Eye (2015) 29, 246–251 & 2015 Macmillan Publishers Limited All rights reserved 0950-222X/15 www.nature.com/eye 1,2 1,2,3 1,2,3 CAMBRIDGE OPHTHALMOLOGICAL SYMPOSIUM Cranial nerve palsies CJ Lyons , F Godoy and E ALQahtani in childhood Abstract in his/her impressive ability for repair, altering the clinical presentation of cranial nerve paresis We review ocular motor cranial nerve palsies in childhood. In this brief review of cranial in childhood and highlight many of the nerve paresis in childhood we highlight some of features that differentiate these from their these differences. occurrence in adulthood. The clinical We previously reported our experience with characteristics of cranial nerve palsies in IIIrd nerve palsy in children,2 aseriesof18 childhood are affected by the child’s children presenting under 15 years of age. The impressive ability to repair and regenerate causes are shown in Table 1. As in other larger after injury. Thus, aberrant regeneration is pediatric series,3 congenital and trauma were very common after congenital III palsy; the most common aetiological factors. The Duane syndrome, the result of early repair frequency of associated neurological after congenital VI palsy, is invariably abnormalities (arachnoid cyst, optic nerve associated with retraction of the globe in hypoplasia, and so on) supported the adduction related to the innervation of the recommendation of neuroimaging of all lateral rectus by the III nerve causing co- children presenting with congenital or contraction in adduction. Clinical features acquired cranial nerve III palsy. Notable that may be of concern in adulthood may not features in our series were the almost be relevant in childhood; whereas the universal presence of aberrant regeneration presence of mydriasis in III palsy suggests a because of misrouting of regenerating III fibres compressive aetiology in adults, this is not 1 in congenital palsy (5 of 6 (83%)) and the Department of the case in children. However, the frequency frequent presence of pupil involvement that, Ophthalmology, BC of associated CNS abnormalities in III palsy Children’s Hospital, in contrast to the adult, did not suggest an and the risk of tumour in VI palsy can be Vancouver, British increased likelihood of a compressive indications for early neuroimaging Columbia, Canada aetiology. As in Adie’s pupil, symptomatic depending on presenting features elicited mydriasis can be treated with Pilocarpine 0.1% 2Department of through a careful history and clinical drops in the affected eye. In addition, like Ophthalmology and Visual examination. The latter should include the Adie’s pupil, the mydriatic pupil of III palsy is Sciences, University of neighbouring cranial nerves. We discuss the British Columbia, frequently observed to become miotic, often impact of our evolving knowledge of Vancouver, British over a period of years. congenital cranial dysinnervation syndromes Columbia, Canada Congenital III palsy may present with on this field. complete ptosis and ophthalmoplegia or a Correspondence: Eye (2015) 29, 246–251; doi:10.1038/eye.2014.292; partial palsy with or without aberrant CJ Lyons, Department of published online 9 January 2015 Ophthalmology, BC regeneration. The degree of paralysis and Children’s Hospital, Room subsequent recovery determines the likelihood A136, 4480 Oak Street, of achieving a reasonable visual acuity in the Introduction Vancouver, British Columbia affected eye; satisfactory alignment with the V6H 3V4, Canada Tel: +1 604 875 3117; Palsies of cranial nerves III, IV, and VI are rare use of an anomalous head posture may be Fax: +1 604 875 3561. in childhood, with an estimated incidence of 7.6 associated with a good visual outcome. This E-mail: [email protected] per 100 000.1 The affected child differs from the was the case in 6 of our patients (33%). Other 3 These authors contributed adult in several ways. In the presence of cranial important amblyogenic factors include equally to this work. nerve paresis, the child’s developing visual reduced accommodation in the affected eye. In system is liable to develop strabismic, the presence of underlying hypermetropia, so Received: 15 October 2014 Accepted: 24 October 2014 deprivation, or anisometropic amblyopia. common in children, this is equivalent to Published online: 9 January Fusion and stereopsis may be reduced or penalization of the affected eye. Correction of 2015 abolished. The child also differs from the adult the hypermetropia and use of a bifocal lens for Cranial nerve palsies CJ Lyons et al 247 Table 1 Causes of III palsy in childhood manifestations of ptosis with vertical movement deficits Ng and Lyons2 Biglan and colleagues3 and reduction of horizontal eye movements. Pupillary signs are occasionally evident as these disorders reflect Congenital 33% 38% variable congenital involvement of the III nerve. We Trauma 28% 32% examined an affected infant under general anaesthesia at Tumour 22% 11% Vascular 11% 11% the age of 10 months and noted free forced duction Meningitis 6% testing. The same examination repeated in this patient at Idiopathic 2% the age of 9 years showed marked restriction, Ng and Lyons2 and percentages from Biglan series.3 particularly in elevation. ‘Congenital Fibrosis’ is thus a misnomer as the restrictive ‘fibrosis’ is a feature that develops secondary to disuse related to primary near is helpful, along with an appropriate occlusion congenital dysinnervation. regime for the contralateral eye. The phenotypic patterns were named CFEOM 1–3, but A congenital or acquired III palsy with subsequent as is often the case in pediatric ophthalmology, the repair and aberrant regeneration should be underlying genetic mutations that arise anywhere from distinguished from the much more worrying history of the brainstem to the orbit are forcing a rethink of this a previously normal child who has slowly (often over a group of conditions that are now referred to as the period of years) developed a III palsy, with progressive congenital cranial dysinnervation disorders (CCDDs)7,8 ptosis and exotropia (with or without pupil signs) Fourth (trochlear) nerve palsy is the commonest but who has evidence of aberrant regeneration. congenital cranial nerve palsy.1 Physically slender, with a The temporal pattern of this ‘primary aberrant long intracranial course, this nerve is subject to traumatic regeneration’ should alert the clinician to the possibility damage. Unilateral or bilateral fourth nerve palsy results ofnervedamagefromacompressiveprocesswith in characteristic motility patterns including elevation in simultaneous ongoing repair. This is a classical sign of a adduction, V-pattern related to reduced abduction force slow-growing lesion in the cavernous sinus such as a in downgaze with unopposed adduction by the inferior schwannoma or meningioma.4 The corneal sensation recti, and excyclotorsion. Chin-down head posture for may also be decreased indicating concurrent Vth nerve bilateral and contralateral head tilt for unilateral palsy involvement. This clinical scenario should prompt are noted, and the diagnosis is made clinically with magnetic resonance imaging (MRI) of the brain with support from orthoptic testing that reveals large vertical particular attention to the cavernous sinus. fusional ranges for long-standing or congenital cases. Neurofibromatosis 2, a tumour-suppressor mutation, Thus, neuroimaging is rarely indicated. has a relative predilection for tumour formation in However, several imitators exist. In particular, the cranial nerves III and V, probably because of their craniofacial disorders are known to produce ocular relative bulk compared with cranial nerves IV and VI. motility patterns that are virtually identical. Some Rarely, repair does not result in resolution of III palsy patients may also present with this characteristic ocular with or without aberrant regeneration. Instead, motility pattern without overt craniofacial signs children with oculomotor nerve paresis with cyclic (Figure 1). In the presence of an unexplained primary spasms have a history of unilateral congenital III palsy V-pattern with bilateral superior oblique underaction or, with ptosis, esotropia, and mydriasis. Every 2 min or so, conversely, a primary A-pattern with bilateral superior bursts of III function result in elevation of the ptotic oblique overaction, we recommend a careful examination eyelid as the globe starts to adduct and the pupil of the lid fissure, as a marked mongoloid or anti- constricts. This ‘spastic phase’ lasts B30 s before III mongoloid slant may be the only indicator of underlying function reverts to the ‘paretic phase’.5 This condition, ex- or in-cyclo rotation of the orbital contents as seen in sometimes also known as ‘Cyclical III palsy’, likely craniofacial disorders. An accompanying oblique results from disrupted repair processes following astigmatism may confirm this entity. Coronal cuts on congenital III; Miller6 demonstrated very similar orbital MRI will highlight the lateral displacement of the findings in two adults who had previously undergone superior recti and medial displacement of the inferior skull-base irradiation with subsequent repair, a process recti, superior displacement of the medial recti, and that the author felt was similar to the development of inferior shift of the lateral recti, emphasizing the orbital neuromyotonia. cause of this primary V-pattern ocular motility disorder. In recent years, there has been a rapid evolution in our An analogous condition has been described with primary understanding