33 Neurogenic Ptosis: Evaluation and Management
Abstract
In this chapter, we discuss neurogenic ptosis using an anatomical approach. Neurogenic forms of ptosis are important to recognize; in fact, in some cases ptosis is a key sign leading to the diagnosis of a life-threatening condition. The neuroanatomical circuitry is well characterized; however, following damage, interesting and complex reorganization can take place. Accurate diagnosis and appropriate intervention depends on a solid understanding of the underlying pathophysiology of these aberrant regeneration syndromes. We will cover the most common of these entities here, with representative examples throughout.
33.1 Introduction
Most cases of blepharoptosis seen in clinical practice are due to aponeurotic or myopathic causes. While relatively rare, neurogenic blepharoptosis is important to recognize due to potential life-threatening concerns in some cases. Frequently, there are associated oculomotor and/or pupillary findings as well as other neurologic findings. Most cases of neurogenic ptosis seen in clinical practice are due to lesions of the oculomotor nerve (cranial nerve [CN] III) or disruption of the oculosympathetic pathway (Horner’s syndrome). Rarely, cortical pathology may lead to neurogenic ptosis. In this chapter, we discuss neurogenic ptosis through a neuroanatomical lens, further differentiating patients who present with congenital versus acquired ptosis.
33.2 Neuroanatomic Considerations
Understanding neural pathways is critical to understanding the pathophysiology behind neurogenic ptosis. The important neurocircuitry discussed in this chapter includes cortical and supranuclear pathways, the oculomotor nerve nucleus and pathway, oculosympathetic projections, and the neuromuscular junction.
33.2.1 Cortical and Supranuclear Pathways
Ptosis produced by cerebral hemisphere dysfunction has been reported to be bilateral or unilateral. 1 ID#b2a851a200_2 – ID#b2a851a200_3 4 Apraxia of eyelid opening, an inability to initiate voluntary eyelid opening in the presence of spontaneous lid elevation, hemispheric stroke, degenerative conditions, and blepharospasm fall under this rubric.
33.2.2 Oculomotor Nerve
Damage to the third nerve anywhere in its course from its nucleus in the dorsal mesencephalon, its fascicles in the brainstem parenchyma, the nerve root in the subarachnoid space, or in the cavernous sinus or posterior orbit can cause ptosis (Fig. 33.1). Visual acuity is typically unaffected. The affected eye position is usually down and out (exotropic and hypotropic position) in cases with complete involvement. Limitation of eye elevation, depression, and adduction are noted due to innervation deficits to the superior rectus, inferior rectus, and medial rectus muscles, respectively. The pupil may be dilated and not light-responsive, reactive with normal response to light, or partially dilated and slightly responsive to light.
33.2.3 Oculosympathetic Pathway
A patient with a Horner’s syndrome may present with ptosis, reverse ptosis of the lower eyelid, miosis in dim illumination, dilation lag, anhidrosis, lower intraocular pressure, and enhanced accommodation. In congenital cases, decreased iris pigmentation is often seen. A Horner syndrome can result from a lesion or pathology anywhere along the three neuron adrenergic (sympathetic) pathway (Fig. 33.2). The first-order neuron descends caudally from the hypothalamus to the first synapse at the lower cervical spinal cord (C8–T2; ciliospinal center of Budge). The second-order neuron travels from the sympathetic trunk through the brachial plexus, to the lung apex, and then ascends to the superior cervical ganglion located near the angle of the mandible and common carotid bifurcation. The third-order neuron then ascends adjacent to the internal carotid artery, through the cavernous sinus in close proximity to CN VI. The oculosympathetic pathway then joins the fifth CN (V1; ophthalmic division) to proceed to innervate the iris dilator muscle, Müller’s muscle of the upper eyelid, and tarsal muscle of the lower eyelid. Postganglionic sympathetic fibers that are responsible for sweating follow the external carotid artery to the facial sweat glands.
33.2.4 Neuromuscular Junction
Autoantibodies at the neuromuscular junction acetylcholine (Ach) nicotinic postsynaptic receptors can cause variable ptosis, as seen in myasthenia gravis (MG) (Fig. 33.3). A reduction in the number of active Ach receptors results in the characteristic pattern of progressively diminished muscle strength with repeated use (fatigue) and recovery with rest. Other ocular findings may include double vision and a weakening of eyelid closure. The pupil is typically spared.
33.3 Localization
33.3.1 Supranuclear/Cortical Localization
Pathology above the third nerve nucleus and sympathetic pathways can lead to ptosis. Lesions in the hemispheres, brainstem, and degenerative conditions can all cause neurogenic ptosis.
Cerebral Hemorrhage
Large nondominant hemispheric strokes can lead to bilateral cortical ptosis. This ptosis, which is usually transient, lasting days to months, can be asymmetric and accompanied by gaze palsies with the eyes being deviated toward the nondominant, involved hemisphere. 5 Interestingly, a small prospective series of patients with large hemispheric strokes found complete bilateral or asymmetric ptosis to be the first sign of imminent herniation, preceding pupillary dilation and ophthalmoplegia. Cases of cortical ptosis resulting from bilateral frontal lobe infarcts have also been reported. 6
Degenerative Conditions
Degeneration of the extrapyramidal tracts in the midbrain has been associated with eyelid apraxia. Eyelid apraxia is characterized by bilateral transient (on the order of 30 seconds) inability to open the eyelids after initiation of the blink reflex. Generally seen in patients with Parkinson’s disease and progressive supranuclear palsy, 7 , 8 eyelid apraxia has also been described in Creutzfeldt–Jakob disease, amyotrophic lateral sclerosis, and Huntington’s disease. 9 , 10 Electromyographic (EMG) studies divide patients with eyelid apraxia into three groups: (1) patients with intermittent inhibition of levator contraction without orbicularis oculi contraction, (2) patients with transient pretarsal orbicularis oculi contraction (atypical blepharospasm), and (3) patients who are unable to relax transient pretarsal contraction after blinking. This may explain variable responses to Botox injections. In addition to Botox, reports suggest some benefit from several drugs including L-dopa, desipramine, olanzapine, and riluzole. Blepharoplasty with orbicularis muscle extirpation should be considered in patients with dermatochalasis in conjunction with eyelid apraxia to alleviate any associated mechanical ptosis.
33.3.2 Brainstem Localization
Central First-Order Neuron Horner’s Syndrome
Sympathetic innervation to Müller’s muscle originates in the hypothalamus and travels paramedian down the entire length of the brainstem before synapsing in the ciliospinal center of Budge, located between C8–T2. Given the long, nondecussating, course of the central first-order sympathetic neuron, it is no wonder that brainstem lesions such as hemorrhage, ischemia, demyelination, and metastatic disease can cause ipsilateral Horner’s syndrome with resulting ptosis. Patients with a first-order Horner syndrome will demonstrate the typical triad of ptosis, miosis, and facial anhidrosis due to involvement of ipsilateral facial sudomotor fibers. Given that Müller’s muscle accounts for approximately 2 mm of upper lid elevation, ptosis is mild in Horner’s syndrome relative to CN III palsies (discussed in Section 33.3.5). As sympathetic fibers also innervate the inferior lid retractors, inverse ptosis of the lower eyelids can also be observed (Fig. 33.4).
Central/first-order Horner’s syndrome can usually be distinguished from lower order syndromes involving the second- or third-order sympathetic fibers by involvement of other localizing clinical signs. For example, in Wallenberg’s syndrome, damage to the lateral medulla results in ipsilateral Horner’s syndrome, ataxia, ipsilateral face with contralateral body pain and temperature hypoesthesia, and lateropulsion (deviating to the side of the lesion) secondary to co-disruption of the descending oculosympathetics, ipsilateral spinal trigeminal tract, ascending decussated spinothalamic tract fibers, and vestibular nuclei, respectively. Infarction of the anterior inferior cerebellar artery can result in Foville’s syndrome, which is characterized by ipsilateral Horner’s syndrome and CN V, VI, VII, and sometimes even VIII palsy, with contralateral hemiparesis. If a first-order Horner syndrome is suspected, a magnetic resonance imaging (MRI) of the brain with and without contrast is the investigation of choice.
Potent direct sympathomimetic agents such as phenylephrine will demonstrate mild improvement in ptosis in patients with Horner’s syndrome. Instillation of apraclonidine, a weak alpha-1 adrenergic agent, can result in reversal (or significant reduction of) anisocoria, due to denervation supersensitivity, which can develop within 48 hours of damage to the sympathetic chain in acute cases. Cocaine (4% or 10%) drops may still be useful in the most acute of presentations (blocks reuptake of noradrenaline, hence development of supersensitivity is not required); however, apraclonidine testing has all but replaced use of cocaine drops in all other settings. Neither drop helps differentiate between pre- and post-ganglionic presentations, but can be very helpful to confirm diagnostic suspicion of a Horner’s syndrome.
Thalamic Hemorrhage
Similar to cases of cortical ptosis, transient bilateral ptosis after thalamic hemorrhage has been reported in the literature. 11 Ptosis is thought to result from concurrent involvement of either the rostral interstitial medial longitudinal fasciculus (which lies caudal to the thalamus) or the posterior limb of the internal capsule (which lies temporal to the thalamus), leading to disruption of supranuclear cortical control of the central caudal nucleus of CN III.
Dorsal Midbrain (Parinaud’s) Syndrome
Classically, dorsal midbrain syndrome leads to eyelid retraction (Collier’s sign, Fig. 33.5) from release of inhibition on the central caudal nucleus of CN III by inhibitory neurons of the posterior commissure. However, when damage to the dorsal midbrain is severe and results in concurrent damage to the central caudal nucleus of CN III, patients can experience severe bilateral ptosis.
Familial Dysautonomia/Riley–Day Syndrome
Riley–Day syndrome is an inherited dysautonomia whose ophthalmic examination is characterized by corneal hypoesthesia, decreased lacrimation, exodeviations, retinal vasculature tortuosity, anisocoria, and ptosis. 12 Described most often in patients of Ashkenazy descent, ptosis in this inherited dysautonomia is thought to result from sympathetic denervation and has been found to improve with instillation of dilute sympathomimetics. 13
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