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Monocular Nystagmus in Infancy and Early Childhood
MONOCULAR NYSTAGMUS IN INFANCY A N D EARLY C H I L D H O O D JAMES F A R M E R , M . D . ,
AND C R E I G S. H O Y T ,
San Francisco,
M.D.
California
Of 11 young children (six girls and five boys, ranging in age from 4 to 14 months) with monocular nystagmus, six were found to have chiasmal tumors whereas only four had spasmus nutans. Differentiating features between these two groups included decreased vision and optic nerve anomalies (including four cases of optic nerve hypoplasia) in the tumor group. However, we found that no consistent clinical finding absolutely separates these groups. We therefore recommend that all infants and children with monocular nystagmus or the other features of spasmus nutans should undergo computed tomographic scanning.
Monocular nystagmus, a rhythmic os cillation of only one eye on direct forward gaze, represents a peculiar manifestation of dissociated nystagmus. 1,2 Both congeni tal and acquired monocular nystagmus in infants have been ascribed to spasmus nutans. 3 4 Spasmus nutans is a transient syndrome of nystagmus, involuntary head nodding, and anomalous head posi tions that varies substantially in its mani festation of these features. The cause of this syndrome is unknown. Although the nystagmus in spasmus nutans is usually described as binocular and asymmetric, several authors have noted that monocu lar nystagmus may occur in this syn drome. 3,0 ' 10 The benign prognosis of spas mus nutans was well documented in the long-term follow-up series of Norton and Cogan 3 and Hoefnagel and Biery. 4 HowAccepted for publication July 18, 1984. From the Department of Ophthalmology, Univer sity of California, San Francisco, and the Clinical Research Center, That Man May See, Inc., San Francisco, California. This study was supported in part by a grant from the Children's Eye Care Foun dation, Washington, D.C. Dr. Hoyt is the Research for Prevention of Rlindness Robert E. McCormick Scholar. Reprint requests to Creig Hoyt, M.D., Room A-704, University of California, San Francisco, San Francisco, CA 94143. 504
ever, case reports of chiasmal tumors simulating monocular nystagmus and spasmus nutans in infants and children are becoming increasingly frequent.11"16 We studied the clinical and diagnostic features in 11 children less than 15 months old who had monocular nystag mus. S U B J E C T S AND M E T H O D S
We reviewed the findings for 11 chil dren referred to the University of Califor nia, San Francisco, with monocular nys tagmus from August 1977 to February 1984. Each child underwent a complete pédiatrie ophthalmic examination and computed axial tomography of the head and orbits. Central visual acuity was esti mated by fixation patterns and, whenever possible, pattern visual-evoked poten tials. We ascertained the monocularity of the nystagmus by direct observation as we believed this to be most applicable in the clinical examination of young chil dren. The diagnosis of chiasmal tumor was established on finding a suprasellar mass on computed tomographic scanning. RESULTS
The 11 children ranged in age at the time of diagnosis from 4 to 14 months
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TABLE 1 SUMMARY O F CLINICAL FINDINGS IN SIX C H I L D R E N W I T H CHIASMAL TUMORS
Clinical Findings Age (mos) Sex Involved eye Visual acuity R.E. L.E.
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
9 M Right
11 M Left
14 F Left
9 F Left
13 M Left
10 F Left
Central, Central, Central, Central, Central, Central, maintained maintained maintained maintained maintained maintained Peripheral Peripheral Central, Central, Central, — maintained maintained maintained Present, Present, Present, Absent Absent Present, LE. R.E. R.E. L.E.
Afferent pupillary defect Optic nerve status Hypoplasia R.E. Normal L.E. Nystagmus Head shake Head tilt
Vertical Present Present
Normal Atrophy Vertical Present Present
Normal Possible hypoplasia Horizontal Absent Absent
(average age, 8.3 months). There were six girls and five boys (Tables 1 and 2). The six children with chiasmal tumors had an average age of 11 months. The left
Normal Hypoplasia Horizontal Absent Absent
Atrophy Severe atrophy Vertical Present Present
Hypoplasia — Horizontal Present Absent
eye was involved in five of the six. The directionality of the nystagmus was even ly divided between horizontal and verti cal. Four of the six had decreased vision,
TABLE 2 SUMMARY O F CLINICAL FINDINGS IN T H E FIVE C H I L D R E N W I T H O U T CHIASMAL TUMORS
Clinical Findings Age (mos) Sex Involved eye Visual acuity R.E. L.E. Afferent pupillary defect Optic nerve status Nystagmus
Head tilt Head shake Diagnosis
Time to resolution of nystagmus (mos)
Patient 7
Patient 8
Patient 9
Patient 10
Patient 11
5 M Right
4 F Left
4 F Right
8 M Right
4 F Right
Central, maintained Central, maintained Absent
Central, maintained Central, maintained Absent
Central, maintained Central, maintained Absent
Central, maintained Central, maintained Absent
Normal Horizontal
Normal Horizontal
Normal Horizontal
Present Absent Spasmus nutans
Present Present Spasmus nutans
Present Present Spasmus nutans
Normal Horizontal, R.E. Vertical, L.E. Present Absent Spasmus nutans
19
13
20
Present after 3 mos
No fixation Central, maintained Present, R.E. Normal Horizontal
Absent Absent Persistent hypeiplastic primary vitreous —
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manifested as peripheral or central unmaintained fixation. In all of the patients the optic nerve in the eye with nystagmus was abnormal. Three patients had optic nerve hypoplasia and three had optic atrophy. One patient had atrophy in the involved eye and optic nerve hypoplasia in the uninvolved eye. The diagnosis of optic nerve hypoplasia is sometimes diffi cult and we made the diagnosis by direct ophthalmoscopic criteria outlined else where. 17 Four of the children had head shaking with the nystagmus, but only one demonstrated a head tilt at any time. Of the other five children, two met the criteria for spasmus nutans on the basis of negative computed tomographic scanning and concomitant features of head shak ing. Four of these infants showed a head tilt, the other clinically variable sign. Two of these children (Patients 8 and 9) were twins and were described previous ly.10 The average age of the four children with spasmus nutans was 4.5 months, and they all had normal vision and optic nerves. The right eye predominated in four of the five patients in this group. Horizontal nystagmus was the rule in these patients. Nystagmus resolved in three of the four children with spasmus nutans within 20 months (range, three to 20 months). At the conclusion of the study, one child still had nystagmus (after three months of follow-up). Of the 11 patients with monocular nys tagmus, six had chiasmal tumors. Certain features differentiated these children from the four with spasmus nutans. As a group they were older (11 months vs 4.5 months). Decreased vision was a frequent finding, present in four of the six pa tients. Of the 11 patients with nystagmus, five had decreased vision; four of these five had chiasmal tumors. All of the pa tients with chiasmal tumors had abnormal optic nerves. None of the patients with spasmus nutans had decreased vision or abnormal optic nerves. The direction of nystagmus was not a useful differentiating
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feature. Curiously, the group with chias mal tumors had marked left eye involve ment compared with the right eye in volvement in the group with spasmus nutans. Only one of the 11 children had ante rior segment disease (persistent hyperplastic primary vitreous) and decreased vision as a cause of monocular nystagmus. This contrasted sharply with our experi ence with young children with monocular media opacities in whom visual rehabili tation has been unsuccessful. Indeed, in a series of 74 children under 2 years of age seen during this same period of time with monocular opacities of the media, only one developed monocular nystagmus (un published data). DISCUSSION
The sinister nature of acquired monoc ular nystagmus in infants and children has been addressed by Donin in 196711 and Shulman, Schults, and Jones in 1979.13 These investigators reported three cases of chiasmal gliomas with mo nocular nystagmus in patients aged 7 months to 3 years. On initial examination two of the three children had decreased vision in the eye with nystagmus. Simi larly, spasmus nutans as a harbinger of chiasmal gliomas was reported by Kelly in 1970,12 Antony, Ouvrier, and Wise in 1980.14 and Koenig, Naidich, and Zaparackas in 1982,15 in a total of five chil dren aged 8 months to 3 years. Only one child was noted to have decreased visual function at the initial examinations al though no report of visual function was given for two children (ages 8 and 13 months), nor was there any mention of afferent pupillary reaction indicative of abnormal visual function. Lavery and associates 16 detailed the clinical features often infants from seven different medical centers in whom ac quired and asymmetric nystagmus was the initial sign of chiasmal-parachiasmal glioma. This retrospective study empha-
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sized that the nystagmus was difficult to differentiate from spasmus nutans. The nystagmus was horizontal in seven cases but there were episodes of vertical oblique, torsional, or circular nystagmus in three of these patients. Two patients had primarily vertical nystagmus. Four of the ten patients exhibited decreased visu al function as assessed by fixation patterns and three had optic atrophy. We know that assessment of visual function in young children is a difficult and demanding task, and subtle abnor malities are easy to overlook. Attempts at quantification of visual acuity in normal infants, for example, have yielded differ ent estimates depending on the method used—fixation patterns vs psychophysical tests, and even among the various psy chophysical tests. 18 Critical evaluation of the pupillary light response can yield valuable information regarding the pres ence of abnormal visual function. Halpern 19 suggested, with reference to two of the cases reported by Antony, Ouvrier, and Wise 14 that discovery of an afferent pupillary defect might have led to a diag nosis other than spasmus nutans. Unfor tunately, Lavery and associates 16 report ed testing for an afferent pupillary defect in only two cases. From these reports and our series, evidence of visual loss appar ently is not a universal feature accompa nying the monocular nystagmus associat ed with chiasmal tumors in infants. However, a careful assessment of visual function should be completed in all in fants with monocular nystagmus and any abnormality should prompt a search for intracranial tumors. The role of visual loss in the pathogenesis of monocular nystagmus in children with chiasmal tumors remains to be com pletely defined. It is well established in adults that monocular visual loss alone may be a cause of monocular nystag mus8,20"24; indeed, this is common al though easily overlooked. 25 Yet, in infants and children uniocular visual loss alone
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seldom causes monocular nystagmus. Of 74 infants under the age of 2 years seen at the University of California Medical Cen ter with monocular visual loss secondary to lens or corneal opacities, only one has exhibited monocular nystagmus (unpub lished data). Even in children with optic nerve gliomas, monocular nystagmus is uncommon. In Chutorian and associ ates' 26 series of 56 children with optic gliomas, 26 had gliomas confined to the optic nerve alone. Twenty-five of these had decreased monocular visual acuity but only one had nystagmus. Conversely, of the 30 children in this series with chiasmal tumors, 28 had either monocu lar or binocular decreased vision. Thir teen of these had nystagmus. 26 We found four patients with decreased vision and chiasmal tumors. Certainly more than pure afferent deficit must be invoked to explain the nystagmus accom panying chiasmal tumors. However, the three children with vertical nystagmus and chiasmal tumors suggested that loss of vision and vertical nystagmus in chil dren may indicate chiasmal tumor. 27 Diffuse gliomas involving the intracra nial portion of the optic nerve and chiasm most frequently involve loss of vision, optic atrophy, headache or eye pain, stra bismus, or papilledema. 27 However, there are many reports of nystagmus as a feature of optic chiasmal gliomas in the large, published series of optic gliomas (Table S).28"33 Most of the reports, howev er, do not specify the type of nystagmus or the eye involved. White and Ross,34 in their review of the inanition syndrome, characterized by wasting, pale skin, hyperhidrosis, and neuroendocrine distur bances secondary to anterior hypothalamic neoplasm, commented on the frequency with which horizontal or verti cal nystagmus is displayed in infants with these tumors. The two commonest tumors involving the anterior visual pathways in children are gliomas and craniopharyngiomas.
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TABLE 3 SUMMARY O F PUBLISHED SERIES O F OPTIC GLIOMAS
Optic Nerve Glioma
Year
Investigators
Total No. of Cases
1958 1964 1973 1973 1974 1979 1981
Dodge and associates28 Chutorian and associates26 Myles and Murphy29 Lloyd30 Miller, Iliff, and Green31 DeSousa and associates32 Iraci and associates33
46 56 20 41 40 29 24
These tumors are thought to originate from developmental anomalies dating from embryonic life and are thus prenatal in origin. 30 The occurrence of mild to severe optic nerve hypoplasia in children with suprasellar tumors was emphasized by Taylor,36 who suggested that a causal relationship exists. Such a relationship is compatible with the thesis that optic nerve hypoplasia characteristically re sults from excessive degeneration of optic nerve axons and retinal ganglion cells during the development of the visual pathway. 37,38 In this view embryogenesis of the retina proceeds normally. The gan glion cells grow centrally and at a later stage, either coincident with or after the normal phase of ganglion cell death, a much larger number than normal degen erate because of an insult to the brain, which presumably prevents them from forming or maintaining appropriate con nections at the target sites. Four infants in our series with chiasmal tumors had optic nerve hypoplasia that was only mild to moderate in degree. The two cases of mild hypoplasia could have been overlooked if they had not been specifically sought out. Therefore, when examining infants with monocular nystag mus one must carefully look for subtle forms of optic nerve hypoplasia. The importance of the proper diagnosis in infants with monocular nystagmus can not be overstated. We were able to dem
Chiasmal Glioma
No. of Cases
No . With Nystagmus
No. of Cases
No . With Nystagmus
12 26 5 9 11 3 5
0 1 0 0 0 0 0
34 30 15 32 29 26 19
3 13 3 11 8 1 1
onstrate certain clinical features that help distinguish children with chiasmal tu mors from those with spasmus nutans. The young children with chiasmal tumors were older (average age, 11 months) and had visual loss and optic nerve abnormali ties (hypoplasia and atrophy) in the affect ed eye. Significantly, we found, as did Lavery and associates, 16 that the direc tionality of the nystagmus was not a use ful feature in separating the groups. It should be reemphasized as well that ante rior segment abnormalities rarely cause monocular nystagmus in young children. However, there is no consistent clinical feature that safely rules out central nerv ous system tumor in these children. Therefore, we strongly agree with Smith, Flynn, and Spiro 21 in recommending a high-quality thin-resolution computed tomographic brain scan in all young chil dren with monocular nystagmus, even if the clinical features suggest spasmus nu tans. REFERENCES 1. Cogan, D. G.: Dissociated nystagmus with le sions in the posterior fossa. Arch. Ophthalmol. 70:361, 1963. 2. Nathanson, M., Bergman, P. S., and Bender, M. B.: Monocular nystagmus. Am. J. Ophthalmol. 40:685, 1955. 3. Norton, E. W. D., and Cogan, D. G.: Spas mus nutans. A clinical study of 20 cases followed two years or more since onset. Arch. Ophthalmol. 52:442, 1954. 4. Hoefnagel, D., and Biery, B.: Spasmus nutans. Dev. Med. Child. Neurol. 10:32, 1968.
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5. Herrman, C : Head shaking with nystagmus in infants. A study of 64 cases. Am. J. Dis. Child. 16:179, 1918. 6. Post, L. : Unilateral nystagmus. Am. J. Ophthal mol. 8:632, 1925. 7. Cox, R. A. : Congenital head nodding and nys tagmus. Report of a case. Arch. Ophthalmol. 15:1032, 1936. 8. Moorad, P. J. : Nystagmus in infants. Report of a case of monocular horizontal type. Arch. Ophthal mol. 13:238, 1935. 9. Jayalakshmi, P., McNair Scott, T. F., Tucker, S. H., and Schaffer, D. B.: Infantile nystagmus. A prospective study of spasmus nutans, congenital nys tagmus, and unclassified nystagmus of infancy. J. Pediatr. 77:177, 1970. 10. Hoyt, C. S., and Aicardia, E.: Acquired mo nocular nystagmus in monozygous twins. J. Pediatr. Ophthalmol. Strabismus 16:115, 1979. 11. Donin, J. F.: Acquired monocular nvstagmus in children. Can. J. Ophthalmol. 2:212, 1967. 12. Kelly, T. W. : Optic glioma presenting as spas mus nutans. Pediatrics 45:295, 1970. 13. Schulman, J. A., Shults, W. T., and Jones, J. M., Jr.: Monocular vertical nystagmus as an initial sign of chiasmal glioma. Am. J. Ophthalmol. 87:87, 1979. 14. Antony, J. H., Ouvrier, R. A., and Wise, G.: Spasmus nutans. A mistaken identity. Arch. Neurol. 37:373, 1980. 15. Koenig, S. B., Naidich, T. P., and Zaparackas, Z. : Optic glioma masquerading as spasmus nutans. J. Pediatr. Ophthalmol. Strabismus 19:20, 1982. 16. Lavery, M. A., O'Neill, J. F., Chu, F. C , and Martyn, L. T.: Acquired nystagmus in early childhood. A presenting sign of intracranial tumor. Ophthalmology 91:425, 1984. 17. Frisen, L., and Holmegaard, L. : Spectrum of optic nerve hypoplasia. Br. J. Ophthalmol. 62:7, 1978. 18. Hoyt, C. S., Nickel, B. L., and Billson, F. A.: Ophthalmological examination of the infant. Devel opmental aspects. Surv. Ophthalmol. 26:1777, 1982. 19. Halpern, J.: Spasmus nutans. Arch. Neurol. 37:737, 1980. 20. Duane, A.: Unilateral rotatory nystagmus. Trans. Am. Ophthalmol. Soc. 11:63, 1906. 21. Smith, J. L., Flynn, J. T., and Spiro, H. J.: Monocular vertical oscillation with amblyopia. The Heimann-Bielschowsky phenomena. J. Clin. NeuroOphthalmol. 2:85, 1982. 22. Kattah, J. C , Cohan, S. L., Cahill, W., and Buas, M.: Monocular rotatory nystagmus. J. Clin. Neuroophthalmol. 3:49, 1983.
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23. Dufour, A., Guccione, G., and Tamburrino, V. : Considerations electro-nystagmus-graphiques sur deux cas do nystagmus monoculaire. Rev. Otoneuroophtalmol. 44:125, 1972. 24. Korner, F.: Erworbender und Kongenitaler Monokularer Pendelnystagmus. Eine vergleichende elektronystagmographische studie an zwei Fallen. Albrecht von Graefes Arch. Klin. Exp. Ophthalmol. 197:165, 1975. 25. Yee, R. D., Jelks, G. W., Baloh, R. W., and Honrubia, V.: Uniocular nystagmus in monocular visual loss. Ophthalmology 86:511, 1979. 26. Chutorian, A. M., Schwartz, J. F., Evans, R. A., and Carter, S.: Optic gliomas in children. Neurology 14:83, 1964. 27. Walsh, F. B.: The ocular signs of tumors involving the anterior visual pathways. The Tenth Francis I. Proctor Lecture. Am. J. Ophthalmol. 42:347, 1956. 28. Dodge, H. W., Love, J. G., Craig, W., Dockerty, M. B., Kerns, T. P., Holman, C. B., and Hayles, A.: Gliomas of the optic nerves. Arch. Neurol. Psychiatry 79:607, 1958. 29. Myles, S. T., and Murphy, S. B.: Gliomas of the optic nerve and chiasm. Can. J. Ophthalmol. 8:508, 1973. 30. Lloyd, L. A.: Gliomas of the optic nerve and chiasm in childhood. Trans. Am. Ophthalmol. Soc. 71:488, 1973. 31. Miller, N. R., Iliff, W. J., and Green, W. R.: Evaluation and management of gliomas of the ante rior optic pathways. Brain 97:743, 1974. 32. DeSousa, A. L., Kalsbeck, J. E., Mealey, J., Jr., Ellis, F. D., and Müller, J.: Optic chiasmic glioma in children. Am. J. Ophthalmol. 87:376, 1979. 33. Iraci, G., Gerosan, M., Tomazzoli, L., Pardatscher, K., Fiore, D. L., Javicoli, R., and Secchi, A. G.: Gliomas of the optic nerve and chiasm. A clinical review. Childs Brain 8:326, 1981. 34. White, P. T , and Ross, A. T.: Inanition syn drome in infants with anterior hypothalamic neo plasms. Neurology 13:974, 1963. 35. Taylor, D. : Chiasmal syndromes in childhood. In Wybar, K. C , and Taylor, D. S. (eds.): Pédiatrie Ophthalmology. Current Aspects. New York, Marcel Dekker, 1982, p. 255. 36. : Congenital tumors of the anterior visual system with dysplasia of the optic disc Br. J. Ophthalmol. 66:455, 1982. 36. Hotchkiss, M. L., and Green, W. R.: Optic nerve aplasia and hypoplasia. J. Pediatr. Ophthalmol. Strabismus 16:225, 1979. 38. Skarf, B., and Hoyt, C. S.: Optic nerve aplasia in children. Association with anomalies of the endo crine and CNS. Arch. Ophthalmol. 102:62, 1984.
AND C R E I G S. H O Y T ,
San Francisco,
M.D.
California
Of 11 young children (six girls and five boys, ranging in age from 4 to 14 months) with monocular nystagmus, six were found to have chiasmal tumors whereas only four had spasmus nutans. Differentiating features between these two groups included decreased vision and optic nerve anomalies (including four cases of optic nerve hypoplasia) in the tumor group. However, we found that no consistent clinical finding absolutely separates these groups. We therefore recommend that all infants and children with monocular nystagmus or the other features of spasmus nutans should undergo computed tomographic scanning.
Monocular nystagmus, a rhythmic os cillation of only one eye on direct forward gaze, represents a peculiar manifestation of dissociated nystagmus. 1,2 Both congeni tal and acquired monocular nystagmus in infants have been ascribed to spasmus nutans. 3 4 Spasmus nutans is a transient syndrome of nystagmus, involuntary head nodding, and anomalous head posi tions that varies substantially in its mani festation of these features. The cause of this syndrome is unknown. Although the nystagmus in spasmus nutans is usually described as binocular and asymmetric, several authors have noted that monocu lar nystagmus may occur in this syn drome. 3,0 ' 10 The benign prognosis of spas mus nutans was well documented in the long-term follow-up series of Norton and Cogan 3 and Hoefnagel and Biery. 4 HowAccepted for publication July 18, 1984. From the Department of Ophthalmology, Univer sity of California, San Francisco, and the Clinical Research Center, That Man May See, Inc., San Francisco, California. This study was supported in part by a grant from the Children's Eye Care Foun dation, Washington, D.C. Dr. Hoyt is the Research for Prevention of Rlindness Robert E. McCormick Scholar. Reprint requests to Creig Hoyt, M.D., Room A-704, University of California, San Francisco, San Francisco, CA 94143. 504
ever, case reports of chiasmal tumors simulating monocular nystagmus and spasmus nutans in infants and children are becoming increasingly frequent.11"16 We studied the clinical and diagnostic features in 11 children less than 15 months old who had monocular nystag mus. S U B J E C T S AND M E T H O D S
We reviewed the findings for 11 chil dren referred to the University of Califor nia, San Francisco, with monocular nys tagmus from August 1977 to February 1984. Each child underwent a complete pédiatrie ophthalmic examination and computed axial tomography of the head and orbits. Central visual acuity was esti mated by fixation patterns and, whenever possible, pattern visual-evoked poten tials. We ascertained the monocularity of the nystagmus by direct observation as we believed this to be most applicable in the clinical examination of young chil dren. The diagnosis of chiasmal tumor was established on finding a suprasellar mass on computed tomographic scanning. RESULTS
The 11 children ranged in age at the time of diagnosis from 4 to 14 months
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TABLE 1 SUMMARY O F CLINICAL FINDINGS IN SIX C H I L D R E N W I T H CHIASMAL TUMORS
Clinical Findings Age (mos) Sex Involved eye Visual acuity R.E. L.E.
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
9 M Right
11 M Left
14 F Left
9 F Left
13 M Left
10 F Left
Central, Central, Central, Central, Central, Central, maintained maintained maintained maintained maintained maintained Peripheral Peripheral Central, Central, Central, — maintained maintained maintained Present, Present, Present, Absent Absent Present, LE. R.E. R.E. L.E.
Afferent pupillary defect Optic nerve status Hypoplasia R.E. Normal L.E. Nystagmus Head shake Head tilt
Vertical Present Present
Normal Atrophy Vertical Present Present
Normal Possible hypoplasia Horizontal Absent Absent
(average age, 8.3 months). There were six girls and five boys (Tables 1 and 2). The six children with chiasmal tumors had an average age of 11 months. The left
Normal Hypoplasia Horizontal Absent Absent
Atrophy Severe atrophy Vertical Present Present
Hypoplasia — Horizontal Present Absent
eye was involved in five of the six. The directionality of the nystagmus was even ly divided between horizontal and verti cal. Four of the six had decreased vision,
TABLE 2 SUMMARY O F CLINICAL FINDINGS IN T H E FIVE C H I L D R E N W I T H O U T CHIASMAL TUMORS
Clinical Findings Age (mos) Sex Involved eye Visual acuity R.E. L.E. Afferent pupillary defect Optic nerve status Nystagmus
Head tilt Head shake Diagnosis
Time to resolution of nystagmus (mos)
Patient 7
Patient 8
Patient 9
Patient 10
Patient 11
5 M Right
4 F Left
4 F Right
8 M Right
4 F Right
Central, maintained Central, maintained Absent
Central, maintained Central, maintained Absent
Central, maintained Central, maintained Absent
Central, maintained Central, maintained Absent
Normal Horizontal
Normal Horizontal
Normal Horizontal
Present Absent Spasmus nutans
Present Present Spasmus nutans
Present Present Spasmus nutans
Normal Horizontal, R.E. Vertical, L.E. Present Absent Spasmus nutans
19
13
20
Present after 3 mos
No fixation Central, maintained Present, R.E. Normal Horizontal
Absent Absent Persistent hypeiplastic primary vitreous —
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manifested as peripheral or central unmaintained fixation. In all of the patients the optic nerve in the eye with nystagmus was abnormal. Three patients had optic nerve hypoplasia and three had optic atrophy. One patient had atrophy in the involved eye and optic nerve hypoplasia in the uninvolved eye. The diagnosis of optic nerve hypoplasia is sometimes diffi cult and we made the diagnosis by direct ophthalmoscopic criteria outlined else where. 17 Four of the children had head shaking with the nystagmus, but only one demonstrated a head tilt at any time. Of the other five children, two met the criteria for spasmus nutans on the basis of negative computed tomographic scanning and concomitant features of head shak ing. Four of these infants showed a head tilt, the other clinically variable sign. Two of these children (Patients 8 and 9) were twins and were described previous ly.10 The average age of the four children with spasmus nutans was 4.5 months, and they all had normal vision and optic nerves. The right eye predominated in four of the five patients in this group. Horizontal nystagmus was the rule in these patients. Nystagmus resolved in three of the four children with spasmus nutans within 20 months (range, three to 20 months). At the conclusion of the study, one child still had nystagmus (after three months of follow-up). Of the 11 patients with monocular nys tagmus, six had chiasmal tumors. Certain features differentiated these children from the four with spasmus nutans. As a group they were older (11 months vs 4.5 months). Decreased vision was a frequent finding, present in four of the six pa tients. Of the 11 patients with nystagmus, five had decreased vision; four of these five had chiasmal tumors. All of the pa tients with chiasmal tumors had abnormal optic nerves. None of the patients with spasmus nutans had decreased vision or abnormal optic nerves. The direction of nystagmus was not a useful differentiating
OCTOBER, 1984
feature. Curiously, the group with chias mal tumors had marked left eye involve ment compared with the right eye in volvement in the group with spasmus nutans. Only one of the 11 children had ante rior segment disease (persistent hyperplastic primary vitreous) and decreased vision as a cause of monocular nystagmus. This contrasted sharply with our experi ence with young children with monocular media opacities in whom visual rehabili tation has been unsuccessful. Indeed, in a series of 74 children under 2 years of age seen during this same period of time with monocular opacities of the media, only one developed monocular nystagmus (un published data). DISCUSSION
The sinister nature of acquired monoc ular nystagmus in infants and children has been addressed by Donin in 196711 and Shulman, Schults, and Jones in 1979.13 These investigators reported three cases of chiasmal gliomas with mo nocular nystagmus in patients aged 7 months to 3 years. On initial examination two of the three children had decreased vision in the eye with nystagmus. Simi larly, spasmus nutans as a harbinger of chiasmal gliomas was reported by Kelly in 1970,12 Antony, Ouvrier, and Wise in 1980.14 and Koenig, Naidich, and Zaparackas in 1982,15 in a total of five chil dren aged 8 months to 3 years. Only one child was noted to have decreased visual function at the initial examinations al though no report of visual function was given for two children (ages 8 and 13 months), nor was there any mention of afferent pupillary reaction indicative of abnormal visual function. Lavery and associates 16 detailed the clinical features often infants from seven different medical centers in whom ac quired and asymmetric nystagmus was the initial sign of chiasmal-parachiasmal glioma. This retrospective study empha-
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sized that the nystagmus was difficult to differentiate from spasmus nutans. The nystagmus was horizontal in seven cases but there were episodes of vertical oblique, torsional, or circular nystagmus in three of these patients. Two patients had primarily vertical nystagmus. Four of the ten patients exhibited decreased visu al function as assessed by fixation patterns and three had optic atrophy. We know that assessment of visual function in young children is a difficult and demanding task, and subtle abnor malities are easy to overlook. Attempts at quantification of visual acuity in normal infants, for example, have yielded differ ent estimates depending on the method used—fixation patterns vs psychophysical tests, and even among the various psy chophysical tests. 18 Critical evaluation of the pupillary light response can yield valuable information regarding the pres ence of abnormal visual function. Halpern 19 suggested, with reference to two of the cases reported by Antony, Ouvrier, and Wise 14 that discovery of an afferent pupillary defect might have led to a diag nosis other than spasmus nutans. Unfor tunately, Lavery and associates 16 report ed testing for an afferent pupillary defect in only two cases. From these reports and our series, evidence of visual loss appar ently is not a universal feature accompa nying the monocular nystagmus associat ed with chiasmal tumors in infants. However, a careful assessment of visual function should be completed in all in fants with monocular nystagmus and any abnormality should prompt a search for intracranial tumors. The role of visual loss in the pathogenesis of monocular nystagmus in children with chiasmal tumors remains to be com pletely defined. It is well established in adults that monocular visual loss alone may be a cause of monocular nystag mus8,20"24; indeed, this is common al though easily overlooked. 25 Yet, in infants and children uniocular visual loss alone
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seldom causes monocular nystagmus. Of 74 infants under the age of 2 years seen at the University of California Medical Cen ter with monocular visual loss secondary to lens or corneal opacities, only one has exhibited monocular nystagmus (unpub lished data). Even in children with optic nerve gliomas, monocular nystagmus is uncommon. In Chutorian and associ ates' 26 series of 56 children with optic gliomas, 26 had gliomas confined to the optic nerve alone. Twenty-five of these had decreased monocular visual acuity but only one had nystagmus. Conversely, of the 30 children in this series with chiasmal tumors, 28 had either monocu lar or binocular decreased vision. Thir teen of these had nystagmus. 26 We found four patients with decreased vision and chiasmal tumors. Certainly more than pure afferent deficit must be invoked to explain the nystagmus accom panying chiasmal tumors. However, the three children with vertical nystagmus and chiasmal tumors suggested that loss of vision and vertical nystagmus in chil dren may indicate chiasmal tumor. 27 Diffuse gliomas involving the intracra nial portion of the optic nerve and chiasm most frequently involve loss of vision, optic atrophy, headache or eye pain, stra bismus, or papilledema. 27 However, there are many reports of nystagmus as a feature of optic chiasmal gliomas in the large, published series of optic gliomas (Table S).28"33 Most of the reports, howev er, do not specify the type of nystagmus or the eye involved. White and Ross,34 in their review of the inanition syndrome, characterized by wasting, pale skin, hyperhidrosis, and neuroendocrine distur bances secondary to anterior hypothalamic neoplasm, commented on the frequency with which horizontal or verti cal nystagmus is displayed in infants with these tumors. The two commonest tumors involving the anterior visual pathways in children are gliomas and craniopharyngiomas.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
OCTOBER, 1984
TABLE 3 SUMMARY O F PUBLISHED SERIES O F OPTIC GLIOMAS
Optic Nerve Glioma
Year
Investigators
Total No. of Cases
1958 1964 1973 1973 1974 1979 1981
Dodge and associates28 Chutorian and associates26 Myles and Murphy29 Lloyd30 Miller, Iliff, and Green31 DeSousa and associates32 Iraci and associates33
46 56 20 41 40 29 24
These tumors are thought to originate from developmental anomalies dating from embryonic life and are thus prenatal in origin. 30 The occurrence of mild to severe optic nerve hypoplasia in children with suprasellar tumors was emphasized by Taylor,36 who suggested that a causal relationship exists. Such a relationship is compatible with the thesis that optic nerve hypoplasia characteristically re sults from excessive degeneration of optic nerve axons and retinal ganglion cells during the development of the visual pathway. 37,38 In this view embryogenesis of the retina proceeds normally. The gan glion cells grow centrally and at a later stage, either coincident with or after the normal phase of ganglion cell death, a much larger number than normal degen erate because of an insult to the brain, which presumably prevents them from forming or maintaining appropriate con nections at the target sites. Four infants in our series with chiasmal tumors had optic nerve hypoplasia that was only mild to moderate in degree. The two cases of mild hypoplasia could have been overlooked if they had not been specifically sought out. Therefore, when examining infants with monocular nystag mus one must carefully look for subtle forms of optic nerve hypoplasia. The importance of the proper diagnosis in infants with monocular nystagmus can not be overstated. We were able to dem
Chiasmal Glioma
No. of Cases
No . With Nystagmus
No. of Cases
No . With Nystagmus
12 26 5 9 11 3 5
0 1 0 0 0 0 0
34 30 15 32 29 26 19
3 13 3 11 8 1 1
onstrate certain clinical features that help distinguish children with chiasmal tu mors from those with spasmus nutans. The young children with chiasmal tumors were older (average age, 11 months) and had visual loss and optic nerve abnormali ties (hypoplasia and atrophy) in the affect ed eye. Significantly, we found, as did Lavery and associates, 16 that the direc tionality of the nystagmus was not a use ful feature in separating the groups. It should be reemphasized as well that ante rior segment abnormalities rarely cause monocular nystagmus in young children. However, there is no consistent clinical feature that safely rules out central nerv ous system tumor in these children. Therefore, we strongly agree with Smith, Flynn, and Spiro 21 in recommending a high-quality thin-resolution computed tomographic brain scan in all young chil dren with monocular nystagmus, even if the clinical features suggest spasmus nu tans. REFERENCES 1. Cogan, D. G.: Dissociated nystagmus with le sions in the posterior fossa. Arch. Ophthalmol. 70:361, 1963. 2. Nathanson, M., Bergman, P. S., and Bender, M. B.: Monocular nystagmus. Am. J. Ophthalmol. 40:685, 1955. 3. Norton, E. W. D., and Cogan, D. G.: Spas mus nutans. A clinical study of 20 cases followed two years or more since onset. Arch. Ophthalmol. 52:442, 1954. 4. Hoefnagel, D., and Biery, B.: Spasmus nutans. Dev. Med. Child. Neurol. 10:32, 1968.
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5. Herrman, C : Head shaking with nystagmus in infants. A study of 64 cases. Am. J. Dis. Child. 16:179, 1918. 6. Post, L. : Unilateral nystagmus. Am. J. Ophthal mol. 8:632, 1925. 7. Cox, R. A. : Congenital head nodding and nys tagmus. Report of a case. Arch. Ophthalmol. 15:1032, 1936. 8. Moorad, P. J. : Nystagmus in infants. Report of a case of monocular horizontal type. Arch. Ophthal mol. 13:238, 1935. 9. Jayalakshmi, P., McNair Scott, T. F., Tucker, S. H., and Schaffer, D. B.: Infantile nystagmus. A prospective study of spasmus nutans, congenital nys tagmus, and unclassified nystagmus of infancy. J. Pediatr. 77:177, 1970. 10. Hoyt, C. S., and Aicardia, E.: Acquired mo nocular nystagmus in monozygous twins. J. Pediatr. Ophthalmol. Strabismus 16:115, 1979. 11. Donin, J. F.: Acquired monocular nvstagmus in children. Can. J. Ophthalmol. 2:212, 1967. 12. Kelly, T. W. : Optic glioma presenting as spas mus nutans. Pediatrics 45:295, 1970. 13. Schulman, J. A., Shults, W. T., and Jones, J. M., Jr.: Monocular vertical nystagmus as an initial sign of chiasmal glioma. Am. J. Ophthalmol. 87:87, 1979. 14. Antony, J. H., Ouvrier, R. A., and Wise, G.: Spasmus nutans. A mistaken identity. Arch. Neurol. 37:373, 1980. 15. Koenig, S. B., Naidich, T. P., and Zaparackas, Z. : Optic glioma masquerading as spasmus nutans. J. Pediatr. Ophthalmol. Strabismus 19:20, 1982. 16. Lavery, M. A., O'Neill, J. F., Chu, F. C , and Martyn, L. T.: Acquired nystagmus in early childhood. A presenting sign of intracranial tumor. Ophthalmology 91:425, 1984. 17. Frisen, L., and Holmegaard, L. : Spectrum of optic nerve hypoplasia. Br. J. Ophthalmol. 62:7, 1978. 18. Hoyt, C. S., Nickel, B. L., and Billson, F. A.: Ophthalmological examination of the infant. Devel opmental aspects. Surv. Ophthalmol. 26:1777, 1982. 19. Halpern, J.: Spasmus nutans. Arch. Neurol. 37:737, 1980. 20. Duane, A.: Unilateral rotatory nystagmus. Trans. Am. Ophthalmol. Soc. 11:63, 1906. 21. Smith, J. L., Flynn, J. T., and Spiro, H. J.: Monocular vertical oscillation with amblyopia. The Heimann-Bielschowsky phenomena. J. Clin. NeuroOphthalmol. 2:85, 1982. 22. Kattah, J. C , Cohan, S. L., Cahill, W., and Buas, M.: Monocular rotatory nystagmus. J. Clin. Neuroophthalmol. 3:49, 1983.
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23. Dufour, A., Guccione, G., and Tamburrino, V. : Considerations electro-nystagmus-graphiques sur deux cas do nystagmus monoculaire. Rev. Otoneuroophtalmol. 44:125, 1972. 24. Korner, F.: Erworbender und Kongenitaler Monokularer Pendelnystagmus. Eine vergleichende elektronystagmographische studie an zwei Fallen. Albrecht von Graefes Arch. Klin. Exp. Ophthalmol. 197:165, 1975. 25. Yee, R. D., Jelks, G. W., Baloh, R. W., and Honrubia, V.: Uniocular nystagmus in monocular visual loss. Ophthalmology 86:511, 1979. 26. Chutorian, A. M., Schwartz, J. F., Evans, R. A., and Carter, S.: Optic gliomas in children. Neurology 14:83, 1964. 27. Walsh, F. B.: The ocular signs of tumors involving the anterior visual pathways. The Tenth Francis I. Proctor Lecture. Am. J. Ophthalmol. 42:347, 1956. 28. Dodge, H. W., Love, J. G., Craig, W., Dockerty, M. B., Kerns, T. P., Holman, C. B., and Hayles, A.: Gliomas of the optic nerves. Arch. Neurol. Psychiatry 79:607, 1958. 29. Myles, S. T., and Murphy, S. B.: Gliomas of the optic nerve and chiasm. Can. J. Ophthalmol. 8:508, 1973. 30. Lloyd, L. A.: Gliomas of the optic nerve and chiasm in childhood. Trans. Am. Ophthalmol. Soc. 71:488, 1973. 31. Miller, N. R., Iliff, W. J., and Green, W. R.: Evaluation and management of gliomas of the ante rior optic pathways. Brain 97:743, 1974. 32. DeSousa, A. L., Kalsbeck, J. E., Mealey, J., Jr., Ellis, F. D., and Müller, J.: Optic chiasmic glioma in children. Am. J. Ophthalmol. 87:376, 1979. 33. Iraci, G., Gerosan, M., Tomazzoli, L., Pardatscher, K., Fiore, D. L., Javicoli, R., and Secchi, A. G.: Gliomas of the optic nerve and chiasm. A clinical review. Childs Brain 8:326, 1981. 34. White, P. T , and Ross, A. T.: Inanition syn drome in infants with anterior hypothalamic neo plasms. Neurology 13:974, 1963. 35. Taylor, D. : Chiasmal syndromes in childhood. In Wybar, K. C , and Taylor, D. S. (eds.): Pédiatrie Ophthalmology. Current Aspects. New York, Marcel Dekker, 1982, p. 255. 36. : Congenital tumors of the anterior visual system with dysplasia of the optic disc Br. J. Ophthalmol. 66:455, 1982. 36. Hotchkiss, M. L., and Green, W. R.: Optic nerve aplasia and hypoplasia. J. Pediatr. Ophthalmol. Strabismus 16:225, 1979. 38. Skarf, B., and Hoyt, C. S.: Optic nerve aplasia in children. Association with anomalies of the endo crine and CNS. Arch. Ophthalmol. 102:62, 1984.