Mitochondrial ocular disorder characterized by bilateral progressive ptosis and ophthalmoplegia

Clinical History

8-year-old without significant antenatal history presented with gradual drooping of both eyelids for 2-3 years and occasional double-vision. Examination revealed bilateral ptosis with restricted eye movements in all directions and diplopia. No other deficits were noted. Evaluation by magnetic resonance imaging (MR) of the brain and orbits was done.

Imaging Findings

MR of orbits revealed symmetrical thinning of all the extra-ocular muscles (EOM) with normal signal intensities within both orbits (Fig. 1). Bilateral globes were normal in size, the lens was normal in position and no mass lesion was noted within orbits or at the apices. Bilateral optic nerves were normal along their course. The brain parenchyma was normal in signal intensity with maintained grey-white matter differentiation. No mass lesion, atrophy or hydrocephalus was seen. Based on the clinical and imaging findings, diagnosis of chronic progressive external ophthalmoplegia was made.

Discussion

First described by Von Graefe [1], chronic progressive external ophthalmoplegia (CPEO) was initially thought to represent denervation atrophy. However, developments in mitochondrial genetics now support a myopathic origin [2]. It can occur at any age (more commonly 2nd decade), in either sex and usually manifests as ptosis followed by progressive weakness of EOM. Exclusion of other causes of restive ocular movements such as neuromuscular junction disorders (myasthenia gravis, thyroid ophthalmopathy), Guillain-Barre syndrome, brainstem and cavernous lesions must be done. CPEO is not a specific disorder but a clinical sign and can occur in association with multiple conditions such as myotonic dystrophy, Kearns-Sayre syndrome, Stephen syndrome and oculopharyngeal dysplasia. Various other neurological symptoms such as exercise-induced or permanent paresis, myalgia, cardiac/retinal manifestations, peripheral neuropathy and hypacusis make CPEO a part of ophthalmoplegia plus (CPEO+) [3].

MR plays a role in the work-up of such patients for narrowing the differential diagnosis by virtue of exclusion. The various intra-cranial findings range from loss of parenchymal volume [4] to increased signal intensity on T2W in subcortical white matter, cerebellar white matter, thalami and deep grey matter. Atrophy, with a predilection for cerebellum, is more commonly seen in the subgroup of patients with CPEO + features [5]. In the orbit, symmetrical thinning of EOM may be noted (as in our case) and its presence must be recorded and looked for by neuro-radiologists [6]. Ortube et al. demonstrated the presence of increased signal intensity within EOM on T1W images and suggested that minimal EOM volume reduction despite severe clinical weakness could aid in diagnosis of CEPO [7].

MR Spectroscopy (voxel in the parietal white matter and brainstem) can show various findings and range from normal metabolite ratios in pure mitochondrial myopathies [8] to variable reduction in N-acetyl-aspartate and presence of lactate peak depending on neurological progression in Kearns-Sayre syndrome [9]. However, these changes (when voxel grid is over bilateral possibly involved centrum semiovale) are less severe in CPEO and mitochondrial myopathies. Diffusion weighted imaging of the brain may be normal (average mean diffusivity value of 0.713 10−3 mm2/s), except if associated foci of demyelination exist (increased mean diffusivity values) [10].

High resolution orbital MRI may, thus, have a high specificity for diagnosing CPEO in problematic clinical scenarios [7].

Differential Diagnosis List

Final Diagnosis

Chronic progressive external ophthalmoplegia

URL:	https://www.eurorad.org/case/12648
DOI:	10.1594/EURORAD/CASE.12648
ISSN:	1563-4086