Atypical Acquired Pediatric Horner Syndrome

SMALL CASE SERIES

SECTION EDITOR: W. RICHARD GREEN, MD

nal site emerges the postganglionic the brain, the neck, and the chest. Atypical Acquired Pediatric neuron, which forms a plexus Now, we do not routinely scan the Horner Syndrome around the external and internal ca- brain because we know that neuron rotid arteries. The plexus around the 1 and neuron 3 lesions occur almost internal carotid artery follows the ar- exclusively in adults. In children, we Horner syndrome poses a chal- tery through the foramen lacerum currently routinely scan the neck and lenge for the physician. Confusion into the cavernous sinus. Most of the chest as Horner syndrome is almost in the diagnostic process may arise sympathetic fibers to the eye join the always associated with neuron 2 (pre- because some patients with Horner ophthalmic division of the trigemi- ganglionic) lesions. syndrome do not exhibit the clas- nal nerve, while some travel with the In this study, we discuss several sic findings of simultaneously oc- oculomotor nerve and the ophthal- unusual manifestations of Horner curring miosis and mild ptosis. mic artery. The fibers to the eye in- syndrome in infants. Two cases were When that is the case, the diagno- nervate the dilator muscle of the iris associated with preganglionic le- sis may be missed and essential life- and Müller muscle in the upper and sions and 1 occurred with a post- saving treatment not rendered. lower eyelids. ganglionic lesion. These manifesta- In classic Horner syndrome find- Horner syndrome in children is tions were uncharacteristic in mode ings, the physician observes mild differentiated from adult Horner syn- of appearance for several reasons. At ptosis and miosis. The less com- drome by the location of the in- times, miosis was present without mon secondary symptoms of anhy- volved neuron. The most frequent ptosis; in other instances, ptosis ap- drosis and inverse ptosis of the ip- anatomical location of childhood peared without miosis. Adding to the silateral lower eyelid may also be Horner syndrome is the pregangli- perplexity of diagnosis, we also ob- present. In Horner syndrome that is onic or second-order neuron. At this served a child with intermittent Hor- congenital or has occurred very early site, the most common cause of ac- ner syndrome whom we diagnosed in life, one may see heterochromia quired Horner syndrome is a neu- as having a neuroblastoma. of the iris with the lighter colored iris roblastoma of the paravertebral sym- on the side of the Horner syn- pathetic chain. Damage to this Report of Cases. Case 1. A 6-month- drome. The physician must not neuron can be caused by either birth old boy had a 2-week history of an- eliminate the possibility of Horner trauma to the brachial plexus or me- isocoria. When examined, he had a syndrome when only miosis or only diastinal tumors. Often, with con- small pupil on the left side but no mild ptosis is seen. Subsequently, genital Horner syndome, the iris on ptosis. The mother reported that the both symptoms may occur at the the involved side can be hypopig- pupil was sometimes normal in size. same time, elucidating the diagno- mented. Central, or neuron 1, le- Initially, no tests were ordered. How- sis of Horner syndrome. sions are primarily seen in adults and ever, the child returned 1 week later Anatomically, Horner syn- encompass tumors or hemorrhages because the mother had observed the drome is produced when there is an of the brain stem. Pancoast tumor, occurrence of ptosis for the first time. interruption of the oculosympa- with involvement of the apex of the The ptosis was on the same side as thetic pathway in 1 of 3 sites. The lung, is one of the best-known causes the miosis (Figure 1). The mother first site of Horner syndrome is the of a preganglionic lesion in an adult. noted that there were times when central neuron, which originates in The third-order neuron lesion is seen there was no ptosis or pupillary in- the hypothalamus. The fibers leav- mainly in adults. This lesion is of- volvement (Figure 2). At times during the hypothalamus descend ipsi- ten associated with a dissection of ing the office examination, only an- laterally in the reticular formation of the internal carotid artery or naso- isocoria without ptosis was observed. the brain stem. They continue in the pharyngeal carcinoma spreading Occasionally, we saw anisocoria with anterolateral columns of the spinal along the internal carotid artery. a trace of ptosis of the upper eyelid, cord in the lower cervical and up- Years ago, in the workup of a child but careful scrutiny showed re- per thoracic area. They synapse in with Horner syndrome, we scanned verse ptosis of the lower eyelid the intermediolateral column, which is also known as the ciliospinal center of Budge. From here, the second neuron, also called the preganglionic neuron, leaves the intermediolateral column via the ventral roots and joins the white rami com- municantes to enter the paravertebral sympathetic chain. These fibers synapse in the superior cervical ganglion located just below the base Figure 1. Case 1 showing left-sided Horner syndrome with miosis and ptosis of the left upper eyelid with of the skull. From this third neuro- reverse ptosis of the left lower eyelid.

(REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 7), JULY 2010 WWW.ARCHOPHTHALMOL.COM 937

©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 sympathetic chain. The tumor was completely removed and no chemotherapy was required. At the 6-month follow-up appointment, this patient had persistent left- sided Horner syndrome. Case 2. A 4-month-old boy had a small left pupil observed by his mother during a 2-week period. Pto- sis was not present, and the child was in good health. The mother was ad- Figure 2. Case 1 showing a time with no ptosis and no miosis. vised that although the eye examination results were normal, she should call us immediately if a droopy eyelid developed. Ten days later, the child’s mother reported that her son had developed ptosis on the same side as the miosis. An appointment was promptly scheduled for that same day. The child did in- deed have ptosis, and positive results on an apraclonodine hydrochloride (Iopidine), 0.5%, test showed dilation of the miotic pupil Figure 3. Case 1 showing miosis with only a trace of ptosis of the left upper eyelid. Reverse ptosis of the left lower eyelid is present. and reversal of the ptosis 30 minutes after the apraclonidine was administered (Figure 5 and Figure 6). A CT scan of the neck and thorax revealed a tumor of the paravertebral sympathetic chain in the neck. Results of a biopsy were positive for neuroblastoma, and the child was successfully treated with chemotherapy. Case 3. A 12-month-old boy had a 2-week history of a smaller pupil on the left side. The eye examina- Figure 4. Case 1 showing no miosis but significant ptosis on the left side. tion showed subtle anisocoria with a left miotic pupil. The anisocoria was greater in dark than in light (Figure 7). There was no ptosis and the cocaine test was negative. Four months later, the child returned with 2.5 mm of ptosis on the left side combined with the miosis. A diagnosis of Horner syndrome was made. A CT scan showed a mass imping- ing on the carotid artery on the same side as the Horner syndrome. A biopsy showed an enlarged benign Figure 5. Case 2 showing miosis prior to apraclonodine hydrochloride, 0.5%, testing. lymph node.

(Figure 3). At other times, we ob- CT scan because of concerns about Comment. Smolin1 described a 30- served significant ptosis without an- radiation exposure. Ultimately, she year-old man with congenital Hor- isocoria (Figure 4). The mother consented. The radiology depart- ner syndrome who had episodes of was informed that this manifesta- ment preferred a CT to a magnetic intermittent pupil dilation on the tion was rare and most likely physi- resonance image as calcium, which side of the Horner syndrome. The ological in nature. We recom- is sometimes seen in neuroblas- patient had positive results on a co- mended a computed tomographic toma, is easier to see with a CT. The caine test. Mutalib et al2 reported ac- (CT) scan of the neck and thorax to CT revealed a neck mass, and 5 days quired Horner syndrome second- be certain there was no tumor. The later surgery was performed for a ary to a spontaneous pneumothorax mother was reluctant to approve a neuroblastoma of the paravertebral in a 14-year-old boy. The Horner

(REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 7), JULY 2010 WWW.ARCHOPHTHALMOL.COM 938

©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 syndrome was believed to be secondary to pressure on the sympathetic fibers in the area of the api- cal pleura. After the pneumothorax resolved, the miosis disappeared but the patient was left with a small re- sidual ptosis. In 2000, Slavin3 described a 47- year-old man who developed a 2-mm ptosis of the left upper eyelid with inverse ptosis of the ipsilat- eral lower eyelid with equal pupils. Positive results on a hydroxyam- phetamine hydrobromide, 1%, test Figure 6. Case 2 showing reversal of miosis 30 minutes after administration of apraclonodine localized the Horner syndrome to the hydrochloride, 0.5%. There is also reversal of the ptosis after administration of the apraclonodine. third neuron. Hydroxyamphet- amine stimulates the release of nor- epinephrine from nerve endings. This drug will dilate a first- or second-neuron Horner syndrome but not a third-neuron Horner syndrome. The Horner syndrome in this patient was believed to be associated with cluster headaches. Dur- ing the next 2 weeks, the ptosis im- proved to only a 1-mm difference between the 2 sides, but then the Figure 7. Case 3 with subtle miosis of the left pupil and no ptosis. right pupil was 3.5 mm and the left was 4.0 mm in the light. The right pupil was 4.0 mm in the dark and the left was 4.5 mm. Slavin sur- mised that the patient had developed Horner syndrome on the same side as a physiologically larger pupil, causing the 2 sides to be equal at the time of the initial visit. Hopf4 described a 32-year-old man with an alternating Horner syndrome. The syndrome first appeared on his left side, and 2 weeks later it appeared only on the right side. Five days later, it rotated again to his left side. He Figure 8. Congenital Horner syndrome showing a lighter iris on the involved left side. had an intramedullary papillary ep- We have found no reports of in- Computed tomography was cho- endymoma extending from the C5 complete or varying Horner syn- sen as the best diagnostic modality to the C8-T1 level, and it was successfully removed. drome in children. for demonstrating neuroblastoma ra- Rosenkranz et al5 described sev- These cases illustrate the vari- diologically. Calcification has been eral patients who developed tran- ability in the manifestation of Hor- reported to appear between 50% and sient Horner syndrome after stent ner syndrome. The fact that the mio- 90% of neuroblastoma tumors, with placement for carotid stenosis. sis might precede the ptosis by 1 CT being the most sensitive for 7,8 They felt that a carotid wall hema- week to several months is a critical showing this. Calcifications are less toma caused stretching or com- consideration. Physicians should commonly seen with magnetic reso- 9 pression of the periarterial sympa- consider cocaine or apraclonidine, nance imaging. Calcification is far thetic fibers. One of their patients 0.5%, pupil testing in infants with more frequent in neuroblastoma had partial Horner syndrome with anisocoria even if ptosis is absent. If than in any other pediatric tumor. only pupillary involvement but no pharmacological testing results are Time is of the essence when elu- ptosis. negative or if the testing is not done, cidating the cause of Horner syn- In a literature search, Mokri6 the family of an infant with aniso- drome so that diseases that are po- found a case of incomplete Horner coria must be advised to look for the tentially life-threatening can be syndrome with the absence of fa- subsequent development of ptosis. treated. One should also be aware cial anhydrosis. He also found 1 case If that should occur, the child must that Horner syndrome can be with the absence of ptosis. return for an immediate evaluation. intermittent.

(REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 7), JULY 2010 WWW.ARCHOPHTHALMOL.COM 939

©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/24/2021 Remember that heterochromia is a rare clumping of atypical find- 1. Smolin G. Unilateral intermittent pupillary di- usually associated with congenital ings, it is also possible that such non- lation: report of a case. Arch Ophthalmol. 1969; 81(5):705-706. Horner syndrome but can occur in classic findings may be more com- 2. Mutalib M, Vandervelde C, Varghese A, et al. lesions with the onset before 2 years mon than previously recognized. Horner’s syndrome secondary to asymptomatic of age (Figure 8). The lighter- pneumothorax in an adolescent. Eur J Pediatr. colored iris is on the side of the Hor- Zane F. Pollard, MD 2007;166(5):507-508. Marc F. Greenberg, MD 3. Slavin ML. Horner syndrome with equal-sized pu- ner syndrome as the sympathetic pils in a case underlying physiologic anisocoria. innervation is needed for the depo- Mark Bordenca, MD J Neuroophthalmol. 2000;20(1):1-2. sition of pigment in the stroma of the Julie Lange, MD 4. Hopf HC. Intermittent Horner’s syndrome on al- ternate sides: a hint for locating spinal lesions. iris. Author Affiliations: James Hall Eye J Neurol. 1980;224(2):155-157. An additional caveat alerts the Center, and Children’s Healthcare of 5. Rosenkranz M, Eckert B, Niesen WD, Weiller physician that just as anisocoria can C, Sliwka U. Horner syndrome related to ipsi- Atlanta, Scottish Rite Children’s Hos- lateral carotid wall hematoma after stent place- at times be present without ptosis in pital, Atlanta, Georgia (Drs Pol- ment for the treatment of carotid stenoses. AJNR infantile Horner syndrome, ptosis lard, Greenberg, and Bordenca); and Am J Neuroradiol. 2003;24(8):1508-1511. can sometimes be present without Section of Pediatric Ophthalmol- 6. Mokri B. Hemicrania with partial Horner’s syn- anisocoria. And lastly, Horner syndrome, but not Raeder’s syndrome. Arch Neurol. ogy and Adult Strabismus, Depart- 1984;41(7):704. drome in infants may be present ment of Ophthalmology, The Ohio 7. Martin-Simmerman P, Cohen MD, Siddiqui A, intermittently. State University College of Medi- Mirkin D, Provisor A. Calcification and uptake While our 3 cases do not fit the cine, Columbus (Dr Lange). of Tc-99m diphosphonates in neuroblastomas: concise communication. J Nucl Med. 1984;25 classic description of Horner syn- Correspondence: Dr Pollard, James (6):656-660. drome, they do represent 33% of the Hall Eye Center, 5445 Meridian 8. Bousvaros A, Kirks DR, Grossman H. Imaging infantile Horner syndrome cases Mark Rd, Ste 220, Atlanta, GA 30342 of neuroblastoma: an overview. Pediatr Radiol. seen in our pediatric ophthalmol- ([email protected]). 1986;16(2):89-106. 9. Donnelly LF. Genitourinary Tract: Fundamen- ogy practice in the past 5 years. Al- Financial Disclosure: None re- tals of Pediatric Radiology. Philadelphia, PA: WB though these cases could represent ported. Saunders; 2001:164.

(REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 7), JULY 2010 WWW.ARCHOPHTHALMOL.COM 940