Congenital isolated unilateral third nerve palsy in children: the diagnostic contribution of high-resolution MR imaging.

PURPOSE: To describe the neuroanatomical correlates of unilateral congenital isolated oculomotor palsy by means of high-resolution MRI. METHODS: Children with a clinical diagnosis of congenital isolated oculomotr palsy and with a high-resolution MRI acquisition targeted on the orbits and cranial nerves were selected and included in the study. An experienced pediatric neuroradiologist evaluated all the exams, assessing the integrity and morphology of extraocular muscles, oculomotor, trochlear and abducens nerves as well as optic nerves and globes. Clinical data and ophthalmologic evaluations were also collected. RESULTS: Six children (age range: 1-16 years; males: 3) were selected. All patients showed, on the affected side (left:right = 5:1), anomalies of the III nerve and extraocular muscles innervated by the pathological nerve. One patient had complete nerve agenesis, two patients showed a diffuse thinning of the nerve, from the brainstem to the orbit and 3 patients showed a distal thinning of the oculomotor nerve, starting at the level of the cavernous sinus. In all cases atrophy of corresponding muscles was noticed, but the involvement of the affected muscles varied with the nervous pattern of injury. CONCLUSIONS: High-resolution MRI represents a valuable tool for the diagnosis of III nerve anomalies in unilateral congenital IOP, showing different patterns of nerve involvement and muscular atrophy.

The Oculomotor Nerve: Anatomy and Pathology.

The oculomotor nerve is the third cranial nerve, exiting the brainstem in the medial border of the cerebral peduncle, from where it crosses straight to the superior orbital fissure. It is a purely motor nerve responsible for the innervation of all the extraocular muscles, except the superior oblique and lateral rectus muscles. It also has parasympathetic pre-ganglionic fibers, responsible for the innervation of sphincter pupillae and ciliary muscles. Magnetic resonance imaging (MRI) is the best imaging exam to evaluate patients with clinical signs of third cranial nerve palsy. The oculomotor nerve can be affected by several diseases, such as congenital malformations, trauma, inflammatory or infectious diseases, vascular disorders, and neoplasms. This article aims to review the oculomotor nerve anatomy, discuss the best MRI techniques to evaluate each nerve segment, and demonstrate the imaging aspect of the diseases that most commonly affect it.

Rare neurovascular conflict between oculomotor nerve and posterior communicating artery.

Paroxysmal diplopia could be the expression of a multitude of clinical or anatomical conditions. Both ophthalmological and neurological pathologies could be responsible of this symptom. Rarely, a neurovascular conflict involving the oculomotor nerve is the etiology. We present the case of a 75-year-old man who presented for a 20-year history of transient vertical diplopia. The radiological exams demonstrated the presence of a neurovascular conflict between the right oculomotor nerve and a fetal-type posterior communicating artery. This fetal posterior communicating artery had an aberrant downward course that compressed the third cranial nerve. Few cases of neurovascular conflict interesting the third cranial nerve were described in the literature whom the responsible artery was generally the superior cerebellar artery. No case of oculomotor nerve compression by the posterior communicating artery was published. Authors have reviewed the literature and discuss the embryology of the posterior communicating artery, pathophysiology, radiological findings, and therapeutic possibility.

Loss of CXCR4/CXCL12 Signaling Causes Oculomotor Nerve Misrouting and Development of Motor Trigeminal to Oculomotor Synkinesis.

Purpose: Proper control of eye movements is critical to vision, but relatively little is known about the molecular mechanisms that regulate development and axon guidance in the ocular motor system or cause the abnormal innervation patterns (oculomotor synkinesis) seen in developmental disorders and after oculomotor nerve palsy. We developed an ex vivo slice assay that allows for live imaging and molecular manipulation of the growing oculomotor nerve, which we used to identify axon guidance cues that affect the oculomotor nerve. Methods: Ex vivo slices were generated from E10.5 IslMN-GFP embryos and grown for 24 to 72 hours. To assess for CXCR4 function, the specific inhibitor AMD3100 was added to the culture media. Cxcr4cko/cko:Isl-Cre:ISLMN-GFP and Cxcl12KO/KO:ISLMN-GFP embryos were cleared and imaged on a confocal microscope. Results: When AMD3100 was added to the slice cultures, oculomotor axons grew dorsally (away from the eye) rather than ventrally (toward the eye). Axons that had already exited the midbrain continued toward the eye. Loss of Cxcr4 or Cxcl12 in vivo caused misrouting of the oculomotor nerve dorsally and motor axons from the trigeminal motor nerve, which normally innervate the muscles of mastication, aberrantly innervated extraocular muscles in the orbit. This represents the first mouse model of trigeminal-oculomotor synkinesis. Conclusions: CXCR4/CXCL12 signaling is critical for the initial pathfinding decisions of oculomotor axons and their proper exit from the midbrain. Failure of the oculomotor nerve to innervate its extraocular muscle targets leads to aberrant innervation by other motor neurons, indicating that muscles lacking innervation may secrete cues that attract motor axons.

Isolated Congenital Absence of Cranial Nerves: Report of Two Cases.

Isolated cranial nerve absence is a rare condition that can be diagnosed using high-resolution cranial nerve magnetic resonance (MR) imaging. Thorough clinical examination with proper knowledge of the course of cranial nerves may help diagnose this rare condition. We describe two cases, one each of, isolated congenital absence of the third and seventh cranial nerve with their clinical presentation. High-resolution T2-weighted MR imaging was done in both patients which revealed absence of cisternal segment of the right-sided third nerve and cisternal with canalicular segment of the right-sided facial nerve.

Congenital Third Nerve Palsy Associated With Midbrain Hypoplasia Due to Bilateral Segmental Internal Carotid Artery Agenesis.

A 15-year-old girl, diagnosed with a partial right third nerve palsy, was found to have bilateral internal carotid artery agenesis. Neuroimaging with 3D-constructive interference in steady state scanning identified the possible etiology of the third nerve palsy as midbrain hypoplasia.

Premanifest Huntington's disease: Examination of oculomotor abnormalities in clinical practice.

INTRODUCTION: Different oculomotor abnormalities have been reported to occur in premanifest Huntington's disease. The aim of this study is to investigate which oculomotor items of the Unified Huntington's Disease Rating Scale (UHDRS) are affected in premanifest individuals compared to healthy controls, and if CAG repeat length and age are correlated with oculomotor abnormalities in premanifest Huntington's disease gene carriers. METHODS: We compared baseline data of 70 premanifest individuals and 27 controls who participated in the Enroll-HD study at the Leiden University Medical Center, the Netherlands. Premanifest gene carriers were divided in individuals near to disease onset and individuals far from disease onset. RESULTS: Using a logistic regression model, only horizontal ocular pursuit of the six oculomotor items of the UHDRS was significantly more frequently affected in premanifest individuals close to disease onset compared to controls (p = 0.044, OR 13.100). Age was significantly higher in premanifest individuals with affected horizontal ocular pursuit (p = 0.016, OR 1.115) and with affected vertical ocular pursuit (p = 0.030, OR 1.065) compared to premanifest individuals without ocular pursuit deficits. CONCLUSIONS: Our results suggest that horizontal ocular pursuit is the only affected oculomotor item of the UHDRS in premanifest individuals and could be used to assess early clinical signs of Huntington's disease. Saccade initiation and saccade velocity do not seem useful for detecting differences between premanifest individuals and controls.

Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements.

Magnetic resonance imaging in congenital Brown syndrome.

AIMS: Our aim was to elucidate the etiology of Brown syndrome by evaluating the trochlea position, morphologic characteristics of the extraocular muscles including superior oblique muscle/tendon complex, and the presence of the cranial nerves (CN) III, IV, and VI using magnetic resonance imaging (MRI) in eight patients with unilateral congenital Brown syndrome and one patient with bilateral congenital Brown syndrome. METHODS: Nine consecutive patients diagnosed with congenital Brown syndrome had a comprehensive ocular examination and MRI for the CN III, CN VI, and the extraocular muscles. Five of the nine patients underwent additional high resolution MRI for CN IV. The distance from the annulus of Zinn to the trochlea was measured. RESULTS: Normal sized CN III, IV, and VI, as well as all extraocular muscles, could be identified bilaterally in all patients with available MRI. The distance from the annulus of Zinn to the trochlea was the same in both eyes. CONCLUSIONS: The findings for our patients, particularly in those who underwent additional high resolution MRI, did not provide evidence of a lack of CN IV as a cause of Brown syndrome.

Thromboembolism and congenital malformations: from Duane syndrome to thalidomide embryopathy.

OBJECTIVE: To propose a pathophysiologic mechanism to unify a variety of disparate sporadic congenital malformations. METHODS: Inductive and deductive analyses to correlate malformation laterality with asymmetries in thoracic anatomy, critical analysis of malformations with female predominance, and concepts of hydrodynamic pressure gradients in vascular growth were applied to the ensuing development of guiding tissue scaffolds for cellular proliferation, differentiation, and apoptosis. RESULTS: Duane syndrome may develop following a focal vascular insult to the sixth nerve trunk with axonal degeneration, allowing for substitutive innervation from third nerve axons to the lateral rectus muscle. Causative fibrin clots may originate from the venous system and paradoxically migrate through physiological right-to left shunts, or they may arise directly from the heart. Hence, the unilateral, left-sided, and female predominance of Duane syndrome results from the asymmetry in the thoracic anatomy and from thrombosis risk factors. Embolic occlusions may also alter local hemodynamic pressure gradients, leading to the compensatory enlargement and persistence of the fetal vasculature and may dysregulate tissue growth. Within the eye, this results in forms of Peters anomaly, unilateral congenital cataracts, and the morning glory disc anomaly, all in the vascular territory of the carotid arteries that also share a propensity for left-sided involvement in girls. Most aberrant misinnervation phenomena (eg, jaw-winking syndrome, crocodile tear syndrome, Brown syndrome, and congenital fibrosis syndrome) and, by extrapolation, the hypoplasia or dysgenesis of noncephalic anatomical structures (including limbs) may be similarly explained. Such malformations will occur more frequently under thrombogenic conditions, such as those induced by thalidomide. CONCLUSIONS: Fibrin emboli and focal hypoperfusion may explain the development of many sporadic congenital malformations.

Marcus Gunn jaw winking synkinesis: report of two cases.

Marcus Gunn jaw winking synkinesis (MGJWS) is caused by congenital miswiring of a branch of the fifth cranial nerve into the branch of the third cranial nerve supplying the levator muscle. It has been observed in 2-13% of patients with congenital ptosis. Although bilateral cases were reported, most were unilateral and occurred more frequently on the left side than the right. We report two cases of children who presented with ptosis and were diagnosed with MGJWS.

Primary nerve repair following resection of a neurenteric cyst of the oculomotor nerve.

Neurenteric cysts are rare congenital lesions of endodermal origin occurring in the spinal canal and infrequently in the posterior cranial fossa. The authors report the case of a 3-year-old child who presented with a recurrent third cranial nerve palsy. Magnetic resonance imaging showed a large cystic mass lesion in the ambient cistern on the right side, with compression of the anterolateral aspect of the brainstem. The patient underwent a craniotomy, complete excision, and a primary third cranial nerve repair. While there have been 3 reported cases of neurenteric cysts arising from the oculomotor nerve, this is the first documented case with a primary nerve repair.

Atypical Duane's retraction syndrome: congenital adduction palsy with synergistic divergence in association with aberrant trigeminal innervation and facial hypoplasia.

The authors describe the atypical and unique features of trigeminal-oculomotor synkinesis in a 6-year-old boy with left congenital adduction palsy and synergistic divergence with facial hypoplasia. Adducting movements of the left eye were also seen on mastication. To the best of the authors' knowledge, a case of this nature has not previously been reported. This case illustrates the absence of changes in palpebral aperture and globe retraction on attempted adduction and also the complete absence of any abduction deficit of the involved eye. Additionally, presence of adducting movements on mastication suggests a trigemino-oculomotor synkinesis. Hypothesis favors an anomalous innervation of the medial rectus muscle from the motor branch of the trigeminal nerve that innervates the external pterygoids.

Duane retraction syndrome type I, Marcus Gunn jaw-winking and crocodile tears in the same eye.

Duane retraction syndrome type I, Marcus Gunn jaw-winking and crocodile tears are all syndromes of congenital aberrant innervation. The authors describe a 17-month-old boy with Duane retraction syndrome type I, Marcus Gunn Jaw-winking, and crocodile tears in the same eye and discuss the proposed mechanisms of these conditions.