Internuclear ophthalmoplegia (INO) is a discrete localizing neuro-ophthalmic sign. Lesions in the medial longitudinal fasciculus cause an adduction deficit in the eye on the side of the lesion, with abducting nystagmus in the contralateral eye. INO occurs unilaterally, bilaterally, or in conjunction with other lesions affecting ocular motility (1).
The causes of INO are well delineated in the adult population, with brainstem ischemia and multiple sclerosis comprising approximately three-quarters of cases. Other less common etiologies in adults include trauma, tentorial herniation, infection, tumor, iatrogenic, hemorrhage, and vasculitis. The incidence in men nearly equals that of women (1). Bilateral INO suggests a demyelinative etiology, whereas unilateral INO is more commonly due to a brainstem vascular disease. Approximately half of adult cases of INO resolve within 1 year (2).
In contrast to INO occurring in adults, descriptions of INO in the pediatric population are sparse. We report 3 pediatric patients with INO illustrating the variety of causes of this eye movement disorder in children.
A retrospective chart review was performed at the University of California Davis Eye Center to include pediatric patients from birth to 15 years of age. The patients included in the study were those diagnosed with INO, confirmed by clinical findings from 2004 through 2011. A single pediatric ophthalmologist (M.O.H.) examined each patient and made or confirmed the diagnosis of INO. Medical records were examined to collect data and prepare a descriptive case series.
REPORT OF CASES
An 18-month-old Hispanic girl presented to clinic with a history of normal birth. At age 3 days she suffered left-sided posterior intracerebral and subdural hemorrhages of unknown etiology. Her subsequent history included feeding problems requiring a gastric tube, microcephaly, neonatal seizures, and extensive encephalomalacia, particularly on the left side, as detected on magnetic resonance imaging (MRI). Her ophthalmic examination revealed an intermittent exotropia, and a conservative approach with close follow-up was recommended.
The patient returned 6 months later. Visual acuity appeared intact. On right and left gaze she had an exotropia of 20 prism diopters accompanied by limitation of adduction bilaterally with abducting nystagmus in the fellow eye. There was no ptosis, anisocoria, or skew deviation, and the eye movement disorder was consistent with bilateral INO.
The INO improved over the next year. Examination at age 3 years showed an exotropia of 10 prism diopters in primary position. The patient was orthophoric on right gaze and had an exotropia of 20 prism diopters on left gaze. On subsequent examinations over the following year, the INO completely resolved in the left eye, while the right eye continued to demonstrate an adduction deficit with abducting nystagmus in the left eye. During the course of follow-up, the child was treated for amblyopia of the right eye.
A 5-year-old Caucasian boy with a history of prenatal cerebrovascular accident resulting in panhypopituitarism, respiratory distress, and seizures presented with bilateral INO and a compensatory head turn. MRI of the brain (Fig. 1) demonstrated an ectopic bright spot and a hypodeveloped pituitary, without other abnormalities. One year after the initial diagnosis of INO, the patient underwent left eye muscle surgery for exotropia. At age 8 years, he experienced the onset of new seizures and was noted to have a left gaze palsy and V-pattern exotropia. The motility pattern progressed to right gaze palsy, leaving the patient with very little horizontal eye movement. The remainder of the ophthalmic examination was normal. MRI was ordered, but not obtained as the child went into foster care for suspected abuse.
The etiology of the gaze palsy and V-pattern exotropia was never determined. Evaluation was hampered by the patient's frequent changes in foster care and eventual reestablishment with the maternal family. The child was examined by a neurologist and serologic testing for myasthenia gravis was negative. The V-pattern exotropia did resolve, but the gaze palsies persisted. The child was last seen at age 11 years with no further changes in his ocular motility or evidence of new neurologic findings.
A 10-year-old Hispanic boy, with a history of multiple surgical resections and radiation therapy for high-grade astrocytoma of the cerebellum involving the pons and midbrain, presented with bilateral INO. There was limitation of adduction in both eyes with nystagmus of the contralateral eye on abduction. He had limitation of upgaze and gaze-evoked nystagmus in both vertical directions. There was no evidence of ptosis or skew deviation. Four years later, he required a ventriculoperitoneal shunt for obstructive hydrocephalus but his bilateral INO remained unchanged.
INO occurs rarely in childhood. Previously, the youngest reported patient with INO was a 3-year-old boy with a benign aqueductal cyst causing hydrocephalus and bilateral INO after placement of an external ventricular drain (3). Surgery was undertaken to open the cyst and restore cerebrospinal fluid drainage with resolution of the INO within 14 days.
Neoplasms of the brainstem causing INO were reported in 6 pediatric patients (ages: 4–17 years) by Cogan and Wray (4). Four occurred in the first decade of life, and 2 occurred in the second decade. Two of the patients had unilateral INO, 2 had bilateral INO, and 2 had one-and-a-half syndrome. The tumor types included medulloblastoma, glioma, and glioblastoma multiforme. The underlying disease was fatal in 4 patients, one improved, and another remained stable. Sharpe et al (5) described a 6-year-old boy who developed a one-and-a-half syndrome due to a left-sided pontine glioma.
A wide variety of other causes of INO in the pediatric population have been reported. Vascular infarcts in the brainstem associated with INO have been documented in patients with sickle cell trait (6), systemic lupus erythematosus (7), Fabry disease (8), and periarteritis nodosa (9). Additional etiologies of pediatric INO include head trauma (10,11), viral meningoencephalitis (12), iatrogenic embolism from cardiac catheterization (13), and brainstem hemorrhage (14). To the authors' knowledge, no children with INO due to demyelinating disease have been reported.
All 3 patients in our series had bilateral INOs with different etiologies: hemorrhage, infarction, and tumor. All had multiple eye movement disorders that confounded the diagnosis of INO. One patient, a 2-year-old girl with neonatal intracerebral hemorrhage, experienced improvement with complete resolution of INO in the left eye and partial resolution in the right eye. She is the youngest reported child with INO.
The diagnosis of INO in a young child can be difficult due to the level of cooperation. Because of this, close follow-up and a conservative approach to surgery are appropriate. Treatment for amblyopia is often warranted during the follow-up care of these patients.
1. Keane JR. Internuclear ophthalmoplegia: unusual causes in 114 of 410 patients. Arch Neurol. 2005;62:714–717.
2. Bolanos I, Lozano D, Cantu C. Internuclear ophthalmoplegia: causes and long-term follow-up in 65 patients. Acta Neurol Scand. 2004;110:161–165.
3. Shin M, Nishihara T, Iai S, Eguchi T. Benign aqueductal cyst causing bilateral internuclear ophthalmoplegia and external ventricular drainage. J Neurosurg. 2000;92:490–492.
4. Cogan DG, Wray SH. Internuclear ophthalmoplegia as an early sign of brainstem tumors. Neurology. 1970;20:629–633.
5. Sharpe JA, Rosenberg MA, Hoyt WF, Daroff RB. Paralytic pontine exotropia. A sign of acute unilateral pontine gaze palsy and internuclear ophthalmoplegia. Neurology. 1974;24:1076–1081.
6. Leavitt JA, Butrus SI. Internuclear ophthalmoplegia in sickle cell trait. J Neuroophthalmol. 1994;14:49–51.
7. Sugie Y, Okada Y, Ishitsuka T, Sadoshima S, Fujishima M. A case of systemic lupus erythematosus associated with lateral medullary syndrome and unilateral internuclear ophthalmoplegia. Clin Neurol. 1989;29:75–79.
8. Ho PC, Feman SS. Internuclear ophthalmoplegia in Fabry's disease. Ann Ophthalmol. 1981;13:949–951.
9. Kirkali PR, Topaloglu R, Kansu T, Bakkaloglu A. Third nerve palsy and internuclear ophthalmoplegia in periarteritis nodosa. J Pediatr Ophthalmol Strabismus. 1991;28:45–46.
10. Muller C, Koch S, Toifl K. Transient bilateral internuclear ophthalmoplegia after minor head trauma. Dev Med Child Neurol. 1993;35:163–166.
11. Muthukumar N, Veerarajkumar N, Madeswaran K. Bilateral internuclear ophthalmoplegia following mild head injury. Childs Nerv Syst. 2001;17:366–369.
12. Bodziner RA, Singer W, Hedges TR. Bilateral internuclear ophthalmoplegia in meningoencephalitis. Dev Med Child Neurol. 1983;26:819–820.
13. Rennie IG, Wright JG, Wilkinson JL. Iatrogenic internuclear ophthalmoplegia. J Neurol Neurosurg Psychiatry. 1986;49:942.
14. Wutthiphan S, Foster SR, Poonyathalang A, Pongpech S. Abducens-oculomotor synkinesis associated with internuclear ophthalmoplegia and acquired abducens nerve palsy. J Pediatr Ophthalmol Strabismus. 2006;43:246–249.