Rare Cause and Manifestation of Horner Syndrome in an Infant

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Rare Cause and Manifestation of Horner Syndrome in an Infant Grace S. Yin, BA, Sam P. Gurney, MBChB, FRCOphth, Arun Y. Reginald, MD, FRCSC, Juan Putra, MD, Michael J. Wan, MD, FRCSC A 6-day-old patient was transferred to a pediatric hospital because of stridor. She was born at 36 weeks’ gestational age by vaginal delivery, which was induced because of intrauterine growth restriction. Inspiratory stridor was noted at delivery but resolved by 10 minutes of life, with Appearance, Pulse, Grimace, Activity, and Respiration scores of 9 at 1 minute and 9 at 5 minutes. The stridor reoccurred at approximately 1 hour of life. She remained stable on room air, but the stridor gradually worsened, leading to transfer from an adult hospital NICU to the Hospital for Sick Children. On admission, otolaryngology identified severe laryngomalacia with collapse of the supraglottic structures as the likely cause of stridor. The patient began having intermittent episodes of oxygen desaturation and was scheduled for an urgent supraglottoplasty. Just before surgery, 8 days after admission, right eye upper eyelid ptosis was first noted. On review, her mother reported that the right eye had not opened as much as the left eye since birth. Ophthalmology assessed the patient and noted moderate right eye upper eyelid ptosis without obvious reverse ptosis. The right pupil was smaller than the left by approximately 1 mm in light and 2 mm in dark. Topical cocaine eyedrops (4%) were instilled into the eyes twice, 5 minutes apart. One hour later, the anisocoria increased from 1 to 2.5 mm, indicating a positive test for Horner syndrome. The ocular examination was otherwise unmarkable. Urinary levels of homovanillic acid and vanillylmandelic acid were tested and found to be normal. An urgent MRI of the head, neck, and chest was performed and revealed a solid and cystic mass encasing the right common carotid artery with mass effect on the trachea, thyroid, and esophagus. An ultrasound-guided biopsy of the mass was performed. Histologically, the lesion showed a myofibroblastic proDepartment of Ophthalmology and Vision Sciences (GSY, SPG, YAR, MJW), Hospital for Sick Children, Toronto, Canada; Department of Ophthalmology and Vision Sciences (GSY, SPG, YAR, MJW), University of Toronto, Toronto, Canada; and Department of Paediatric Laboratory Medicine (JP), Hospital for Sick Children, Toronto, Canada. The authors report no conflicts of interest. Address correspondence to Michael J. Wan, MD, FRCSC, Department of Ophthalmology and Vision Sciences, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8; E-mail: Michael. [e-mail] Yin et al: J Neuro-Ophthalmol 2023; 43: e233-e234 liferation arranged in fascicles. The lesional cells showed long, tapering nuclei, inconspicuous nucleoli, vesicular nuclear chromatin, and pale pink cytoplasm (Fig. 1). There was no significant nuclear atypia. Necrosis and atypical mitoses were absent. The lesional cells were immunoreactive for vimentin and smooth muscle actin, while negative for pan-TRK, desmin, CD34, S100, epithelial membrane antigen, and pankeratin. The pathologic and molecular findings of the PDGFRB variant (PDGFRBp.D850V) on RNA sequencing supported a diagnosis of infantile myofibroma. The patient was treated with a tracheostomy followed by low-dose methotrexate and vinorelbine. The patient tolerated the treatment well, and the respiratory distress resolved. After 6 months of treatment, repeat MRI showed an interval decrease in size of the neck mass with persistent encasement of the right carotid artery and persistent mass effect on the subglottic airway. The right upper eyelid ptosis and anisocoria remained stable. Notably, the patient’s mother reported that just before vomiting, the anisocoria would reverse and the ptosis would resolve, which would revert to baseline shortly afterward (Fig. 2). Horner syndrome presents classically with the triad of ocular miosis, ptosis, and anhidrosis, which are caused by disruption of the oculosympathetic pathway. In infants, it is most commonly idiopathic or caused by birth trauma. However, a small but significant number of cases have a serious underlying etiology, with the most common malignant causes being neuroblastoma, paraganglioma, and ganglioneuroma (1). A serious but rare cause of Horner syndrome in infancy is a myofibroma. Infantile myofibroma is a histologically benign spindle cell tumor that can enlarge over time and cause morbidity by compression of adjacent structures. There have been 2 previous case reports of infantile myofibroma presenting as Horner syndrome. Nabavizadeh et al (2) reported the case of a 5-month-old who presented with isolated left Horner syndrome and a myofibroma of the carotid space. Tierney et al (3) reported the case of a newborn who presented with an elevated hemidiaphragm and an upper brachial plexus, who was found to have a myofibroma of the left lung apex. We present the first case of an infantile myofibroma presenting with Horner syndrome and respiratory distress, rapid reversal of ptosis e233 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Tumor histology. A. The spindle cell proliferation is characterized by bland-appearing myofibroblasts arranged in fascicles (hematoxylin and eosin, ·4). B. The spindle cell proliferation is characterized by bland-appearing myofibroblasts arranged in fascicles; no nuclear atypia or increased mitotic activity is seen (hematoxylin and eosin, ·10). C. The lesional cells are diffusely immunoreactive for smooth muscle actin, confirming their myofibroblastic origin (SMA, ·10). SMA, smooth muscle actin. FIG. 2. A. Baseline photograph of the infant with right Horner syndrome showing 2 mm of upper eyelid ptosis and miosis. B. Just before vomiting, the right pupil dilated dramatically with resolution of the ptosis. and anisocoria just before vomiting, and the first to require urgent treatment. Identification of the Horner syndrome and urgent imaging were critical, given the impact on management. This case highlights the importance of considering Horner syndrome, especially when there are additional signs such as respiratory distress, which may indicate a common lesion along the oculosympathetic pathway. One interesting finding in this case was that just before emesis, the smaller right pupil would dilate and the ptosis would transiently resolve (Fig. 2). This physiologic effect resembles the reversal of anisocoria that is observed when topical apraclonidine drops are instilled into the eyes of a person with Horner syndrome (4). Apraclonidine has a weak alpha-1 agonist effect, which has minimal effect on the normal pupil but causes the Horner pupil to dilate because of denervation supersensitivity of the iris dilator muscle. For this case, the exact underlying mechanism of the anisocoria reversal is uncertain. It is possible that circulating catecholamines associated with nausea/vomiting caused a weak alpha-1 agonist effect on the iris, leading to dilation of the Horner pupil with minimal effect on the fellow pupil, analogous to the effect of apraclonidine. Whatever the true underlying mechanism, we believe that it may be related to the denervation supersensitivity of the Horner pupil in some way. If this is true, we would not expect to see the same effect in a patient with physiologic anisocoria. As such, when a child presents with anisocoria, a history of spontaneous reversal with nausea/vomiting is a strong indication that it is a true Horner syndrome. e234 Overall, this case highlights the importance of considering a mass lesion in patients presenting with Horner syndrome and respiratory distress and describes spontaneous reversal of anisocoria as a possible sign of Horner syndrome. STATEMENT OF AUTHORSHIP Conception and design: G. S. Yin, S. P. Gurney, M. J. Wan; Acquisition of data: G. S. Yin, S. P. Gurney, J. Putra, M. J. Wan; Analysis and interpretation of data: G. S. Yin, S. P. Gurney, Y. A. Reginald, J. Putra, M. J. Wan. Drafting the manuscript: G. S. Yin, S. P. Gurney, Y. A. Reginald, J. Putra, M. J. Wan; Revising it for intellectual content: S. P. Gurney, Y. A. Reginald, J. Putra, M. J. Wan. Final approval of the completed manuscript: G. S. Yin, S. P. Gurney, Y. A. Reginald, J. Putra, M. J. Wan. REFERENCES 1. Kadom N, Rosman NP, Jubouri S, Trofimova A, Egloff AM, Zein WM. Neuroimaging experience in pediatric Horner syndrome. Pediatr Radiol. 2015;45(10):1535–1543. 2. Nabavizadeh SA, Zimmerman RA, Mattei P, Liu GT. Infantile myofibroma of the carotid space presenting as Horner syndrome. J Neuroophthalmol. 2017;37(4):459–460. 3. Tierney TS, Tierney BJ, Rosenberg AE, Krishnamoorthy KS, Butler WE. Infantile myofibromatosis: a nontraumatic cause of neonatal brachial plexus palsy. Pediatr Neurol. 2008;39(4):276–278. 4. Koc F, Kavuncu S, Kansu T, Acaroglu G, Firat E. The sensitivity and specificity of 0.5% apraclonidine in the diagnosis of oculosympathetic paresis. Br J Ophthalmol. 2005;89(11):1442–1444. Yin et al: J Neuro-Ophthalmol 2023; 43: e233-e234 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.