Journal of Pediatric Ophthalmology and Strabismus

The articles prior to January 2012 are part of the back file collection and are not available with a current paid subscription. To access the article, you may purchase it or purchase the complete back file collection here

Neuroradiological Features of Patients With Optic Nerve Hypoplasia

Sabah M Zeki, MScMedSci, FRCS, FCOphth; Anne S Hollman, MRCP(UK), FRCR; Gordon N Dutton, MD, FRCS, FCOphth

Abstract

ABSTRACT

Optic nerve hypoplasia (ONH) is associated with a wide range of neurological and endocrine disorders. A series of 21 patients is reported. This comprised 17 with ONH in association with manifest neurological and endocrine disturbance, 3 who were blind but who were otherwise normal, and 1 with bilateral impaired visual acuity only. AH patients underwent neuroradiological and detailed ophthalmic assessment. A wide range of abnormalities was observed. The most common findings were absent septum pel lucid urn, hydrocephaly, and porencephaly. Evidence of hypothalamic/pituitary hormone deficiency was present in nine patients, six of whom had demonstrable intracranial radiological abnormalities. All patients except one had bilateral optic nerve hypoplasia. Most patients had poor visual acuities and nystagmus. Astigmatism was also common. Two conditions which have not previously been reported in association with optic nerve hypoplasia were found: an intracranial arachnoid cyst and an intracranial epidermoid cyst.

Abstract

ABSTRACT

Optic nerve hypoplasia (ONH) is associated with a wide range of neurological and endocrine disorders. A series of 21 patients is reported. This comprised 17 with ONH in association with manifest neurological and endocrine disturbance, 3 who were blind but who were otherwise normal, and 1 with bilateral impaired visual acuity only. AH patients underwent neuroradiological and detailed ophthalmic assessment. A wide range of abnormalities was observed. The most common findings were absent septum pel lucid urn, hydrocephaly, and porencephaly. Evidence of hypothalamic/pituitary hormone deficiency was present in nine patients, six of whom had demonstrable intracranial radiological abnormalities. All patients except one had bilateral optic nerve hypoplasia. Most patients had poor visual acuities and nystagmus. Astigmatism was also common. Two conditions which have not previously been reported in association with optic nerve hypoplasia were found: an intracranial arachnoid cyst and an intracranial epidermoid cyst.

INTRODUCTION

Optic nerve hypoplasia (ONH) is a congenital abnormality of one or both optic nerves associated with a diminished number of axons.1,2 Despite underdevelopment of optic nerve fibers, normal development of the mesodermal and glial supporting tissue takes place and the retinal vascular system is normal. ONH is a common anomaly and is one of the major causes of visual loss in infancy.3 It is an enigmatic condition which may be associated with several endocrine and central nervous system disorders.4 A wide range of concomitant neuroradiological abnormalities has been reported (Table 1). The most common is septo-optic dysplasia (SOD), in which the septum pellucidum is deficient or absent. An apparently normal septum pellucidum on computerized tomography (CT) does not invalidate a clinical diagnosis of the mild form of the condition.5

The neurological features of SOD include mental retardation, spasticity, abnormalities of taste, and impaired olfaction.6 However, some individuals may exhibit only mild deficits with normal intelligence.

A CT scan is usually indicated in cases of bilateral ONH to exclude midline or other cerebral structural abnormalities.7 In particular, it has been recommended that infants and children with bilateral ONH, nystagmus, and poor vision should undergo a thorough neuroradiological and endocrine work up.8

Real time cranial ultrasound (U/S) examination, through the anterior fontanelle, also provides an effective means of investigating cerebral structures in infants.9 In a report of four cases, in which both cranial U/S and CT scans were performed, no additional information was gained from CT, Two patients had absence of the septum pellucidum and two had intracranial cystic lesions.10 This technique can only be used prior to closure of the cranial sutures but has the advantage of not requiring sedation or irradiation.

We wished to establish the prevalence and characteristics of neuroradiological disorders in children in the west of Scotland diagnosed as having ONH or SOD, who had significant visual handicap, in association with neuroendocrine dysfunction. By this means, we sought to determine the relationship between the features detected by the ophthalmologist and those reported by the radiologist. Therefore, we have carried out detailed ophthalmic assessment on a cohort of individuals with ONH/SOD who had previously undergone neuroradiological evaluation.

PATIENTS AND METHODS

The Royal Hospital for Sick Children (RHSC), Glasgow, provides a referral service for a population of 2.5 million.

Thirty-five patients with ONH or SOD were identified by means of the hospital disease indices. Of these, 14 demonstrated few neurological features, but 21 warranted neuroradiological assessment. Twenty of these 21 patients demonstrated the well known "double ring" sign1,4,8,9 while all 21 patients demonstrated small optic discs with visual deficits (Table 2). Of this group of 21 patients, 11 had undergone CT with a second generation CT scanner only (Elscint 820), 5 underwent CT and real time U/S examination (using an ATL MK 100 system), and an additional 5 underwent U/S examination only. The CT brain examinations had been performed using 10-millimeter axial cuts, with the baseline parallel to the orbitomeatal Une. All the U/S films and CT scans were reevaluated by a consultant pediatrie radiologist (A.S.H.) and the presence or absence of each of the features listed in Table 1 was determined. The protocol of assessment was drawn up prospectively to include previously reported neuroradiological abnormalities. The films were reviewed independently of the previous reports. (In only one case was there a discordance between the original report and the révaluation. This was patient no. 3 who had initially been diagnosed as having a porencephalic cyst but on review was deemed to have the neuronal migration disorder, Type 2 schizencephaly.)11

Table

TABLE 1Showing lntracranial Radiological Abnormalities Reported in Association With ONH

TABLE 1

Showing lntracranial Radiological Abnormalities Reported in Association With ONH

Enlargement of the pituitary stalk has been demonstrated by CT in patients with SOD and diabetes insipidus, and is best seen after contrast enhancement.12 Kaufman et al have reported pituitary stalk hypoplasia, on magnetic resonance imaging (MRI), in two patients who showed normal midline brain anatomy on prior CT scan.13 Both patients had bilateral ONH and hypothalamicpituitary endocrine abnormalities. Assessment of the diameters of the optic nerves was not possible as thin section CT through the orbits had not been undertaken on these patients. Similarly, it proved impossible to evaluate the pituitary stalk in this study as high resolution thin CT sections had not been performed through the pituitary gland. MRI is a more sensitive investigative tool to visualize the pituitary stalk.13 Estimation of the degree of dilatation of the suprasellar and chiasmatic cisterns was sometimes incomplete because the structures were either not demonstrated, or the resolution was inadequate.

The ophthalmic assessment comprised visual acuity, retinoscopic examination, and ophthalmoscopy with fundus photography. Retinoscopy was performed one-half hour after having instilled 1% cyclopentolate eye drops. Evidence of nystagmus and strabismus was also sought.

Table

TABLE 2Details of Patients and Their Visual Acuities

TABLE 2

Details of Patients and Their Visual Acuities

RESULTS

ONH was bilateral in 20 of the 21 patients, and 9 were blind in both eyes. Seventeen had an initial clinical diagnosis of a manifest systemic abnormality (neurological and/or endocrine) in addition to ONH. Three of the patients who were blind in both eyes were not thought to have any obvious systemic abnormality on presentation. One other patient (no. 20) also had no apparent systemic abnormality. However, he had nystagmus and his best visual acuities were 6/60 in the right eye and 6/36 in the left. Therefore, the indications for referral for radiological assessment were confined to severe visual dysfunction associated, in the majority of cases, with clinical evidence of systemic disorders.

Eighty-one percent (17 cases) of the radiological assessments of the 21 patients were found to be abnormal.

Ultrasound Assessment

Ten patients underwent cranial U/S. The abnormalities identified included hydrocephaly, porencephaly, absent septum pellucidum, and absent corpus callosum. Table 3 provides details of these findings.

Table

TABLESResults of Ultrasound Findings of the 10 Patients Who Underwent This Examination

TABLES

Results of Ultrasound Findings of the 10 Patients Who Underwent This Examination

Five patients underwent both U/S and CT examination. Cerebral atrophy and/or cerebellar atrophy was not found in any of the patients examined by U/S. However, these were revealed in one patient (no. 13) by CT.

CT Scan

Sixteen patients underwent CT examination. Table 4 summarizes the abnormalities identified. The most common abnormality was a deficient septum pellucidum (Fig A), which was seen in 11 cases. Of these, six also showed evidence of hydrocephaius. Porencephaly (Fig B) was seen in five cases, three of whom had a concomitant absent septum pellucidum, and two of whom also had hydrocephaius.

As can be seen from Table 4, the other combinations of features were found to be idiosyncratic. Hydranencephaly and cerebral infarction, which have been reported previously,14 were not found either by U/S or by CT.

Only one patient had unilateral ONH (no. 21). The anecdotal finding of a normal CT scan in this patient is in accordance with previous reports that unilateral ONH is less commonly associated with intracranial abnormalities than bilateral ONH.8-15 The septum pellucidum can be abnormally thin and, therefore, only partially present, as shown in two patients in this series. The corpus callosum deficiency can also be incomplete, as demonstrated in one case.

Ophthalmic Assessment

Table 2 lists the visual acuities of the patients. Patient no. 18 has died, and no information is available about the condition of her refraction. However, she was thought to have been blind in both eyes. There was a high prevalence of complete blindness (53%) among the 17 patients who had been investigated radiologically and who had detectable intracranial abnormalities. All patients who were blind in both eyes demonstrated intracranial radiological abnormalities. All patients with intracranial abnormalities had bilateral ONH. Nystagmus was common with a prevalence of 52%, and manifest squint was also common (43%). These figures support a previous report which has documented a high prevalence of neuroradiological deficits in patients with ONH who have bilateral disease, severe visual deficit, and nystagmus.8

Endocrine Status

Evidence of hypothalamic/pituitary hormone deficiency was obtained from the case records of the patients. This was present in nine patients (43%), six of whom (patient nos. 1, 8, 11, 12, 13, and 18} had intracranial radiological abnormalities (Tables 3-4). Growth retardation was common, being present in six of the nine patients.

Neurological Status

Mental retardation was the principal diagnosis in six patients. However, an additional five patients were later found to have developed some degree of mental retardation. Of these 11 patients, 8 patients had abnormal intracranial radiological findings. Six patients had cerebral palsy. Four of these six had radiological abnormalities. Patients nos. 3 and 6 were found to have large heads on presentation. Both showed intracranial abnormalities (Table 4). Patient no. 15 was reported to have "behavioral problems," and patient no. 11 was reported to have self-mutilating behavior. Both of these patients showed intracranial radiological abnormalities.

DISCUSSION

Pediatrie intracranial neurological abnormalities in association with ONH are not simply anatomical curiosities but carry significant management implications. They signal the need for participation of different disciplines in the management of an affected child, including the pediatrie endocrinologist, pediatrie neurologist, pediatrie ophthalmologist and, on occasion, the pediatrie psychologist. The parents and the educational authorities also play a major role. It is generally agreed that an isolated defect of the septum pellucidum is not associated with any specific set of clinical features.16 However, multiple intracranial developmental anomalies may also be present.17'27

Table

TABLE 4CT Scan Findings of 16 Patients Who Underwent This Examination

TABLE 4

CT Scan Findings of 16 Patients Who Underwent This Examination

The early discovery of intracranial abnormalities is of clinical importance for a number of reasons. The associated hypothalamic/pituitary dysfunction may require treatment, especially when complicated by life-threatening hypoglycemia. Late presentation of latent pituitary dysfunction should also be sought with a view to preventing subsequent growth retardation. Parental counselling regarding the possible "nonocular" associations of ONH is important, especially with regard to educational implications. Special schooling may be required for some children.

The in-patient disease index was the principal means whereby children with ONH who underwent neuroradiological assessment were identified. This gave rise to a high number of patients with identifiable neuroradiological abnormalities among patients who were investigated.

Review of the case records indicated that most of the children had been primarily under the care of a neurologist and that ONH was, in most cases, one of a number of neurological defects. Patients with relatively mild ONH would probably not be admitted to a hospital. It is also possible that a number of patients with isolated ONH, particularly in its milder forms, are not referred to, or detected in this center.

The results demonstrate absence (partial or complete) of the septum pellucidum (52%), hydrocephaly (38%), porencephaly (24%), dilatation of the suprasellar and chiasmatic cisterns (19%), while absence (partial or complete) of the corpus callosum (14%) were relatively common abnormalities. These results are comparable to work published by previous authors.9·15 It should be remembered, however, that a normal CT scan does not necessarily presage normal brain development.5·28 In one patient (no. 4) with bilateral ONH, a huge, bilobed, intracranial cyst was identified. Histológica! examination following surgery found it to be an arachnoid cyst <Fig C ). In another patient (no. 18), a similar cystic appearance was found to be an intracranial epidermoid cyst (Fig D). To the best of our knowledge, these associations with ONH have not previously been reported.

FIGURE: (A) Axial CT scan demonstrating absence of septum pellucidum. Increased CSF over the frontal lobes (long arrow), dilated salci, and dilated interhemispheric fissure (short arrow) which indicate diffuse cerebral atrophy (patient no. 13). (B) Axial CT scan illustrating a porencephalic cyst (long arrow) communicating with the anterior horn of the left lateral ventricle. The high density shadow (short arrow) represents a shunt inserted into the right lateral ventricle which is dilated (patient no. 6). (C) Axial CT scare showing a huge "arachnoid cyst" on the right side of the picture (short arrows). The interhemispheric fissure can be seen displaced to the left (long arrow). On the left side of the picture a dilated left lateral ventricle is seen (patient no. 4). (D) A huge bilobed suprasellar cystic mass, an "epidermoid cyst" (arrow), as seen on high axial CT scanning. Dilated ventricles are seen lying posterior to the mass (patient no. 18).

FIGURE: (A) Axial CT scan demonstrating absence of septum pellucidum. Increased CSF over the frontal lobes (long arrow), dilated salci, and dilated interhemispheric fissure (short arrow) which indicate diffuse cerebral atrophy (patient no. 13). (B) Axial CT scan illustrating a porencephalic cyst (long arrow) communicating with the anterior horn of the left lateral ventricle. The high density shadow (short arrow) represents a shunt inserted into the right lateral ventricle which is dilated (patient no. 6). (C) Axial CT scare showing a huge "arachnoid cyst" on the right side of the picture (short arrows). The interhemispheric fissure can be seen displaced to the left (long arrow). On the left side of the picture a dilated left lateral ventricle is seen (patient no. 4). (D) A huge bilobed suprasellar cystic mass, an "epidermoid cyst" (arrow), as seen on high axial CT scanning. Dilated ventricles are seen lying posterior to the mass (patient no. 18).

Behavioral problems were noted in two of the patients in association with ONH (nos. 11 and 15). This is in accordance with a previous report by Margolith et al.14 They reported behavioral problems which ranged from attention deficit disorders to autistic, aggressive, or violent behavior, in 10 out of 51 cases of ONH.

The diagnostic value of cranial U/S and CT scan was compared for the five patients who underwent both investigations. It has been reported that cranial U/S and CT are equally effective in demonstrating the absence of the septum pellucidum.10 However, in one patient (no. 8) whose septum pellucidum was readily diagnosed as being absent on CT, no comment could be made concerning its presence or absence from the cranial U/S films. This suggests that CT may be more effective in identifying the absence of the septum pellucidum than cranial U/S. Modern high resolution U/S technology produces similar appearances to CT scans when imaging for the absence of the septum pellucidum or for porencephaly. CT scanning gives complete cross-sectional images with superior resolution,9 and is better than U/S when imaging for cerebral or cerebellar atrophy, optic nerve hypoplasia, and posterior fossa lesions. It should be emphasized, however, that cranial U/S has the advantage of being noninvasive and does not require sedation.10 In patient no. 9, who had a CT finding of porencephaly, cranial U/S was of no value due to a small anterior fontanelle.

The demonstration of the pituitary stalk requires high resolution coronal CT, or MRI.

Therefore, enlargement of the pituitary stalk will have been underdiagnosed in patients in this series. Hydranencephaly could, on the other hand, be effectively demonstrated or excluded by both U/S and CT.

A second-generation CT scanner had been used for patients in the present retrospective study. Third- and fourth-generation scanners now provide superior resolution. However, the second-generation equipment effectively demonstrated or excluded the majority of intracranial structural abnormalities associated with ONH.

With the exception of patient nos. 4, 11, 12, 13, 15, and 17, all the patients described in this series had initially presented with neurological or endocrine symptomatology and the opinion of the ophthalmologist was sought as a sequel to the neuroendocrine abnormality. By contrast, patient no. 12 initially presented to the ophthalmologist only with ophthalmic symptomatology (esotropia associated with ONH), and was found at the time of initial clinical assessment to have spastic hemiparesis, and was thus referred for a pediatrie opinion. No other patient was identified who presented to the ophthalmologist initially, and was found to have neuroendocrine disturbance as a hitherto undetected phenomenon.

Patient no. 4 initially presented with urinary tract infection and was referred to the ophthalmologist because of poor vision, where ONH was diagnosed. Patient nos. 11, 13, 15, and 17 initially presented to the neonatal pediatrician with poor vision and nystagmus.

It has recently been found out that astigmatism is common in patients with ONH.17 Fifteen patients in the present study comprise a subgroup of that report. The astigmatism (mean of the astigmatism in the two eyes of a patient with bilateral disease) in patients who had demonstrable radiological abnormality was 1.72 diopters, compared to 1.22 D in patients without detectable neuroradiological disorders; but this difference was not found to be statistically significant (Wilcoxon rank sum test: P > .5). Two patients who had cerebral palsy had a mean astigmatism greater than 4.00 D. It is also of interest that patients who had severe neuroradiological abnormalities in this series included three who showed mixed astigmatism (nos. 12, 17, and 19), and two patients who had astigmatism with opposite axes in the two eyes (nos. 6 and 14). These features were not detected in other patients in the present series.

In conclusion, the results indicate that when ONH is accompanied by poor visual acuity in both eyes or by manifest neuroendocrine disorder, neuroradiological evaluation is necessary. U/S examination is the initial investigation of choice while the fontanelles remain open. As U/S is noninvasive, it should be considered in all infants with bilateral ONH, even if there is no clinically apparent neuroendocrine abnormality, to anticipate potential pituitary dysfunction, in particular, deficiency of growth hormone. Astigmatism was common and often marked, especially in patients with severe developmental disorder of neural tissue. Early retinoscopic examination should be performed on such children to optimize their visual function and visual development.

REFERENCES

1. Moeier MA, Lieberman MF, Green WR, Knox DL. Hypoplasia of the optic nerve. Arch Ophthalmol. 1978 ;96: 1437- 1442.

2. Hotchkias ML, Green WR. Optic nerve aplasia and hypOplasia. J Pediatr Ophthalmol Strabismus. 1979;16:225-240.

3. Hoyt CS. Optic nerve hypoplasia: changing perspective. Aust NZJ Ophthalmol. 1986; 14: 325-331.

4. Acers TE. Optic nerve hypoplasia: septo-optic-pituitary dysplasia syndrome. TransAm Ophthalmol Soc. 1981;79:425-457.

5. Wilson DM, Enzmann DR, Hintz RL, Rosenfeld G. Computed tomography findings in septo-optic dysplasia: discordance between clinical and radiological findings. Neuroradiohgy. 1984;26:279-283.

6. Swaiman KF, Jacobson RI. Developmental abnormalities of the central nervous system. In: Baker AB, Baker LH, eds. Clinical Neurology. Philadelphia, Pa: Harper and Bow; 1984;4:51.

7. Weleber RG, Palmer EA. Selected causes of blindness in infants and children. Perspectives in Ophthalmology. 1981;5:13-20.

8. Lambert SR, Hoyt CS, Narahara MH. Optic nerve hypoplasia. Surv Ophthalmol. 1987;32:l-9.

9. Levene MI, Williams JL, Fawer CL. Ultrasound of the In/ant Brain. Oxford: Blackwell Scientific; 1985: 142-144.

10. Fielder AR, Levene MI, Trounce JQ, Tanner MS. Optic nerve hypoplasia in infancy. Journal of the Royal Society of Medicine. 1986;79:25-29.

11. Byrd SE, Naidich TP. Common congenital brain anomalies. Radiai Clin North Am. 1988 i26:755-772.

12. Mahelfe C, Rochiccioli P. CT of septooptic dysplasia. American Journal ofRoentgenology. 1979;133:1157-1160.

13. Kaufman LM, Miller MT, Mafee MF. Magnetic resonance imaging of pituitary stalk hypoplasia. Arch Ophthalmol. 1989; 107: 1485- 1489.

14. Margolith D, Jan JE, McCormick AQ, Tze WJ, Lapointe J. Clinical spectrum of optic nerve hypoplasia: review of 51 patients. Dev Med Child Neurol. 1984;26:3 11-322.

15. Skarf B, Hoyt CS. Optic nerve hypoplasia in children. Association with anomalies of the endocrine and CNS. Arch Ophthalmol. 1984;102:6267.

16. St John JR, Reeves DL. Congenital absence of the septum pellucidum. Am J Surg. 1957;94:974-980.

17. Zeki SM. Optic nerve hypoplasia and astigmatism. A new association, Br J Ophthalmol. 1990;74:297-299.

18. De Morsier G. Agenesis du septum lucidura avec malformation du tractus optique. Schweiz Arch Neurol NeurochirPsychiatr. 1956;77:267292.

19. Roger GL, Brown D, Gray I, Bremer D. Bilateral optic nerve hypoplasia associated with cerebral atrophy. J Pediatr Ophthalmol Strabismus. 1981; 18: 18-22.

20. Boniuck V, Ho PK. Ocular findings in anencephaly. Am J Ophthalmol. 1979;88:613-617.

21. Zimmerman RA, Bilaniuk LT, Grossman HI. Computed tomography in migratory disorders of human brain development. Neuroradiology. 1983;25:257-63.

22. Kaplan SL, Grumbach MM, Hoyt WF. A syndrome of hipopituitary dwarfism, hypoplasia of the optic nerve and malformation of prosencephalon: report of6 patients. PedtatrRes. 1970;4:480-481.

23. Gold h am mer Y, Smith JL. Optic nerve anomalies in basal encephalocele. Arch Ophthalmol. 1975;93:115-118.

24. Garg BP. Colpocephaly. An error of morphogenesis? Arch Neurol. 1982;39:243-247.

25. Taylor D. Congenital tumours of the anterior visual system with dysplasia of the optic discs. Br J Ophthalmol. 1 982 ;66: 455-463.

26. Manelfe C, Rochiccioli P. CT of septo-optic dysplasia. American Journal of Roentgenology. 1979;133:1157-1160.

27. Istuhara M. Optic hypoplasia with pituitary dwarfism. Endocrinologia Japónica CIbkyo). 1983;30:7-14.

28. Roberts-Harry J, Green SH, Willshaw HE. Optic nerve hypoplasia: associations and management. Arch Dix Child. 1990;65:103?06.

TABLE 1

Showing lntracranial Radiological Abnormalities Reported in Association With ONH

TABLE 2

Details of Patients and Their Visual Acuities

TABLES

Results of Ultrasound Findings of the 10 Patients Who Underwent This Examination

TABLE 4

CT Scan Findings of 16 Patients Who Underwent This Examination

10.3928/0191-3913-19920301-11

Sign up to receive

Journal E-contents