Apraxia of lid opening (ALO) is a nonparalytic motor abnormality “characterized by difficulty initiating the act of lid elevation after lid closure.”[1] Controversy surrounds the designation of this syndrome. Strictly speaking, ALO is not truly an apraxia or “inability to perform a motor action to command despite both an adequate understanding of the action and the elementary ability to carry out.”[2]
Nevertheless, the designation ALO does address the main feature of the condition—namely, the inability to open the eyes at will with preservation of the ability to open them and keep them open at other times.[3, 4, 5, 6, 7] ALO may present either in isolation or in association with blepharospasm.[8, 9, 10] The challenge for management lies in differentiating these 2 entities.
Although the underlying mechanisms of ALO have not been clearly elucidated, it is believed that this condition may involve an abnormality in the supranuclear control of voluntary eyelid elevation, which requires the activation of the levator palpebrae superioris (LPS) and the concurrent inhibition of orbicularis oculi (OO) activity.
Electromyographic studies of the LPS and the OO have demonstrated that the following may cause ALO:
The LPS is innervated bilaterally from the central caudal subdivision of the oculomotor (III) nucleus, and the OO is innervated unilaterally from the facial (VII) nucleus. The cortex, extrapyramidal motor systems, and rostral midbrain structures may control LPS motoneuron activity (see the image below).[16]
View Image | Diagram of the possible central pathways involved in the generation of inhibitory responses of the levator palpebrae superioris muscle. Caudal central.... |
Disturbances in burst, tonic, or pause neurons within any of the aforementioned premotor structures may result in abnormal inhibitor inputs to the LPS motoneurons. Some patients may experience an associated disruption in reciprocal activation of the LPS and the OO.
ALO has been attributed to a variety of central nervous system (CNS) lesions in various parts of the brain, including the following:
ALO has been described in association with the following CNS diseases:
In addition, the use of the following medications has been reported to induce ALO[1, 15, 23, 29] :
A diagnosis of Wilson disease was made in one patient after he presented with a severe, intermittent inability to open his lids; the original diagnosis was ALO.[31]
Apraxia of lid opening (ALO) has been reported in 7%,[9] 10%,[8] and 55%[32] of patients with blepharospasm. Benign essential blepharospasm has a prevalence of 12 per million in Japan,[33] 17 per million in Rochester, MN, in the United States,[34] 30 per million in northern England,[35] and 36 per million in the Epidemiologic Study of Dystonia in Europe.[36] The wide variation in these figures may reflect sample bias.
The peak age of onset is in the sixth and seventh decades of life. ALO appears to be more common in women than in men. In a report describing 10 new individuals with ALO and reviewing 11 cases previously mentioned in the literature, Defazio et al found a female-to-male preponderance of 2:1.[37] No racial differences have been reported.
ALO does not directly cause mortality. The morbidity noted in patients with this condition is mostly related to the underlying disease and to the visual impairment in individuals with severe eye closure.
In patients with isolated ALO, the prognosis is excellent. In ALO patients who have other underlying diseases, morbidity or mortality may result as a consequence of the associated condition.
Apraxia of lid opening (ALO) can present spontaneously in otherwise healthy individuals.[11, 37] In patients with Parkinson disease, progressive supranuclear palsy, and Shy-Drager syndrome, Lepore and Duvoisin reported that extrapyramidal symptoms preceded the inability to open the eyelids by a mean of 9.7 years.[15]
ALO is typically a chronic disorder, but spontaneous remission has been reported in patients within 1 month of strokes involving the nondominant hemisphere.[38, 17, 39] In instances of ALO that may be drug induced, symptoms have been reported to remit within 2 weeks of withdrawal of the agent[21] ; however, in one individual, the symptoms persisted for 7 months.[22]
The inability to reopen the lids is not evident during spontaneous or reflex blinking. The premotor pathways that regulate and control the state of voluntary activity of the levator palpebrae superioris (LPS) and make it parallel with OO inhibition differ, at least in part, from the pathways of spontaneous and reflex blinking.
View Video | A man with apraxia of lid opening is unable to open his lids at will. Eye movements were full. Attempted eye opening resulted in frontalis muscle contraction, backward thrusting of the head, and pretarsal orbicularis oculi activity. Spontaneous reflex blinking was normal. The lids remained open following manual elevation. |
Once the lids have been opened, however, the patient has no difficulty in keeping them open. LPS tonic activity is normal while the lids are open.
Intermittent involuntary closure of the eyes may occur in some patients, both in the presence and in the absence of spasmodic contractions of the OO in blepharospasm. ILPI not accompanied by blepharospasm may cause the eyelid to drop and to be kept closed as long as inhibition of the LPS activity persists.
Attempted eye opening can result in forceful contraction of the frontalis, backward thrusting of the head, and delay in lid closure.
Different tricks may be used to help open the eyes, such as manually lifting the lids, opening the mouth, lightly touching the temporal region, and massaging the lids. The physiology of these maneuvers is unknown.
Some patients have been reported to have associated supranuclear limitation of eye movements.[15] In general, the coordination of eyelid movement is preserved.
Neuroimaging studies using computed tomography (CT) scanning or magnetic resonance imaging (MRI) may help reveal whether a pathologic condition (eg, atrophy or infarct) is present in the cortex, basal ganglia, or rostral midbrain.
Positron emission tomography (PET) may be used to assess brain function by mapping glucose metabolism in neurons. PET studies of patients with apraxia of lid opening (ALO) have demonstrated glucose hypometabolism in the basal ganglia,[18] the medial frontal lobe (unilaterally or bilaterally),[18, 19] and the primary visual cortex,[19] suggesting abnormal neuronal activity.
Levator palpebrae superioris (LPS) and orbicularis oculi (OO) activity may be assessed by using electromyographic (EMG) recordings from these muscles during lid movements. Neuropsychological testing may reveal the presence or absence of frontal lobe pathology.
Injection of onabotulinumtoxinA (BOTOX; Allergan, Inc, Irvine, CA) into the pretarsal portion of the orbicularis oculi (OO) may be beneficial in individuals with apraxia of lid opening (ALO) associated with blepharospasm. It may also benefit those in whom ALO is due to pretarsal OO motor activity persistence, but not those in whom ALO is due to involuntary levator palpebrae inhibition (ILPI).[41, 42] Patients who benefit from onabotulinumtoxinA injection should be observed every 2-3 months; repeat injections may be required.
Levodopa (benserazide 25 mg plus levodopa 100 mg; carbidopa 50 mg plus levodopa 200 mg) was reported to improve the symptoms of ALO in a patient with progressive supranuclear palsy in whom electromyography (EMG) confirmed that the ALO resulted from involuntary levator palpebrae inhibition (ILPI).[43] Levodopa has also been reported to improve ALO symptoms in patients with Parkinson disease.[44, 25]
In isolated individuals, the symptoms of ALO have been reported to improve with the use of sodium valproate[45] and the anticholinergic agent trihexyphenidyl.[46]
Patients with ALO may benefit from frontalis suspension.[47, 48] In this procedure, the contraction of the frontalis elevates the eyelids. Orbicularis oculi (OO) resection may be carried out in combination with frontalis suspension if essential blepharospasm is present.[47, 49]
Levator palpebrae superioris (LPS) aponeurosis reinsertion may be necessary in some individuals. Disinsertion may result from manual traction on the lids or the repeated OO contraction.
Blepharitis
Drugs used in the management of apraxia of lid opening (ALO) include neuromuscular blocker agents, antiparkinson agents, anticholinergic agents, and anticonvulsants.
Clinical Context: A dose of 1 U of botulinum toxin type A corresponds to the calculated median intraperitoneal lethal dose (LD50) in mice. Each vial contains 100 U of Clostridium botulinum type A neurotoxin complex, 0.5 mg of human albumin, and 0.9 mg of sodium chloride in a sterile, vacuum-dried form without a preservative. It blocks neuromuscular transmission by binding to receptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine.
Clinical Context: Abobotulinumtoxin A is a type A neurotoxin produced by Clostridium botulinum spore, forming anaerobic bacilli. Its activity appears to affect only the presynaptic membrane of the neuromuscular junction in humans. Muscle inactivation persists until new fibrils grow from the nerve and form junction plates on new areas of the muscle cell walls.
Neuromuscular blocker agents help produce symptomatic improvement of orbicularis oculi (OO) spasm and autonomic symptoms.
Clinical Context: Levodopa formulations include benserazide 25 mg plus levodopa 100 mg (not available in the United States) and carbidopa 50 mg plus levodopa 200 mg. Levodopa, the metabolic precursor of dopamine, crosses the blood-brain barrier and presumably is converted to dopamine in the brain to relieve the symptoms of neurologic diseases that are related to depletion of dopamine. Carbidopa inhibits decarboxylation of peripheral levodopa, making more levodopa available for transport to the brain.
Antiparkinson agents reduce the morbidity associated with dopamine deficiency.
Clinical Context: Trihexyphenidyl is a centrally-acting anticholinergic that tends to diminish muscle spasms.
Clinical Context: By blocking striatal cholinergic receptors, benztropine may help balance cholinergic and dopaminergic activity in striatum. This agent can be used as an alternative to trihexyphenidyl.
Anticholinergic agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.
Clinical Context: Delayed-release or extended-release formulations of valproic acid are used for prophylaxis of migraine headaches. Although the mechanism of action is not established, the drug's activity may be related to increased brain levels of gamma-aminobutyric acid (GABA) or to enhanced GABA action.
A man with apraxia of lid opening is unable to open his lids at will. Eye movements were full. Attempted eye opening resulted in frontalis muscle contraction, backward thrusting of the head, and pretarsal orbicularis oculi activity. Spontaneous reflex blinking was normal. The lids remained open following manual elevation.
A man with apraxia of lid opening is unable to open his lids at will. Eye movements were full. Attempted eye opening resulted in frontalis muscle contraction, backward thrusting of the head, and pretarsal orbicularis oculi activity. Spontaneous reflex blinking was normal. The lids remained open following manual elevation.