Title: Radiographic evidence for denervation atrophy of extraocular muscles due to chronic intracavernous compressive third nerve palsy
Abstract: Case 1: A male in his 70s noted chronic progressive painless diplopia. His right pupil was larger and less reactive to light than his left as a teenager, but he was asymptomatic. Photographs revealed exotropia during his 30s. Ophthalmologic evaluation was suggestive of right third nerve palsy. Three sets of noncontrast cranial magnetic resonance imaging (MRI) and computed tomography were reportedly “negative.” Strabismus surgery temporarily improved the exotropia. In his 60s, he experienced development of progressive right-sided ptosis. Examination showed complete right-sided ptosis without aberrant regeneration. The right pupil was 5 mm and poorly reactive, and the left was 3 mm and reactive without a relative afferent pupillary defect. He had−4 underaction of elevation, adduction, and depression with intact intorsion on the right, consistent with complete third nerve palsy with intact fourth nerve function. A right-sided abduction deficit was present, likely because of prior strabismus surgery. MRI of the brain and orbits showed small asymmetry and enhancement in the right cavernous sinus (Fig. 1A) and atrophy of extraocular muscles (EOMs) innervated by the right third nerve (Fig. 1B). Case 2: A male in his 20s noted chronic progressive painless diplopia. He first experienced exotropia at 4 years old. After 2 failed strabismus surgeries, examination showed left upper eyelid ptosis. The right pupil was 4 mm and brisk, and the left was 8 mm and poorly reactive without relative afferent pupillary defect. He had near-complete left-sided deficits in adduction, elevation, and depression with intact abduction and intorsion, consistent with left third nerve palsy. A third strabismus surgery improved alignment for 2 years, but he noted gradual ptosis and recurrence of exotropia. Examination showed complete left-sided ptosis. The right pupil was 3 mm and brisk, and the left was 8 mm and nonreactive. He had near-total left-sided ophthalmoplegia. MRI of the brain and orbits showed an enhancing mass in the left cavernous sinus (Fig. 2A) and left superior, inferior, and medial rectus atrophy (Fig. 2B). Imaging in both cases revealed impressive atrophy of EOMs innervated by the third nerve and an ipsilateral enhancing intracavernous mass. Atrophy is secondary to denervation from chronic third nerve palsy. The patients’ symptom duration indicates a slow-growing lesion, and enhancement on postcontrast MRI suggests schwannoma, although we acknowledge that we cannot exclude other conditions (e.g., granulomatous diseases, meningioma) without histopathologic evaluation. EOM atrophy has been reported secondary to cranial nerve palsies,1Kau H.C. Tsai C.C. Ortube M.C. Demer J.L. High-resolution magnetic resonance imaging of the extraocular muscles and nerves demonstrates various etiologies of third nerve palsy.Am J Ophthalmol. 2007; 143: 280-287Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar EOM palsies,2Demer J.L. Clark R.A. Kono R. Wright W. Velez F. Rosenbaum A.L. A 12-year, prospective study of extraocular muscle imaging in complex strabismus.J AAPOS. 2002; 6: 337-347Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar third and fourth nerve neuroma,1Kau H.C. Tsai C.C. Ortube M.C. Demer J.L. High-resolution magnetic resonance imaging of the extraocular muscles and nerves demonstrates various etiologies of third nerve palsy.Am J Ophthalmol. 2007; 143: 280-287Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 3Smoker W.R. Reede D.L. Denervation atrophy of motor cranial nerves.Neuroimaging Clin N Am. 2008; 18 (xi): 387-411Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar and meningioma.2Demer J.L. Clark R.A. Kono R. Wright W. Velez F. Rosenbaum A.L. A 12-year, prospective study of extraocular muscle imaging in complex strabismus.J AAPOS. 2002; 6: 337-347Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar Denervation atrophy has been studied extensively in animals, with superior oblique atrophy visible on MRI in monkeys as early as 5 weeks after trochlear neurectomy.4Demer J.L. Poukens V. Ying H. Shan X. Tian J. Zee D.S. Effects of intracranial trochlear neurectomy on the structure of the primate superior oblique muscle.Invest Ophthalmol Vis Sci. 2010; 51: 3485-3493Crossref PubMed Scopus (39) Google Scholar Kau et al.1Kau H.C. Tsai C.C. Ortube M.C. Demer J.L. High-resolution magnetic resonance imaging of the extraocular muscles and nerves demonstrates various etiologies of third nerve palsy.Am J Ophthalmol. 2007; 143: 280-287Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar have demonstrated extraocular volume reduction using high-resolution MRI performed by a 1.5-Tesla scanner enhanced by surface coils embedded in a face mask to improve signal-to-noise ratio with 2-mm slices through the orbit. Demer et al.2Demer J.L. Clark R.A. Kono R. Wright W. Velez F. Rosenbaum A.L. A 12-year, prospective study of extraocular muscle imaging in complex strabismus.J AAPOS. 2002; 6: 337-347Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar have repeatedly shown that high-resolution MRI is useful for diagnosis of cranial nerve palsy and visualization of EOM anatomy. However, because their technique involves the use of special surface coil2Demer J.L. Clark R.A. Kono R. Wright W. Velez F. Rosenbaum A.L. A 12-year, prospective study of extraocular muscle imaging in complex strabismus.J AAPOS. 2002; 6: 337-347Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar (to increase the signal-to-noise ratio; hence high-resolution despite the use of 1.5 Tesla), which is available in only a few research laboratories in the world, their findings have not been validated in other centers. Our images were obtained using a 3-Tesla scanner that routinely makes 3-mm cuts through the orbit. Our findings reveal that profound EOM atrophy is visible using less specialized techniques available at most centers. Both patients had chronic, pupil-involving third nerve palsies, symptom onset during youth, symptom progression and recurrence despite multiple strabismus surgeries, and radiographic findings of denervation atrophy and ipsilateral intracavernous enhancement. Recurrence of exotropia is highly suggestive of a compressive lesion and not strabismus, and neuroimaging may reveal the diagnosis. Denervation atrophy is a helpful sign to increase clinical suspicion of an underlying chronic, compressive lesion.