Ptosis and lid retraction
Drooping eyelids may come to clinical attention independently, but are more often part of a larger neurological syndrome. Understanding the potential sites of pathology is essential to localizing the responsible lesion correctly (Figure 7.1).
The supranuclear control of lid position is incompletely understood. Hemispheric strokes or other large hemispheric lesions, however, may lead to contralateral, or in some cases bilateral, ptosis.1 Because these lesions are generally large and produce hemiparesis among other neurological symptoms, ptosis is often overlooked on examination.
Nuclear and nerve lesions
Oculomotor nuclear and nerve lesions
The Edinger–Westphal subnuclei of the oculomotor nuclear complex, which control eyelid elevation, are located within a shared midline complex in the midbrain. The oculomotor nerve innervates the levator palpebrae, the main elevator of the lid. Oculomotor nuclear lesions produce bilateral ptosis. Oculomotor nerve lesions cause eyelid dysfunction in combination with extraocular muscle dysfunction, described in Chapter 6. Lesions within the anterior cavernous sinus or orbit, however, may produce deficits restricted to the levator palpebrae and superior rectus.
The oculosympathetic fibers innervate Muller’s muscle, a minor elevator of the lid (see Figure 7.2 and “Anisocoria” below). Ptosis that arises from oculosympathetic dysfunction is milder than ptosis due to oculomotor nerve dysfunction. Unlike oculomotor nerve dysfunction, however, ptosis is often the main or only finding in oculosympathetic dysfunction (i.e. a partial Horner’s syndrome). Oculosympathetic dysfunction may also lead to inverted ptosis in which the lower eyelid is slightly elevated.
The facial nerve innervates the frontalis, the least important of the lid elevators: dysfunction of the facial nerve usually does not lead to clinically important ptosis.
Neuromuscular junction lesions
Myasthenia gravis is the most important cause of ptosis localized to the neuromuscular junction. Problems tend to fluctuate or worsen towards the end of the day. Ptosis is common in patients with both ocular and generalized myasthenia gravis (Chapters 6 and 10). Botulism is the other neuromuscular junction disorder that may lead to ptosis (Chapter 12). Ptosis in foodborne botulism is almost always overshadowed by bulbar dysfunction or generalized weakness. Iatrogenic botulism, however, may lead to isolated ptosis: patients who receive botulinum toxin injections in the forehead or around the eyes for cosmetic purposes, tension headaches, or blepharospasm may develop symptoms several hours to days after the injection as a result of diffusion of the toxin into the levator palpebrae or Muller’s muscle. Because many patients do not spontaneously reveal that they are using botulinum toxin, it is important to ask about an exposure history in patients with undiagnosed ptosis.
Myopathies produce ptosis, which is usually bilateral, symmetric, and fixed. Oculopharyngeal muscular dystrophy (OPMD) is inherited in an autosomal-dominant fashion and is usually associated with swallowing dysfunction or other signs of extraocular muscle dysfunction (Chapter 8). Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial myopathy that also produces fixed bilateral ptosis. Patients with CPEO also
Figure 7.1 Schematic of the three pathways that control elevation of the eyelids.
Figure 7.2 Schematic of the oculosympathetic pathway. Lesions of this pathway result in Horner’s syndrome. ECA = external carotid artery, ICA = internal carotid artery.
usually have weakness of eye movement, but rarely complain of diplopia.
Soft tissue lesions
As a neurologist, it is easy to overlook non-neurological causes of ptosis. Soft tissue problems are often responsible for isolated ptosis. Degeneration of the aponeurosis of the levator palpebrae results in involutional ptosis. This is common in older patients, but may also occur as a result of trauma. Dermatochalasis is also a disorder of older patients, and results from drooping of redundant skin and other soft tissue over the eyes. Peeling back this excess skin reveals that eyelid elevation is actually normal.
In some cases, the eye with the widened palpebral fissure is actually the abnormal one because the eyelid is retracted. Although lid retraction is often bilateral (as in Graves’ disease and dorsal midbrain or Parinaud’s syndrome), it may be unilateral, as in Bell’s palsy.
Treatment of ptosis and lid retraction
Many patients with ptosis and lid retraction have mild symptoms that do not necessarily require treatment. Some causes, such as myasthenia gravis, Bell’s palsy, and Graves’ disease, are directly treatable. Others, such as iatrogenic botulism, resolve over time. Patients with disabling, irreversible ptosis may require referral to an orbital surgeon for consideration of eyelid crutches or lid surgery.
Other disorders of the eyelids
Blepharospasm is a focal dystonia characterized by intermittent sustained contraction of the orbicularis oculi muscles resulting in tight eye closure. Although it may affect only one eye at onset, almost all patients eventually develop bilateral symptoms.2 Blepharospasm may be a mild problem or may be severe and frequent enough to cause functional blindness. Eye strain tends to worsen symptoms. Similar to other dystonias (Chapter 14), blepharospasm may improve with sensory tricks such as gently stroking the eyelids or forehead. When blepharospasm is associated with oromandibular dystonia, it is known as Meige’s syndrome. In most cases, blepharospasm is an idiopathic condition, but it may also be associated with Parkinson’s disease, other extrapyramidal disorders, or neuroleptic exposure. Blepharospasm responds best to local treatment with botulinum toxin injections. Anticholinergic agents such as trihexyphenidyl and dopaminergic agents including levodopa are only modestly effective.
Eyelid-opening apraxia is a disorder defined by the combination of:3
• inability to open the eyes
• excessive frontalis contraction during attempted eyelid opening
• no evidence of orbicularis oculi contraction to suggest blepharospasm
• no evidence of oculomotor or oculosympathetic dysfunction
• no evidence of ocular myopathy
It may be present in isolation, but is often associated with an extrapyramidal disorder, particularly progressive supranuclear palsy or Parkinson’s disease. Symptomatic improvement with levodopa or focal botulinum toxin injection is typically modest.4
Because of its association with ominous disorders such as posterior communicating artery aneurysm and uncal herniation, anisocoria often leads to urgent neurological consultation. With the possible exception of mild photophobia produced by an abnormally dilated pupil, isolated anisocoria is unlikely to cause specific symptoms. If old photographs of the patient are available, examine them carefully to determine whether the anisocoria is longstanding (and likely benign) or more recent in onset. An important sign of chronic developmental anisocoria is hypochromia iridis, a bluish or grayish discoloration of the iris associated with a small pupil.
The first step in determining the source of anisocoria is to figure out which pupil is abnormal: the big one (mydriasis) or the small one (miosis). This is accomplished by examining the pupils in light and dark. Anisocoria that is worse in light points to an abnormality of the large pupil and the parasympathetic system. Anisocoria that is worse in the dark implies a problem with the smaller pupil and, therefore, the sympathetic system.
Anisocoria worse in light (parasympathetic dysfunction)
The paired Edinger–Westphal nuclei lie in the oculomotor complex of the midbrain and give rise to pupilloconstricting fibers. Because lesions of the Edinger–Westphal nuclei are bilateral, they should cause symmetric pupillary dilation and should not lead to anisocoria.
Fascicular and subarachnoid lesions
The pupilloconstrictor fibers travel anteriorly through the midbrain with the fascicles of the oculomotor nerve. Fascicular lesions, therefore, produce pupillary dilation accompanied by extraocular muscle weakness (Chapter 6). As they emerge from the anterior aspect of the midbrain in the interpeduncular fossa, the superficial pupilloconstricting fibers of the third nerve are susceptible to compression by structural lesions. The two most important of these are expanding aneurysms of the posterior communicating artery (PCOM) and the herniating uncus of the temporal lobe, both of which are neurological emergencies. Although anisocoria secondary to a PCOM aneurysm may be isolated, anisocoria secondary to uncal herniation must be accompanied by altered mental status, coma, and other focal neurological findings (Chapter 1).
Cavernous sinus lesions
The pupilloconstricting fibers course through the cavernous sinus in the oculomotor nerve (Chapter 6). Adjacent structures include the trochlear, ophthalmic, maxillary, and abducens nerves. Isolated anisocoria is therefore unlikely in cavernous sinus lesions.
Ciliary ganglion lesions
The oculoparasympathetic fibers pass through the ciliary ganglion within the orbit. Lesions at this site result in a large, dilated, unreactive pupil. The classical ciliary ganglion lesion is Adie’s tonic pupil, an idiopathic condition that is most common in young to middle-aged women. Adie’s pupil is diagnosed by finding denervation supersensitivity of the pupilloconstricting fibers: a dilute (0.1%) solution of the cholinergic agent pilocarpine causes brisk pupilloconstriction.
The pupilloconstricting fibers in the iris are susceptible to damage during ocular surgery or other trauma. The oculoparasympathetic fibers may also be blocked by anticholinergic medications such as atropine or scopolamine. These agents are used to treat bradycardia, reactive airway disease, and motion sickness, and may accidentally be splashed in the eye. In some cases, these medications are placed into the eye intentionally by malingerers. The key finding of a pharmacologically dilated pupil is that it will not constrict, even in response to concentrated (1%) pilocarpine.
Obviously, the first step in evaluating oculoparasympathetic dysfunction is to perform a thorough history and physical examination to define dysfunction of adjacent structures and to uncover any relevant history of eye surgery or trauma. It is especially important to exclude the possibility of a compressive lesion of the third nerve – because an aneurysm of the posterior communicating artery cannot be missed, considering a magnetic resonance angiography (MRA) or even a conventional angiogram in all patients with isolated oculoparasympathetic dysfunction is worthwhile.
In patients with isolated pupilloconstriction defects that remain undiagnosed after history and physical examination, use dilute pilocarpine drops to investigate for the possibility of an Adie’s tonic pupil. If denervation supersensitivity is absent, then use concentrated pilocarpine drops to investigate for pharmacological blockade. One final consideration is benign episodic unilateral mydriasis, a diagnosis of exclusion that may be associated with migraine.5
Oculoparasympathetic dysfunction that remains undiagnosed after comprehensive investigation may require referral to an ophthalmologist.
Anisocoria worse in the dark (sympathetic dysfunction)
Damage to the oculosympathetic pathway is known as Horner’s syndrome, and when complete, is characterized by ipsilateral miosis, ptosis, and facial anhidrosis. The oculosympathetic fibers follow a three-neuron pathway (Figure 7.2):
The first-order neuron is found in the hypothalamus. Its axons descend through the lateral brainstem and cervical spinal cord. Anisocoria is unlikely to be the major finding of a lateral brainstem lesion, as nearby structures are also likely to be affected, producing Wallenberg’s syndrome (Chapter 21). Spinal cord lesions are similarly unlikely to produce anisocoria as the major complaint.
The first synapse in the oculosympathetic pathway occurs at the C8–T1 level of the spinal cord in the ciliospinal center of Budge. Axons that arise from the second-order neuron pass through the mediastinum, traveling superior to the apex of the lung and inferior to the subclavian artery. This is a common site for the oculosympathetic tract to be compressed by an apical lung cancer (Pancoast tumor), usually in association with a painful ipsilateral brachial plexopathy (Chapter 16). The second-order neuron is also vulnerable to injury from attempted subclavian venous catheter placement.
The axons of the second-order neuron synapse in the superior cervical ganglion. Axons to the eyelid and pupil travel with the internal carotid artery, while those that control facial perspiration follow the external carotid artery. Lesions of the first- and second-order neurons therefore produce the complete triad of Horner’s syndrome, whereas a lesion of the third-order neuron leads to anisocoria and ptosis without facial anhidrosis. Carotid artery dissection is the most serious cause of Horner’s syndrome affecting the third-order neuron and is associated with severe ipsilateral headache and facial pain (Chapter 19). Cluster headache and the indomethacin-responsive headaches may present identically. Intracranial oculosympathetic fibers travel with the ophthalmic nerve through the cavernous sinus and into the orbit with the long ciliary nerves to reach the pupillodilators.
Although eye drops containing cocaine and hydroxyamphetamine help to localize the site of Horner’s syndrome, using them is too time-consuming to be employed effectively in the emergency setting. The diagnosis of Horner’s syndrome is largely made by the company it keeps: Wallenberg’s syndrome in a patient with a lateral brainstem lesion, painful ipsilateral brachial plexopathy in a patient with a Pancoast tumor, ipsilateral headache in a patient with carotid artery dissection, and ipsilateral ocular motor abnormalities in a patient with a cavernous sinus lesion. Patients in whom none of these neighboring signs is present require imaging studies to help localize the dysfunction, including MRI of the brain (paying particular attention to the lateral brainstem and cavernous sinus), MR or CT angiography of the cervical vessels, and CT scan of the chest.
Anisocoria of up to 1 mm, usually worse in the dark, may be observed in the absence of any recognizable sympathetic or parasympathetic pathology. Physiological anisocoria is usually longstanding and is best diagnosed by examining old photographs. In many cases, however, it remains a diagnosis of exclusion, and careful evaluation for other sources of anisocoria should be conducted first.
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