Pediatr Radiol DOI 10.1007/s00247-015-3341-9
ORIGINAL ARTICLE
Neuroimaging experience in pediatric Horner syndrome Nadja Kadom & N. Paul Rosman & Shams Jubouri & Anna Trofimova & Alexia M. Egloff & Wadih M. Zein
Received: 30 September 2014 / Revised: 31 January 2015 / Accepted: 6 March 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Background Horner syndrome in children is rare. The frequency and spectrum of malignancy as the cause of Horner syndrome in children remains unclear. Also unclear is whether the imaging work-up should include the entire oculosympathetic pathway or should be more targeted. In addition, the value of cross-sectional angiographic imaging in Horner syndrome is uncertain. Objective To review imaging pathology in a cohort of children with Horner syndrome at a major academic pediatric medical center. Materials and methods We reviewed a 22-year period of CT and MR imaging studies in children with a clinical diagnosis of Horner syndrome referred for imaging. Results We found 38 patients who fulfilled study criteria of Horner syndrome and 6/38 had relevant imaging findings: 2/6 etiologies were neoplastic (congenital neuroblastoma and N. Kadom (*) Department of Radiology, Boston University Medical Center, Boston University School of Medicine, 820 Harrison Ave., FGH Building, 3rd Floor, Boston, MA 02118, USA e-mail: [email protected] N. P. Rosman Division of Pediatric Neurology, Departments of Pediatrics and Neurology, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA S. Jubouri : A. Trofimova : A. M. Egloff Department of Radiology and Diagnostic Imaging, Children’s National Medical Center, Washington, DC, USA W. M. Zein National Eye Institute (NEI), Bethesda, MD, USA
central astrocytoma), 1/6 had a vascular abnormality (hypoplastic carotid artery), 1/6 had maldevelopment (Chiari I malformation), and 2/6 had inflammatory/traumatic etiology (viral cervical lymphadenopathy, post jugular vein cannulation). There was a similar number of congenital and acquired pathologies. The malignancies were found at any level of the oculosympathetic pathway. Conclusion There are treatable causes, including malignancies, in children presenting with Horner syndrome, which justify imaging work-up of the entire oculosympathetic pathway, unless the lesion level can be determined clinically. Keywords Children . Computed tomography . Horner syndrome . Magnetic resonance imaging . Oculosympathetic pathway Abbreviations CT Computed tomography CTA CT angiogram MRI Magnetic resonance imaging MRA MRI angiogram ICU Intensive care unit
Introduction Horner syndrome is a disorder of the oculosympathetic pathway [1]. The incidence of Horner syndrome in children is low, estimated to be 1.42 per 100,000 patients under the age of 19 years [2]. While the diagnosis is made through clinical examination, imaging studies are critical in delineating the nature and extent of any underlying pathology along the oculosympathetic pathway. During the past 20 years, there have been numerous case reports of Horner syndrome, but
Pediatr Radiol
only a few systematic reports on the spectrum of crosssectional imaging findings in children referred for Horner syndrome imaging [3–5]. The oculosympathetic pathway provides sympathetic innervation to the eye through three orders of neurons in specific anatomical locations (Figs. 1 and 2). The first order neurons (central) arise in the posterolateral hypothalamus and descend through the brainstem to spinal cord levels C8-T2 where they synapse with second order neurons at the ciliospinal center (of Budge). Second order neurons (pre-ganglionic) exit the ciliospinal center of the thoracic cord and ascend in the cervical sympathetic trunk, through the brachial plexus, over the lung apex, to synapse in the superior cervical ganglion, located near the common carotid artery bifurcation. Third order neurons (post-ganglionic) leave the superior cervical ganglion and ascend within the adventitia of the internal carotid artery to enter the skull and then the cavernous sinus. Here, these fibers join the ophthalmic division of the trigeminal nerve to enter the orbit. There, the fibers innervate the dilator pupillae muscle and the superior tarsal muscle (Müller’s muscle). Other third order neuron fibers supply sweat glands of the ipsilateral forehead [6]. Hence, Horner syndrome typically presents with a triad of ipsilateral miosis (pupil constriction, due to loss of innervation to the dilator pupillae muscle), ptosis (drooping of the eyelid, due to loss of innervation to the superior tarsal muscle) and anhidrosis (lack of sweat production, due to loss of innervation to the forehead sweat glands).
Horner syndrome can be congenital or acquired. Congenital Horner syndrome is usually symptomatic within the first year of life. Causes of congenital Horner syndrome include birth trauma [7] and congenital abnormalities of the internal carotid arteries, particularly agenesis, because of the intimate relationship between the sympathetic chain and the internal carotid arteries [8–10]. Additional reported causes of congenital Horner syndrome include ectopic thymus in the neck [11] and congenital neuroblastoma in the neck [3]. Rarely, congenital Horner syndrome may be of autosomal dominant inheritance [12]. There are many causes of acquired Horner syndrome. Those seen in children can be of neoplastic or nonneoplastic etiology. Mahoney et al. [4] suggested that in children a neoplastic cause should be presumed until proven otherwise. The most common childhood tumors causing acquired Horner syndrome are neuroblastoma [13], paraganglioma [14, 15] and ganglioneuroma [16]; a less common neoplastic cause is childhood thyroid cancer [17]. A vascular cause is arterial dissection [13]. External trauma causing lower brachial plexus palsy (Klumpke) can result in Horner syndrome [13]. An intraspinal cause of acquired Horner syndrome is syringomyelia [18]. Intrathoracic etiologies are pneumothorax [19] and thoracic empyema [20]. In children, Horner syndrome is acquired in up to 23% of patients [4]. Since many acquired causes of Horner syndrome can be treated, imaging becomes very important in delineating the nature and extent of any underlying disease. Here, we describe our experience using CT and MR imaging protocols in children with a diagnosis of Horner syndrome referred to the Radiology Department at Children’s National Medical Center in Washington, D.C., during a 22-year period.
Materials and methods
Fig. 1 Three levels of the oculo-sympathetic pathway
We retrospectively reviewed CT and MR imaging studies in children with Horner syndrome referred from 1991 to 2012 to the Department of Radiology and Diagnostic Imaging at Children’s National in Washington, D.C. The study was IRB approved. All patients, from newborn to 20 years of age, in whom the outpatient radiology referral stated Horner syndrome, were considered for this study. Since any referral diagnosis was transcribed in the patient history field of the radiology report, we could search for the term “Horner syndrome” with a radiology search engine (Montage Healthcare Solutions, Inc., Philadelphia, PA). Inclusion criteria were selected to maximize the accuracy of the diagnosis Horner syndrome. These criteria were the required presence of unilateral miosis and, in addition, the presence of one or more of the following: ipsilateral ptosis, ipsilateral heterochromia, and/or a positive cocaine eye drop test. Cocaine eye drops block the synaptic reuptake of
Pediatr Radiol
Fig. 2 Normal anatomy of oculosympathetic pathway. First order neurons (dashed line) arises from posterolateral hypothalamus, descends into brainstem and intermediolateral column of the spinal cord, and exits at cervical (C8) and thoracic (T1–T2) levels of spinal cord as second- order neuron (dotted line). Second order pre-ganglionic neurons exit ventral spinal roots (a) and arch over apex of lung to ascend in cervical sympathetic chain, synapsing in the superior cervical ganglion (b) and exiting as third- order neurons (solid lines). Neural fibers for sweating of face, except medial forehead, travel with external carotid artery. Third order post-ganglionic neurons travel with carotid artery (c) into
cavernous sinus and with the ophthalmic branch (d) of the fifth cranial nerve join the nasociliary branch of fifth cranial nerve or pass through ciliary ganglion (e) directly, reaching eye as long (f) and short (g) ciliary nerves. Pre-ganglionic parasympathetic fibers (gray lines) arise from the accessory oculomotor nucleus (h), exit as the oculomotor nerve (i), synapse at the ciliary ganglion, and reach the eye as the short ciliary nerves (Reprinted with permission from Lee JH, Lee HK, Lee DH, et al. [2007] Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location. AJR Am J Roentgenol DOI:10.2214/AJR.05.1588)
norepinephrine, which causes dilatation of a normal pupil, but in Horner syndrome the lack of norepinephrine prevents this mydriatic effect. We could not use anhidrosis as a diagnostic criterion because its presence or absence was not documented in the medical records to which we had access. All clinical information was retrieved from each patient’s medical record. Lastly, only patients who met the above requisite clinical criteria and who also had diagnostic CT or MRI of the brain were included in the review. Many of these patients also had CT or MRI imaging of the neck and upper chest, as well as vascular studies, and those results were included as well.
A single observer (S.J.) conducted the medical records search for all relevant clinical and ophthalmological data. The following clinical information was recorded for every patient: patient age, gender, age of onset of the Horner syndrome, affected side, ophthalmological findings (miosis, ptosis, heterochromia, cocaine eye drop test results), and the portion of the oculosympathetic pathway that was involved (e.g., first, second and/or third order neurons). The following imaging parameters were documented from review of radiology reports in the Medical Center’s Radiology Information System: patient age at time of imaging for Horner syndrome, type of imaging used (CT and/or MRI, vascular imaging studies)
Pediatr Radiol
and the imaging findings recorded. In addition, all imaging studies with findings were again reviewed and interpreted for this study; there were no disagreements with the original interpretation. All cases were then categorized as congenital or acquired and specific causes for the Horner syndrome were further classified as: 1) neoplastic, 2) vascular, 3) maldevelopment and 4) inflammatory/traumatic. Imaging protocols varied for both CT and MRI throughout the 22-year study interval. The most recent imaging protocols were: – –
–
–
–
– –
CT brain: Pre- and post-contrast axial 5-mm images from orbital roof through vertex with coronal reformats. CT neck/upper chest: Post-contrast axial 2.5-mm images (patient weight: 0–11.4 kg) or 3.75 mm helical images from aortic arch to supraorbital ridge with coronal and sagittal reformats. CT angiogram neck/brain: Post-contrast axial 1.25-mm images from aortic arch through lateral ventricles, contrast flow rate 2–4 cc/s, usual image delay 9–14 s (if bolus tracking unavailable) with sagittal and coronal reformats. MRI brain: Pre-contrast sagittal T1 spoiled gradient recalled acquisition (SPGR), axial fast spin echo (FSE) T2, axial fluid attenuated inversion recovery (FLAIR), axial diffusion weighted imaging (DWI) (b=0 and b=1, 000), coronal T1 orbits to pons, coronal T2 orbits to pons, and post-contrast axial T1 brain, coronal T1 orbits through pons with fat saturation, axial T1 orbits to hypothalamus with fat saturation. MRI neck/upper chest: Cover skull base to aortic arch. Pre-contrast sagittal T1 SPGR and sagittal FSE T1, axial spin echo T1, axial FSE T2 with fat saturation, coronal T1, coronal T2, and post-contrast axial and coronal T1 with fat saturation, and sagittal T1 without fat saturation. MR angiography neck: 2-D time-of-flight imaging of the neck with superior saturation pulse, multiplanar maximum intensity projections (MIPs). MR angiography brain: 3-D time-of-flight imaging of the neck with superior saturation pulse with 3-D reformats and multiplanar maximum intensity projections (MIPs).
Descriptive statistical analysis was performed using Stata v13.1 (StataCorp LP, Texas, USA).
Results Our report field search yielded a total of 70 patients in the 22year observation period who had an imaging referral diagnosis of Horner syndrome. There were 38/70 (54%) who fulfilled our inclusion criteria for Horner syndrome: 38/38 (100%) of patients had miosis; 31/38 (82%) of patients had miosis and ptosis; 6/38 (16%) of patients had miosis, ptosis and ipsilateral
iris heterochromia, and 1/38 (2%) patient had miosis and a positive cocaine eye drop test. All these 38 patients had diagnostic imaging studies. The most commonly done imaging study was a complete MRI of the brain, neck, upper chest and an MR angiography of the head and neck (n=32; 84%). The second most common imaging study was a complete CT of the brain, neck, upper chest and a CT angiogram of the head and neck (n=3; 8%), followed by a brain MRI alone (n=2; 5%) and a brain CT alone (n=1; 3%). There were 20 males and 18 females. The mean age at the time of onset of Horner syndrome was 4.1 years (standard deviation [SD]: 6.0 years; median: 1 year; range: newborn20 years) and the mean age at time of imaging was 4.6 years (SD: 5.8 years; median: 6 months; range: 2 months–20 years). The Horner syndrome was right-side in 21 patients and leftside in 17. In 32/38 patients, there were no abnormal imaging findings. In 6/38 (16%) patients, a specific cause for Horner syndrome was found on imaging, with first order neuron (central) pathology in 2 patients (multifocal cerebral astrocytoma, Chiari I malformation), second order neuron (preganglionic) lesions in 3 patients (carotid bifurcation neuroblastoma, inflammatory complication after jugular cannulation, viral/neck lymphadenopathy), and third order neuron (post-ganglionic) lesions in 1 patient (hypoplastic internal carotid artery). The distribution of congenital versus acquired etiologies in the six patients with abnormal imaging findings relative to their age and gender is shown in Table 1. There was a similar number of congenital (n=3) and acquired (n=4) pathologies. Of the six pathologies, five were in the age group 0–4 years and only one patient was 20 years old. A neoplastic etiology was found in 2/38 (5%) patients, one congenital and one acquired. One patient had a congenital carotid bifurcation stage 2A neuroblastoma (Fig. 3), while the other had an acquired Horner syndrome caused by a multifocal cerebral astrocytoma, World Health Organization grade II-III that also involved the hypothalamus (Fig. 4). This patient was treated, but documentation about resolution of Horner syndrome was not found. Interestingly, one patient who was referred for Horner syndrome imaging, but who did not fulfill the minimum clinical criteria to be included in the study, had an imaging diagnosis of a large rhabdoid tumor involving the lung apex, with intraspinal epidural extension from C6-T1 (Fig. 5). A vascular etiology was found in one patient who had a hypoplastic internal carotid artery (Fig. 6). A maldevelopmental etiology was seen in a patient with a Chiari I malformation and hydrocephalus who also had a Horner syndrome; following decompressive surgery for the Chiari I malformation, her Horner syndrome improved. An inflammatory/traumatic etiology was seen in two patients:
Pediatr Radiol Table 1
Seven lesions found on imaging of Horner syndrome
Imaging pathologies
Age at diagnosis
Gender
Type
Neuronal level (presumed)
Imaging modality
Congenital neuroblastoma CNS multifocal astrocytoma WHO II-III *Rhabdoid tumor Hypoplastic internal carotid artery Chiari I malformation Neck viral lymphadenopathy Jugular cannulation/neck inflammation
2 weeks 4 years 4 years 1 year 3 years 20 years 2 months
Female Female Female Female Female Male Male
Congenital Acquired Acquired Congenital Congenital Acquired Acquired
3rd order 1st order 2nd order 3rd order 1st order 3rd order 2nd order
MRI/MRA MRI/MRA CT MRI/MRA CT/CTA MRI/MRA MRI/MRA
CNS central nervous system, WHO II-III World Health Organization grade II-III *One patient with an imaging referral for Horner syndrome did not fulfill study inclusion criteria because she had only miosis; she had a lesion that by location and extent could cause Horner syndrome
one patient developed Horner syndrome as a complication of a viral cervical lymphadenopathy, the other developed inflammatory changes in the neck following cannulation of a jugular vein and a Horner syndrome that later resolved. There were 32 patients in our cohort who fulfilled criteria of Horner syndrome but did not have any abnormal imaging findings. The clinical information shows that 18/32 did not have follow-up to establish a diagnosis. A follow-up clinical diagnosis of congenital Horner syndrome was documented in 4/32 patients. Physiological anisocoria and/or ptosis was documented in 3/32 patients. In 4/32 patients, the Horner syndrome was considered post-inflammatory. In 1/32 patients, the Horner syndrome was congenital and attributed to an unfavorable fetal position; in 1/32 patients, it was attributed to a prior brain insult and in 1/32 patients, a diagnosis of autism was documented, which can be associated with anisocoria and an abnormal pupillary light reflex [21].
For our study, we confirmed the diagnosis of Horner syndrome in patients who were referred for radiological imaging and in whom we found clinically documented miosis in conjunction with at least one of the following: ptosis, iris heterochromia and/or a positive cocaine eye drop test. Anhidrosis could not be used as a diagnostic criterion because of lack of clinical data concerning its presence in the patient records available to us for review. Reflecting the low incidence of Horner syndrome in children (1.42 per 100,000) [2], imaging for Horner syndrome at our institution was requested only 70 times in 22 years, which represents an average of about 3 patients/year. There were two Horner syndrome patients with a malignant neoplasm (multifocal cerebral/hypothalamic astrocytoma of the brain, bifurcation stage 2A neuroblastoma). We found a third malignancy in
Fig. 3 A 2-week-old girl with left-sided Horner syndrome. Axial postcontrast fat-saturated T1 of the neck at the level of the carotid bifurcation shows enhancing mass of the left carotid bifurcation (arrow). Surgical pathology showed a stage 2A neuroblastoma
Fig. 4 Axial post-contrast T1 image at the level of the midbrain in a 4year-old girl with left-sided Horner syndrome. Surgical pathology showed multifocal cerebral astrocytoma World Health Organization grade II-III. Note the enhancing lesions in the left mesial temporal lobe (thick arrow) and the left hypothalamus (thin arrow), the latter explaining this patient’s left Horner syndrome
Discussion
Pediatr Radiol Fig. 5 Post-contrast CT of the neck, axial (a) and coronal reformatted image of chest CT (b) in a 4-year-old girl with left-side miosis. Large brachial plexus mass in the left lower neck und upper chest (a and b, thick arrows) invades the spinal canal (a, thin arrow) and left lung apex (b, thin arrow). Surgical pathology showed a rhabdoid tumor
a patient with a referring diagnosis of Horner syndrome but with only miosis (therefore not included in our analysis); that patient had a large rhabdoid tumor of the neck involving the lung apex with intraspinal epidural extension. These malignant lesions were ipsilateral to the Horner syndrome and involved the anatomically anticipated central, pre- and post-ganglionic portions of the oculosympathetic pathway. Counting only the first two of those patients, our rate of causative malignancy rate was 2/38 (5%), much lower than the up to 23% reported in other studies [4]. Nonetheless, our data, in conjunction with previous imaging reports in patients with Horner syndrome [2, 4], illustrate the importance of carrying out imaging studies in patients with acquired Horner syndrome to try to identify all potentially treatable causes, particularly malignancies. There is some debate regarding the use of imaging modalities and the extent of anatomical coverage required for the radiological work-up of Horner syndrome. Several studies
have suggested a targeted imaging approach for adults [22–24]. The imperative to localize lesions clinically to central, pre- or post-ganglionic levels has long been emphasized in adults [25, 26]. In adults, pre-ganglionic lesions are more likely to be malignant than post-ganglionic ones; thus, clinical localization has important prognostic value. The majority of our patients 35/38 (92%), underwent imaging of the entire oculo-sympathetic pathway with either MRI or CT. This may indicate that clinical examinations may not be as helpful in children as in adults in determining levels of oculosympathetic pathway pathology. Malignancies in our cohort involved central (multifocal cerebral/hypothalamic astrocytoma), pre-ganglionic (rhabdoid neck tumor, in a patient who did not meet all of our study criteria) and post-ganglionic levels (bifurcation stage 2A cervical neuroblastoma). At our institution, we image the entire oculosympathetic pathway in all patients in whom the clinical examination does not provide enough information to localize the lesion with certainty, an
Fig. 6 A 1-year-old girl with right-sided Horner syndrome since birth. MRI axial post-contrast T1 with fat saturation (a) and 3-D time-of flight MR angiogram MIP projection (b). There is a diminutive flow signal in the right cavernous internal carotid artery (a, arrow). The right internal carotid artery is smaller than the left, extending from the upper neck to the
supraclinoid portion (b, arrow). Differential considerations were congenital carotid artery hypoplasia vs. carotid artery dissection. There was no clinical history of trauma. There was no follow-up imaging or clinical follow-up information
Pediatr Radiol
approach previously recommended specifically for adults [23, 24]. There have been several reports suggesting an association between Horner syndrome and anomalies of the internal carotid artery [27–30]. One postulated mechanism is that a Horner syndrome can be caused by an internal carotid artery dissection that disrupts the oculosympathetic pathway [27, 30]. Another suggested mechanism is that congenital absence of the internal carotid artery can result in a Horner syndrome because an absent internal carotid artery can deprive the oculosympathetic nerves of their developmental pathway to the cranium [28]. Digre et al. [26] investigated a cohort of 33 patients with Horner syndrome and found vascular anomalies in all patients in whom the clinical examination indicated a post-ganglionic lesion. This suggests that cross-sectional angiographic studies in Horner syndrome patients with post-ganglionic localization might appropriately be limited to the carotid bifurcation and the circle of Willis. We have no proof that vascular anomalies in our cohort resulted in a Horner syndrome, with the possible exception of one patient who had narrowing of the internal carotid artery – felt to be congenital, but possibly post-dissection – that was ipsilateral to the patient’s Horner syndrome. We have continued to include MR and CT angiograms in our imaging protocol for Horner syndrome to enable detection of carotid dissection because patients with that diagnosis may require life-saving clinical management [29]. One of our patients had a Chairi I malformation and Horner syndrome. A reported patient with a Chiari I malformation and extensive syringomyelia had a Horner-like pupil reaction ipsilateral to marked hand wasting, indicative of a sympathetic lesion at T1 [31]. Another reported patient with a Chiari I malformation and a syrinx at C2-4 presented with an isolated Horner syndrome [32]. In our patient with a Chiari I malformation, there was no syringomyelia, but his symptoms improved after Chiari decompression surgery. Another patient in our cohort had Horner syndrome in conjunction with influenza and presumed viral cervical lymphadenopathy (Fig. 7). Horner syndrome has been reported in patients with lymphoma [33], but it has not previously been reported in conjunction with inflammatory lymphadenopathy. Another of our patients was in the intensive care unit for sepsis and developed Horner syndrome after cannulation of a jugular vein (Fig. 8). It is unclear if Horner syndrome resulted from the jugular cannulation or from inflammatory changes in the neck related to sepsis. There has been a report of Horner syndrome related to failed jugular cannulation in a 19-month-old child that resulted in permanent Horner syndrome [34]. A limitation of our review was the lack of clinical information regarding anhidrosis to further support the diagnosis of Horner syndrome in our patients. This occurred mainly because of lack of availability of complete clinical records prior to implementation of the electronic health records system at
Fig. 7 A 20-year-old man with left-sided Horner syndrome, influenza and presumed viral neck lymphadenopathy. MRI axial post-contrast axial T1 with fat saturation. Two left-sided inflamed lymph nodes are seen (arrows), one of which (thin arrow) borders the left internal carotid artery (asterisk)
our institution. Given this limitation, we settled on what we felt was an appropriate set of strict clinical criteria to support (or refute) the diagnosis of Horner syndrome in patients sent to us for radiologic study. Another limitation of our study is the fact that only patients with a referring diagnosis of Horner syndrome were considered, and not patients with anisocoria, which alone we felt was inadequate to establish a diagnosis of
Fig. 8 MRI axial T1 with fat saturation in a 2-month-old boy with sepsis and right-sided Horner syndrome after jugular vein cannulation shows bilateral diffuse soft-tissue enhancement compatible with inflammatory changes (thick arrows), some of which borders the right common carotid artery (asterisk). There is posterior and lateral displacement of the right internal jugular vein (thin arrow)
Pediatr Radiol
Horner syndrome. This may have caused an underestimation of the total number of Horner syndrome patients that were referred for imaging during the 22-year period of study. Also, a few patients, whom we included because they met our requisite clinical criteria, had incomplete imaging studies (brain only and/or no angiographic studies). It is unclear if these studies were targeted based on the clinical examination or whether the referring health professional had simply failed to request study of the entire oculosympathetic pathway when ordering the radiologic study; in some such circumstances, important underlying pathology could have been missed. In summary, relatively few children are referred for radiological study of Horner syndrome. An imaging study of the entire oculosympathetic pathway, often with accompanying cross-sectional angiography, is usually indicated. MRI is nowadays favored to reduce radiation exposure in children, although sedation may be required. This will help to ensure that treatable causes of Horner syndrome, especially those with underlying neoplastic disease, will be detected.
Conclusion By sharing our imaging experience in children with Horner syndrome, we hope to raise awareness of treatable causes, including malignancies, which justify imaging work-up of the entire oculosympathetic pathway. Imaging may be targeted to specific levels of the oculosympathetic pathway as indicated by complete neurological and ophthalmological examinations. Both MRI and CT were very effective imaging modalities in our patients. Additionally, cross-sectional angiographic studies were helpful, particularly in identifying underlying vascular dissections. Conflicts of interest None
References 1. Fulton JF (1929) Edward Selleck Hare (1812–1838) and the syndrome of paralysis of the cervical sympathetic. Proc R Soc Med 23: 152–157 2. Smith SJ, Diehl N, Leavitt JA et al (2010) Incidence of pediatric Horner syndrome and the risk of neuroblastoma: a populationbased study. Arch Ophthalmol 128:324–329 3. George ND, Gonzalez G, Hoyt CS (1998) Does Horner’s syndrome in infancy require investigation? Br J Ophthalmol 82:51–54 4. Mahoney NR, Liu GT, Menacker SJ et al (2006) Pediatric horner syndrome: etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol 142:651–659 5. Al-Moosa A, Eggenberger E (2011) Neuroimaging yield in isolated Horner syndrome. Curr Opin Ophthalmol 22:468–471, Review 6. Walton KA, Buono LM (2003) Horner syndrome. Curr Opin Ophthalmol 14:357–363, Review
7. Jeffery AR, Ellis FJ, Repka MX et al (1998) Pediatric Horner syndrome. J AAPOS 2:159–167 8. Singh RR, Thomas AA, Barry MC et al (2004) Traumatic pseudoaneurysm of the internal carotid artery presenting with oculosympathetic palsy. Ir J Med Sci 173:162–163 9. Starr BE, Shubert RA, Baumann B (2004) A child with isolated Horner’s syndrome after blunt neck trauma. J Emerg Med 26:425– 427 10. Gupta M, Dinakaran S, Chan TK (2005) Congenital Horner syndrome and hemiplegia secondary to carotid dissection. J Pediatr Ophthalmol Strabismus 42:122–124 11. Mihora LD, Jatla KK, Enzenauer RW (2006) Horner syndrome due to ectopic cervical thymus. J Pediatr Ophthalmol Strabismus 43:46– 48 12. Online Mendelian Inheritance in Man (OMIM). An online catalog of human genes and genetic disorders. Updated 30 Jan 2015. http:// www.omim.org/entry/143000. Accessed 1 Feb 2015 13. Barkovich AJ, Raybaud C (2012) Pediatric neuroimaging, 5th edn. Lippincott Williams & Wilkins, Philadelphia, p 690 14. Kansal A, Lahiri A, Nishikawa H (2006) Sympathetic paraganglioma presenting with Horner’s syndrome in a child. J Plast Reconstr Aesthet Surg 59:772–774 15. Challapalli A, Howell L, Farrier M et al (2007) Cervical paraganglioma – a case report and review of all cases reported to the Manchester Children’s Tumour Registry 1954–2004. Pediatr Blood Cancer 48:112–116 16. Cannady SB, Chung BJ, Hirose K et al (2006) Surgical management of cervical ganglioneuromas in children. Int J Pediatr Otorhinolaryngol 70:287–294 17. Yip D, Drachtman R, Amorosa L et al (2010) Papillary thyroid cancer presenting as Horner syndrome. Pediatr Blood Cancer 55:739–741 18. Moreno TA, El-Dairi MA, Cabrera MT (2012) Isolated Horner syndrome and syringomyelia in a child. J AAPOS 16:569–570 19. Mutalib M, Vandervelde C, Varghese A et al (2007) Horner’s syndrome secondary to asymptomatic pneumothorax in an adolescent. Eur J Pediatr 166:507–508 20. Bhaskar G, Lodha R, Kabra SK (2006) Unusual complications of empyema thoracis: diaphragmatic palsy and Horner’s syndrome. Indian J Pediatr 73:941–943 21. Fan X, Miles JH, Takahashi N et al (2009) Abnormal transient pupillary light reflex in individuals with autism spectrum disorders. J Autism Dev Disord 39:1499–1508 22. Martin TJ (2007) Horner’s syndrome, Pseudo-Horner’s syndrome, and simple anisocoria. Curr Neurol Neurosci Rep 7:397–406, Review 23. Reede DL, Garcon E, Smoker WR et al (2008) Horner’s syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am 18: 369–385, xi 24. Almog Y, Gepstein R, Kesler A (2010) Diagnostic value of imaging in horner syndrome in adults. J Neuroophthalmol 30:7–11 25. Thompson HS (1977) Diagnosing Horner’s syndrome. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol 83:840–842 26. Digre KB, Smoker WR, Johnston P et al (1992) Selective MR imaging approach for evaluation of patients with Horner’s syndrome. AJNR Am J Neuroradiol 13:223–227 27. Chan CC, Paine M, O’Day J (2001) Carotid dissection: a common cause of Horner’s syndrome. Clin Experiment Ophthalmol 29:411– 415 28. Fons C, Vasconcelos M, Vidal M et al (2009) Agenesis of internal carotid artery in a child with ipsilateral Horner’s syndrome. J Child Neurol 24:101–104 29. Pirouzian A, Holz HA, Ip KC et al (2010) Acquired infantile Horner syndrome and spontaneous internal carotid artery dissection: a case report and review of literature. J AAPOS 14:172–174, Review 30. Flaherty PM, Flynn JM (2011) Horner syndrome due to carotid dissection. J Emerg Med 41:43–46, Review
Pediatr Radiol 31. Stovner LJ, Kruszewski P, Shen JM (1993) Sinus arrhythmia and pupil size in Chiari I malformation: evidence of autonomic dysfunction. Funct Neurol 8:251–257 32. Kerrison JB, Biousse V, Newman NJ (2000) Isolated Horner’s syndrome and syringomyelia. J Neurol Neurosurg Psychiatry 69:131–132
33. Ruiz E, Resende LS, Gaiolla RD et al (2012) Post-ganglionic Horner’s syndrome: an unusual presentation of non-Hodgkin lymphoma. Case Rep Neurol 4:43–46 34. Guccione P, Gagliardi MG, Bevilacqua M et al (1992) Cardiac catheterization through the internal jugular vein in pediatric patients. An alternative to the usual femoral vein access. Chest 101:1512–1514
ORIGINAL ARTICLE
Neuroimaging experience in pediatric Horner syndrome Nadja Kadom & N. Paul Rosman & Shams Jubouri & Anna Trofimova & Alexia M. Egloff & Wadih M. Zein
Received: 30 September 2014 / Revised: 31 January 2015 / Accepted: 6 March 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Background Horner syndrome in children is rare. The frequency and spectrum of malignancy as the cause of Horner syndrome in children remains unclear. Also unclear is whether the imaging work-up should include the entire oculosympathetic pathway or should be more targeted. In addition, the value of cross-sectional angiographic imaging in Horner syndrome is uncertain. Objective To review imaging pathology in a cohort of children with Horner syndrome at a major academic pediatric medical center. Materials and methods We reviewed a 22-year period of CT and MR imaging studies in children with a clinical diagnosis of Horner syndrome referred for imaging. Results We found 38 patients who fulfilled study criteria of Horner syndrome and 6/38 had relevant imaging findings: 2/6 etiologies were neoplastic (congenital neuroblastoma and N. Kadom (*) Department of Radiology, Boston University Medical Center, Boston University School of Medicine, 820 Harrison Ave., FGH Building, 3rd Floor, Boston, MA 02118, USA e-mail: [email protected] N. P. Rosman Division of Pediatric Neurology, Departments of Pediatrics and Neurology, Boston University School of Medicine, Boston Medical Center, Boston, MA, USA S. Jubouri : A. Trofimova : A. M. Egloff Department of Radiology and Diagnostic Imaging, Children’s National Medical Center, Washington, DC, USA W. M. Zein National Eye Institute (NEI), Bethesda, MD, USA
central astrocytoma), 1/6 had a vascular abnormality (hypoplastic carotid artery), 1/6 had maldevelopment (Chiari I malformation), and 2/6 had inflammatory/traumatic etiology (viral cervical lymphadenopathy, post jugular vein cannulation). There was a similar number of congenital and acquired pathologies. The malignancies were found at any level of the oculosympathetic pathway. Conclusion There are treatable causes, including malignancies, in children presenting with Horner syndrome, which justify imaging work-up of the entire oculosympathetic pathway, unless the lesion level can be determined clinically. Keywords Children . Computed tomography . Horner syndrome . Magnetic resonance imaging . Oculosympathetic pathway Abbreviations CT Computed tomography CTA CT angiogram MRI Magnetic resonance imaging MRA MRI angiogram ICU Intensive care unit
Introduction Horner syndrome is a disorder of the oculosympathetic pathway [1]. The incidence of Horner syndrome in children is low, estimated to be 1.42 per 100,000 patients under the age of 19 years [2]. While the diagnosis is made through clinical examination, imaging studies are critical in delineating the nature and extent of any underlying pathology along the oculosympathetic pathway. During the past 20 years, there have been numerous case reports of Horner syndrome, but
Pediatr Radiol
only a few systematic reports on the spectrum of crosssectional imaging findings in children referred for Horner syndrome imaging [3–5]. The oculosympathetic pathway provides sympathetic innervation to the eye through three orders of neurons in specific anatomical locations (Figs. 1 and 2). The first order neurons (central) arise in the posterolateral hypothalamus and descend through the brainstem to spinal cord levels C8-T2 where they synapse with second order neurons at the ciliospinal center (of Budge). Second order neurons (pre-ganglionic) exit the ciliospinal center of the thoracic cord and ascend in the cervical sympathetic trunk, through the brachial plexus, over the lung apex, to synapse in the superior cervical ganglion, located near the common carotid artery bifurcation. Third order neurons (post-ganglionic) leave the superior cervical ganglion and ascend within the adventitia of the internal carotid artery to enter the skull and then the cavernous sinus. Here, these fibers join the ophthalmic division of the trigeminal nerve to enter the orbit. There, the fibers innervate the dilator pupillae muscle and the superior tarsal muscle (Müller’s muscle). Other third order neuron fibers supply sweat glands of the ipsilateral forehead [6]. Hence, Horner syndrome typically presents with a triad of ipsilateral miosis (pupil constriction, due to loss of innervation to the dilator pupillae muscle), ptosis (drooping of the eyelid, due to loss of innervation to the superior tarsal muscle) and anhidrosis (lack of sweat production, due to loss of innervation to the forehead sweat glands).
Horner syndrome can be congenital or acquired. Congenital Horner syndrome is usually symptomatic within the first year of life. Causes of congenital Horner syndrome include birth trauma [7] and congenital abnormalities of the internal carotid arteries, particularly agenesis, because of the intimate relationship between the sympathetic chain and the internal carotid arteries [8–10]. Additional reported causes of congenital Horner syndrome include ectopic thymus in the neck [11] and congenital neuroblastoma in the neck [3]. Rarely, congenital Horner syndrome may be of autosomal dominant inheritance [12]. There are many causes of acquired Horner syndrome. Those seen in children can be of neoplastic or nonneoplastic etiology. Mahoney et al. [4] suggested that in children a neoplastic cause should be presumed until proven otherwise. The most common childhood tumors causing acquired Horner syndrome are neuroblastoma [13], paraganglioma [14, 15] and ganglioneuroma [16]; a less common neoplastic cause is childhood thyroid cancer [17]. A vascular cause is arterial dissection [13]. External trauma causing lower brachial plexus palsy (Klumpke) can result in Horner syndrome [13]. An intraspinal cause of acquired Horner syndrome is syringomyelia [18]. Intrathoracic etiologies are pneumothorax [19] and thoracic empyema [20]. In children, Horner syndrome is acquired in up to 23% of patients [4]. Since many acquired causes of Horner syndrome can be treated, imaging becomes very important in delineating the nature and extent of any underlying disease. Here, we describe our experience using CT and MR imaging protocols in children with a diagnosis of Horner syndrome referred to the Radiology Department at Children’s National Medical Center in Washington, D.C., during a 22-year period.
Materials and methods
Fig. 1 Three levels of the oculo-sympathetic pathway
We retrospectively reviewed CT and MR imaging studies in children with Horner syndrome referred from 1991 to 2012 to the Department of Radiology and Diagnostic Imaging at Children’s National in Washington, D.C. The study was IRB approved. All patients, from newborn to 20 years of age, in whom the outpatient radiology referral stated Horner syndrome, were considered for this study. Since any referral diagnosis was transcribed in the patient history field of the radiology report, we could search for the term “Horner syndrome” with a radiology search engine (Montage Healthcare Solutions, Inc., Philadelphia, PA). Inclusion criteria were selected to maximize the accuracy of the diagnosis Horner syndrome. These criteria were the required presence of unilateral miosis and, in addition, the presence of one or more of the following: ipsilateral ptosis, ipsilateral heterochromia, and/or a positive cocaine eye drop test. Cocaine eye drops block the synaptic reuptake of
Pediatr Radiol
Fig. 2 Normal anatomy of oculosympathetic pathway. First order neurons (dashed line) arises from posterolateral hypothalamus, descends into brainstem and intermediolateral column of the spinal cord, and exits at cervical (C8) and thoracic (T1–T2) levels of spinal cord as second- order neuron (dotted line). Second order pre-ganglionic neurons exit ventral spinal roots (a) and arch over apex of lung to ascend in cervical sympathetic chain, synapsing in the superior cervical ganglion (b) and exiting as third- order neurons (solid lines). Neural fibers for sweating of face, except medial forehead, travel with external carotid artery. Third order post-ganglionic neurons travel with carotid artery (c) into
cavernous sinus and with the ophthalmic branch (d) of the fifth cranial nerve join the nasociliary branch of fifth cranial nerve or pass through ciliary ganglion (e) directly, reaching eye as long (f) and short (g) ciliary nerves. Pre-ganglionic parasympathetic fibers (gray lines) arise from the accessory oculomotor nucleus (h), exit as the oculomotor nerve (i), synapse at the ciliary ganglion, and reach the eye as the short ciliary nerves (Reprinted with permission from Lee JH, Lee HK, Lee DH, et al. [2007] Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location. AJR Am J Roentgenol DOI:10.2214/AJR.05.1588)
norepinephrine, which causes dilatation of a normal pupil, but in Horner syndrome the lack of norepinephrine prevents this mydriatic effect. We could not use anhidrosis as a diagnostic criterion because its presence or absence was not documented in the medical records to which we had access. All clinical information was retrieved from each patient’s medical record. Lastly, only patients who met the above requisite clinical criteria and who also had diagnostic CT or MRI of the brain were included in the review. Many of these patients also had CT or MRI imaging of the neck and upper chest, as well as vascular studies, and those results were included as well.
A single observer (S.J.) conducted the medical records search for all relevant clinical and ophthalmological data. The following clinical information was recorded for every patient: patient age, gender, age of onset of the Horner syndrome, affected side, ophthalmological findings (miosis, ptosis, heterochromia, cocaine eye drop test results), and the portion of the oculosympathetic pathway that was involved (e.g., first, second and/or third order neurons). The following imaging parameters were documented from review of radiology reports in the Medical Center’s Radiology Information System: patient age at time of imaging for Horner syndrome, type of imaging used (CT and/or MRI, vascular imaging studies)
Pediatr Radiol
and the imaging findings recorded. In addition, all imaging studies with findings were again reviewed and interpreted for this study; there were no disagreements with the original interpretation. All cases were then categorized as congenital or acquired and specific causes for the Horner syndrome were further classified as: 1) neoplastic, 2) vascular, 3) maldevelopment and 4) inflammatory/traumatic. Imaging protocols varied for both CT and MRI throughout the 22-year study interval. The most recent imaging protocols were: – –
–
–
–
– –
CT brain: Pre- and post-contrast axial 5-mm images from orbital roof through vertex with coronal reformats. CT neck/upper chest: Post-contrast axial 2.5-mm images (patient weight: 0–11.4 kg) or 3.75 mm helical images from aortic arch to supraorbital ridge with coronal and sagittal reformats. CT angiogram neck/brain: Post-contrast axial 1.25-mm images from aortic arch through lateral ventricles, contrast flow rate 2–4 cc/s, usual image delay 9–14 s (if bolus tracking unavailable) with sagittal and coronal reformats. MRI brain: Pre-contrast sagittal T1 spoiled gradient recalled acquisition (SPGR), axial fast spin echo (FSE) T2, axial fluid attenuated inversion recovery (FLAIR), axial diffusion weighted imaging (DWI) (b=0 and b=1, 000), coronal T1 orbits to pons, coronal T2 orbits to pons, and post-contrast axial T1 brain, coronal T1 orbits through pons with fat saturation, axial T1 orbits to hypothalamus with fat saturation. MRI neck/upper chest: Cover skull base to aortic arch. Pre-contrast sagittal T1 SPGR and sagittal FSE T1, axial spin echo T1, axial FSE T2 with fat saturation, coronal T1, coronal T2, and post-contrast axial and coronal T1 with fat saturation, and sagittal T1 without fat saturation. MR angiography neck: 2-D time-of-flight imaging of the neck with superior saturation pulse, multiplanar maximum intensity projections (MIPs). MR angiography brain: 3-D time-of-flight imaging of the neck with superior saturation pulse with 3-D reformats and multiplanar maximum intensity projections (MIPs).
Descriptive statistical analysis was performed using Stata v13.1 (StataCorp LP, Texas, USA).
Results Our report field search yielded a total of 70 patients in the 22year observation period who had an imaging referral diagnosis of Horner syndrome. There were 38/70 (54%) who fulfilled our inclusion criteria for Horner syndrome: 38/38 (100%) of patients had miosis; 31/38 (82%) of patients had miosis and ptosis; 6/38 (16%) of patients had miosis, ptosis and ipsilateral
iris heterochromia, and 1/38 (2%) patient had miosis and a positive cocaine eye drop test. All these 38 patients had diagnostic imaging studies. The most commonly done imaging study was a complete MRI of the brain, neck, upper chest and an MR angiography of the head and neck (n=32; 84%). The second most common imaging study was a complete CT of the brain, neck, upper chest and a CT angiogram of the head and neck (n=3; 8%), followed by a brain MRI alone (n=2; 5%) and a brain CT alone (n=1; 3%). There were 20 males and 18 females. The mean age at the time of onset of Horner syndrome was 4.1 years (standard deviation [SD]: 6.0 years; median: 1 year; range: newborn20 years) and the mean age at time of imaging was 4.6 years (SD: 5.8 years; median: 6 months; range: 2 months–20 years). The Horner syndrome was right-side in 21 patients and leftside in 17. In 32/38 patients, there were no abnormal imaging findings. In 6/38 (16%) patients, a specific cause for Horner syndrome was found on imaging, with first order neuron (central) pathology in 2 patients (multifocal cerebral astrocytoma, Chiari I malformation), second order neuron (preganglionic) lesions in 3 patients (carotid bifurcation neuroblastoma, inflammatory complication after jugular cannulation, viral/neck lymphadenopathy), and third order neuron (post-ganglionic) lesions in 1 patient (hypoplastic internal carotid artery). The distribution of congenital versus acquired etiologies in the six patients with abnormal imaging findings relative to their age and gender is shown in Table 1. There was a similar number of congenital (n=3) and acquired (n=4) pathologies. Of the six pathologies, five were in the age group 0–4 years and only one patient was 20 years old. A neoplastic etiology was found in 2/38 (5%) patients, one congenital and one acquired. One patient had a congenital carotid bifurcation stage 2A neuroblastoma (Fig. 3), while the other had an acquired Horner syndrome caused by a multifocal cerebral astrocytoma, World Health Organization grade II-III that also involved the hypothalamus (Fig. 4). This patient was treated, but documentation about resolution of Horner syndrome was not found. Interestingly, one patient who was referred for Horner syndrome imaging, but who did not fulfill the minimum clinical criteria to be included in the study, had an imaging diagnosis of a large rhabdoid tumor involving the lung apex, with intraspinal epidural extension from C6-T1 (Fig. 5). A vascular etiology was found in one patient who had a hypoplastic internal carotid artery (Fig. 6). A maldevelopmental etiology was seen in a patient with a Chiari I malformation and hydrocephalus who also had a Horner syndrome; following decompressive surgery for the Chiari I malformation, her Horner syndrome improved. An inflammatory/traumatic etiology was seen in two patients:
Pediatr Radiol Table 1
Seven lesions found on imaging of Horner syndrome
Imaging pathologies
Age at diagnosis
Gender
Type
Neuronal level (presumed)
Imaging modality
Congenital neuroblastoma CNS multifocal astrocytoma WHO II-III *Rhabdoid tumor Hypoplastic internal carotid artery Chiari I malformation Neck viral lymphadenopathy Jugular cannulation/neck inflammation
2 weeks 4 years 4 years 1 year 3 years 20 years 2 months
Female Female Female Female Female Male Male
Congenital Acquired Acquired Congenital Congenital Acquired Acquired
3rd order 1st order 2nd order 3rd order 1st order 3rd order 2nd order
MRI/MRA MRI/MRA CT MRI/MRA CT/CTA MRI/MRA MRI/MRA
CNS central nervous system, WHO II-III World Health Organization grade II-III *One patient with an imaging referral for Horner syndrome did not fulfill study inclusion criteria because she had only miosis; she had a lesion that by location and extent could cause Horner syndrome
one patient developed Horner syndrome as a complication of a viral cervical lymphadenopathy, the other developed inflammatory changes in the neck following cannulation of a jugular vein and a Horner syndrome that later resolved. There were 32 patients in our cohort who fulfilled criteria of Horner syndrome but did not have any abnormal imaging findings. The clinical information shows that 18/32 did not have follow-up to establish a diagnosis. A follow-up clinical diagnosis of congenital Horner syndrome was documented in 4/32 patients. Physiological anisocoria and/or ptosis was documented in 3/32 patients. In 4/32 patients, the Horner syndrome was considered post-inflammatory. In 1/32 patients, the Horner syndrome was congenital and attributed to an unfavorable fetal position; in 1/32 patients, it was attributed to a prior brain insult and in 1/32 patients, a diagnosis of autism was documented, which can be associated with anisocoria and an abnormal pupillary light reflex [21].
For our study, we confirmed the diagnosis of Horner syndrome in patients who were referred for radiological imaging and in whom we found clinically documented miosis in conjunction with at least one of the following: ptosis, iris heterochromia and/or a positive cocaine eye drop test. Anhidrosis could not be used as a diagnostic criterion because of lack of clinical data concerning its presence in the patient records available to us for review. Reflecting the low incidence of Horner syndrome in children (1.42 per 100,000) [2], imaging for Horner syndrome at our institution was requested only 70 times in 22 years, which represents an average of about 3 patients/year. There were two Horner syndrome patients with a malignant neoplasm (multifocal cerebral/hypothalamic astrocytoma of the brain, bifurcation stage 2A neuroblastoma). We found a third malignancy in
Fig. 3 A 2-week-old girl with left-sided Horner syndrome. Axial postcontrast fat-saturated T1 of the neck at the level of the carotid bifurcation shows enhancing mass of the left carotid bifurcation (arrow). Surgical pathology showed a stage 2A neuroblastoma
Fig. 4 Axial post-contrast T1 image at the level of the midbrain in a 4year-old girl with left-sided Horner syndrome. Surgical pathology showed multifocal cerebral astrocytoma World Health Organization grade II-III. Note the enhancing lesions in the left mesial temporal lobe (thick arrow) and the left hypothalamus (thin arrow), the latter explaining this patient’s left Horner syndrome
Discussion
Pediatr Radiol Fig. 5 Post-contrast CT of the neck, axial (a) and coronal reformatted image of chest CT (b) in a 4-year-old girl with left-side miosis. Large brachial plexus mass in the left lower neck und upper chest (a and b, thick arrows) invades the spinal canal (a, thin arrow) and left lung apex (b, thin arrow). Surgical pathology showed a rhabdoid tumor
a patient with a referring diagnosis of Horner syndrome but with only miosis (therefore not included in our analysis); that patient had a large rhabdoid tumor of the neck involving the lung apex with intraspinal epidural extension. These malignant lesions were ipsilateral to the Horner syndrome and involved the anatomically anticipated central, pre- and post-ganglionic portions of the oculosympathetic pathway. Counting only the first two of those patients, our rate of causative malignancy rate was 2/38 (5%), much lower than the up to 23% reported in other studies [4]. Nonetheless, our data, in conjunction with previous imaging reports in patients with Horner syndrome [2, 4], illustrate the importance of carrying out imaging studies in patients with acquired Horner syndrome to try to identify all potentially treatable causes, particularly malignancies. There is some debate regarding the use of imaging modalities and the extent of anatomical coverage required for the radiological work-up of Horner syndrome. Several studies
have suggested a targeted imaging approach for adults [22–24]. The imperative to localize lesions clinically to central, pre- or post-ganglionic levels has long been emphasized in adults [25, 26]. In adults, pre-ganglionic lesions are more likely to be malignant than post-ganglionic ones; thus, clinical localization has important prognostic value. The majority of our patients 35/38 (92%), underwent imaging of the entire oculo-sympathetic pathway with either MRI or CT. This may indicate that clinical examinations may not be as helpful in children as in adults in determining levels of oculosympathetic pathway pathology. Malignancies in our cohort involved central (multifocal cerebral/hypothalamic astrocytoma), pre-ganglionic (rhabdoid neck tumor, in a patient who did not meet all of our study criteria) and post-ganglionic levels (bifurcation stage 2A cervical neuroblastoma). At our institution, we image the entire oculosympathetic pathway in all patients in whom the clinical examination does not provide enough information to localize the lesion with certainty, an
Fig. 6 A 1-year-old girl with right-sided Horner syndrome since birth. MRI axial post-contrast T1 with fat saturation (a) and 3-D time-of flight MR angiogram MIP projection (b). There is a diminutive flow signal in the right cavernous internal carotid artery (a, arrow). The right internal carotid artery is smaller than the left, extending from the upper neck to the
supraclinoid portion (b, arrow). Differential considerations were congenital carotid artery hypoplasia vs. carotid artery dissection. There was no clinical history of trauma. There was no follow-up imaging or clinical follow-up information
Pediatr Radiol
approach previously recommended specifically for adults [23, 24]. There have been several reports suggesting an association between Horner syndrome and anomalies of the internal carotid artery [27–30]. One postulated mechanism is that a Horner syndrome can be caused by an internal carotid artery dissection that disrupts the oculosympathetic pathway [27, 30]. Another suggested mechanism is that congenital absence of the internal carotid artery can result in a Horner syndrome because an absent internal carotid artery can deprive the oculosympathetic nerves of their developmental pathway to the cranium [28]. Digre et al. [26] investigated a cohort of 33 patients with Horner syndrome and found vascular anomalies in all patients in whom the clinical examination indicated a post-ganglionic lesion. This suggests that cross-sectional angiographic studies in Horner syndrome patients with post-ganglionic localization might appropriately be limited to the carotid bifurcation and the circle of Willis. We have no proof that vascular anomalies in our cohort resulted in a Horner syndrome, with the possible exception of one patient who had narrowing of the internal carotid artery – felt to be congenital, but possibly post-dissection – that was ipsilateral to the patient’s Horner syndrome. We have continued to include MR and CT angiograms in our imaging protocol for Horner syndrome to enable detection of carotid dissection because patients with that diagnosis may require life-saving clinical management [29]. One of our patients had a Chairi I malformation and Horner syndrome. A reported patient with a Chiari I malformation and extensive syringomyelia had a Horner-like pupil reaction ipsilateral to marked hand wasting, indicative of a sympathetic lesion at T1 [31]. Another reported patient with a Chiari I malformation and a syrinx at C2-4 presented with an isolated Horner syndrome [32]. In our patient with a Chiari I malformation, there was no syringomyelia, but his symptoms improved after Chiari decompression surgery. Another patient in our cohort had Horner syndrome in conjunction with influenza and presumed viral cervical lymphadenopathy (Fig. 7). Horner syndrome has been reported in patients with lymphoma [33], but it has not previously been reported in conjunction with inflammatory lymphadenopathy. Another of our patients was in the intensive care unit for sepsis and developed Horner syndrome after cannulation of a jugular vein (Fig. 8). It is unclear if Horner syndrome resulted from the jugular cannulation or from inflammatory changes in the neck related to sepsis. There has been a report of Horner syndrome related to failed jugular cannulation in a 19-month-old child that resulted in permanent Horner syndrome [34]. A limitation of our review was the lack of clinical information regarding anhidrosis to further support the diagnosis of Horner syndrome in our patients. This occurred mainly because of lack of availability of complete clinical records prior to implementation of the electronic health records system at
Fig. 7 A 20-year-old man with left-sided Horner syndrome, influenza and presumed viral neck lymphadenopathy. MRI axial post-contrast axial T1 with fat saturation. Two left-sided inflamed lymph nodes are seen (arrows), one of which (thin arrow) borders the left internal carotid artery (asterisk)
our institution. Given this limitation, we settled on what we felt was an appropriate set of strict clinical criteria to support (or refute) the diagnosis of Horner syndrome in patients sent to us for radiologic study. Another limitation of our study is the fact that only patients with a referring diagnosis of Horner syndrome were considered, and not patients with anisocoria, which alone we felt was inadequate to establish a diagnosis of
Fig. 8 MRI axial T1 with fat saturation in a 2-month-old boy with sepsis and right-sided Horner syndrome after jugular vein cannulation shows bilateral diffuse soft-tissue enhancement compatible with inflammatory changes (thick arrows), some of which borders the right common carotid artery (asterisk). There is posterior and lateral displacement of the right internal jugular vein (thin arrow)
Pediatr Radiol
Horner syndrome. This may have caused an underestimation of the total number of Horner syndrome patients that were referred for imaging during the 22-year period of study. Also, a few patients, whom we included because they met our requisite clinical criteria, had incomplete imaging studies (brain only and/or no angiographic studies). It is unclear if these studies were targeted based on the clinical examination or whether the referring health professional had simply failed to request study of the entire oculosympathetic pathway when ordering the radiologic study; in some such circumstances, important underlying pathology could have been missed. In summary, relatively few children are referred for radiological study of Horner syndrome. An imaging study of the entire oculosympathetic pathway, often with accompanying cross-sectional angiography, is usually indicated. MRI is nowadays favored to reduce radiation exposure in children, although sedation may be required. This will help to ensure that treatable causes of Horner syndrome, especially those with underlying neoplastic disease, will be detected.
Conclusion By sharing our imaging experience in children with Horner syndrome, we hope to raise awareness of treatable causes, including malignancies, which justify imaging work-up of the entire oculosympathetic pathway. Imaging may be targeted to specific levels of the oculosympathetic pathway as indicated by complete neurological and ophthalmological examinations. Both MRI and CT were very effective imaging modalities in our patients. Additionally, cross-sectional angiographic studies were helpful, particularly in identifying underlying vascular dissections. Conflicts of interest None
References 1. Fulton JF (1929) Edward Selleck Hare (1812–1838) and the syndrome of paralysis of the cervical sympathetic. Proc R Soc Med 23: 152–157 2. Smith SJ, Diehl N, Leavitt JA et al (2010) Incidence of pediatric Horner syndrome and the risk of neuroblastoma: a populationbased study. Arch Ophthalmol 128:324–329 3. George ND, Gonzalez G, Hoyt CS (1998) Does Horner’s syndrome in infancy require investigation? Br J Ophthalmol 82:51–54 4. Mahoney NR, Liu GT, Menacker SJ et al (2006) Pediatric horner syndrome: etiologies and roles of imaging and urine studies to detect neuroblastoma and other responsible mass lesions. Am J Ophthalmol 142:651–659 5. Al-Moosa A, Eggenberger E (2011) Neuroimaging yield in isolated Horner syndrome. Curr Opin Ophthalmol 22:468–471, Review 6. Walton KA, Buono LM (2003) Horner syndrome. Curr Opin Ophthalmol 14:357–363, Review
7. Jeffery AR, Ellis FJ, Repka MX et al (1998) Pediatric Horner syndrome. J AAPOS 2:159–167 8. Singh RR, Thomas AA, Barry MC et al (2004) Traumatic pseudoaneurysm of the internal carotid artery presenting with oculosympathetic palsy. Ir J Med Sci 173:162–163 9. Starr BE, Shubert RA, Baumann B (2004) A child with isolated Horner’s syndrome after blunt neck trauma. J Emerg Med 26:425– 427 10. Gupta M, Dinakaran S, Chan TK (2005) Congenital Horner syndrome and hemiplegia secondary to carotid dissection. J Pediatr Ophthalmol Strabismus 42:122–124 11. Mihora LD, Jatla KK, Enzenauer RW (2006) Horner syndrome due to ectopic cervical thymus. J Pediatr Ophthalmol Strabismus 43:46– 48 12. Online Mendelian Inheritance in Man (OMIM). An online catalog of human genes and genetic disorders. Updated 30 Jan 2015. http:// www.omim.org/entry/143000. Accessed 1 Feb 2015 13. Barkovich AJ, Raybaud C (2012) Pediatric neuroimaging, 5th edn. Lippincott Williams & Wilkins, Philadelphia, p 690 14. Kansal A, Lahiri A, Nishikawa H (2006) Sympathetic paraganglioma presenting with Horner’s syndrome in a child. J Plast Reconstr Aesthet Surg 59:772–774 15. Challapalli A, Howell L, Farrier M et al (2007) Cervical paraganglioma – a case report and review of all cases reported to the Manchester Children’s Tumour Registry 1954–2004. Pediatr Blood Cancer 48:112–116 16. Cannady SB, Chung BJ, Hirose K et al (2006) Surgical management of cervical ganglioneuromas in children. Int J Pediatr Otorhinolaryngol 70:287–294 17. Yip D, Drachtman R, Amorosa L et al (2010) Papillary thyroid cancer presenting as Horner syndrome. Pediatr Blood Cancer 55:739–741 18. Moreno TA, El-Dairi MA, Cabrera MT (2012) Isolated Horner syndrome and syringomyelia in a child. J AAPOS 16:569–570 19. Mutalib M, Vandervelde C, Varghese A et al (2007) Horner’s syndrome secondary to asymptomatic pneumothorax in an adolescent. Eur J Pediatr 166:507–508 20. Bhaskar G, Lodha R, Kabra SK (2006) Unusual complications of empyema thoracis: diaphragmatic palsy and Horner’s syndrome. Indian J Pediatr 73:941–943 21. Fan X, Miles JH, Takahashi N et al (2009) Abnormal transient pupillary light reflex in individuals with autism spectrum disorders. J Autism Dev Disord 39:1499–1508 22. Martin TJ (2007) Horner’s syndrome, Pseudo-Horner’s syndrome, and simple anisocoria. Curr Neurol Neurosci Rep 7:397–406, Review 23. Reede DL, Garcon E, Smoker WR et al (2008) Horner’s syndrome: clinical and radiographic evaluation. Neuroimaging Clin N Am 18: 369–385, xi 24. Almog Y, Gepstein R, Kesler A (2010) Diagnostic value of imaging in horner syndrome in adults. J Neuroophthalmol 30:7–11 25. Thompson HS (1977) Diagnosing Horner’s syndrome. Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol 83:840–842 26. Digre KB, Smoker WR, Johnston P et al (1992) Selective MR imaging approach for evaluation of patients with Horner’s syndrome. AJNR Am J Neuroradiol 13:223–227 27. Chan CC, Paine M, O’Day J (2001) Carotid dissection: a common cause of Horner’s syndrome. Clin Experiment Ophthalmol 29:411– 415 28. Fons C, Vasconcelos M, Vidal M et al (2009) Agenesis of internal carotid artery in a child with ipsilateral Horner’s syndrome. J Child Neurol 24:101–104 29. Pirouzian A, Holz HA, Ip KC et al (2010) Acquired infantile Horner syndrome and spontaneous internal carotid artery dissection: a case report and review of literature. J AAPOS 14:172–174, Review 30. Flaherty PM, Flynn JM (2011) Horner syndrome due to carotid dissection. J Emerg Med 41:43–46, Review
Pediatr Radiol 31. Stovner LJ, Kruszewski P, Shen JM (1993) Sinus arrhythmia and pupil size in Chiari I malformation: evidence of autonomic dysfunction. Funct Neurol 8:251–257 32. Kerrison JB, Biousse V, Newman NJ (2000) Isolated Horner’s syndrome and syringomyelia. J Neurol Neurosurg Psychiatry 69:131–132
33. Ruiz E, Resende LS, Gaiolla RD et al (2012) Post-ganglionic Horner’s syndrome: an unusual presentation of non-Hodgkin lymphoma. Case Rep Neurol 4:43–46 34. Guccione P, Gagliardi MG, Bevilacqua M et al (1992) Cardiac catheterization through the internal jugular vein in pediatric patients. An alternative to the usual femoral vein access. Chest 101:1512–1514
