British Journal of Ophthalmology, 1980, 64, 272-275

The Sylvian aqueduct syndromeand neurofibromatosisJOHN S. LEANFrom the National Hospital for Nervous Diseases, Queen Square, London

SUMMARY A 23-year-old man initially presented with the Sylvian aqueduct syndrome and sub-seqently developed cutaneous neurofibromata. The case is reported and the possibility that theserepresent manifestations of the same genetic abnormality is discussed.

Ophthalmic manifestations of neurofibromatosisare well recognised, and indeed involvement of theeye and its adnexa with neurofibromata has beenreported in every structure except the lens andvitreous.' However, these are usually seen in theanterior visual system2 and reflect the regionalhypertrophy of the neural and connective tissueelements that occurs in this condition.3 Abnormali-ties of the central nervous system are less commonlyfound in neurofibromatosis, and apart from the wellrecognised association with optic nerve and chiasmalglioma* these rarely present to the ophthalmologist.The purpose of this paper is to report a case withthe classical neuro-ophthalmic presentation of theSylvian aqueduct syndrome in which subcutaneousneurofibromata have subsequently developed.The Sylvian aqueduct syndrome is most commonly

due to a pineal tumour, although occasionallyencephalitis, vascular occlusion, or a midbrainglioma may produce similar symptoms.5 However,the precise diagnosis is usually presumptive, basedon the presence of associated clinical signs and asuccessful trial of radiotherapy, since surgicalexploration is still hazardous in this area. In thecase under review the original presentation wasthought typical of a pineal tumour. However, thesubsequent development of characteristic cutaneousstigmata suggests that the initial midbrain syndromewas an unusual manifestation of neurofibromatosis.So far as we are aware this association has notpreviously been reported.

Case report

A 23-year-old man was admitted to hospital in May1969 with symptoms of raised intracranial pressureand diplopia. He had first presented to an optician

Correspondence to Mr J. S. Lean, Moorfields Eye Hospital,City Road, London EC1V 2PD.

9 months earlier complaining of difficulty with hisdistance vision. He was prescribed a small myopiccorrection for distance vision in both eyes, withinitial improvement. However, 2 months beforeadmission he began to have difficulty with nearvision and to notice vertical diplopia. Both thesesymptoms persisted, and in addition he developedsevere headaches and vomiting, which precipitatedhis admission.On examination he was found to have a correc-

table vision of 6/5, N5 in each eye. There was adissociated deficit of upgaze with relative loss ofsaccadic movement but preservation of smoothpursuit movement. Attempts at rapid upwardsaccades evoked convergence retraction nystagmus.A skew deviation was present, with left hypotropia.The pupillary responses showed light near disso-ciation. There was bilateral chronic papilloedema.A clinical diagnosis of the Sylvian aqueduct syn-drome was made.

Investigation by pneumoencephalography re-vealed symmetrical hydrocephalus (Fig. 1) withobstruction of the Sylvian aqueduct (Fig. 2). ATorkildsen shunt was performed and the midbrainregion treated with 5000 rads in divided doses. Hissymptoms of raised intracranial pressure wererapidly relieved, but the oculomotor and pupillarydisturbance have persisted.He had no further problems until 1976, when he

presented to the Skin Department with smallpainless lumps on his abdomen; these had appearedover the previous year. A biopsy of one of themshowed the typical features of neurofibromata(Fig. 3). Since then these lesions have remainedunchanged.

Discussion

The Sylvian aqueduct syndrome is a classicalconstellation of neuro-ophthalmological signs which

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273The Sylvian aqueduct syndrome and neurofibromatosis

Fig. 1 Air ventriculogram. Towne's projection. Thereis mairked hydrocephalus, with considerable enlargementof the third ventricle.

were initially described by Parinaud and attributedto compression of the pretectal region. The initialpresentation of this patient with acquired myopia isunusual but well recorded.6 The commonest cause ofthe syndrome is a pineal tumour, of which themajority are atypical teratomas.7 However, in a recentseries of neurosurgical explorations 25% of tumoursin this region were found to be nonpineal in origin.8In this patient the development of cutaneousneurofibromata 8 years after the original midbrainsyndrome suggests that the 2 lesions are related andthe underlying pathology the same.

Abnormalities of the central nervous system arewell recognised in neurofibromatosis. The incidencein published series ranges from 3%9 to 19%.10 Awide range of abnormalities have been reported,from neoplastic gliomata to glial heterotopias andother dysplastic malformations. The most frequentlyfound glioma is the optic nerve and chiasmalastrocytoma of childhood,4 but similar gliomataoccur in the intracranial cavity, either as single11 oras multiple lesions'213 and occasionally as diffuselyinfiltrative tumours.14 Meningiomas are also asso-ciated, and they may be multipleY5 Non-neoplasticmalformations of the central nervous system arealso regularly found in neurofibromatosis and haverecently been extensively reviewed.16 These centralforms of neurofibromatosis are often found in theabsence of extensive peripheral disease. Indeed, tosome extent the peripheral and central manifesta-tions of neurofibromatosis are mutually exclusive.'7In a recent review of 10 cases of neurofibromatosis

Fig. 2 Lateral projection,'brow up' position. Jophendylate(Myodil) has now been injected.It outlines the posterior end ofthe third ventricle and thedilated upper portion of theSylvian aqueduct, but does notpass beyond this (arrow). Thesuprapineal recess is prominent,but there is no evidence oj anextrinsic mass lesion. Theappearances are those of'occlusion of the aqueduct.

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John S. Lean

Fig. 3 A composite photo-micrograph showing an extensiveneurofibroma in the deeperlevels of the reticular dermis.(x 75.)

with tumours of the central nervous system 4 showedno cutaneous disease, while the remaining 6 had onlylimited skin pigmentation and a few subcutaneousnodules.'8 The paucity of cutaneous stigmata in thecase under review is therefore entirely compatiblewith an underlying diagnosis of neurofibromatosis.

However, despite the extensively described in-volvement of the central nervous system in neuro-fibromatosis we have been unable to find a previousexample presenting with the neuro-ophthalmicsigns of the Sylvian aqueduct syndrome. The onlyclinically similar case in the literature presented thepathology of Sylvian aqueduct stenosis in an 11-year-old girl with cutaneous pigmentation, a con-vergent squint, poorly reacting pupils, and bilateralsixth nerve weakness. Clinical photographs in thisreport appear to show a skew deviation, but nofurther neuro-ophthalmological information is avail-able. The obstructed aqueduct was found to havepolypoid ependymal granulations beneath theposterior colliculus.'9 One other case report hasdocumented isolated stenosis of the Sylvian aqueductin neurofibromatosis but without the characteristiceye movement disorder of the Sylvian aqueductsyndrome.20

Without a definite biopsy the exact relationshipbetween the midbrain pathology and peripheralneurofibromata in this case must remain conjec-tural. However, it seems likely that they are mani-festations of the same genetic abnormality. It hasrecently been suggested that all the protean mani-festations of von Recklinghausen's disease mayresult from primary dysontogenesis of primitive

neural ectoderm and neural crest derivatives.3 Byproliferation, differentiation, and migration cells ofthe neural crest form a major component of theadult nervous system. The sensory and autonomicganglia, leptomeninges, Schwann cells, and somesupportive connective tissue elements are all derivedfrom this embryonic tissue. In addition some glialand neurilemmal cells of the central nervous systemmay arise from the neural crest or may originate as adistinct cell population in the neural folds.2' Dys-plastic or frankly neoplastic change in this secondgroup of cells is thought to be responsible for thelesions seen in central forms of neurofibromatosis.In the case under review the absence of progressionsuggests that dysplasia of these central glial orneurilemmal cells is the most likely cause of themidbrain syndrome, and furthermore, that a com-mon origin in neural ectoderm forms the linkbetween these 2 apparently unrelated clinicalsymptoms.

I am grateful to Professor John Marshall for permission topublish details of this case and to Mr M. D. Sanders forhelpful criticism in the preparation of the text. Dr IvanMoseley kindly provided the radiographic reports, and theDepartment of Dermatology, St Thomas's Hospital, pro-vided histopathology of the skin biopsy. My thanks are alsodue to Miss Denise Bryant for secretarial assistance.

References

'Marshall D. Glioma of the optic nerve as a manifestationof von Recklinghausen's disease. Am J Ophthalmol 1954;37: 15-36.2Krill AE. Hereditary Retinal and Choroidal Diseases.Hagerstown: Harper and Row, 1977: 2: 1210-3.

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The Sylvian aqueduct syndrome and neurofibromatosis

3Bolande RP. The neurocristopathies-a unifying conceptof disease arising in neural crest maldevelopment. HumPathol 1974; 5: 409-29.4Davis FA. Primary tumours of the optic nerve (a phenome-non of von Recklinghausen's disease). Arch Ophthalmol1940; 23: 735, 957.5Walshe FB, Hoyt FW. Clinical Neuro-ophthalmology.Baltimore: Williams and Wilkins, 1969: 1: 228."Sanders MD, Bird AC. The supranuclear abnormalities ofthe vertical oculomotor system. Trans Ophthalmol Soc UK1970; 90: 433-49.7Russell DS, Rubinstein LJ. Pinealomas. Pathology ofTumours of the Nervous System. London: Arnold, 1971:171-82."Poppen JL, Marino R. Pinealomas and tumours of theposterior portion o the third ventricle. J Neurosurg 1968;28: 357-61.9Crowe FW, Schull WJ, Neel JV. Multiple Neurofibroma-tosis. Springfield: Thomas, 1956: 43.°0Harkin JC, Reed RJ. Tumours o the peripheral nervoussystem. Atlas of Tumour Pathology. Washington DC:Armed Forces Institute of Pathology: fascicle 3, series 2.

L'Canale DJ, Bebin J, Knighton RS. Neurological manifes-tations of von Recklinghausen's disease of the nervoussystem. Confin Neurol 1964; 24: 359-403.

12Davison C. Von Recklinghausen's disease with glioblas-toma multiforme and ganglioneuroma. J Nerv Ment Dis1941; 93: 73-4.1Pearce J. The central nervous system pathology in multipleneurofibromatosis. Neurology 1967; 17: 691-7.

14Nevin S. Gliomatosis cerebri. Brain 1938; 61: 170-91.15Cushing HW, Eisenhardt L. The Menigiomas. Springfield:Thomas, 1938: 103-5.'6Kramer W. Lesions of the central nervous system inmultiple neurofibromatosis. Psychiatr Pol 1971 ; 74: 349-65.

"Alliez J. Localisations centrales dans la neurogliomatosede Recklinghausen. In: Handbook of Clinical Neurology.New York: North Holland Publishing and AmericanElsevir Publishing, 1933: 14: 33-4.

"'Russell DS, Rubinstein LJ. Central nervous system.Pathology of Tumours of the Nervous System. London:Arnold, 1973: 32-3.

'Russell DS. Observations on the pathology of hydroce-phalus. Med Res Cncl Rep 1949; 265: 48-50.

20Descuns P, Charbonnel A, Collet M, Giudicelli G, RescheF, Lajat Y. Stenose extrinsique de l'aquedic de Sylvius etmaladie de Recklinghausen. Otol Neurol Ophthalmol1973; 45: 85-8.

2'Weston JA. The migration and differentiation of neuralcrest cells. Adv Morphol 1970; 8: 11-20.

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