Neuroanatomical Strabismus

■Strabismus may arise from identifiable structural abnormalities of the extraocular muscles (EOMs) or their innervation. Congenital or acquired myopathies a ect EOM function or structure to impair normal relaxation and force generation. Abnormalities of EOM paths may produce strabismus by altering EOM pulling directions. Path abnormalities arise from abnormalities of the location and stability of the connective tissue pulleys that influence EOM paths. Pulley disorders may be congenital or acquired, and produce pattern strabismus, divergence paralysis esotropia, and horizontal or vertical incomitant strabismus. Structural abnormalities of EOMs or their associated connective tissues may be demonstrated by clinical orbital imaging.

■Strabismus may also arise from abnormalities of peripheral innervation of the EOMs. Congenital cranial dysinnervation disorders (CCDDs) typically produce hypoplasia and loss of function of insu ciently innervated EOMs, with contracture of their more normally innervated antagonists. High resolution imaging can directly demonstrate hypoplastic and misdirected motor nerves to the EOMs in the CCDDs, sometimes with additional abnormalities of the optic or other cranial nerves. Some forms of strabismus may be associated with abnormalities of the brainstem or cerebellum that are demonstrable by clinical imaging. However, typical forms of developmental strabismus such as concomitant esotropia and exotropia are not associated with EOM abnormalities.

6.1 General Etiologies of Strabismus

Strabismus, defined as misalignment of the visual directions of the two eyes, may arise from several general causes. These include primary myopathies of extraocular muscles (EOMs), disorders of the connective tissues that comprise the globe’s gimbal system, peripheral disorders of nerves controlling the EOMs, and central disorders of fusional vergence commands (Table 6.1). This chapter emphasizes causes of strabismus that can be characterized as mechanistically specific pathologies of the subcortical nervous system, EOMs, and associated connective tissues. Such pathologies are termed neuroanatomical because their causes can, at least in principle, be demonstrated anatomically using appropriate clinical methods, and are distinct from developmental forms of strabismus that arise from complex abnormalities in cerebral cortex.

6.2Extraocular Myopathy

6.2.1Primary EOM Myopathy

Primary EOM myopathy may be due to congenital metabolic disorder, acquired inflammation, or mechanical trauma. Chronic progressive external ophthalmoplegia (CPEO) features insidious onset of slowly progressive, typically symmetric, external ophthalmoplegia [1]. Manifestations of CPEO range from involvement limited to the eyelids and EOMs to systemic and encephalopathic features. Tissues with high oxidative metabolism such as muscle, brain, and heart are most a ected [2]. The association between CPEO and heart block is called Kearns– Sayre syndrome [3]. Ragged red fibers, as demonstrated on modified trichrome stain, can be seen in limb and EOMs in nearly all cases of Kearns–Sayre syndrome and occasionally in isolated CPEO [3]. Molecular diagnosis of

CPEO is problematic, since most cases are caused by sporadic mitochondrial DNA deletions. More clinically useful may be T1-weighted magnetic resonance imaging (MRI), which in CPEO demonstrates abnormal bright signal within clinically weak EOMs having generally normal size [1] (Fig. 6.1). Other cases of chronic, fixed EOM weakness are associated with obvious EOM atrophy (Table 6.2).

6.2.2Immune Myopathy

Immune EOM myopathy, also known as endocrine myopathy or thyroid eye disease (TED), is typically associated with immune dysthyroidism but may follow an independent temporal course [4]. TED begins with inflammation and infiltration of EOMs, orbital connective tissues, or both. A classical presentation of TED involves inflammatory enlargement of EOMs producing upper eyelid retraction, proptosis, and restrictive ophthalmoplegia. Chronic EOM enlargement and fibrosis persists following resolution of inflammation. Orbital imaging by MRI or computed X-ray tomography (CT) typically demonstrates enlargement of EOM bellies, sparing the terminal tendons. MRI demonstrates abnormal internal signal in involved EOMs (Fig. 6.2). Rectus EOMs, particularly the inferior and medial rectus (MR) muscles, demonstrate the most common clinical involvement, although all EOMs, including the obliques (Fig. 6.2), may be involved. Restrictive strabismus is typical in TED, most commonly involving limitation of supraduction.

Fig. 6.1 Coronal T1-weighted magnetic resonance imaging (MRI) of a right orbit of a patient with chronic progressive external ophthalmoplegia (CPEO) demonstrating abnormal bright signal within extraocular muscles that are of generally normal size. IR inferior rectus muscle; LR lateral rectus muscle; ON optic nerve; SO superior oblique muscle; SR superior rectus muscle

Fig. 6.2 Coronal T1-weighted MRI of both orbits of a patient with thyroid eye disease (TED) demonstrating enlargement and in all rectus and the SO muscles. IR inferior rectus muscle; LR lateral rectus muscle; MR medial rectus muscle; ON optic nerve; SO superior oblique muscle; SR superior rectus muscle

Another presentation in TED is inflammatory enlargement of the nonmuscular orbital connective tissues, particularly orbital fat. Proptosis is the main feature, but strabismus may arise due to forward displacement of the globe relative to fixed structures such as the fixed anchors of the trochlea and the soft pulley system of the other EOMs.

6.2.3Inflammatory Myositis

Myositis of EOMs not due to thyroid ophthalmopathy typically involves both the EOM belly and tendon. Immunologic mechanisms with a host of triggers are believed to be the cause [5].

6.2.4Neoplastic Myositis

Primary or metastatic neoplasms may cause strabismus by inducing EOM weakness or restriction. In such cases, orbital imaging may demonstrate nodular EOM enlargement or a contiguous orbital mass [6]. Biopsy of the involved EOM may be helpful for diagnosis if likely metastatic source is not already known.

Summary for the Clinician

■Old orbital fractures may complicate the presentation of strabismus of recent origin.

■Patients may not recall old orbital fractures.

6.2.5 Traumatic Myopathy

Direct trauma to EOMs may compromise their function and produce strabismus. Sharp objects penetrating the orbit may disinsert EOM tendons from the globe,

transect or avulse EOM bellies, or avulse motor nerves to EOMs. Clinically unrecognized penetration of the orbit by thin, sharp objections may occur in the setting of more widespread facial trauma, since entry wounds through the eyelid crease or conjunctival fornix are concealed by edema and heal very quickly. High-resolution orbital imaging by CT or MRI may be valuable in the evaluation of strabismus associated with facial trauma, to detect direct EOM trauma and distinguish this from weakness of structurally intact EOMs due to traumatic cranial neuropathy [7].

Blunt orbital trauma may produce blow-out fractures of the orbital walls, most commonly the thinner medial and inferior walls [8, 9]. In larger orbital fractures, EOMs and orbital connective tissues herniate into the adjacent sinuses via relatively large bony defects. Large blow-out fractures are associated with enophthalmos, but not often with strabismus unless there is direct EOM trauma.Smaller orbital fractures may exhibit a trap-door mechanism, with a displaced bone fragment trapping an EOM or part of the connective tissue pulley system. Especially in children in whom inflammatory signs may not be clinically evident, an EOM may become entrapped and strangulated in a trap-door orbital fracture. Entrapment and strangulation of an EOM constitutes a situation demanding emergent surgical release, while immediate repair is not typically critical for most blow-out fractures. An entrapped EOM is very likely to exhibit clinical weakness on force generation testing, as well as producing a mechanical restriction to forced duction testing. Old, forgotten blow-out fractures may complicate the presentation of acquired strabismus due to other causes [10].

Even in the absence of EOM entrapment in an orbital fracture, connective tissues of the orbital pulley system may become entrapped in the fracture. Such a situation