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\begin{document}

\title{Iatrogenic Harlequin syndrome after thoracic spine surgery: a case
report and literary review}



\author[1]{Zeyad Abousabie}%
\author[2]{Mohamed Almzeogi}%
\author[3]{aleksandar janicijevic}%
\author[1]{Jelena  Kostic}%
\author[3]{Goran  Tasic }%
\affil[1]{Klinicki centar Srbije}%
\affil[2]{Univerzitetski klinički centar Srbije}%
\affil[3]{klinicki centar srbije klinika za neurohirurgiju}%


\vspace{-1em}



  
  \date{May 03, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Here we present a unique case of Harlequin syndrome without Horner
syndrome after contralateral Th3 intradural tumor resection. Harlequin
sign in our case presented probably to resection of sympathetic nerves
while removing meningioma. Syndrome is rare in neurosurgical procedure,
but we think that surgeons must be aware of it.%
\end{abstract}%



\sloppy


Iatrogenic Harlequin syndrome after thoracic spine surgery: a case
report and literary review\selectlanguage{english}
\begin{longtable}[]{@{}l@{}}
\toprule
Kostic J , Abousabie.A.Zeyad, Almzeogi.A.Mohamed,
Janicijevic.M.Aleksandar, Tasic.Goran\tabularnewline
\midrule
\endhead
Clinic of Neurosurgery, Clinical center Serbia.\tabularnewline
Zeyad Ali Salem Abousabie,.Email :ziad.znati@gmail.com, Mobile: +381
695218287\tabularnewline
\bottomrule
\end{longtable}

\textbf{Clinical message}

The Iatrogenic Harlequin syndrome is still a rare complication,
especially in neurosurgical procedure but we think that the surgeons
must be aware of this condition as a possible complication after the
neurosurgical procedure.

\textbf{Background}

\textbf{Case summary:} 36 years old male with back pain with paresthesia
of the right leg for over a one-year period. Magnetic resonance imaging
(MRI) showed intraduralextramedullary tumor. Tumor resection was
performed. Control magnetic resonance imaging (MRI) showed no signs of
residual tumor, recurrence of tumor or signs of ischemia. Six months
after the operation, the patient developed Harlequin syndrome with no
Horner's syndrome.

\textbf{Method:} The PubMed database was searched online (PubMed,
http:// pubmed.com). A search query using Harlequin syndrome revealed
129 published cases of which 23 was iatrogenic. Of 23 patients female
sex was predominant -15:8 ratio in which 8 were pediatric patients.

\textbf{Objective:} Harlequin syndrome in neurosurgical procedure is
rare, but we think that the surgeons must be aware of this condition as
a possible complication after the neurosurgical procedure.

\textbf{Conclusion:} Harlequin syndrome as a condition often frightens
the patients since it happens after the operation, while they perform
their usual activities. In most cases (about 80\%) it resolves by itself
within few hours.

\textbf{Keywords} : Case report, harlequin syndrome, thoracic spinal
cord, autonomic disorder.

\textbf{Introduction} :

Harlequin syndrome is still a rare, uncommon autonomic disorder caused
by dysfunction of sympathetic innervation of the face. The symptoms that
characterize it are unilateral loss of flushing of the face and neck and
anhidrosis with compensatory flushing and sweating on the contralateral
side. Horner's syndrome may be present.\textsuperscript{1}

In most of the casesit is primarily idiopathic, but it can be associated
with diabetic neuropathy, GuillianBarre syndrome, Bradbury-Eggleston
syndrome, brain stem infarction,

superior mediastinal neurinoma and internal carotid artery dissection
(secondary Harlequin syndrome) or as accidental injury to the
sympathetic nervous system after invasive procedure - surgical
procedures, central line insertion, or a peripheral nerve block
(iatrogenic Harlequin syndrome) \textsuperscript{2,3,4,}This syndrome
may be transient or permanent.\textsuperscript{5,6,7}

To the best of our knowledge the syndrome has been associated with
invasive procedures such as thoracotomy, cervical discectomy or
paravertebral nerve block. Here we present a unique case of Harlequin
syndrome without Horner syndrome after contralateral Th3 intradural
tumor resection.

Case report:

36 years old male presented with the occasional back pain with
paresthesia of the right leg for over a one-year period. Magnetic
resonance imaging (MRI) showed intraduralextramedullary tumor,
hyperintense mass on T1 - weighted contrast images, ventrolateral to the
right in the level of Th3 corpus, dimensions 1.7mm x 1mm (figure 1).

Neurological examination on admission was entirely normal,without any
neurological deficit, without sensory level. The decision was made to
proceed with the resection of the tumor.

Right sided hemilaminectomy was performed at the level of Th3. After the
initial exposure of the tumor, which was solid, adherent to adjacent
nerves, the tumor was totally resected. No intraoperative complications
were noted.After the operation patient recovered well, without any
neurological deficit. Subsequent histological analysis revealed that the
tumor was transitional meningioma WHO grade I.

The patient was doing well, he returned to his regular activities. Six
months after the operation, during the exercise the patient developed
left side facial flushing, following sweating on the left side of the
torso and face. Neurological examination was normal; there were neither
Horner's syndrome nor any history of this occurring previously. No other
symptoms were evident.(figure 2 was provided by patient).Control
magnetic resonance imaging (MRI) showed no signs of residual tumor,
recurrence of tumor or signs of ischemia (figure 3 and 4). On follow-up
there was no recurrence of Harlequin syndrome.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 1(preoperative MRI)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Figure 3 (postoperative MRI axial T1 with contrast)\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image5/image5}

\end{center}
\end{figure}

Figure 4 (postoperative MRI T2 sagital view)

Discussion:

The first description of Harlequin syndrome was in 1988 by Lance at
al.\textsuperscript{1}They described five cases of adult patients with
unilateral flushing and sweating with contralateral anhidrosis. In years
that followed (1993) this phenomenon was described as a dysfunction of
the pregangliotic and postganglioticcervical sympathetic nerve fibers
and parasympathetic neurons of ciliary ganglion\textsuperscript{5}.

The anatomy of sympathetic fibers innervating the face are made of a
three- neuron chain pathway: first neurons originate in hypothalamus and
synapse in the intermediolateral cell column of the upper thoracic
spinal cord with preganglionic fibers (second neurons) - somewhere
between Th1 -- Th3 \textsuperscript{9}. Preganglionic fibers leave the
spinal cord at Th2 -Th3, synapsing with the postganglionic fibers (third
neurons) in superior cervical ganglion. Then, postganglionic fibers
leave cervical ganglion passing either along internal carotid artery to
supply forehead, nose and eye, or along external carotid artery to
supply the rest of the face. Preganglionic oculosympathetic neurons
originate at the level of Th1.

In our case the lesion is at the level of inferior cervical ganglion
(stellate ganglion) given the symptoms -- unilateral facial flushing and
upper extremity and trunk, without Horner's syndrome. Harlequin sign in
our case presented probably due to resection of sympathetic nerves while
removing meningioma.

The PubMed database was searched online (PubMed, http:// pubmed.com). A
search query using Harlequin syndrome revealed 129 published cases of
which 23 was iatrogenic. (Table 1) Of 23 patients female sex was
predominant -15:8 ratio in which 8 were pediatric patients.

Most of the patients had undergone a thoracic surgery (8 patients),
Intrathecal pump in 3 patients, total thyroidectomy and neck surgery (3
patients), five patients underwent spinal nerve block, and only two had
neurosurgical procedure.

Conclusion:

Harlequin syndrome as a condition often frightens the patients since it
happens after the operation, while they perform their usual activities.
In most cases (about 80\%) it resolves by itself within few hours. The
patient fear and anxiety can be calmed by explaining the benign nature
of the condition. If the patient has long term sequelae and the symptoms
aren't tolerable, a contralateral sympathectomy or stellate ganglion
block are options for symptom relief\textsuperscript{32,33}.\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& Authors & Age & Sex & Pathology & Procedure & Horner's
sy.\tabularnewline
\midrule
\endhead
1 & Kydes A. T. et al.\textsuperscript{13} & 2 y. & M & Paraspinal
neuroganglioma & Thoracotomy Th2-Th6 & no\tabularnewline
2 & Zinboonyahgoon N. et al.\textsuperscript{14} & 58y & F & Metastatic
non small sell lung cancer & Intrathecal pump --tip at Th8 level &
no\tabularnewline
3 & Zinboonyahgoon N. et al.\textsuperscript{14} & 37y & F & Metastatic
breast cancer & Intrathecal pump --tip at Th8 level & no\tabularnewline
4 & Soto G.D. et Al.\textsuperscript{15} & 45y & F & Pituitary
macroadenoma & Transsphenoidal endoscopic surgery & no\tabularnewline
5 & Jai N. Darvall et Al.\textsuperscript{16} & 26m & M & Left side neck
mass & Resection of the mass (adherent to jugular vein, carotid artery,
trachea and esophagus) & yes\tabularnewline
6 & Jeon Y.J. et al.\textsuperscript{17} & 6y & M & Mass in posterior
mediastinum extension to Th2-Th5 & Thoracotomy Th2- Th5 &
no\tabularnewline
7 & Lee D.H et Al\textsuperscript{18} & 11y & M & Right side neck mass &
Resection of the mass underneath Vagus nerve & yes\tabularnewline
8 & Jung J.M. et al\textsuperscript{19} & 43y & F & Solitary pulmonary
nodule & Endoscopic resection & no\tabularnewline
9 & Hussein N. et al\textsuperscript{20} & 58y & F & Squamocellular
carcinoma of right upper lobe & Right lobectomy & no\tabularnewline
10 & Lefevre A. et al\textsuperscript{21} & 10y & M & Thorasic epidural
anesthesia & Nuss procedure & no\tabularnewline
11 & Fringeli Y. et al.\textsuperscript{22} & 55y & F & disc herniation
C6-7 & Anterior C6-7 discectomy with cage fusion & yes\tabularnewline
12 & Viswanath O et al\textsuperscript{23} & & F & left lower lobe of
the lung mass & Th3 --Th11 nerve block & no\tabularnewline
13 & Irtan S. et al\textsuperscript{24} & 9m & F & Left stellate gangla
neuroblastoma & Resection of the tumor with extension to Th2 &
yes\tabularnewline
14 & Nagasaka Y. et al.\textsuperscript{25} & 64y & F & breast
adenocarcinoma & Paravertebral block & no\tabularnewline
15 & Wagner R. et al.\textsuperscript{26} & 2y & F & tracheoesophageal
fistula & Thoracoscopic operation & no\tabularnewline
17 & Sullivan T. et. al.\textsuperscript{27} & / & F & breast cancer &
erector spine plane block & no\tabularnewline
18 & Yamaguchi H. et al.\textsuperscript{28} & 1y & M & Esophageal
atresia & Rightsided thoracotomy & no\tabularnewline
19 & Mohindraet al.\textsuperscript{29} & 84y & M & left-sided neck lump
/papillary thyroid carcinoma/ & total thyroidectomy with left side neck
dissection & yes\tabularnewline
21 & Tyrell J.R.J. et al.\textsuperscript{30} & 76y & M & lung
adenocarcinoma & extra pleural bupivacaine infusion after thoracotomy &
no\tabularnewline
22 & Redondo J. M. et al.\textsuperscript{31} & 31y & F & epidural
anesthesia in labor & Cesarean section & yes\tabularnewline
23 & Sribnik E.A. et al.\textsuperscript{32} & 42y & F & metastatic
breast cancer & mastectomy and right partial pneumonectomy &
no\tabularnewline
\bottomrule
\end{longtable}

Table (iatrogenic cases of Harlequin syndrome)

Data Availability Statement: All data are fully available without
restriction

UNIVERSITY CLINICAL CENTER

OF SERBIA

\textbf{11000 Belgrade; Pasterova St. No. 2, REPUBLIC OF SERBIAETHICS
COMMITTEE}11000 Belgrade, Pasterova St. No. 2 +381 11 366 2080, 264
4850, Fax: +381 11 306 7180 Ref. o.: 175/6 Date: 27.04.2021 Based on the
provisions of the Republic of Serbia Healthcare Law (,,Official Gazette
of the Republic of Serbia'' no. 25/2019 ), Law on Patients' Rights
(,,Official Gazette of the Republic of Serbia'', no. 45/13), Law on
Personal Data Protection (,,OfficialGazette of the Republic of Serbia''
no. 97/2008, 104/2009 and other laws), Law on health documentation and
records in the field of health (,,Official Gazette of the Republic of
Serbia'' , no. 123/2014 , 106/2015 , 105/2017), acting in accordance
with the provisions of the Rulebook of procedures for the Ethics
Committee of the University Clinica l Center of Serbia no. 432/8 from
28.02.2020, the Ethics Committee of the University Clinical Center of
Serbia, in the composition, as follows: Prof. Andrija Bogdanovic MD PhD
- Chairman, Prof. Brani slava Milenkovic MD, PhD, Prof. Branislava
Ivanovic MD, PhD, Prof. Marina Svetel MD PhD, Dijana Sefer MD, Prof.
Aleksandra Jotic MD, PhD, Prof. Aleksandra Peric-Popadic MD, PhD, Prof.
Milos Korac MD, PhD, Prof. Aleksandar Stefanovic MD, PhD, Prof. Milan
Latas MD, PhD and Docent Danijel Galun MD, PhD - all Specialists
employed in the University Clinical Center of Serbia, ruling on request
of Clinic for Neurosurgery of the University Clinical Center of Serbia
on its 2\textsuperscript{nd} e-meeting, held on 27.04.2021, adopted the
following DECISION It is granted publication of the paper/ case report
called: Latrogenic Harlequin syndrome after thoracic spine surgery: a
case report and literary review. Authors of the paper (case report) are:
Jelena kostic MD, Zayed Abousabie MD, Mohamed Almezogi MD, Aleksandar
Janicijevic MD and Prof. Goran Tasic MD, PhD. Expert collegiate of the
Clinic for Neurosurgery of the University Clinical Center of Serbia gave
the consent for publication of the case report. Paper would be published
in the foreign medical journals. {[}Place of the stamp: round official
seal{]} CHAIRMAN OF THE ETHICS COMMITTEE sgd. Professor Andrija
Bogdanovic MD, PhD\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image7/image7}

\end{center}
\end{figure}

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