- Email: [email protected]
Benign Unilateral Apraxia of Eyelid Opening
Benign Unilateral Apraxia of Eyelid Opening Veneetha Cherian, MD, Rod Foroozan, MD Purpose: To report a case series of patients with benign unilateral apraxia of eyelid opening. Design: Retrospective, observational case series. Participants: Five patients with unilateral transient ptosis after sleep from a single neuro-ophthalmology practice. Methods: A list of 208 patients with ptosis seen at a single neuro-ophthalmology practice was drawn through the computer coding system. Transcribed reports of the outpatient visits of these patients were reviewed from this database to identify the final diagnoses. All patients with a diagnosis of ptosis resulting from underlying neurologic, myopathic, or neuromuscular problems were excluded. Five patients with ptosis that occurred on awakening and resolved after mechanical eyelid elevation were included. Main Outcome Measures: The main outcome measure was identifying and defining a group of patients with a benign clinical entity causing ptosis that can cause a clinical dilemma. Results: Three of 5 patients were women. Ages ranged from 49 to 71 years. All patients experienced complete ptosis only on awakening after sleep. The ptosis was unilateral and did not recur after manual elevation of the eyelid. None of the patients had any underlying neurologic problem that could be contributory and were thoroughly investigated with neuroimaging and laboratory testing, including acetylcholine receptor antibodies. Examination revealed no ocular cause for the ptosis in each patient. In all patients, follow-up telephone reports noted no subsequent condition that could be responsible for ptosis. Conclusions: The identification and diagnosis of this form of isolated ptosis, which herein is termed benign unilateral apraxia of eyelid opening, is of importance in that extensive evaluation is not warranted unless there are other neurologic or ocular findings. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010;117:1265–1268 © 2010 by the American Academy of Ophthalmology.
Apraxia of eyelid opening is a nonparalytic motor abnormality characterized by difficulty initiating the act of eyelid elevation.1 This deficit in eyelid elevation is considered to be an apraxia because it is an intermittent loss of volitional ability to open the eyes with preservation of the ability to open the eyelids and keep them open at other times.2 Apraxia of eyelid opening is likely caused by an alteration of the supranuclear control of voluntary eyelid elevation.3 Initiation of eyelid elevation requires activation of the levator palpebrae superioris (LPS) and the concurrent inhibition of orbicularis oculi activity. Apraxia of eyelid opening is thought to occur with prolonged inhibition of the LPS with or without concurrent clinical or subclinical contraction of the pretarsal portion of the orbicularis oculi, which is detectable with electromyography. Hence, the apraxia also has been included in the dystonic spectrum of eyelid disorders.4,5 Apraxia of eyelid opening, which has been described as a bilateral phenomenon, has been noted in degenerative, vascular, and drug-induced conditions. There are rare reports of this phenomenon occurring in an idiopathic form, without underlying neurologic disease.6,7 To the authors’ knowledge, unilateral apraxia of eyelid opening, where there is selective inability of one eye opening related to arousal after sleep and that resolves after mechanical maneuvers to open the eyelid, has not been described previously. This article presents a case © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
series of unilateral eyelid apraxia that occurred transiently after sleep and that resolved after mechanical elevation of the eyelid. This type of apraxia, which occurs in the absence of known neurologic precipitants, is defined as benign unilateral apraxia of eyelid opening (BUAEO).
Patients and Methods Institutional review board approval was obtained to review all patients with a diagnosis of ptosis seen in a single neuro-ophthalmology practice. All patients with ptosis from November 2002 to July 2008 were screened using the International Statistical Classification of Diseases and Related Health Problems Ninth Edition codes to generate a list of 208 patients. The records of these patient visits were reviewed from the database to identify the final diagnoses in each patient. Patients with known causes of ptosis, such as IIIrd cranial nerve palsy, Horner’s syndrome, myasthenia gravis, and chronic progressive external ophthalmoplegia, were excluded. Five patients who had ptosis that occurred only on awakening and resolved after mechanical eyelid elevation were included in this case series.
Patient 1 A 71-year-old otherwise healthy woman noted a 1-month history of transient episodes of complete right upper eyelid ptosis on awakening in the morning (Fig 1). She stated that she had to lift the ISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.10.032
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Figure 1. External photograph taken by a family member of patient 1 on awakening, with complete ptosis on the right. There is slight ptosis on the left with elevation of both eyebrows, suggestive of compensatory frontalis overaction.
eyelid mechanically and that, after it opened, it remained open throughout the day. Past ocular history included dry eyes, for which she was using artificial tears bilaterally. She had no diplopia, visual loss, or any other symptoms suggestive of myasthenia gravis or giant cell arteritis. Visual acuities were 20/15 in each eye with normal color vision, full confrontation visual fields, and normal exophthalmometry readings. There was no ocular misalignment with alternate cover testing. Pupils were normal and there was no ptosis or eyelid synkinesis with extraocular movement. Slit-lamp examination revealed nuclear sclerosis bilaterally, and funduscopic examination showed a choroidal nevus on the left. She was seen again 2 years later and noted an improvement in the frequency of ptosis, which now occurred once every 2 to 3 months. She maintained good general health with no other neurologic signs or symptoms.
Patient 2 A 49-year-old woman with a history of systemic lupus erythematosus noted ptosis of the left upper eyelid for the previous year, present only on awakening and after a nap. The ptosis was complete and resolved with manual opening of the left upper eyelid. Past medical history included colitis, migraine, arthritis, and mitral valve prolapse. Past ocular history included an unspecified ocular injury at age 22 years. She was taking prednisone, Rituximab, oxycodone, propanolol, mesalamine, S-omeprazole, hydrochlorothiazide, trazodone, and was receiving corticosteroid injections every 6 to 8 weeks. There was no history suggestive of diurnal variation of the ptosis, diplopia, or any other symptom suggestive of myasthenia gravis. Visual acuity was 20/25 on each side with normal color vision, pupils, full visual fields to confrontation, and normal funduscopy results. Ocular motility was normal, and she was orthotropic in all positions of gaze with alternate cover testing. She had 1 mm of left upper lid ptosis with no fatigability or lid twitch and normal position of the lower lids. Magnetic resonance imaging of the brain demonstrated normal results and acetylcholine receptor antibodies were negative. Erythrocyte sedimentation rate was normal. Follow-up telephone contact 4 years after the onset of ptosis revealed that she continued to have recurrent daily episodes on arousal from sleep. The episodes lasted for approximately 60 seconds and involved only the left upper eyelid. She also noted that the episodes would not occur if her duration of sleep was less than 3 to 4 hours. Her general health remained unchanged with no new neurologic problems.
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Patient 3 A 52-year-old woman with history of iron deficiency anemia, transient ischemic attacks, and chronic headache noted transient episodes of complete left upper eyelid ptosis over an 8-month period. The ptosis occurred only on attempting to open the eyes in the morning. She stated that she had to lift the eyelid mechanically, and after being open, the ptosis did not recur for the remainder of the day. She did not have any symptoms suggestive of myasthenia gravis or giant cell arteritis. Her medications included clopidogrel, folic acid, calcium, and ibuprofen. Visual acuities were 20/20 in the right eye and 20/15 on the left, with normal color vision, full confrontation visual fields, and normal exophthalmometry. Pupils were normal and there was no ptosis or eyelid synkinesis with extraocular movement. She was orthotropic in all positions of gaze with alternate cover testing. Slit-lamp examination showed nuclear sclerosis bilaterally, and funduscopy results were normal. Magnetic resonance imaging results of the brain were normal. She was contacted by telephone more than 3.5 years after the onset of symptoms. Her episodes lasted almost 1 year in total and had resolved completely. Her general health remained unchanged.
Patient 4 A 60-year-old man with history of hypertension, diabetes mellitus, and transient ischemic attack noted episodes of complete right upper eyelid ptosis occurring on awakening. He was able to open his eyelids after mechanically elevating the eyelid. He had 2 other episodes that lasted for 30 minutes, during which both eyelids were ptotic and he had to lift the eyelids mechanically. There was no evidence of any other systemic illness such as giant cell arteritis or myasthenia gravis. Visual acuities were 20/50 in the right eye and 20/25 in the left eye, with normal color vision, pupils, ocular motility, and alignment with minimal brow ptosis on each side. Slit-lamp examination showed a right corneal scar with pseudophakia and some old keratic precipitates. Magnetic resonance imaging and magnetic resonance angiography results of the brain were normal. On follow-up after 4 months, the episodes of unilateral complete ptosis had decreased to twice over 6 months. On telephone follow-up 4.5 years after the onset of symptoms, he reported that the ptosis lasted only 6 months in total. He had no other neurologic problems.
Cherian and Foroozan 䡠 Benign Unilateral Apraxia of Eyelid Opening Patient 5 A 63-year-old man with a history of hypertension, coronary artery disease, headaches, arthritis, renal calculi, transient ischemic attacks with transient visual loss, and short-term memory loss noted episodic complete ptosis of the left upper eyelid occurring on awakening. There was no associated diplopia or any symptoms suggestive of myasthenia gravis. His visual acuities were 20/25 in both eyes with normal pupils and normal color vision. He had minimal dermatochalasis and brow ptosis with no fatigability or lid twitch. He was orthotropic with full extraocular movements. He had normal optic discs with bilateral posterior vitreous detachments. Magnetic resonance imaging results of the brain were normal and acetylcholine receptor antibodies were negative. Follow-up telephone contact with the patient 4.5 years after the initial visit revealed that his symptoms had resolved 1 year after their onset. Magnetic resonance imaging results of the brain carried out 3.5 years after the onset of symptoms remained unchanged.
Results Three of 5 patients were women and ages varied from 49 to 71 years. All patients experienced ptosis on awakening and only after sleeping. Four patients had unilateral involvement, and in the fifth patient (patient 4), there were 2 episodes involving both upper eyelids and all of the other episodes were unilateral. The ptosis was complete in each case, was overcome by manually opening the eyelids, and was never associated with diplopia or findings suggestive of an ocular misalignment. None of the patients had any underlying neurologic problems that were associated with ptosis, and all were thoroughly investigated, including with magnetic resonance imaging scans of the brain and other laboratory testing, such as acetylcholine receptor antibody screening. Ophthalmic examination revealed no ocular cause for ptosis, including no evidence of retained foreign body after upper eyelid eversion. In all 5 patients, follow-up telephone reports from 2 to 6 years after the onset of symptoms noted no subsequent neurologic disease that would be associated with ptosis. In 4 of 5 patients, symptoms had resolved in 6 months to 1 year. In the fifth patient, a follow-up telephone report at 3 years after the onset of symptoms indicated the episodes continued to occur with no other neurologic symptoms. In the review of the records, no patients with bilateral ptosis related to apraxia of eyelid opening from known neurologic precipitants were found.
Discussion Eyelid apraxia has been associated with degenerative and vascular neurologic disorders.8 It has been described variously as either an inability to close the eyes on command (apraxia of eyelid closing) or inability to open the eyes volitionally (apraxia of eyelid opening). Apraxia also has been correlated with blepharospasm and has been included within the spectrum of eyelid dystonia.9 These 5 patients are unique in that they had isolated, complete ptosis that was unilateral and developed only after a period of sleep. Apraxia of eyelid opening resulting from stroke and neurodegenerative disorders localizes to the left inferior parietal lobe, frontal lobes, or corpus callosum. Eyelid apraxia from disorders of the basal ganglia, including neurologic problems like Parkinsonism, progressive supranu-
clear palsy, and Shy-Drager syndrome, typically is thought to occur from involvement of the rostral midbrain, which is believed to be involved in the supranuclear control of the levator palpebrae nuclear complex.3 In other patients, the cause of apraxia of eyelid opening is not clear.6,7 In one report of 10 patients of “so called apraxia of eyelid opening,” the ptosis was transient and isolated and occurred in the absence of predisposing neurologic disorders.7 However, all of these patients had ptosis that was bilateral and was not confined to the period after sleep. The authors found an abstract of 1 case report of a 35-year-old patient in whom apraxia of eyelid opening developed that occurred only after sleep (Sleep Research 1996;25:42). However in this patient, the ptosis was always bilateral and even manual opening of the eyelids did not alleviate the ptosis until the episodes resolved spontaneously. These reports are in contradistinction to the current patients who had isolated, complete ptosis that was unilateral and developed only after a period of sleep. The cause of BUAEO limited to awakening is difficult to explain. Sleep is thought to be a passive state of withdrawal from sensory awareness initiated by activity of the ventrolateral preoptic nucleus of the anterior hypothalamus, acting as a switch through release of inhibitory neurotransmitters like ␥ amino butyric acid and galanin that inhibit the wakepromoting regions of the brain.10 The switch is stabilized further by hypocretin (orexin) neurons in the lateral hypothalamus.11,12 The tuberoinfundibular tract that connects the brainstem to the rostral thalamus and the cortex inhibits the ascending cholinergic tracts, resulting in disconnection between higher centers and the brainstem. On awakening, there is reversal of this inhibition through a spreading electrical impulse mediated through an electrical coupling mechanism.13 The cells of the pedunculopontine nucleus and neurons of the subcaeruleus nucleus are thought to fire together, generating a rhythm that is transmitted to other parts of the brain to induce the awake state.13 Eyelid opening is an integral part of the physiology of awakening with activation of the levator muscles. The motor neurons for the levator muscles are located in an unpaired central caudal nuclear complex of the IIIrd cranial nerve with higher centers of control from the cortex, extrapyramidal motor systems, and rostral brainstem structures. Although the central caudal nuclear complex is unpaired, the premotor control of the levator palpebrae is at least partially lateralized. The phylogenetically old consideration of the LPS being innervated by contralateral neurons is thought to be retained partially at the premotor level.14 The central caudal nuclear complex has inputs from ventral periaqueductal grey matter, the nucleus of the posterior commissure, and the caudal supraoculomotor area.14 The ventral periaqueductal grey area (PAG) receives afferents from the limbic system and reticular formation. The PAG is thought to be involved in functions intimately related to the level of arousal and also in generating tonic levator palpebrae neuronal activity. Electrical stimulation of the PAG causes unilateral eyelid retraction, and lesions in this area can cause asymmetric ptosis. A patient with a spreading astrocytoma infiltrating the PAG has been reported with markedly asymmetric ptosis.15 The region of the nucleus of
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the posterior commissure is involved in lid– eye coordination and provides inhibitory modulation of the levator palpebrae nuclear complex. Lesions of this region can cause bilateral eyelid retraction.14 The caudal supraoculomotor area mediates converging inhibitory responses onto levator palpebrae motor neurons. In the eyelid apraxia described in the present patients, BUAEO, it is possible that activation on awakening by the spreading electrical impulse of premotor control pathways of the IIIrd cranial nerve nucleus is delayed temporarily. This results in continued inhibition of the levator palpebrae superioris on one side more than the other. The PAG is thought to generate tonic LP motor neuron activity, whereas the nucleus of the posterior commissure mainly provides inhibitory modulation of levator palpebrae motor neuronal activity with lid– eye coordination. In BUAEO, there may be continued inhibition and delay in reversal of one or more of these pathways, resulting in the patient unable to elevate the eyelid. The unilaterality may be explained by a possible delay in activation of the ventral PAG area, the lateralized region of premotor control.14 The reported resolution of ptosis with the mechanical elevation of the eyelid seen in the current patients may indicate a geste antagoniste as seen in blepharospasm and hemifacial spasm. In the second patient, when the period of sleep was limited to less than 3 to 4 hours, the apraxia did not develop. This suggests that there may be a critical duration of sleep that results in the inhibition of LPS activity. It may be that the current patients, as has been suggested by others (Sleep Research 25:42, 1996), have a previously unrecognized movement disorder of sleep characterized by unilateral ptosis. One of the shortcomings of this retrospective study is that each patient was not evaluated with ancillary studies in a systematic way. Nor was it possible to examine these patients during the symptomatic episodes. Only one patient brought a photograph (Fig 1) taken by a family member to document the ptosis. Furthermore, disorders like myasthenia gravis cannot be excluded completely with clinical evaluation and antibody testing, although this disorder of neuromuscular transmission is highly unlikely, given the stereotypic onset of symptoms occurring only after sleep, a period when symptoms from myasthenia gravis generally are at a minimum. Other causes that were considered included atypical hemifacial spasm or asymmetrical blepharospasm. Exaggerated subclinical myogenic spasm of the orbicularis oculi could be contributory in the current patients. However, these conditions would be expected to declare themselves in the wakeful, active period and not only after sleep. The name apraxia may be controversial because the absence of motor deficits may not be a valid assumption in
the circumstance of arousal from sleep. However, the term apraxia was chosen because in the present cohort, no reproducible motor deficits could be identified. In a patient with complete unilateral ptosis occurring only on awakening and resolving with mechanical eyelid opening, and in the absence of pupillary or ocular motor abnormalities, BUAEO should be considered. The patient can be reassured and followed up without the need for additional ancillary testing. The identification and diagnosis of this benign condition is of importance in that extensive evaluation may not be warranted unless there is development of other unexplained neurologic findings.
References 1. Goldstein JE, Cogan DG. Apraxia of lid opening. Arch Ophthalmol 1965;73:155–9. 2. Boghen D. Apraxia of lid opening: a review. Neurology 1997; 48:1491– 4. 3. Lepore FE, Duvoisin RC. “Apraxia” of eyelid opening: an involuntary levator inhibition. Neurology 1985;35:423–7. 4. Jordan DR, Anderson RL, Digre KB. Apraxia of lid opening in blepharospasm. Ophthalmic Surg 1990;21:331– 4. 5. Krack P, Marion MH. “Apraxia of lid opening,” a focal eyelid dystonia: clinical study of 32 patients. Mov Disord 1994;9: 610 –5. 6. Jebasingh YK, Menon KB, Jawahar M, et al. Apraxia of lid opening. Ann Indian Acad Neurol 2006;9:163–5. 7. Defazio G, Livrea P, Lamberti P, et al. Isolated so-called apraxia of eyelid opening: report of 10 cases and a review of the literature. Eur Neurol 1998;39:204 –10. 8. Abe K, Fujimura H, Tatsumi C, et al. Eyelid “apraxia” in patients with motor neuron disease. J Neurol Neurosurg Psychiatry 1995;59:629 –32. 9. Aramideh M, Ongerboer de Visser BW, Speelman JD. Motor persistence of orbicularis oculi muscle in eyelid-opening disorders. Neurology 1995;45:897–902. 10. Siegel JM. Clues to the functions of mammalian sleep. Nature 2005;437:1264 –71. 11. Siegel JM, Moore R, Thannickal T, Niehuis R. A brief history of hypocretin/orexin and narcolepsy. Neuropsychopharmacology 2001;25(suppl):S14 –S20. 12. Espana RA, Scammell TE. Sleep neurobiology for the clinician. Sleep 2004;27:811–20. 13. Garcia-Rill E, Heister DS, Ye M, et al. Electrical coupling: novel mechanism for sleep-wake control. Sleep 2007;30: 1405–14. 14. Schmidtke K, Buttner-Ennever JA. Nervous control of eyelid function: a review of clinical, experimental and pathological data. Brain 1992;115:227– 47. 15. Buttner-Ennever JA, Acheson JF, Buttner U, et al. Ptosis and supranuclear downgaze paralysis. Neurology 1989;39:385–9.
Footnotes and Financial Disclosures Originally received: August 4, 2009. Final revision: September 20, 2009. Accepted: October 14, 2009. Available online: February 16, 2010.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2009-1054.
Neuro-ophthalmology Service, Alkek Eye Center, Baylor College of Medicine, Houston, Texas.
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Correspondence: Rod Foroozan, MD, Neuro-ophthalmology Service, Alkek Eye Center, Baylor College of Medicine, 7200B Cambridge, Houston, TX 77030. E-mail: [email protected].
Apraxia of eyelid opening is a nonparalytic motor abnormality characterized by difficulty initiating the act of eyelid elevation.1 This deficit in eyelid elevation is considered to be an apraxia because it is an intermittent loss of volitional ability to open the eyes with preservation of the ability to open the eyelids and keep them open at other times.2 Apraxia of eyelid opening is likely caused by an alteration of the supranuclear control of voluntary eyelid elevation.3 Initiation of eyelid elevation requires activation of the levator palpebrae superioris (LPS) and the concurrent inhibition of orbicularis oculi activity. Apraxia of eyelid opening is thought to occur with prolonged inhibition of the LPS with or without concurrent clinical or subclinical contraction of the pretarsal portion of the orbicularis oculi, which is detectable with electromyography. Hence, the apraxia also has been included in the dystonic spectrum of eyelid disorders.4,5 Apraxia of eyelid opening, which has been described as a bilateral phenomenon, has been noted in degenerative, vascular, and drug-induced conditions. There are rare reports of this phenomenon occurring in an idiopathic form, without underlying neurologic disease.6,7 To the authors’ knowledge, unilateral apraxia of eyelid opening, where there is selective inability of one eye opening related to arousal after sleep and that resolves after mechanical maneuvers to open the eyelid, has not been described previously. This article presents a case © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
series of unilateral eyelid apraxia that occurred transiently after sleep and that resolved after mechanical elevation of the eyelid. This type of apraxia, which occurs in the absence of known neurologic precipitants, is defined as benign unilateral apraxia of eyelid opening (BUAEO).
Patients and Methods Institutional review board approval was obtained to review all patients with a diagnosis of ptosis seen in a single neuro-ophthalmology practice. All patients with ptosis from November 2002 to July 2008 were screened using the International Statistical Classification of Diseases and Related Health Problems Ninth Edition codes to generate a list of 208 patients. The records of these patient visits were reviewed from the database to identify the final diagnoses in each patient. Patients with known causes of ptosis, such as IIIrd cranial nerve palsy, Horner’s syndrome, myasthenia gravis, and chronic progressive external ophthalmoplegia, were excluded. Five patients who had ptosis that occurred only on awakening and resolved after mechanical eyelid elevation were included in this case series.
Patient 1 A 71-year-old otherwise healthy woman noted a 1-month history of transient episodes of complete right upper eyelid ptosis on awakening in the morning (Fig 1). She stated that she had to lift the ISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.10.032
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Figure 1. External photograph taken by a family member of patient 1 on awakening, with complete ptosis on the right. There is slight ptosis on the left with elevation of both eyebrows, suggestive of compensatory frontalis overaction.
eyelid mechanically and that, after it opened, it remained open throughout the day. Past ocular history included dry eyes, for which she was using artificial tears bilaterally. She had no diplopia, visual loss, or any other symptoms suggestive of myasthenia gravis or giant cell arteritis. Visual acuities were 20/15 in each eye with normal color vision, full confrontation visual fields, and normal exophthalmometry readings. There was no ocular misalignment with alternate cover testing. Pupils were normal and there was no ptosis or eyelid synkinesis with extraocular movement. Slit-lamp examination revealed nuclear sclerosis bilaterally, and funduscopic examination showed a choroidal nevus on the left. She was seen again 2 years later and noted an improvement in the frequency of ptosis, which now occurred once every 2 to 3 months. She maintained good general health with no other neurologic signs or symptoms.
Patient 2 A 49-year-old woman with a history of systemic lupus erythematosus noted ptosis of the left upper eyelid for the previous year, present only on awakening and after a nap. The ptosis was complete and resolved with manual opening of the left upper eyelid. Past medical history included colitis, migraine, arthritis, and mitral valve prolapse. Past ocular history included an unspecified ocular injury at age 22 years. She was taking prednisone, Rituximab, oxycodone, propanolol, mesalamine, S-omeprazole, hydrochlorothiazide, trazodone, and was receiving corticosteroid injections every 6 to 8 weeks. There was no history suggestive of diurnal variation of the ptosis, diplopia, or any other symptom suggestive of myasthenia gravis. Visual acuity was 20/25 on each side with normal color vision, pupils, full visual fields to confrontation, and normal funduscopy results. Ocular motility was normal, and she was orthotropic in all positions of gaze with alternate cover testing. She had 1 mm of left upper lid ptosis with no fatigability or lid twitch and normal position of the lower lids. Magnetic resonance imaging of the brain demonstrated normal results and acetylcholine receptor antibodies were negative. Erythrocyte sedimentation rate was normal. Follow-up telephone contact 4 years after the onset of ptosis revealed that she continued to have recurrent daily episodes on arousal from sleep. The episodes lasted for approximately 60 seconds and involved only the left upper eyelid. She also noted that the episodes would not occur if her duration of sleep was less than 3 to 4 hours. Her general health remained unchanged with no new neurologic problems.
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Patient 3 A 52-year-old woman with history of iron deficiency anemia, transient ischemic attacks, and chronic headache noted transient episodes of complete left upper eyelid ptosis over an 8-month period. The ptosis occurred only on attempting to open the eyes in the morning. She stated that she had to lift the eyelid mechanically, and after being open, the ptosis did not recur for the remainder of the day. She did not have any symptoms suggestive of myasthenia gravis or giant cell arteritis. Her medications included clopidogrel, folic acid, calcium, and ibuprofen. Visual acuities were 20/20 in the right eye and 20/15 on the left, with normal color vision, full confrontation visual fields, and normal exophthalmometry. Pupils were normal and there was no ptosis or eyelid synkinesis with extraocular movement. She was orthotropic in all positions of gaze with alternate cover testing. Slit-lamp examination showed nuclear sclerosis bilaterally, and funduscopy results were normal. Magnetic resonance imaging results of the brain were normal. She was contacted by telephone more than 3.5 years after the onset of symptoms. Her episodes lasted almost 1 year in total and had resolved completely. Her general health remained unchanged.
Patient 4 A 60-year-old man with history of hypertension, diabetes mellitus, and transient ischemic attack noted episodes of complete right upper eyelid ptosis occurring on awakening. He was able to open his eyelids after mechanically elevating the eyelid. He had 2 other episodes that lasted for 30 minutes, during which both eyelids were ptotic and he had to lift the eyelids mechanically. There was no evidence of any other systemic illness such as giant cell arteritis or myasthenia gravis. Visual acuities were 20/50 in the right eye and 20/25 in the left eye, with normal color vision, pupils, ocular motility, and alignment with minimal brow ptosis on each side. Slit-lamp examination showed a right corneal scar with pseudophakia and some old keratic precipitates. Magnetic resonance imaging and magnetic resonance angiography results of the brain were normal. On follow-up after 4 months, the episodes of unilateral complete ptosis had decreased to twice over 6 months. On telephone follow-up 4.5 years after the onset of symptoms, he reported that the ptosis lasted only 6 months in total. He had no other neurologic problems.
Cherian and Foroozan 䡠 Benign Unilateral Apraxia of Eyelid Opening Patient 5 A 63-year-old man with a history of hypertension, coronary artery disease, headaches, arthritis, renal calculi, transient ischemic attacks with transient visual loss, and short-term memory loss noted episodic complete ptosis of the left upper eyelid occurring on awakening. There was no associated diplopia or any symptoms suggestive of myasthenia gravis. His visual acuities were 20/25 in both eyes with normal pupils and normal color vision. He had minimal dermatochalasis and brow ptosis with no fatigability or lid twitch. He was orthotropic with full extraocular movements. He had normal optic discs with bilateral posterior vitreous detachments. Magnetic resonance imaging results of the brain were normal and acetylcholine receptor antibodies were negative. Follow-up telephone contact with the patient 4.5 years after the initial visit revealed that his symptoms had resolved 1 year after their onset. Magnetic resonance imaging results of the brain carried out 3.5 years after the onset of symptoms remained unchanged.
Results Three of 5 patients were women and ages varied from 49 to 71 years. All patients experienced ptosis on awakening and only after sleeping. Four patients had unilateral involvement, and in the fifth patient (patient 4), there were 2 episodes involving both upper eyelids and all of the other episodes were unilateral. The ptosis was complete in each case, was overcome by manually opening the eyelids, and was never associated with diplopia or findings suggestive of an ocular misalignment. None of the patients had any underlying neurologic problems that were associated with ptosis, and all were thoroughly investigated, including with magnetic resonance imaging scans of the brain and other laboratory testing, such as acetylcholine receptor antibody screening. Ophthalmic examination revealed no ocular cause for ptosis, including no evidence of retained foreign body after upper eyelid eversion. In all 5 patients, follow-up telephone reports from 2 to 6 years after the onset of symptoms noted no subsequent neurologic disease that would be associated with ptosis. In 4 of 5 patients, symptoms had resolved in 6 months to 1 year. In the fifth patient, a follow-up telephone report at 3 years after the onset of symptoms indicated the episodes continued to occur with no other neurologic symptoms. In the review of the records, no patients with bilateral ptosis related to apraxia of eyelid opening from known neurologic precipitants were found.
Discussion Eyelid apraxia has been associated with degenerative and vascular neurologic disorders.8 It has been described variously as either an inability to close the eyes on command (apraxia of eyelid closing) or inability to open the eyes volitionally (apraxia of eyelid opening). Apraxia also has been correlated with blepharospasm and has been included within the spectrum of eyelid dystonia.9 These 5 patients are unique in that they had isolated, complete ptosis that was unilateral and developed only after a period of sleep. Apraxia of eyelid opening resulting from stroke and neurodegenerative disorders localizes to the left inferior parietal lobe, frontal lobes, or corpus callosum. Eyelid apraxia from disorders of the basal ganglia, including neurologic problems like Parkinsonism, progressive supranu-
clear palsy, and Shy-Drager syndrome, typically is thought to occur from involvement of the rostral midbrain, which is believed to be involved in the supranuclear control of the levator palpebrae nuclear complex.3 In other patients, the cause of apraxia of eyelid opening is not clear.6,7 In one report of 10 patients of “so called apraxia of eyelid opening,” the ptosis was transient and isolated and occurred in the absence of predisposing neurologic disorders.7 However, all of these patients had ptosis that was bilateral and was not confined to the period after sleep. The authors found an abstract of 1 case report of a 35-year-old patient in whom apraxia of eyelid opening developed that occurred only after sleep (Sleep Research 1996;25:42). However in this patient, the ptosis was always bilateral and even manual opening of the eyelids did not alleviate the ptosis until the episodes resolved spontaneously. These reports are in contradistinction to the current patients who had isolated, complete ptosis that was unilateral and developed only after a period of sleep. The cause of BUAEO limited to awakening is difficult to explain. Sleep is thought to be a passive state of withdrawal from sensory awareness initiated by activity of the ventrolateral preoptic nucleus of the anterior hypothalamus, acting as a switch through release of inhibitory neurotransmitters like ␥ amino butyric acid and galanin that inhibit the wakepromoting regions of the brain.10 The switch is stabilized further by hypocretin (orexin) neurons in the lateral hypothalamus.11,12 The tuberoinfundibular tract that connects the brainstem to the rostral thalamus and the cortex inhibits the ascending cholinergic tracts, resulting in disconnection between higher centers and the brainstem. On awakening, there is reversal of this inhibition through a spreading electrical impulse mediated through an electrical coupling mechanism.13 The cells of the pedunculopontine nucleus and neurons of the subcaeruleus nucleus are thought to fire together, generating a rhythm that is transmitted to other parts of the brain to induce the awake state.13 Eyelid opening is an integral part of the physiology of awakening with activation of the levator muscles. The motor neurons for the levator muscles are located in an unpaired central caudal nuclear complex of the IIIrd cranial nerve with higher centers of control from the cortex, extrapyramidal motor systems, and rostral brainstem structures. Although the central caudal nuclear complex is unpaired, the premotor control of the levator palpebrae is at least partially lateralized. The phylogenetically old consideration of the LPS being innervated by contralateral neurons is thought to be retained partially at the premotor level.14 The central caudal nuclear complex has inputs from ventral periaqueductal grey matter, the nucleus of the posterior commissure, and the caudal supraoculomotor area.14 The ventral periaqueductal grey area (PAG) receives afferents from the limbic system and reticular formation. The PAG is thought to be involved in functions intimately related to the level of arousal and also in generating tonic levator palpebrae neuronal activity. Electrical stimulation of the PAG causes unilateral eyelid retraction, and lesions in this area can cause asymmetric ptosis. A patient with a spreading astrocytoma infiltrating the PAG has been reported with markedly asymmetric ptosis.15 The region of the nucleus of
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the posterior commissure is involved in lid– eye coordination and provides inhibitory modulation of the levator palpebrae nuclear complex. Lesions of this region can cause bilateral eyelid retraction.14 The caudal supraoculomotor area mediates converging inhibitory responses onto levator palpebrae motor neurons. In the eyelid apraxia described in the present patients, BUAEO, it is possible that activation on awakening by the spreading electrical impulse of premotor control pathways of the IIIrd cranial nerve nucleus is delayed temporarily. This results in continued inhibition of the levator palpebrae superioris on one side more than the other. The PAG is thought to generate tonic LP motor neuron activity, whereas the nucleus of the posterior commissure mainly provides inhibitory modulation of levator palpebrae motor neuronal activity with lid– eye coordination. In BUAEO, there may be continued inhibition and delay in reversal of one or more of these pathways, resulting in the patient unable to elevate the eyelid. The unilaterality may be explained by a possible delay in activation of the ventral PAG area, the lateralized region of premotor control.14 The reported resolution of ptosis with the mechanical elevation of the eyelid seen in the current patients may indicate a geste antagoniste as seen in blepharospasm and hemifacial spasm. In the second patient, when the period of sleep was limited to less than 3 to 4 hours, the apraxia did not develop. This suggests that there may be a critical duration of sleep that results in the inhibition of LPS activity. It may be that the current patients, as has been suggested by others (Sleep Research 25:42, 1996), have a previously unrecognized movement disorder of sleep characterized by unilateral ptosis. One of the shortcomings of this retrospective study is that each patient was not evaluated with ancillary studies in a systematic way. Nor was it possible to examine these patients during the symptomatic episodes. Only one patient brought a photograph (Fig 1) taken by a family member to document the ptosis. Furthermore, disorders like myasthenia gravis cannot be excluded completely with clinical evaluation and antibody testing, although this disorder of neuromuscular transmission is highly unlikely, given the stereotypic onset of symptoms occurring only after sleep, a period when symptoms from myasthenia gravis generally are at a minimum. Other causes that were considered included atypical hemifacial spasm or asymmetrical blepharospasm. Exaggerated subclinical myogenic spasm of the orbicularis oculi could be contributory in the current patients. However, these conditions would be expected to declare themselves in the wakeful, active period and not only after sleep. The name apraxia may be controversial because the absence of motor deficits may not be a valid assumption in
the circumstance of arousal from sleep. However, the term apraxia was chosen because in the present cohort, no reproducible motor deficits could be identified. In a patient with complete unilateral ptosis occurring only on awakening and resolving with mechanical eyelid opening, and in the absence of pupillary or ocular motor abnormalities, BUAEO should be considered. The patient can be reassured and followed up without the need for additional ancillary testing. The identification and diagnosis of this benign condition is of importance in that extensive evaluation may not be warranted unless there is development of other unexplained neurologic findings.
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Footnotes and Financial Disclosures Originally received: August 4, 2009. Final revision: September 20, 2009. Accepted: October 14, 2009. Available online: February 16, 2010.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Manuscript no. 2009-1054.
Neuro-ophthalmology Service, Alkek Eye Center, Baylor College of Medicine, Houston, Texas.
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Correspondence: Rod Foroozan, MD, Neuro-ophthalmology Service, Alkek Eye Center, Baylor College of Medicine, 7200B Cambridge, Houston, TX 77030. E-mail: [email protected].