was
obtained holding the axial vector. At 33 months of follow-up, an
increase of the mid vertebral height at thoracic levels of 4.75 mm on
average was documented (Table 1). After four years, we found no decrease
in vertebral height, an improvement of 7 degrees in the kyphotic angle,
and absence of new fractures. In December 2016, the patient underwent
transsphenoidal resection of the sellar lesion and pathology was
adenoma. Post-surgery MRI shows persistence of residual tumor in the
cavernous sinuses (Figure 2 (B)). The patient has not yet achieved the
cure criteria for Cushing disease.

\textbf{DISCUSSION}

One of the first symptoms in patients with Cushing disease is the
fracture of long bones or vertebrae. Therefore, it is common to find
fractures before the diagnosis, so it is necessary to perform an
exhaustive search for underlying causes in patients who arrive with
multiple nontraumatic fractures. Our patient had limitations in
mobility, collapse of the vertebral body resulting in a kyphotic
deformity, and loss of autonomy. It was difficult to identify the
location of the fracture because patients with multiple fractures do not
present with the typical clinical presentation. After PV, the patient
had partial correction of kyphosis and remains without neurological
deficits despite having nine chronic VCFs. Inherent to the treatment,
there is a risk of new fractures, mainly in patients with multilevel
treatment. However, after four years of VP, the patient had not
presented with new vertebral fractures.

Patients treated with PV had statistically significant improvements in
pain relief and a similar incidence of adjacent vertebral fracture
compared with patients who underwent traditional treatment {[}7{]}. The
time of fracture is important for pain relief; the indication for
treatment must focus on the fracture age: acute (6 weeks), subacute
(6--12 weeks), and chronic (12 weeks). Evidence has shown that patients
with severe pain treated within the first six weeks of fracture are
suitable to undergo PV {[}8{]}. The VERTOS {[}9{]}, FREE {[}10{]},
INVEST {[}11{]}, and KAVIAR {[}12{]} studies showed a good outcome in
patients treated with PV compared with the outcomes for patients who
underwent different treatments for osteoporotic VCFs. A meta-analysis
comparing vertebroplasty and kyphoplasty did not show any differences in
back pain or the disability pain scores at any time point {[}13{]};
kyphoplasty is superior to vertebroplasty in restoring the height of
vertebrae (88-93\%), but the control of pain is similar for both
(90-95\%) {[}14{]}. PV may be the best way to relieve pain; conservative
treatment might lead to decrease the incidence of new fractures, and
balloon kyphoplasty might have the lowest risk of all-cause
discontinuation in older people with osteoporotic VCFs {[}15{]}. Some
studies have shown that the endplate fracture reduction gained by
inflation one tamps cannot be maintained after deflation {[}16,17{]}.

During VP, the high-pressure injection of low viscosity cement directly
into the cancellous bone makes it difficult to control the cement in the
vertebral body. The risk of cement leaking outside the vertebral body is
unpredictable {[}18{]}; According to recent results, the rates of cement
leaking may reach 65\% {[}19{]}. Major complications can be cement
embolism as Rahimi reported a case in 2018 {[}20{]}.

Rashid presented similar case of 36-year-old women with VCFs secondary
to hypercortisolism induced by a bronchial carcinoid tumour {[}21{]}.
Furthermore, Tian reported a case of multilevel VCFs related to chronic
glucocorticosteriod use {[}22{]}. In none of these cases did they
achieve PV with the Spine Jack(r) system. The maximum number of vertebrae
that can be injected in one session is debatable; single- level
injection is associated with better outcomes than multilevel injection
{[}23{]}. Some studies have suggested doing no more than three levels of
injection during one session to reduce the complications associated with
PV and to avoid patient discomfort {[}24{]}. Zoarski suggested that only
five levels can be treated simultaneously and that the use of eight
levels is not acceptable {[}25{]}. Mailli found no difference in PV with
more than three levels per session {[}26{]}. A meta-analysis suggested
that the intravertebral cleft, cortical disruption, low cement
viscosity, and high volume of injected cement may constitute a high risk
for cement leak after vertebroplasty or kyphoplasty. The patient's age,
sex, and fracture type, as well as the operation level and surgical
approach, were not significant risk factors {[}27{]}.

To prevent new fractures, prophylactic PV to adjacent vertebrae is
recommended {[}28{]}. Prediction of which vertebrae are at risk is
difficult, and prophylactic vertebroplasty does not avoid the risk of
recurrence {[}29{]}. The incidence of new vertebral fractures adjacent
or distant to the fractured one after PV ranges between 7\% and 37\%
{[}30{]}. It is still unclear whether new fractures are related to the
natural history of the underlying disease or to the treatment {[}24{]}.
The incidence of new fractures after PV varies between 7.8\% {[}26{]} to
37\% {[}31{]}.

\textbf{CONCLUSION}

Based on this case, we suggest that PV with the Spine Jack(r) system is a
safe and effective treatment option for multilevel VCFs due to Cushing
disease, however more cases are needed to be treated in order generalize
this type of treatment. Minimal invasion is an excellent option to treat
patients with underlying diseases that cause fractures such as Cushing
disease, thus avoiding major surgery. This report allowed us to achieve
four aims, as follows: pain management, height vertebral increase,
correction of the kyphotic angle, and improvement of the Oswestry score.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1. Initial imaging studies. (A) Lateral radiograph shows diffuse
osteopenia and biconcave fracture of L1 and L4. (B) Sagittal CT image
demonstrates additional compression fractures involving T12, T11 and T8.
(C) Sagittal T2-weighted MRI shows hyperintensity in body of L5, L4, L3,
L2, L1, T12, T11 and T8 due a compression fracture. The patient also had
compression fracture at T5 (not shown).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2. Pre- and post-surgical MRI of the pituitary gland. (A)
Post-contrast coronal T1-weighted MRI shows sellar mass invading the
cavernous sinuses bilaterally. (B) Post-contrast coronal T1-weighted MRI
after transsphenoidal resection shows persistence of residual tumor in
the cavernous sinuses.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Figure 3. Imaging studies after the
Spine-Jack\selectlanguage{ngerman}®\textsuperscript{~}procedure. (A, B) CT and T2-weighted MRI
show post-procedure changes in the bodies of T5, T8, T11, T12, L1, L2,
L3, L4 and L5, which correspond to the
Spine-Jack®\textsuperscript{~}system.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Figure 4. Patient showed a 30-point improvement for Oswestry score, VAS
score of 0, and achieved autonomous ambulation after PV of nine VCFs.

\textbf{Table 1. Increase in vertebral height in millimeters
post-vertebroplasty at 33 months of follow-up.}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Level\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Anterior vertebral height\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Mid vertebral height\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Posterior vertebral height\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
T5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
T8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
T11\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
T12\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
L1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
L2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
L3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
L4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
L5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Thoracic average\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.25\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.75\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.75\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Lumbar average\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

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