Harlequin syndrome following microwave ablation in a child with a symptomatic paraspinal mass

Abstract

Our goal is to describe a case of Harlequin syndrome associated with microwave ablation in the treatment of a symptomatic paraspinal mass in a child, along with a summary of the literature. Our patient is the only known case of persistent Harlequin syndrome associated with microwave ablation treatment of a symptomatic paraspinal mass. Harlequin syndrome is a rare neurological condition characterised by unilateral sweating and flushing of the face, neck and/or upper chest. The specific mechanism is unclear, but the majority of cases are believed to be a result of contralateral lesions along the sympathetic chain. CT-guided microwave ablation therapy is a minimally invasive technique used as an alternative to surgery in this case due to the risk and morbidity associated with excision of the mass. There is limited literature assessing the use and inherent risk of developing complications following microwave ablation to the paraspinal region in the paediatric population.

Background

Harlequin syndrome is a rare neurological condition characterised by unilateral sweating and flushing of the face, neck and/or upper chest. Although the specific mechanism is unclear, the majority of cases are believed to occur as a result of contralateral nerve damage along the bilaterally symmetric sympathetic chain, in close proximity to the stellate ganglion and the superior cervical ganglion (T2–T3).¹ A lesion in the nerves of the sympathetic trunk can be the cause of Harlequin syndrome, as well as another neurological condition known as Horner syndrome. Although they may present concurrently in patients with sympathetic chain injury, their clinical presentations are clearly distinct. Horner syndrome can be distinguished from Harlequin syndrome as symptoms of Horner’s are ipsilateral in relation to the site of lesion and is characterised by miosis, partial ptosis, anhidrosis and enophthalmos.² While Harlequin syndrome does not affect long-term survival, the quality of a patient’s life may be negatively impacted by the neurological condition. Children and parents of children with Harlequin syndrome may suffer from psychological stresses associated with social embarrassment that arises due to unilateral facial flushing and sweating.^{1 3}

Harlequin syndrome has been characterised as either primary or secondary.³ Primary classification refers to congenital or idiopathic aetiology, while secondary is acquired via organic lesions or iatrogenic causes.³ Herein, an iatrogenic cause of Harlequin syndrome is discussed after the use of microwave ablation of a paraspinal mass. Microwave ablation, a minimally invasive imaging-guided percutaneous technique, uses antennae to deliver electromagnetic microwaves to the target, resulting in coagulative necrosis via agitation of ionic molecules and heat.⁴ Although microwave ablation is a technique commonly used in the treatment and palliation of neoplasms in the adult population, there is no large series in the literature regarding its use in children, especially in the management of paraspinal masses.⁵

Case presentation

We describe a previously healthy 16-month-old girl who presented with 24 hours of bilateral lower extremity weakness, generalised irritability and pain. CT scan of the chest/abdomen/pelvis and then MRI of the spine revealed an infiltrating, extradural, dumbbell-shaped tumour at the T6–T7 site. Due to her symptomatology, she was taken directly to the operating room by neurosurgery for laminectomy decompression. Pathology reported small areas consistent with neuroblastoma with MYCN not amplified, and a diagnosis of intermediate-risk paraspinal thoracic neuroblastoma was made. She was started on a four-cycle Children’s Oncology Group regimen of chemotherapy consisting of carboplatin, etoposide, cyclophosphamide and doxorubicin administered at 3-week intervals and was rescanned after every two cycles. Following completion of the four cycles of chemotherapy, MRI showed an increase in the size of the mass with encroachment of the cervical spinal cord. Subsequently, a metaiodobenzylguanidine (MIGB) scan had increased uptake at the site of mass (measure of tumour activity). A biopsy of the mass showed that the neuroblastoma had differentiated into a benign ganglioneuroblastoma. At our multidisciplinary tumour board, discussion with neurosurgery and paediatric surgery concluded that a resection so close to the T6–T7 sympathetic region would be very risky and morbid. Instead, microwave ablation therapy was offered after informed consent. The patient was 3 years of age at this time. CT-guided microwave ablation at the left T3–T6 region was performed by interventional radiology. Using intermittent CT guidance, three 17 G × 15 cm Certus microwave ablation probes were advanced from a posterior approach into the left paraspinal mass. Three minutes of ablation using 60 W per probe was performed. CT showed the expected ablation effect in the area and the superior and inferior probes were removed. The central probe was retracted approximately 1.5 cm and an additional 4 min of microwave ablation was applied. A final CT scan was taken postablation and compared with the initial CT, showing the expected finding of necrosis, evident by air seen within the ablated area created by the microwave (figures 1 and 2). The procedure was well tolerated by the patient. While in postoperative care, symptoms characteristic of Harlequin syndrome were contralaterally manifested in the patient, namely unilateral (right side) flushing and redness of the face (figure 3).

Figure 1.

CT scan of the patient in prone position taken immediately before microwave ablation therapy was performed. The area of the tumour is marked with an arrow.

Figure 2.

CT scan of the patient in prone position taken immediately following the completion of microwave ablation therapy. Air can be seen within the area of the tumour, marked with an arrow, indicating necrosis in response to the microwaves.

Figure 3.

A postoperative photo of contralateral hemifacial flushing and sweating.

Treatment

Due to the benign nature of Harlequin syndrome, this patient is not receiving any treatment for her persistent symptoms. When the symptoms arise during activity, she is instructed by her parents to rest until the unilateral facial flushing and sweating subside. Typically, Harlequin syndrome is not treated. There are a few potential therapies mentioned in the literature. Surgical sympathectomy may be performed ipsilateral to the symptomatic side, although this may cause compensatory flushing and sweating elsewhere in the body.¹ Less invasive alternative treatments include repeated stellate ganglion blocks or botulinum toxin injections, the latter proving effective and safe with a high degree of satisfaction.^{1 6}

Outcome and follow-up

After completion of the chemotherapy regimen and microwave ablation therapy, the patient followed up with paediatric oncology every 6 months for 2 years, obtaining MRI and MIGB scans for surveillance of the paraspinal mass. Her first follow-up MRI initially performed at 4 months postablation compared with the MRI prior to treatment can be seen in figures 4 and 5. She now continues to get repeat imaging once per year and will do so for an additional 5 years. The latest imaging of the patient at 5 years of age shows a significant decrease in mass size, decompression of the spinal cord and necrosis of the mass, which is also negative on MIGB scans. The patient overall is doing well and is developmentally normal. She has not had any neurological problems such as difficulty walking, pain, tingling, weakness or lack of coordination on physical examination. There is, however, the persistence of unilateral facial flushing and sweating.

Figure 4.

MRI of the tumour (arrow) before microwave ablation was initiated.

Figure 5.

MRI of the tumour (arrow) 4 months following initiation of microwave ablation therapy.

Discussion

Our case explicitly focuses on the iatrogenic cause of Harlequin syndrome in paediatric patients. We conducted a literature search on PubMed and Google Scholar using the keywords and phrases ‘harlequin syndrome’, ‘paraspinal mass’ and ‘pediatric’. In the current literature, there are six reported cases of paediatric patients with Harlequin syndrome associated with iatrogenic treatment of a paraspinal mass. All six cases presented after surgical resection of a mass in the cervical neck or thoracic paraspinal region.^{2 7–11} The characteristics of the patients who developed Harlequin syndrome described in each of these cases are summarised in table 1.

Table 1.

Characteristics of cases of postoperative Harlequin syndrome associated with iatrogenic treatment

Location of mass	Paraspinal mass at T6–T7	Right cervical neck mass	Left cervical neck mass	Left cervical neck mass	Right cervical neck mass	Left cervical neck mass	Left paraspinal mass at T2–T6
Gender	Female*	Male	Female	Male	Not specified	Female	Male
Age at diagnosis	16 months	11 years	3 months	5 years	2 years	9 months	2 years
Initial diagnosis	Neuroblastoma differentiated into benign ganglioneuroblastoma	Schwannoma	Neuroblastoma	Diagnosis not provided	Cystic hygroma	Stellate ganglia neuroblastoma	Ganglioneuroma
Type of invasive procedure	CT-guided microwave ablation therapy at the left T3–T6 region	Radical excision	Radical excision	Radical excision	Radical excision	Radical excision	Thoracoscopic resection
Outcome	Persistent.	Spontaneously resolved within 1 hour postoperation. Concomitant Horner syndrome resolved within the next 3 months.	Persistent.	Spontaneously resolved within 6 hours postoperation. Concomitant Horner syndrome resolved the next morning.	Spontaneously resolved within 3 hours postoperation.	Horner syndrome developed postoperatively and resolved prior to discharge 5 days following surgery. Later developed Harlequinism symptoms 6 months after excision. Symptoms are persistent.	Persistent.
Case authors		Lee et al2	Padda et al7	Kil et al8	Turco and Farber9	Irtan and Auvrignon10	Kydes et al11

*Indicates the patient described in the present report.

Harlequin syndrome was first described in 1988 by Lance et al¹² as the onset of contralateral and unilateral facial flushing and sweating during periods of heat exposure, stress or exertion. It is thought to be due to autonomic dysfunction caused by unilateral disruption to sympathetic fibres, which results in the inability for vascular dilation to occur in response to such stimuli.^{12 13} Consequently, the sympathetic deficit on the injured side causes marked flushing and sweating to appear on the opposite side. The excessive symptoms presenting on the uninjured side is thought to occur secondary to over-reactive sympathetic compensation, which allows for heat regulation to the entire face.³ It can be differentiated from Horner syndrome, another known dysautonomia, by the lack of ocular signs such as ptosis and miosis. Sparing of the T1 spinal cord segment, where preganglionic oculomotor fibres exit the spinal cord, and/or lack of stellate ganglion involvement along the sympathetic chain are postulated mechanisms of the absent ocular symptoms.⁸

Harlequin syndrome has been characterised as being either primary or secondary. Willaert et al³ performed a literature review that identified 83 patients, with an average age of 43 (range 0, 5–74 years), with Harlequin syndrome. Out of those studied, primary Harlequin syndrome was seen in nearly three-quarters of the patients, while the remaining quarter appeared to be due to organic lesions or iatrogenic damage.³ Comparatively, there were also significantly fewer paediatric than adult cases presented in Willaert et al’s review.³ These data are important to note as most, if not majority, of paediatric cases in the literature discuss the secondary aetiology of Harlequin syndrome, just as this report focuses exclusively on the iatrogenic cause.¹⁴

As reported, all the patients who presented with a cervical neck mass (five out of the six) underwent radical surgical excision.^{2 7–10} It can be postulated that sympathetic fibres were directly disrupted during blunt dissection and/or removal of the mass that was in close proximity to the sympathetic chain. Interestingly, three out of those five cervical neck mass cases presented with concomitant Horner syndrome.^{2 8 10} It is likely that damage occurred to both the cervical sympathetic nerves as well as the superior cervical ganglion during surgery that ultimately led to the development of both syndromes.⁸ What is difficult to explain is the transient nature of the syndromes in these three cases, in addition to the case described by Turco and Farber⁹ which presented solely with transient Harlequinism. The latter concluded that an alteration in the sympathetic fibres during surgery, such as stretching as opposed to transection, may explain why the symptoms presented transiently and did not persist.⁹ Another interesting phenomenon presented in the case report written by Irtan and Auvrignon¹⁰ was the 6-month delay in the development of persistent Harlequin syndrome after transient Horner syndrome occurred and resolved postoperatively in a 9-month-old with a stellate ganglia neuroblastoma. This was the only case in our literature search that did not present with immediate symptomatology.

The remaining case of a 2-year-old boy, with a similar diagnosis to our patient, involved a left paraspinal mass at T2–T6. This was the only case in which a minimally invasive surgical approach was used: thoracoscopic resection. Even without open radical surgical resection, there was inevitable injury to the sympathetic chain ganglia during tumour removal that resulted in persistent Harlequin syndrome in this patient.¹¹

Our patient is unique in that surgical excision of her paraspinal mass was not performed. Rather, interventional radiology performed CT-guided microwave ablation therapy due to the risk and morbidity associated with surgical resection of the mass. A disadvantage of using this technique in the spine is the inherent risk of injury to the surrounding neural structures. Although ablated tissue, including the hypoattenuating outer margins, is identified on CT throughout the procedure, the margins of the ablation zone are not exact.⁴ Therefore, our patient’s development of Harlequin syndrome was a complication most likely due to the interdigitation of the ganglioneuroblastoma within the sympathetic chain as well as the proximity of the sympathetic chain ganglia to the area of ablation. To our knowledge, this is the first known case describing the development of Harlequin syndrome following microwave ablation therapy to the paraspinal region. After an extensive search of the literature, information regarding microwave ablation utilisation in the paediatric population is limited to its application in the treatment of osteoid osteomas and unresectable liver tumours.^{15 16} Common complications listed of microwave ablation therapy for these neoplasms include fever, pain, haemoglobinuria (for liver lesions exclusively), subjective numbness surrounding the access site and superficial skin infection at the probe access site; all these symptoms were transient and resolved by subsequent follow-up visits.^{15 16} Further research concerning the efficacy and safety of microwave ablation to the paraspinal area specifically is needed in the paediatric population.

We hope that this case may increase awareness of the risk of iatrogenic Harlequin syndrome when considering microwave ablation, other minimally invasive procedures, as well as surgical excision treatment for children who present with a paraspinal mass.

Patient’s perspective.

Every time my daughter runs, dances, or over-exerts herself, half of her face turns red and has accompanied sweating. When this occurs, I prompt her to take a break and cool down with a glass of water. My daughter is nearing 6 years of age, and recently has begun asking questions pertaining to her symptoms and why they present. She is also starting to feel embarrassed when the redness manifests. Fortunately, she has never complained to me about pain or discomfort associated with the syndrome. I anticipate that as she continues to grow older, she will ask more questions regarding why the symptoms are occurring and may wish to seek out means of treatment. My daughter currently is not complaining about other children questioning or making fun of her regarding her symptoms. I worry about the effects of scrutiny and bullying by peers and believe it may be important to continue to monitor her interactions with other children and to educate them about her condition.

Learning points.

• Harlequin syndrome is a rare, non-life-threatening neurological condition characterised by unilateral sweating and flushing of the face, neck and/or upper chest.

• Harlequin syndrome can be a complication of paraspinal mass excision surgery, even when minimally invasive procedures are performed, such as microwave ablation.

• Although characteristically seen in radical surgical excision, this is the first case in the literature describing the development of Harlequin syndrome following CT-guided microwave ablation to the spine.

• Further research is needed concerning the efficacy and safety of using microwave ablation therapy for the treatment of paraspinal masses in the paediatric population.