Continuing Education Activity

Apraxia of lid opening (ALO) is a relatively rare, nonmotor disorder characterized by a patient's difficulty in initiating the act of lifting the upper eyelid despite normal oculomotor function. There is an inability of voluntary eye reopening without an orbicularis oculi spasm despite sustained frontalis contraction. This condition is not due to weakness, fatigue, or structural abnormalities of the eyelid or its associated muscles. Rather, it is thought to arise from a disruption in the neural networks that coordinate voluntary eyelid movement. This condition poses significant challenges for affected individuals, as it can interfere with daily activities such as reading, driving, and even basic facial expressions. It is most commonly associated with neurodegenerative diseases, particularly Parkinson disease, but can also occur with other basal ganglia disorders and specific frontal lobe lesions.

This educational activity will provide a comprehensive understanding of ALO by exploring the underlying neurological mechanisms involved. Clinical manifestations and diagnostic criteria for ALO will be thoroughly discussed, including differential diagnoses to consider. Management approaches, both pharmacological and nonpharmacological, will be explored, with an emphasis on evidence-based practices and emerging treatments. Collaborative decision-making and interprofessional teamwork will be emphasized, reflecting the reality of clinical practice and optimizing patient outcomes.

Objectives:

• Apply knowledge of the pathophysiology to provide optimal care for patients affected with apraxia of lid opening.

• Implement the methods or techniques used to accurately evaluate and diagnose patients with apraxia of lid opening.

• Assess the evidenced-based management options available for treating apraxia of lid opening.

• Collaborate with an interprofessional team to advance the care, outcomes, and quality of life for patients affected by apraxia of lid opening.

Introduction

Apraxia of lid opening (ALO), synonymous with apraxia of eyelid opening, is a nonmotor abnormality characterized by the patient's difficulty in eyelid elevation bilaterally. There is an inability of voluntary eye reopening without an orbicularis oculi spasm despite sustained frontalis contraction. In other words, ALO is a disorder characterized by a patient's difficulty in voluntarily opening their eyes despite an ability to do so and the absence of any ocular motor or muscular abnormalities. The definition is a misnomer, given that it rarely represents pure and true apraxia.[1] On rare occasions, it can occur as an isolated idiopathic phenomenon.

Max Heinrich Lewandowsky, a renowned German physician and academician, first described ALO in his 1907 essay "Über apraxie des Lidschlusses." Later, Schilder, in 1927, reported 2 patients (1 with Huntington chorea), and Riese, in 1930, 1 patient with frontotemporal injury from a bullet. No other reports were found in the literature until 1965, when Goldstein and Cogan reported 4 patients (Huntington disease, parkinsonism, parkinsonian syndrome after cyanide attempted suicide, and cerebral diplegia).[2]

ALO is often misdiagnosed due to its clinical subtlety and the lack of overt pathognomonic signs. ALO is distinct from blepharospasm, where involuntary muscle contraction forces the eyelids closed, and from ptosis, where a droop in the eyelid occurs due to muscle weakness or mechanical issues.[3]

The eyelid opening mechanism involves a complex interaction of muscles and nerves. The levator palpebrae superioris muscle is primarily responsible for lifting the upper eyelid, and it is innervated by the superior division of the oculomotor nerve (cranial nerve III). The Müller's muscle, innervated by the sympathetic nervous system, also assists in eyelid elevation. Voluntary eyelid control is modulated by neural pathways that connect the basal ganglia, frontal lobes, and supplementary motor area, which are areas involved in initiating and planning voluntary movements. In ALO, the dysfunction appears to lie within these neural pathways rather than in the muscles themselves. The disorder is believed to originate from a disruption in the communication between the brain's intention to open the eyelid and the execution of that action. While the exact pathophysiological mechanism is not fully understood, it is associated with neurodegenerative conditions such as Parkinson disease, progressive supranuclear palsy, and other diseases that affect the basal ganglia.[4]

Patients with ALO typically demonstrate effortful attempts to open their eyelids, often engaging in compensatory maneuvers such as manually lifting the eyelids or using exaggerated facial expressions. These actions suggest a disconnect between the intention to open the eyelids and the actual movement, a hallmark of apraxia. The condition can fluctuate throughout the day and may be influenced by factors such as fatigue, stress, or concentration. While ALO can be an isolated phenomenon, it is often seen as part of a broader neurological syndrome. It may initially present in conjunction with other Parkinsonian features before spreading to involve more extensive areas of motor control. In Parkinson disease, ALO is thought to be a manifestation of the widespread motor planning disruptions that characterize the disease.[5]

The diagnosis of ALO is clinical, relying on the recognition of its characteristic features during examination. There are no specific tests to confirm ALO, and its diagnosis is one of exclusion. It is vital to distinguish ALO from other eyelid movement disorders, as the treatment and prognosis differ significantly. The management of ALO is challenging and is best approached with a multidisciplinary team, including neurologists and ophthalmologists. Treatment strategies may include optimizing therapy for underlying neurological conditions, using botulinum toxin injections to facilitate eyelid opening, or employing surgical interventions in refractory cases.[6]

Understanding ALO's natural history and anatomical basis is crucial for proper diagnosis and treatment. Given its association with neurodegenerative diseases and its impact on patient's quality of life, ALO represents a significant clinical challenge that requires further research and education within the medical community. By increasing awareness and knowledge of this condition, healthcare professionals can better identify and manage this disabling and often overlooked disorder.[7]

Etiology

The most common etiology of ALO is idiopathic focal dystonia. Other causes documented in the literature include the following:

• Blepharospasm or focal dystonia of the eyelids: idiopathic (also known as benign essential blepharospasm), infectious (keratitis, blepharitis, dacryocystitis, conjunctivitis), toxic exposure (extensive sunlight), autoimmune (keratoconjunctivitis sicca from Sjogren's disease), neurodegenerative (Parkinson and Huntington disease) [8]                                                                                                             
• Face or eyebrow ptosis: severe levator palpebrae dysfunction from abnormal development, vascular injury, neuromuscular disease (myasthenia gravis), neuroimmunological (multiple sclerosis), trauma, iatrogenic (eye surgery). Ptosis can easily be corrected by tightening the muscle's tendon that raises the eyelids.[9]                                                                                                                                                          
• Dermatochalasis: excess upper or lower eyelid skin or both. This condition is merely baggy eyelids and can be corrected by removing the excess skin in the eyelids.[10]                                                                                             
• Psychogenic: photophobia, fatigue [11]

Although ALO is often recognized as a distinct clinical entity, it concurrently manifests in association with a range of other neurological disorders. These include benign essential blepharospasm, progressive supranuclear palsy, dystonia-related parkinsonism, motor neuron diseases, and Shy-Drager syndrome. Furthermore, ALO has been linked to cerebral lesions in various anatomical regions such as the non-dominant hemisphere, medial frontal cortex, basal ganglia, and the upper part of the brainstem. The medical literature also documents isolated instances where ALO has been induced by certain medications, including lithium, sulpiride, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), alongside occurrences of ALO triggered during sleep.

ALO can emerge from a diverse spectrum of etiological factors beyond those previously mentioned. Additional etiologies include the following:

• Infections: Central nervous system (CNS) infections that lead to inflammation or damage in the areas controlling eyelid movement may result in ALO. This classification includes viral encephalitis, bacterial meningitis, and prion diseases.[12]                                                                                           
• Metabolic disorders: Certain metabolic disorders that affect the CNS can manifest symptoms, including ALO, highlighting the broad spectrum of potential metabolic imbalances that can impact brain function.[13]                                                                                                                                             
• Toxic exposure: Exposure to certain toxins, not limited to medications like lithium or MPTP, can lead to ALO. This category may include environmental toxins, heavy metals, and neurotoxic chemicals.[14]                                                                                                                                                                    
• Vascular disorders: Stroke or other vascular anomalies affecting the brain regions associated with eyelid movement can lead to ALO, illustrating the impact of vascular health on neural function.[15]                                     
• Autoimmune diseases: Conditions in which the immune system mistakenly attacks parts of the nervous system, such as multiple sclerosis or autoimmune encephalitis, may present with ALO, among other neurological symptoms.[16]                                                                                                           
• Genetic disorders: While less commonly reported, specific genetic syndromes or inherited disorders that affect neural development or function could potentially lead to ALO as part of a broader clinical picture.[17]

Epidemiology

The most common form of blepharospasm is benign essential blepharospasm, and its epidemiology has been extensively studied. The mean annual incidence is about 0.10%, with a peak incidence in the 50- to 60-year-old age group (0.19%). It is slightly more prevalent in females (0.12%) than males (0.07%).[18] It can progress, and within a period of 6 months to 3 years, can lead to impairment of functional independence due to visual disability, job loss, and other quality of life measures.

Increased risk is associated with a high level of urbanization and certain occupations. There are several comorbidities associated, which include dyslipidemia, parasomnias, psychiatric conditions (depression, anxiety, and obsessive-compulsive disorder), dry eye-related diseases (idiopathic or related to Sjögren syndrome), and to a lesser degree, Parkinson disease and rosacea.[19]

Pathophysiology

The exact pathophysiological mechanisms underlying ALO remain elusive, but there are a few hypotheses based on animal model studies. Nigrostriatal basal ganglia pathways may project to the premotor control of eyelid coordination. Therefore, it is associated with dysfunction in the corticothalamic, basal ganglia, and focal cranial nerve circuitry.[20] Structures of the trigeminal blink reflex arc are involved and include sensorimotor cortical regions, substantia nigra pars reticulata, and brainstem motor nuclei. Neuroimaging and electrophysiological studies have implicated both motor and nonmotor areas of the frontal lobe, suggesting that ALO may be a form of motor intention disorder, where the "willed" action to open the eyes does not translate into actual movement. 

At the biochemical level, abnormal dopamine neurotransmission likely underlies abnormal blinking and eyelid muscle contraction. Secondary causes of eyelid opening problems include neuromuscular junction diseases, neurodegenerative diseases, autoimmune diseases, and ocular or central nervous system structural lesions.[21]

ALO is a disorder characterized by difficulty initiating lid elevation despite normal voluntary and reflex blinking. The pathophysiology of ALO is not entirely understood, but several mechanisms are thought to contribute to the condition as follows:

• Basal ganglia dysfunction: The basal ganglia play a critical role in initiating and controlling movement. In ALO, dysfunction within the basal ganglia circuitry, especially in pathways involving the globus pallidus, is believed to be a significant factor. This dysfunction can result from degenerative diseases, structural lesions, or neurochemical imbalances.[22]                                                                                                               
• Supranuclear inhibition: ALO is thought to result from a failure to inhibit the tonic activity of the orbicularis oculi muscle, which is responsible for closing the eyelids. Usually, voluntary lid opening involves a complex neural network that includes supranuclear pathways. Disruption in these pathways can lead to an inability to overcome the orbicularis oculi's tonic contraction, making lid elevation difficult.[9]                                                              
• Levodopa sensitivity: Evidence suggests that ALO may be responsive to levodopa treatment in some cases, particularly when associated with Parkinson disease. This responsiveness implies a possible involvement of dopaminergic pathways in the pathophysiology of ALO.[23]                                                         
• Frontal lobe function: The frontal lobe, especially the prefrontal cortex, is involved in the planning and executing of voluntary movements, including eyelid opening. Damage or dysfunction in this area can impair the ability to initiate lid opening, as seen in ALO.[24]                                               
•  Abnormal blink reflex modulation: ALO may also be related to abnormalities in the blink reflex and its modulation. The reflex should be inhibited during voluntary lid opening, but this inhibition might be compromised in ALO.[25]                                                                                             
• Sensorimotor integration: ALO can be associated with a disruption in sensorimotor integration, which is the process by which the brain integrates sensory feedback with motor commands to produce smooth and coordinated movements.[26]                                                                             
• Neurotransmitter imbalance: An imbalance in various neurotransmitters, not limited to dopamine, may contribute to ALO. This includes changes in the cholinergic, serotonergic, and GABAergic systems.[21]                     
• Neuromuscular anomalies: While not a primary factor, neuromuscular anomalies at the level of the eyelid can contribute to difficulty opening the lid, especially if there is coexisting blepharospasm or ptosis.[9]                                                                                                                                         
• Psychogenic factors: Although ALO is primarily a neurologic issue, psychogenic factors have been considered in some cases, particularly when no clear neurologic cause can be identified.[27]                                         
• Medication effects: Certain medications, especially those with neuromuscular blocking properties, can induce or exacerbate ALO. Understanding the adverse effect profile of such medications is important in the clinical assessment of the condition.[28]

The combination of these factors results in the clinical presentation of ALO, where patients are unable to open their eyelids at will despite having the necessary muscular function to do so. Due to the complexity of the disorder and its overlap with other movement disorders, the exact pathophysiological mechanisms may vary between patients, and more research is needed to understand this condition fully.

Histopathology

The histopathological details of ALO are not as well documented in the literature as its clinical presentations and associated conditions, mainly because ALO is a neurologic rather than a primary muscular or tissue-based disorder.

• Absence of primary muscular pathology: In ALO, the muscle tissue of the eyelids typically does not show primary pathological changes. The condition is a motor dysfunction, meaning the structure of the muscles involved in eyelid opening remains normal, but the control of these muscles is impaired.[9]
• Neurodegeneration: Histopathological findings in patients with ALO often relate to associated neurodegenerative conditions. For example, in cases where ALO is associated with Parkinson disease or progressive supranuclear palsy, one might find the characteristic degenerative changes in the brain associated with these conditions, such as Lewy bodies in Parkinson disease or tauopathies in progressive supranuclear palsy.[29]                                                                 
• Basal ganglia lesions: Since the basal ganglia and their connections play a critical role in the pathophysiology of ALO, histopathological changes in these areas could be present in some patients. These changes might include neuronal loss, gliosis, or other signs of neurodegeneration or damage.[22]   
• Neurochemical alterations: While not visible in standard histopathological examinations, alterations in neurotransmitter systems may underlie ALO. Changes in dopaminergic, cholinergic, and GABAergic neurotransmission have been implicated in ALO and related conditions.[30]                                                        
• Brain stem lesions: Some patients with ALO may exhibit histopathological changes in the brain stem, a critical area for controlling automatic eyelid movements.[31]                                                                              
• Frontal lobe changes: Since voluntary eyelid control involves the frontal lobes, particularly the prefrontal cortex, histopathological changes in this region could potentially be involved in ALO, though these changes are not specific to ALO and might reflect broader neurologic issues.[32]                                   
• Synaptic dysfunction: At the microscopic level, there may be changes in synaptic function or the number of synapses in the neural circuits that control eyelid movement. These changes would not typically be evident in gross histopathological examination but could be discerned through specialized studies.[33]

Since ALO is primarily a disorder of motor planning and execution without primary histopathological changes in the eyelid muscles themselves, the condition is usually diagnosed and assessed through clinical examination and the patient's history rather than tissue biopsy or histopathology. When ALO is secondary to other conditions, the histopathological findings would be consistent with those primary disorders.

History and Physical

In the clinical assessment of ALO, the history and physical examination are pivotal in establishing a diagnosis. Patients with ALO commonly report a challenging inability to initiate the act of eyelid opening and feeling persistent periorbital contractions. Most of the time, it occurs after the patient voluntarily closes the eyes. Patients may exhibit compensatory behaviors such as manually lifting the eyelids, vigorous neck or jaw movements, or increased facial grimacing to overcome the inhibition of eyelid opening. These maneuvers, sometimes referred to as "sensory tricks" or "geste antagoniste," suggest a complex sensorimotor integration issue at the heart of ALO.[34] An external evaluation of the eyelids and facial muscles is essential to assess eyebrow and eyelid ptosis, dermatochalasis, and spasms of the orbicularis oculi, procerus, and corrugator muscles. Assessing mental status, language skills, and other cranial exams may be useful if central causes are suspected.[35]

It is crucial to ascertain the historical progression of symptoms. Typically, the issue emerges gradually, and patients may initially become aware of it upon awakening or during episodes that necessitate frequent blinking or sustained eye closure. This difficulty is not associated with any detectable sensory loss or irritation of the eyes and is not attributable to muscle weakness or fatigue. Patients may experience significant functional limitations that affect daily activities such as reading, watching television, or driving, especially when these activities require shifting or refocusing of gaze.[36] A thorough past medical and ocular history may reveal risk factors associated with the condition. Symptoms of underlying neurological disorders, such as Parkinson disease or various forms of dystonia, may be present, manifesting as tremors, muscle stiffness, or uncontrolled movements. Stress and intense concentration have been known to worsen the condition, whereas periods of relaxation and spontaneous blinking might provide transient relief. A history of neurological interventions, surgical procedures, or specific medications, notably dopamine antagonists or neuroleptics, can explain the onset of ALO.[37]

During the physical examination, clinicians might note the patient's "staring" appearance, characterized by infrequent blinking and difficulty opening the eyelid post-blink. The palpebral fissure may appear narrowed due to an incomplete opening. When the examiner manually opens the patient's eyelids, normal eyelid strength and function are typically observed, negating primary muscle weakness as a cause. Unlike true eyelid weakness or blepharospasm, patients with ALO can perform forceful blinks. An often-seen compensatory mechanism is the overactivity of the frontalis muscle, where patients attempt to lift their eyelids, resulting in pronounced forehead wrinkling. The levator palpebrae superioris muscle function, integral to eyelid lifting, generally remains intact, as demonstrated by a normal levator function test. The blink reflex is preserved, allowing patients to close their eyes voluntarily.[35]

A thorough neurological examination is essential to identify any associated movement disorders or neurological deficits. Moreover, it is critical to differentiate ALO from other conditions that mimic its presentation, such as myasthenia gravis-induced ptosis or mechanical eyelid obstructions. In essence, ALO is distinguished by a non-paralytic challenge in voluntary eye-opening without primary ocular pathology, with patients exhibiting normal eyelid structure and muscle function upon examination, often alongside a history suggestive of an association with neurological disorders or the influence of certain medications.[35] A focal ocular exam is essential, including visual acuity and visual field testing, ocular pressure testing, pupillary reflexes, extraocular movements, dilated fundoscopic examination, and slit-lamp examination. The examination can help reveal the etiology of the symptoms.

Evaluation

ALO is primarily a clinical diagnosis; therefore, a thorough medical history, physical and ocular history, and focused visual exam are essential. Historical inquiry of progression and increased risk can narrow the differential diagnoses to consider. Clinical criteria for the identification of clinical and physical exam phenomenology have been established by Defazio and Berardelli, with validation from expert neurologists and neuro-ophthalmologists.[38] These include orbicularis oculi involuntary spastic eyelid narrowing/closure, bilateral laterality, synchronous spasm frequency, stereotypical spasm pattern, alleviation with a sensory trick, inability to suppress spasms, and high-frequency blink count at rest. Combining these criteria had a 93% sensitivity and 90% specificity for blepharospasm. A focal physical and ocular exam can help identify and confirm the clinical diagnosis.

The evaluation of  ALO is typically centered on clinical assessment, as no specific laboratory or radiographic tests can definitively diagnose the condition. However, specific evaluations can help rule out other causes and identify underlying or associated neurological disorders. Extensive serum laboratories and cerebrospinal fluid analysis, including systemic immune, autoimmune, and infectious causes, may be helpful to exclude secondary causes of blepharospasm.[39] In cases where myasthenia gravis is considered in the differential diagnosis, specific tests such as serum acetylcholine receptor antibody levels and single-fiber EMG may be warranted. Additionally, a trial of edrophonium chloride (Tensilon test) or ice pack test may be employed to rule out myasthenia gravis.[40]

A comprehensive neurological examination is essential. Clinicians may conduct tests to assess for Parkinson disease, dystonia, and other movement disorders that are often associated with ALO. Neurophysiological tests, like electromyography (EMG), can help evaluate the function of the orbicularis oculi and levator palpebrae superioris muscles, distinguishing between neurogenic and myogenic causes.[41] Imaging studies, particularly magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain, are not used to diagnose ALO directly. However, suppose a central nervous system cause, such as a stroke or tumor, is suspected. In that case, a head CT scan or brain MRI with and without contrast can be instrumental in identifying or excluding central nervous system lesions that might contribute to the condition.

Due to the rarity of the condition, national and international guidelines for evaluating ALO may not be well established. However, the guidelines for evaluating movement disorders and blepharospasm, often associated with ALO, can provide a framework for assessment. These guidelines recommend a tailored approach based on the individual's symptoms and history, utilizing a combination of clinical evaluation and diagnostic testing to identify potential underlying causes. In summary, the evaluation of ALO is mainly clinical, supported by neuroimaging and neurophysiological tests to explore associated conditions or to exclude other diagnoses. Given the complexity of ALO and its overlap with various neurological disorders, a multidisciplinary approach is often beneficial. Clinicians should consult the latest national and international guidelines for movement disorders to ensure a comprehensive evaluation.[42]

Treatment / Management

The treatment and management of ALO are mainly symptomatic and may include nonpharmacological and pharmacological approaches and surgical interventions in refractory cases. It is essential to tailor the treatment to the individual patient, considering the severity of ALO, the presence of comorbid conditions, and the patient's response to initial therapies.

The first-line treatment for ALO is the injection of botulinum toxin A.[43][44] Myectomy, which involves the removal of fibers of orbicularis oculi muscle in the central portion of the eyelid, can be performed if botulinum toxin does not produce good results. Nonpharmacological strategies are often also the first line of management. They may include techniques such as sensory tricks or geste antagoniste, where touching certain parts of the face or forehead can help patients open their eyes. Physical therapy exercises to strengthen the eyelid muscles and biofeedback may also be beneficial.[45]

Pharmacological treatment may involve the use of medications that enhance dopaminergic transmission, given the occasional association of ALO with Parkinsonian syndromes. For instance, levodopa or dopamine agonists may be tried. Botulinum toxin injections into the pretarsal orbicularis oculi muscle have successfully reduced the force of involuntary closing of the eyelids, thereby allowing more effortless lid opening.[46] In cases where ALO is secondary to dystonia or blepharospasm, the use of botulinum toxin is often considered the treatment of choice. The injections are administered in a pattern that targets the involved muscles to alleviate involuntary contractions and facilitate voluntary lid opening.[47]

Myectomy with tightening of the levator tendon that elevates the eyelids (also called aponeurotic ptosis repair) and blepharoplasty can be considered for refractory cases. A frontalis sling operation is performed as a last resort, with a suture placed between the frontalis muscles and the eyelids to aid in lid elevation and suspension.

Currently, there are no specific national or international guidelines for treating ALO due to its rarity. However, guidelines for the treatment of associated conditions such as Parkinson disease, dystonia, and blepharospasm may offer insights into management strategies. Clinicians often refer to these related guidelines and rely on evidence from case studies and expert opinion to inform the management of ALO. Interdisciplinary care involving neurologists, ophthalmologists, and, at times, neurosurgeons or rehabilitation specialists is essential. Each case of ALO requires a customized approach guided by the patient's unique clinical presentation and treatment response.[48]

Differential Diagnosis

ALO, as a feature of blepharospasm, carries a complex differential diagnosis most consistent with late-onset dystonia phenomenon, affecting patients older than 50 years. Several disorders will present similarly to ALO and must be excluded to treat them appropriately.

• Idiopathic
  • Benign essential blepharospasm with or without sensory features, including eye-burning pain, keratoconjunctivitis sicca, sensory trick, and photophobia [49][50]
  • Meige's Syndrome: a triad of blepharospasm, oromandibular dystonia, and cervical dystonia.
  • Brueghel's Syndrome: blepharospasm, oromandibular dystonia, with or without torticollis, with or without dystonic writer's cramp, appendicular dystonic posturing of the arms, dystonic respiration, and spasmodic torticollis [51][52]
• Iatrogenic
  • Drug-induced: associated with tardive dyskinesias with the use of mood stabilizers (antidepressants, antipsychotics, antiepileptics), antimicrobials, and antiarrhythmic [53]
  • Levodopa and apomorphine in progressive supranuclear palsy [54]
  • Deep brain stimulation on the subthalamic nucleus and the globus pallidus internus for Parkinson disease patients [55][56]
• Genetic
  • Primary blepharospasm and dystonias can be accompanied by cervical dystonia. Torsin family 1 member A (TOR1A) polymorphism with a mutation on dystonia 1 protein [57][58][59], guanine nucleotide-binding protein [60], anoctamin 3[61], tubulin beta4A [62], and zinc finger protein 1 [57][63]
• Structural
  • Vascular or traumatic injury of the midbrain, basal ganglia, thalamus, cerebellum, and motor cortex [64]
  • Hemifacial spasm: spasmodic unilateral facial contractions, including eyelid blepharospasm due to facial nerve irritation
• Neuroinflammatory
  • Bell palsy: unilateral facial hemiparesis, constitutional symptoms (fever, chills), headaches, neck rigidity, retro auricular or jaw pain, hypersalivation, hyperacoustic phonophobia, dysgeusia, and keratoconjunctivitis sicca
  • Myasthenia gravis: oculomotor fatigue. This autoimmune disorder can lead to variable eyelid ptosis, which can worsen with fatigue and improve with rest. It can mimic ALO but typically presents with fluctuating muscle weakness and may respond to ice pack or edrophonium tests.[65][66] 
• Neurodegenerative
  • Parkinson disease: Eyelid apraxia can sometimes occur in Parkinson disease due to bradykinesia. However, in Parkinson disease, other characteristic symptoms such as tremor, rigidity, and postural instability are also present.[26][27] 
  • Focal, segmental, or generalized dystonia: uncontrolled hyperkinetic movements, including blepharospasm.
• Ptosis: drooping of the upper eyelid due to myogenic, neurogenic, mechanical, or traumatic causes. The distinction is that ptosis involves a physical limitation in lifting the eyelid rather than difficulty initiating the movement.[67]
• Progressive supranuclear palsy (PSP): a condition that can lead to a gaze palsy with difficulty moving the eyes and eyelids. However, PSP usually also causes significant balance problems and falls, which are not features of ALO.[68]
• Tardive dyskinesia: a drug-induced movement disorder characterized by repetitive, involuntary, purposeless movements that can include the eyelids and may be confused with ALO.[69]
• Voluntary nystagmus: Some individuals can voluntarily produce rapid eye movements that might be mistaken for ALO due to the difficulty of keeping the eyes open.[70]
• Functional eyelid disorders: disorders with a perceived inability to open the eyes, often associated with psychological factors but without an organic cause. These may present with symptoms similar to ALO but lack the neurological basis.[9]
• Orbicularis oculi fatigue: Prolonged voluntary closure of the eyes can sometimes lead to temporary fatigue of the orbicularis oculi muscle, which may temporarily mimic ALO upon attempted eyelid opening.[8]

When evaluating a patient suspected of having ALO, it is essential to conduct a thorough history and physical examination, possibly supplemented by specific diagnostic tests, to differentiate ALO from these other conditions. Neurological examination, imaging studies, and electrophysiological testing can help make an accurate diagnosis.

Prognosis

The prognosis for individuals with ALO can vary widely and depends on the chronicity, underlying etiology, associated conditions, and responsiveness to the first-line treatment. ALO may be challenging to treat in many cases. In general, responsiveness to treatment is a good prognostic factor regarding morbidity. Chronicity and refraction to treatment can lead to more disruption in functional independence and disability. Since ALO is not a degenerative disease in itself, the prognosis is more related to management effectiveness and the course of any underlying neurological disorders.[45]

In cases where ALO is associated with treatable conditions, such as blepharospasm or Parkinson disease, the use of botulinum toxin injections or dopaminergic medications, respectively, can offer significant symptomatic relief, leading to a relatively good prognosis for the eyelid apraxia aspect. For some patients, these treatments can substantially improve their quality of life and may be effective for long periods.[71] However, if ALO is part of a more complex or progressive neurological disorder, such as progressive supranuclear palsy or certain forms of parkinsonism, the overall prognosis may be more guarded. In these situations, ALO may persist or progress in line with the underlying disease, and management may become more challenging over time. Surgical interventions, like levator resection or frontalis suspension, may offer a more permanent solution for some patients. Still, the outcomes can vary, and there may be risks of complications or the need for further surgeries.[72]

Despite diverse interventions, ALO often presents a significant therapeutic challenge, and patients may experience only partial improvement. The condition can profoundly impact the quality of life, as affected individuals may struggle with routine activities that require unobstructed vision. Generally, ALO itself does not directly affect lifespan, but the functional impairment can significantly impact a person's daily activities and psychosocial well-being. Early recognition and appropriate treatment are vital to improving the prognosis and quality of life for those affected by ALO. Interdisciplinary care involving neurologists, ophthalmologists, and physical therapists is often required to optimize management and provide comprehensive care.[73]

Complications

Treatments for ALO with botulinum toxin can produce uncommon and transient adverse effects such as ptosis, blurry vision, and diplopia that spontaneously resolves in a few weeks.[74][75][76]

Complications associated with ALO primarily relate to the impact of the condition on daily functioning and quality of life. Some potential complications include the following:

• Functional impairment: Individuals with ALO may have difficulty performing tasks that require sustained or clear vision, such as reading, driving, or operating machinery. This can lead to a decreased ability to perform work-related tasks or engage in hobbies.                                                                       
• Social and psychological impact: The physical appearance of ALO, with difficulty opening the eyes, may lead to self-consciousness or social embarrassment. In turn, this can result in social withdrawal, anxiety, and depression.[77]                                                                                                                       
• Eye health issues: Difficulty opening the eyelids may predispose individuals to eye health problems, such as recurrent corneal abrasions due to inadequate blinking or exposure keratopathy.[78]                                          
• Treatment-related complications: If botulinum toxin is used as part of the treatment, there is a risk of ptosis due to the toxin affecting nearby muscles. Surgical interventions also carry risks such as infection, scarring, or the need for repeat surgeries.[79]                                                                     
• Visual field impairment: In severe cases, if the upper field of vision is obstructed by the inability to lift the eyelids fully, this could lead to difficulties with spatial orientation and mobility.                                                
• Exacerbation of underlying neurological disorders: If ALO is part of a broader neurological condition, the stress of dealing with ALO can potentially exacerbate other symptoms of the underlying disorder.

Proactive management of ALO can help mitigate some of these complications, and healthcare professionals must monitor patients closely for any signs of these issues. Interdisciplinary care and support, including psychological support if needed, can be beneficial in managing the broader impacts of ALO.[80]

Postoperative and Rehabilitation Care

Postoperative and rehabilitation care for ALO is an essential component of treatment, especially if surgical interventions are involved. The goal of postoperative care is to ensure proper healing and maximize the functional outcome of the surgery. At the same time, rehabilitation focuses on optimizing the use of the eyelids and preventing complications.

Postoperative Care

• Monitoring for complications: After surgery, close monitoring is required to detect any signs of complications such as infection, hematoma, or adverse reactions to anesthesia.
• Wound care: Proper care of the surgical site is necessary to prevent infection and promote healing. This may include cleaning the area and applying prescribed topical medications.
• Medication management: Patients may be prescribed medications to manage pain, reduce inflammation, and minimize the risk of infection.
• Follow-up visits: Regular follow-up with the surgical team is crucial to assess healing and the effectiveness of the intervention. The treatment plan may be adjusted based on the patient's progress.[81]

Rehabilitation Care

• Physical therapy: If indicated, physical therapy can help patients learn exercises to strengthen the eyelid muscles and improve coordination for lid opening.
• Occupational therapy: Occupational therapy may assist patients in adapting to any residual functional impairments and incorporating practical strategies into their daily activities.
• Visual aids: In some cases, patients may benefit from visual aids or modifications to their environment to accommodate any visual field limitations.
• Education: Patients should be educated on techniques to manually assist in eyelid opening if needed and strategies to use sensory tricks to facilitate lid elevation.
• Stress management: Since stress can exacerbate ALO, stress management techniques such as relaxation exercises, biofeedback, or counseling may be beneficial.[82]

The specifics of postoperative and rehabilitation care will vary depending on the individual's condition, the type of surgery performed, and any associated neurological conditions. A multidisciplinary approach involving neurologists, ophthalmologists, surgeons, physical and occupational therapists, and, if necessary, mental health professionals provides the most comprehensive care for individuals recovering from ALO surgery. Regular assessment and appropriate adjustments in the care plan are important to address the patient's changing needs.[83]

Consultations

Consultations with various specialists may be necessary to manage ALO and ensure comprehensive care. The interdisciplinary team members may include the following:

• Neurologist: A neurologist can help diagnose ALO, primarily as it may be associated with other neurological conditions such as Parkinson disease, dystonia, or progressive supranuclear palsy (PSP). They can also assist in managing the neurological aspects of the condition and any comorbidities.[68]
• Ophthalmologist: An ophthalmologist, particularly one specializing in neuro-ophthalmology, can evaluate the structural health of the eyes and eyelids, rule out primary ocular causes of eyelid dysfunction, and participate in the management of ALO, including botulinum toxin injections if indicated.[84]
• Movement disorder specialist: If the patient has an underlying movement disorder, a specialist in this field can provide targeted treatment and management strategies.[85]
• Occupational therapist: An occupational therapist can assist with adaptations to daily living activities and suggest devices or strategies to compensate for any visual limitations caused by ALO.[86]
• Physical therapist: Physical therapy may be beneficial for patients who require eyelid-strengthening exercises or other modalities to improve motor control of the eyelids.[87]
• Plastic or reconstructive surgeon: If surgical intervention is considered, a consultation with a plastic surgeon or an oculoplastic surgeon with experience in eyelid surgeries may be necessary.[88]
• Psychologist or psychiatrist: Due to the potential psychological impact of ALO, such as anxiety or depression, mental health support from a psychologist or psychiatrist may be necessary.
• Rehabilitation medicine specialist: This specialist can oversee a comprehensive rehabilitation program postsurgery or as part of the long-term management of ALO.

An interdisciplinary approach involving these specialists can help formulate a holistic treatment plan tailored to the patient’s specific needs and greatly improve the overall prognosis and quality of life for individuals with ALO.

Deterrence and Patient Education

There are no avoidable factors that prevent ALO. However, unresponsiveness to treatment can affect the patient's functional independence. Disability can also result from impairment in visual integrity, which can cause job loss and impact the performance of activities of daily living.

Treatment with botulinum toxin frequently produces good results, but complications from its use can occur. Patients should seek medical attention as ALO can be a symptom of numerous disorders that require additional treatments, including Parkinson and Huntington diseases, myasthenia gravis, Sjogren syndrome, multiple sclerosis, and psychiatric disorders.[45]

Deterrence and patient education are essential components in the management of ALO. Patient education should include the following:

• Understanding of ALO: Patients should be provided with clear information about what ALO is, its symptoms, and how it differs from other eyelid disorders. This helps in setting realistic expectations about the condition and its management.[36]
• Treatment options: Patients should be educated about the available treatment modalities, including nonpharmacological approaches, pharmacological treatments, botulinum toxin injections, and possible surgical interventions. They should know each option's benefits, risks, and expected outcomes.[89]
• Self-help techniques: Patients require strategies that might assist with lid opening, such as using sensory tricks (eg. lightly touching the forehead or temples), maintaining good eyelid hygiene, and performing prescribed eyelid exercises.
• Medication adherence: The importance of adhering to medication regimens, if prescribed, and the potential adverse effects and importance of reporting them to the healthcare provider should be discussed.
• Monitoring: Patients should be encouraged to monitor their symptoms regularly and keep a symptom diary, which can help them manage the condition and adjust treatment plans.
• Lifestyle modifications: Discuss lifestyle modifications that may help manage symptoms, such as stress reduction techniques, optimizing sleep, and avoiding activities that may exacerbate symptoms.
• Regular follow-up: The importance of regular follow-up appointments to monitor their condition, assess the effectiveness of treatments, and make necessary adjustments should be emphasized.[90]
• Support networks: Patients should be informed about support groups or resources for individuals with ALO or associated conditions. Emotional and psychological support can be crucial for coping with chronic conditions.
• Complications: Patients need information about the potential complications of ALO, such as social and psychological impacts, and the importance of seeking help if they experience these issues.
• Prognosis: Information should be provided about the prognosis of ALO, including factors that can influence the condition's progression and management strategies that may improve functional outcomes.[91]

Effective patient education can empower individuals with ALO to actively participate in their care, help them manage their condition more effectively, and improve their overall quality of life.

Pearls and Other Issues

Pertinent take-home points include the following:

Summary

• ALO is a nonmotor abnormality characterized by the patient's difficulty in bilateral eyelid elevation.
• It commonly occurs after the patient voluntarily closes their eyes.
• The definition is a misnomer, given that it rarely contains pure and true apraxia.
• It is associated with dysfunction in the corticothalamic, basal ganglia, and focal cranial nerve circuitry.
• Structures involved include sensorimotor cortical regions, substantia nigra pars reticulata, and brainstem motor nuclei.[92]
• The most common etiology of ALO is idiopathic focal dystonia.
• Other causes include blepharospasm or focal dystonia of the eyelids, infectious, toxic exposure, autoimmune, neurodegenerative, face or eyebrow ptosis, neuromuscular, trauma, iatrogenic, dermatochalasis, ptosis, psychogenic, and fatigue.
• Patients show compensatory behaviors, including thrusting the head backward, manually opening the eyes with their fingers, and rubbing the eyebrows.
• Botulinum toxin A is considered the first-line treatment.[93]
• Several disorders will present, like ALO, and must be excluded to treat them appropriately.
• The prognosis depends on the chronicity, etiology, and responsiveness to the first-line treatment.
• Chronicity and refraction to treatment can lead to more disruption in functional independence and disability.[36]

Pearls

• Early recognition: ALO is often under-recognized. Awareness of the condition among healthcare professionals is crucial for early diagnosis and management, which can significantly improve patients' quality of life.
• Multidisciplinary approach: Effective management of ALO often requires a team that includes neurologists, ophthalmologists, and sometimes neurosurgeons, along with nurses and physical and occupational therapists.
• Customized treatment: Treatment should be tailored to the individual, as ALO can present differently in each patient, and response to treatment can vary widely.
• Potential for improvement: While challenging, ALO can often be effectively managed with treatment, including botulinum toxin A injections, physical therapy, and, in some cases, surgical intervention.
• Disposition: Patients with ALO should have a clear management plan that includes regular follow-up appointments to monitor their condition and response to treatment. They should also be provided with information on seeking urgent care if they experience significant changes or complications related to their condition.[94]

Pitfalls

• Misdiagnosis: ALO can be mistaken for other conditions, such as blepharospasm or myasthenia gravis, leading to inappropriate treatments.
• Overlooking underlying conditions: It's essential not to miss an underlying neurological disorder associated with ALO, as this can impact treatment and prognosis.
• One-size-fits-all approach: Given the variability in presentation and response to treatment, a standardized approach may not be effective.
• Prevention: There are no known measures to prevent ALO, as it is often associated with other neurological conditions. However, understanding the risk factors and early signs can help promptly diagnose and manage.[95]

Additional Information

• Patient education: Patients should be educated about the nature of ALO and the importance of adherence to treatment and follow-up schedules.
• Research advances: It is essential to keep abreast of new research, as understanding ALO and its treatment is evolving.
• Quality of life: Attention should be paid to the impact of ALO on a patient's psychological and social well-being, with appropriate support provided.[96] It is critical to address both the physical aspects of the condition as well as the broader impacts on the patient's life.

Enhancing Healthcare Team Outcomes

Enhancing healthcare team outcomes for patients with ALO requires a coordinated, interprofessional approach that integrates the skills and expertise of various healthcare providers to ensure comprehensive, patient-centered care. The outcomes of ALO depend on the cause. However, prompt consultation with an interprofessional group of specialists is recommended to improve outcomes. Shared decision-making and communication are recommended elements for a good outcome. In conjunction with occupational therapists, the neurologist plays an integral part in the treatment. Botulinum toxin injections are usually performed by the ophthalmologist, oculoplastic surgeon, or plastic surgeon. Sometimes, botulinum toxin can be injected by a neurologist or movement disorder specialist. Social worker and case management evaluation may be required for unresponsive cases as ALO can cause disability to the patient with impairment of activities of daily living and job performance.[45]

Considerations for the interprofessional team include the following:

Skills and Strategy:

• Assessment skills: All team members should be skilled in assessing ALO, recognizing its signs, and distinguishing it from other conditions.
• Treatment planning: Clinicians should strategize the best treatment plan, considering both nonpharmacological and pharmacological options, and tailor this plan to the individual patient’s needs.
• Surgical consideration: If surgery is indicated, surgeons must possess the technical skills to perform procedures that benefit ALO patients, such as eyelid crutches or levator resection.[97]

Ethics and Responsibilities:

• Informed consent: It is the responsibility of the healthcare team to ensure that patients understand the benefits and risks of any proposed treatment.
• Patient autonomy: Patients should be involved in their care decisions, and the team should support their independence and choices.
• Privacy and confidentiality: Team members must maintain patient confidentiality and share health information only among the care team as necessary for patient treatment.[98]

Interprofessional Communication:

• Care coordination: Effective communication among neurologists, ophthalmologists, physical therapists, nurses, and primary care physicians is essential for coordinating care and managing treatments.
• Documentation: Accurate and thorough documentation in a shared electronic health record allows all team members to access patient information, track progress, and adjust treatment plans as needed.[99]

Care Coordination:

• Role clarification: Each team member should understand their role in managing ALO to avoid duplication of efforts and ensure that all aspects of care are addressed.
• Follow-up: Coordinating follow-up appointments and ongoing care management is essential for monitoring treatment effectiveness and adjusting interventions as necessary.
• Patient education: Team members should provide consistent, clear education to the patient and their family about ALO, treatment options, and self-help strategies.[100]

Outcomes and Patient Safety:

• Monitoring for adverse events: Close monitoring for treatment-related adverse events, such as the effects of botulinum toxin, is crucial for patient safety.
• Outcome measurement: The team should measure patient outcomes using validated tools to assess the impact of treatment on quality of life and functional status.

Team Performance:

• Regular team meetings: Interprofessional team meetings can help discuss patient progress, identify issues, and plan future interventions.
• Continuing education: All team members should engage in ongoing education to stay updated on the latest evidence-based practices for ALO.[101]

By fostering an environment of mutual respect and open communication, the healthcare team can enhance care for patients with ALO, improving outcomes, patient satisfaction, and team performance. Each member’s contribution is vital, from diagnosis and treatment to patient education and support.