Friedrich Horner described the clinical syndrome of oculosympathetic denervation in 1869.1 Since 1885, when Klumpke2 noted the association of lower brachial plexus injury with congenital Horner's syndrome, birth trauma has been regarded as a common cause of Horner's syndrome in children.3
In 1958, Giles and Henderson found birth trauma to be the most common etiology in Horner's syndrome patients aged up to 20 years.4 Leone and Russell reported two cases of long-standing Horner's syndrome in children and urged ophthalmologists to avoid over-investigating patients who had had Homers syndrome from birth.5
In 1976, Sauer and Levinsohn described seven children with Horner's syndrome who had serious underlying disease, including five with malignancy.6 In 1978 Beckerman and Seaver reported a 2-month-old child with Horner's syndrome in whom neuroblastoma was later proven.7 Musarella et al reviewed 405 children with a known diagnosis of neuroblastoma: 14 had Horner's syndrome and in nine of them it was a presenting sign.8 In contrast, Weinstein et al reported 11 patients who had onset of Horner's syndrome within the first year of life; in none of their cases was the syndrome thought to be a manifestation of malignancy.9
In view of these disparate reports of the etiology of Horner's syndrome in children, we reviewed patients with the syndrome who had been investigated in the Department of Ophthalmology at The Hospital for Sick Children, Toronto, over an 18-month period.
Patients referred to the department who had narrowing of the interpalpebral fissure and ipsilateral miosis with anisocoria increasing in darkness were studied. Local ocular pathology was excluded by slit-lamp examination. The patients were assessed for heterochromia. Anhydrosis was evaluated by feeling the side of the face and by questioning the parents.
The size of the pupil was measured using a millimeter rule first in bright light and then in semi-darkness. Two drops of 4% cocaine were instilled into each eye initially and after five minutes; 40 minutes later the pupils were remeasured in bright light.
At least 48 hours after testing with cocaine, the pupils were remeasured and two drops of 1% hydroxyamphetamine (Paredrine®, Smith Kline & French Laboratories, Mississauga, Ontario) were instilled into each eye. The application was repeated after five minutes. An increase in anisocoria was taken as evidence of a postganglionic lesion, whereas unchanged or decreased anisocoria was taken as evidence of a preganglionic or central lesion. If the etiology of the Horner's syndrome was uncertain, computed tomography (CT) scans of the head and neck were performed and urinary vanillylmandelic acid (VMA) levels assessed.
Characteristics of 10 Children With Horner's Syndrome
CASE REPORTS (Table)
CASE 1. A newborn girl was noted by her mother to have ptosis on the left side within a few hours of birth. Horner's syndrome was diagnosed in association with a third and sixth cranial nerve lesion at the age of 3 months. There was no anhydrosis, and cocaine and OH-amphetamine testing confirmed postganglionic oculosympathetic paresis with the anisocoria increasing from 1 to 3 mm after OHamphetamine. CT scanning showed a large arachnoid cyst associated with an abnormality in the region of the left cavernous sinus (Figure 1).
CASE 2. Unequal sized pupils were noted in a boy a few days after bi rth. The mother noted that this discrepancy was greater in dim illumination and that left-sided ptosis developed when the baby was tired. Delivery had been normal and spontaneous with no brachial plexus injury. When the child was examined at age 2 weeks he had Horner's syndrome; the anisocoria increased from 1 mm in bright light to 2.5 mm in dim illumination, but cocaine testing was equivocal. Testing with OH-amphetamine suggested a preganglionic lesion, although sweating was the same on each side of the face. A chest radiograph, CT scan of the head, neck, and mediastinum, and 24-hour urinary VMA testing were all normal.
CASE 3. A 3-day-old boy was noted to have left-sided ptosis and, shortly afterward, a difference in the size of his pupils. The baby had been born by spontaneous vaginal delivery. On examination at age 3 weeks he had a left Horner's syndrome, but no other abnormality. There was no anhydrosis, although OH-amphctamine testing was in keeping with a preganglionic lesion. Urinary VMA levels were normal. A CT scan of the head and neck was normal. The child has been followed for 6 months without further developments.
CASE 4. Right ptosis was noted by the mother of a girl within a few hours of birth. At the age of 4 weeks stridor developed, which was at that time attributed to tracheomalacia. At 2 months of age the child had a further episode of upper airway obstruction associated with a right supraclavicular mass evident on clinical examination and chest radiograph. Examination indicated the presence of right Horner's syndrome confirmed by cocaine testing. There was anhydrosis on the left side of the face, which coincided with the preganglionic localization of the lesion with OH-amphetamine testing. Twenty-four hour urinary VMA levels were elevated; CT scanning showed a large mass in the right mediastinum and neck, which biopsy proved to be a neuroblastoma (Figure 2).
CASE 5. A boy with spastic, diplegie cerebral palsy was first seen in our department at the age of 5 years for review of strabismus. His mother had noted ptosis and unequal pupils shortly after birth, but there had been a normal delivery and no perinatal problems. Developmental delay was noted at age 18 months and subsequent investigation demonstrated semilobar holoprosencephaly in association with the cerebral palsy. Cocaine testing confirmed a left Horner's syndrome. After instillation of the OHamphetamine the miotic pupil dilated the same as the normal pupil, suggesting a preganglionic lesion although we could not detect any difference in sweating on the two sides of the face.
FIGURE 1: Case 1. Coronal CT scan showing a calcified lesion in the region of the left cavernous sinus (arrow) and a large arachnoid cyst extending to each side of the midline.
CASE 6. A 7-month-old girl suddenly developed ptosis, miosis, and irritability. One week later she was noted to have a small, anterior cervical lymph node, but a chest radiograph was normal. There was no heterochromia, but ipsilateral facial anhydrosis was present. Cocaine and OHamphetamine testing confirmed preganglionic Horner's syndrome. CT scanning of the head, neck, and chest showed a small, partially calcified 1.5-cm mass in the region of the cervical sympathetic chain (Figure 3), but spot and 12-hour VMA studies were normal. Surgical biopsy of the small lump in the neck demonstrated neuroblastoma.
CASE 7. A 20-month-old boy developed a swollen left upper lid and fever associated with a right superficial cervical lymphadenopathy. On examination 6 months later he had a left Horner's syndrome, confirmed with cocaine testing. There was no facial anhydrosis although the pupil dilated fully with OH-amphetamine. His chest radiograph, CT scan of the head, bone scan, and 24-hour urinary collection for catecholamines were normal.
FIGURE 2: Case 4. Axial CT scan at the T1 level, demonstrating a large hyperdense mass (arrows) causing compression and deviation of the trachea to the left.
CASE 8. An 8-year-old girl noticed the acute onset of swelling of the right upper lid followed by ptosis. Six months later Horner's syndrome was diagnosed with anisocoria increasing from 1.5 mm in bright light to 3.5 mm in darkness. The syndrome was confirmed on cocaine testing. There was no heterochromia. OH-amphetamine testing suggested a preganglionic lesion although there was no anhydrosis. CT scans of the head, neck, and chest, and 24-hour urinary VMA testing were all normal.
CASE 9. A 5-year-old boy underwent surgery for coarctation of the aorta. Three days later his mother noticed left ptosis. On examination he had a left Horner's syndrome associated with conjunctival hyperemia. Cocaine and OH-amphetamine testing indicated a preganglionic sympathetic lesion. Six months later the parents reported that they were no longer able to detect any ptosis or anisocoria.
CASE 10. A 14-week-old boy was noted to have left Horner's syndrome on recovering from surgery for tetralogy of Fallot. Cocaine and OH-amphetamine testing one week after surgery confirmed a preganglionic syndrome, although there was no anhydrosis or conjunctival hyperemia.
Two of our ten patients had neuroblastoma. Ptosis, observed by the parents, was the first manifestation of the disease in both, and in one the mother noticed the ptosis within a few hours of birth. Although both of these children developed Horner's syndrome before the age of 1 year, this tumor commonly affects children over the age of 2, and older patients presenting with Horner's syndrome who have neuroblastoma have been reported.8 In Case 1, where a small tumor and a normal chest radiograph were present, both the spot and the 24-hour VMA tests were normal.
FIGURE 3: Case 7. Axial CT scan just below the level of the superior cervical ganglion, showing a calcified mass (arrows) lying posterior to the internal jugular vein and internal carotid artery.
FIGURE 4: Illustration of second-order neurons arising in the cord at the T1 level and joining the sympathetic chain. These neurons pass through the inferior and middle cervical ganglia to synapse in the superior cervical ganglion. Several fine cords connect the inferior and middle cervical ganglia. One of these cords, the ansa subclavia, takes a circuitous route, descending into the mediastinum to pass around the subclavian artery before ascending in the neck.
Vanillylmandelic acid is a breakdown product of catecholamines, which is characteristically excreted in excess in patients with neuroblastoma. Because of variability in normal VMA excretion, an elevated value is useful, but a normal value does not exclude neuroblastoma. Both patients with neuroblastoma had a preganglionic lesion, indicated both by the presence of anhydrosis and by OHamphetamine testing. CT scans indicated a tumor in the neck and mediastinum in Case 4, and in the region of the cervical sympathetic chain below the level of the superior cervical ganglion in Case 7.
These two patients were the only ones who had anhydrosis coinciding with preganglionic localization by hydroxyamphetamine. There are several possible reasons for divergence between the results of OH-amphetamine testing and clinical assessment of sympathetic function on the side of the face. Weinstein et al argued that patients with pupils dilating only partially on OH-amphetamine testing had primarily preganglionic lesions with postsynaptic degeneration.9 Therefore, we used the strict criterion of an increase in anisocoria to firmly diagnose a postganglionic lesion, but accepted either full or partial mydriasis as indicating a probable preganglionic lesion.
One patient of Weinstein et al responded like our six patients who had preganglionic localization with OH-amphetamine but no disturbance of sweating.9 Their patient had undergone thoracic surgery, as in Cases 9 and 10 in our series. Sympathetic fibers subserving sweating may travel in one of the cords directly connecting the inferior and middle cervical ganglia, while pupillary fibers take a more circuitous route, traveling with the ansa subclavia into the mediastinum before ascending into the neck (Figure 4).
The criterion of dilation lag can be used to help establish the diagnosis of Horner's syndrome.10,11 In this technique, Polaroid flash photographs are taken in bright illumination and after five and 15 seconds of darkness. Anisocoria that is maximal after five seconds is interpreted as evidence of Horner's syndrome. We found that our young patients tended to close their eyes or move out of focus after the initial photography, making the technique unreliable in this age group.
None of our patients had heterochromia. This may have been because of the patients' ages and the brief interval between the onset of Horner's syndrome and the examination. Giles and Henderson4 and Calhoun12 found heterochromia in adult patients in whom the onset of Horner's syndrome had occurred before the age of 2 years, but they did not give information about the time of onset of the heterochromia. Jaffe et al reported a patient with neuroblastoma who was believed to have developed heterochromia at the age of 9 months, but in six other cases that they reviewed the time of onset of the heterochromia could not be determined.13
The most common association of Horner's syndrome coded in our hospital records is cardiothoracic surgery, similar to that undergone by Cases 9 and 10. In the study period there were 12 patients with this diagnosis who were not reviewed. They will be the subject of a further report.
The onset of Horner's syndrome may be a manifestation of neuroblastoma. The two children in our series with this tumor were clearly positive on cocaine testing and demonstrated facial anhydrosis with preganglionic localization on amphetamine testing. In two other patients Horner's syndrome arose in association with an acute febrile illness without any other abnormality. Except in cases precipitated by thoracic surgery, however, onset of the syndrome in childhood or at birth warrants investigation, which should include chest radiograph, CT scanning of the head and neck, and 24-hour urinary catecholamine assay.
1. Horner JF: Über eine Form von Ptosis. Klin Monatsbl Augenheilkd 1869; 7:193.
2. Klumpke A: Contribution à l'étude des paralysies du plexus brachial. Paralysies radiculaires totales. Paralysies radiculaires inférieures. De la participation des filets sympathetiques oculo-pupillaires dane ces paralysies. Revue de médicin (Paris) 1885; 5:591-616 (July), 739-790 (Sept).
3. Miller NR: Walsh and Hoyt's Clinical Neuro-ophthalmology, ed 4. Baltimore, Williams and Wilkins, 1985, vol 2, p 500.
4. Giles CL, Henderson DA: Horner's syndrome: An analysis of 216 cases. Am J Ophthalmol 1958; 46:289.
5. Leone CR, Russell DA: Congenital Horner's syndrome. J Pediatr Ophthalmol Strabismus 1970; 7:152.
6. Sauer C, Levinsohn MN: Horner's syndrome in childhood. Neurology 1976; 26:216.
7. Beckerman BL, Seaver R: Congenital Horner's syndrome and thoracic neuroblastoma. J Pediatr Ophthalmol Strabismus 1978; 15:24.
8. Musarella MA, Chan HSL, DeBoer G, et al: Ocular involvement in neuroblastoma: Prognostic implications. Ophthalmology 1984; 91:936.
9. Weinstein JM, Zweifel TJ, Thompson HS: Congenital Horner's syndrome. Arch Ophthalmol 1980; 98:1074.
10. Pilley SFJ, Thompson HS: Pupillary dilatation in Horner's syndrome. Br J Ophthalmol 1975; 59:731.
11. Van der Wiel HL, van Gijn J: Localization of Horner's syndrome. Use and limitations of the hydroxyamphetamine test. J Neurol Sci 1983; 59:229.
12. Calhoun FP: Causes of heterochromia iridis with special reference to paralysis of the cervical sympathetic. Am J Ophthalmol 1919; 2:255.
13. Jaffe N, Cassady R, Filler RM, et al: Heterochromia and Horner syndrome with cervical and mediastinal neuroblastoma. J Pediatr 1975; 87:75.
Characteristics of 10 Children With Horner's Syndrome