Debunking the Puzzle of Eyelid Apraxia: The Muscle of Riolan Hypothesis : Ophthalmic Plastic & Reconstructive Surgery

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Debunking the Puzzle of Eyelid Apraxia: The Muscle of Riolan Hypothesis

Tawfik, Hatem A. M.D.*; Dutton, Jonathan J. M.D., Ph.D., F.A.C.S.

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Ophthalmic Plastic and Reconstructive Surgery 39(3):p 211-220, May/June 2023. | DOI: 10.1097/IOP.0000000000002291
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Movement disorders are broadly classified in hyperkinetic and hypokinetic varieties. The former group of excessive movements is referred to as hyperkinetic movement disorders and includes conditions like tremors, myoclonus, and dystonia. The latter group, where the amplitude of movement is diminished, is referred to as hypokinetic movement disorders and encompasses conditions like the different forms of parkinsonism, apraxia, catatonia, and the enigmatic freezing phenomenon.1,2

Similarly, eyelid movement disorders are also broken down in hyperkinetic or hypokinetic.3–6 Classical teaching dictates that blepharospasm (BSP) and hemifacial spasm are hyperkinetic movement disorders that are hallmarked by involuntary spasms of the orbicularis oculi muscle (OO), while what has been referred to as apraxia of eyelid opening (AEO) is a hypokinetic movement disorder that is defined by the transient inability of the levator palpebrae superioris muscle (LPS) to elevate the upper eyelids.3–8

The standard definition of AEO is that the condition is a non-paralytic inability to initiate eyelid opening in the absence of a clinically evident contraction of the orbicularis oculi muscle, a myopathy of the LPS, and without an oculomotor nerve or sympathetic dysfunction.9 This curious and rare form of eyelid movement disorder is broadly defined by the visual impairment it causes due to the familiar difficulty in opening the eyelids.10 In 1965, Goldstein and Cogan11 revived the term “apraxia of eyelid opening” which was casually mentioned in the German literature almost 4 decades prior to their seminal paper.12,13

Although the term eyelid apraxia gained wide popularity over the past 4 decades, very little is known about the precise pathophysiology of the condition. However, it is interesting to note that from the very beginning, the term eyelid apraxia was met with great skepticism and was frequently prefixed with the cautionary identifier “so-called AEO.”6 Over the years, there were numerous attempts to drop the apraxic designation and suggest alternative names including focal eyelid dystonia, involuntary levator palpebrae inhibition (ILPI), blepharocolysis, blepharokolysis, pretarsal blepharospasm, atypical blepharospasm, so-called apraxia of eyelid opening (scAEO), eyelid freezing, eyelid akinesia, or blepharoplegia.9,14–18 This vast nomenclatorial catalog was based upon genuine arguments that AEO does not fulfill the standard definition of an apraxic condition and is not technically an apraxia.9,14–20

While the prevailing views regarding the exact pathogenesis of AEO have swerved like a pendulum for the past 4 decades, competing theories have always revolved around the same antagonistic pair of striated eyelid muscles (OO and LPS) that are involved in the blinking mechanism. It should be realized that spontaneous blinking is a complex motor behavior that usually occurs without volition and is under voluntary control only during voluntary intentional blinking.3–6 Under physiological conditions, the LPS muscle is tonically active most of the time to keep the eyelids open except during blinking when it is transiently inhibited.6 However, it is hypothesized that this fleeting reversal of action during a blink probably requires some phasic contribution from the OO to regulate or refresh the activity of the LPS after the blink ends, as the OO has to relax first before the LPS resumes its normal tonic activity and reopens the eyelids.6 Accordingly, involuntary blinks (spontaneous and reflex blinks) normally consist of 2 components: an inhibition of the basal tonic LPS activity which usually precedes and outlasts a second shorter component consisting of concurrent activation of the OO.3–6 When the blink ends, the resumption of LPS activity usually exhibits an initial reinforcement (postinhibition potentiation).6

To date, rival theories about the pathogenesis of AEO included: (1) an isolated involuntary inhibition of the LPS (ILPI) while the OO remains inactive, a notion which fits the classic description of eyelid apraxia, or (2) prolonged clinically undetectable but electromyographically recordable isolated contractions of the pretarsal OO with reciprocal inhibition of the LPS while the LPS function is otherwise normal, which qualifies the condition as a focal eyelid dystonia, and for which the term pretarsal blepharospasm (ptBSP) was coined, or (3) disturbed reciprocal innervation (DRI) of the OO and LPS muscles.3–6,9–18 These seemingly conflicting theories have resulted in significant confusion in the literature, and the condition is still interchangeably described (both clinically and etiologically) either as an eyelid apraxia,4,7,11,21,22 a focal eyelid dystonia,9,15,21,23,24 or as a freezing phenomenon (eyelid motor blocks).14,25–33 Similarly, the singular versus dichotomous nature of the disease remains controversial, and for decades AEO has suffered from a duality paradox where clinicians have wondered whether they are dealing with 2 completely separate conditions (ptBSP, & ILPI)5,7,22 or whether both conditions may be appreciated as the extreme poles of an atypical dystonic spectrum with DRI in the middle.6,17,34–39

The authors of the present study believe that this duality dilemma is counterproductive and prefer to rephrase the question under the broader umbrella of blepharospasm or an even broader context of eyelid dystonias as a whole. It should be remembered that ptBSP is merely a variant of BSP and is not a separate disease entity. Therefore, the purpose of the present study is to test a hypothetical concept proposed by the authors that similar to ptBSP, which is attributable to dystonic spasms of the pretarsal OO, ILPI is also a variant of BSP, but it occurs due to an exclusive dystonic spasm of the muscle of Riolan.

To test this hypothesis, the authors attempted to understand the muscular mechanisms underlying the occurrence of AEO as a clinical phenomenon by addressing the following 3 questions. (1) From a purely clinical point of view, does AEO truly behave as an apraxia, a dystonia, or a freezing phenomenon? (2) What is the etiopathogenic basis of AEO according to existing electromyographic findings? (3) Is scAEO part of the BSP spectrum or is it a completely separate disease entity? Because old eponyms die hard,18,19 the authors found it necessary to retain the term so-called AEO (scAEO) and ILPI throughout a major part of the current discussion, but more coherent nomenclatorial terms are suggested toward the end.


To research this review, the terms “apraxia of eyelid opening,” “pretarsal blepharospasm,” “blepharocolysis,” “blepharokolysis,” “eyelid freezing,” “eyelid akinesia,” “levator inhibition,” “blepharospasm-plus,” as well as “blepharospasm” were queried in PubMed, MEDLINE, PubMed Central (PMC), NCBI Bookshelf, and Embase search engines. scAEO patients were identified based on the classic criteria set by Lepore and Duvoisin.14 In brief, patients with scAEO were considered to share the following characteristics: (1) the inability to initiate eyelid opening; (2) negative Charcot’s sign (lowering of the brows beneath the superior orbital margins due to the contraction of the preseptal/orbital OO), plus no other evidence of OO contraction upon visual inspection; and (3) marked frontalis muscle contraction in an attempt to raise the eyelids.14 Other authors suggested amending the original criteria to include patients who suffer from a transient failure to sustain eyelid elevation (periods of involuntary drooping of the eyelids).8,9,35,40–42 In the current review, patients who failed to meet these 4 clinical criteria were excluded.

Another proposed amendment to the original criteria required an electromyographic study (EMG) to rule out the presence of any subclinical OO activity.6,42–44 This suggestion probably stemmed from the realization that Lepore and Duvoisin’s diagnostic criteria are also fulfilled by a rare subtype of blepharospasm called pretarsal BSP, which is characterized by (1) selective, localized, subclinical contraction of the pretarsal OO as evidenced by EMG, (2) without any clinical evidence of a visible contraction in the preseptal or orbital portions of the OO, and (3) without any recordable EMG activity in the preseptal and orbital OO.35,41–44 However, this last proposed criterion did not meet wide acceptance and was not a requirement for inclusion in the present study. This is because both the true apraxia-like AEO where only levator silence is observed (ILPI),22,41 and ptBSP are nearly identical clinically, and from the very beginning, the authors of the present study have entertained the possibility that both conditions (ILPI & ptBSP) may lie at different points along the same dystonic spectrum, making the inclusion of ptBSP patients in the current study a necessary prerequisite to fully understand scAEO.

scAEO patients who clinically fulfilled Lepore and Duvoisin’s classic criteria were evaluated from the reported literature. This cohort included patients with isolated scAEO and patients who developed scAEO in association with Parkinson’s disease (PD), progressive supranuclear palsy (PSP), or following deep brain stimulation or levodopa therapy. Patients with isolated BSP or dystonic blinks (DB; also referred to in the literature as eyelid flickering, increased blinking, or frequent blinking), were excluded from the clinical review. Similarly, clinical studies exclusively concerned with blepharospasm or titled with the heading “blepharospasm” were only reviewed if they included patients with ptBSP or ILPI. To study the EMG findings in scAEO patients and to explore the potential electrophysiologic relation between BSP, ptBSP, and scAEO, the EMG findings in patients who fulfilled the diagnostic criteria of scAEO were reviewed, but special emphasis was placed on published studies that included synchronous EMG recordings both from the levator muscle (LPS) and the pretarsal orbicularis muscle (OO). In addition, the EMG findings in patients with overt BSP/DB were also reviewed.

A note should be made regarding radiological evidence. So far, conventional neuroimaging studies have failed to identify consistent structural brain lesions in patients with BSP or scAEO,3,45 and despite significant technological advances in non-conventional imaging, particularly functional MRI (fMRI) which has somewhat improved our understanding of the pathophysiology of BSP and other dystonias,45–47 no such studies exist for patients with scAEO. Therefore, the authors of the present study focused more on clinical and neurophysiological evidence. Although clinical observations may be error-prone and less “quantifiable” than EMG,48 they should not be overlooked because a proper clinical examination remains the major integral part in the identification and follow up of any eyelid movement disorder.49,50

Finally, a note should be made about a supposedly related condition called “apraxia of eyelid closure” (AEC). These patients were excluded from the present study because recent data suggest that these 2 allegedly apraxic disorders of eyelid opening (scAEO) and closure (AEC) are quite distinct and may not share the same pathophysiological mechanisms or neural substrates.51


The Clinical Evidence

Over the years, the clinical condition known as “apraxia of eyelid opening” has been likened to either 1 of 3 relevant groups of movement disorders; apraxia, dystonia, or freezing phenomenon. Apraxia is a hypokinetic movement disorder defined by the failure of execution of skilled or learned voluntary motor acts that cannot be explained by an elementary motor or sensory deficit.17,19 Dystonia is defined as a neurological hyperkinetic movement disorder in which sustained muscle contractions result in twisting and repetitive movements or abnormal fixed postures.52,53 Freezing phenomenon (motor blocks) is a clinical condition that refers to transient episodes where the motor activity being attempted by an individual is halted, and its execution is “blocked” despite the patient’s maximum effort to overcome this block.54

scAEO and Apraxia

The praxis conceptual system is a 2-step process that is concerned with the ability to perform skilled or consciously learned motor actions.19 The first step in the system is the ideation or the conceptualization of the movement in the left parietal lobe where an execution plan, or space-time blueprint, is formulated. This plan is transferred across association fibers of the corpus callosum to the right pre- and postcentral and frontal gyri and their underlying white matter tracts. In the second step, the plan is mediated in the basal ganglia where sensorimotor information and sequencing are added to the action plan, and the movement program is executed with signals from the primary motor cortex to various cranial nerve nuclei and lower motor neurons that affect execution of the task.19

Apraxia refers to the inability to carry out such praxis movements in the absence of elementary motor, sensory, or coordination deficits. It has been attributed to cortical pathology or frontal lobe injury.19 Much of our understanding of apraxia has been based on lesion studies, and although most studies show lesions in the left hemisphere, no single area in isolation has consistently been involved in the development of apraxia.19 This suggests that praxis functions are distributed through different neural networks working together.19 Typical praxis errors are characterized by impairment in the timing, sequencing, programming, amplitude, spatial organization of movements, or by their voluntary–automatic dissociation.19,55,56 The condition is subclassified into ideomotor, ideational, conceptual, dissociation, and conduction apraxias.19,55,57 A detailed enumeration of the motor impairments that characterize each type of apraxia is beyond the scope of this review. However, some of the commonly encountered apraxic errors include the failure to produce the correct movement in reply to a verbal command, the failure to accurately pantomime a movement performed by the examiner, the inability to perform an appropriate action in response to a visually presented object, and tool selection errors, where the patient is unable to carry out the correct movement using an actual object. For example, when asked to demonstrate the use of a hammer, the patient may use it as a screwdriver.56

Contrary to apraxias, there is ample evidence to suggest that the praxis conceptual locomotion system is intact in scAEO patients: (1) None of the apraxic errors outlined above is observed in scAEO patients, and the reverse is also true as patients with apraxia do not usually present with eyelid opening difficulties. (2) Eyelid opening and the entire blinking process do not involve actions that must be explicitly learned; instead, they represent a more hardwired repetitive motor pattern. This conceptually defies one of the core components in the definition of praxis errors that it is a disorder of skilled or learned movements. (3) The typical clinical-anatomical correlates of the various types of apraxia which usually show left or bihemispheric cortical damage have not been routinely reported in patients with scAEO. (4) A significant proportion of scAEO patients have extrapyramidal diseases like progressive supranuclear palsy or Parkinson’s disease where the extrapyramidal motor system is not intact, a further testament against an “apraxia” label. (5) Finally, the occurrence of episodes of involuntary drooping of the eyelids in scAEO patients is anathema to the definition of apraxia as this does not involve the conceptualization or the voluntary execution of any movement.6,8,11,14,16–20,34,37,42,55,56

It could be argued that if a very loose etymological definition of the term “apraxia” is applied such as identifying the condition as a “failure of motor command” or “the failure to produce the correct movement in response to a verbal command,”19,58 then the term could be overstretched to include disorders such as eyelid and gate apraxias.9,19,58 However, the overwhelming evidence strongly suggests that the “apraxia” label is a misleading interpretation of the clinical manifestations of scAEO.

scAEO and Dystonia

Blepharospasm fulfills most of the criteria of a dystonic condition and clearly qualifies as a form of focal dystonia.5,6,59,60 Over the past 3 decades there has been a widespread agreement in the literature that scAEO is also a form of focal dystonia.4,6,15,19,61–67 There is mounting evidence that there is a consistent association between blepharospasm and scAEO, as several clinical and demographic features are shared by both conditions.5,15,37,42,61–64 Supporting clinical evidence includes: (1) The relief of scAEO in some patients by gestes antagonistes or “sensory tricks” suggests that the condition is a dystonic phenomenon.6,15,19,65–67 (2) The induction or aggravation of scAEO by external sensory stimuli (sometimes referred to as modulation by action), such as repetitive glabellar tapping or eyelash touching, is also a well-known feature of focal dystonias supporting the concept that scAEO is a dystonic condition.6,17 (3) Increased blinking, a precursor condition which is considered by some authors to be a forme fruste of BSP, may also be associated with scAEO,3–6 and all 3 conditions (DB, BSP, and scAEO) may coexist in the same patient.4,8,35 (4) The favorable response to botulinum toxin injections (BTX) in some patients with scAEO also supports the concept that this condition is a form of dystonia.6,19,21,68 Moreover, scAEO may rarely be unmasked by BTX chemodenervation of the preseptal OO.5,37 (5) The incidence of scAEO in BSP patients may be significantly higher than the classically reported figure of 7%, and the incidence is especially high (88%) among BSP patients who are refractory to BTX.15,61 (6) Both scAEO and BSP are observed in patients suffering from diseases affecting the extrapyramidal system including PD and PSP and they may even coexist in these diseases.16,69 (7) Both scAEO and BSP can be induced (occasionally simultaneously) or relieved by treatment modalities for PD like levodopa treatment or deep brain stimulation of the subthalamic nucleus (STN-DBS).6,7,69 (8) Finally, a combined BSP-scAEO picture has been reported to be induced by lithium intoxication or bilateral subthalamotomy.6

From a purely clinical standpoint, the above-mentioned evidence should not automatically classify scAEO as a focal dystonia as has been repeatedly suggested in the literature because dystonia is a hyperkinetic movement disorder that is defined by its spasmodic muscular contractions and postural abnormalities.7,38,47,70–72 No such movements are clinically observed in patients with scAEO, and it presents clinically as a hypokinetic condition.38,65 In fact, the very definition, as well as the diagnostic criteria of scAEO, require the absence of clinically discernible eyelid muscle contractions which logically disqualifies the condition as a dystonia. It could be counterargued, however, that the transient episodes of eyelid drooping observed in scAEO could be considered a postural abnormality in its own right, and some authors liken episodic eyelid drooping to the familiar postural abnormalities observed in patients with focal dystonia.6 Nevertheless, the absence of other relevant hallmarks of dystonia, such as excessive clinically visible muscle activity and patterned or twisting movements,7 is still in clinical disagreement with a dystonia label.

scAEO and Freezing Phenomenon

The characteristic lack of muscular movement in scAEO has led several authors, particularly recently, to reject labeling the condition as an atypical form of focal dystonia, and to suggest instead that it is more akin to a freezing phenomenon.14,25-33 A freezing phenomenon (motor block) is a term used to describe a poorly understood hypokinetic movement disorder with largely unknown underlying neuromuscular mechanisms. It is characterized by transient periods, usually lasting several seconds, where an attempted motor activity is halted and the organ in question (usually a limb) appears as if it is stuck in place.14,25–33,73,74 The classic example is freezing of gait (FOG), which is one of the most disabling symptoms of PD. FOG patients suffer from episodic attacks where the gait completely freezes and there is an inability to generate forward movements. Rarely, external cues can help alleviate the condition, and when the freezing has cleared, the patient may perform the task normally. It is interesting to note that FOG has also been erroneously termed gait apraxia in the past.19

There are several clinical similarities between scAEO and FOG: (1) In patients with scAEO, the eyelids are transiently closed as if they are frozen in place, and at the same time, the frontalis muscle continues to contract in an attempt to open the eyelids. (2) Both conditions may be aggravated by environmental triggers.74 (3) Both conditions may be relieved by external stimuli although these are quite rare in FOG.25,74 (4) Both conditions can be associated with PD or PSP.26 (5) STN-DBS can either alleviate or deteriorate either condition,7,74,75 and (6) both FOG and scAEO may coexist in the same patient.31,32,67

Despite the striking clinical similarities between FOG and scAEO, there are several profound differences,74,76,77 and some authors find it unjustifiable to simply transfer the term “freezing” to the eyelids.26 In contrast to scAEO where the clinical manifestations are easy to elicit and the symptoms are nearly constant, FOG is characterized by its markedly episodic nature and is hallmarked by its high clinical variability, which makes the condition exceedingly difficult to observe in the clinic.74,77 More importantly, sensory input modifiers (gestes antagonistes) are common in patients with scAEO, BSP, and in patients with other focal dystonias, but are highly unusual in patients with gait freezing.76 If such modifiers are present, they are not considered gestes antagonistes because, by definition, a sensory trick should be applied to the same body region where the abnormal movement is originally observed, which is not the case in FOG. Consequently, in patients with FOG, these are referred to as “compensation strategies” and not sensory tricks, because they involve other external or internal cues including various auditory, proprioceptive, or visual stimuli.76,78

The Electromyographic Evidence

In the previous section, it was shown that based on clinical criteria, scAEO does not clearly fit in the accepted definitions of apraxia, dystonia, or freezing phenomenon. Over the past several decades, EMG analysis of the LPS and pretarsal OO muscles has been the major focus of studies to explain the etiology of scAEO.3,5,6,9–18 Although a limited number of studies evaluating the EMG patterns in the LPS and pretarsal OO in scAEO patients have been published between 1985 and 2022,6,8,10,17,34–37,42,79,80 as a group these studies suffer from inconsistencies in methodology so that direct comparisons are not always possible. In some studies with a mixed cohort of patients (scAEO, BSP, and DB) it was difficult to identify those who fulfilled the clinical criteria of scAEO from patients who did not. In others, it was not always possible to determine precisely whether the measurements concerning scAEO patients were obtained solely from the pretarsal orbicularis, or from the preseptal and orbital OO as well.8,17,34,42 Some studies took EMG tracings from both the LPS and OO after some of their patients recently received botulinum toxin injections,8,10,42,80 but they did not stratify the results according to the BTX injection status. Despite these limitations, the empirical evidence or rough data from these studies is consistent enough to make cautious generalized assumptions about the EMG patterns in scAEO patients. Furthermore, there are some technical difficulties in obtaining reliable EMG measurements from the LPS muscle.4,56

Although some electrophysiologic studies found as many as 6 different EMG patterns in patients with scAEO, after exclusion of patients with isolated BSP or DB, and patients where BSP or frequent blinking simultaneously coexisted with eyelid opening impairment, 3 distinct electrophysiologic patterns were identified among the 94 cases reported.8,10,17,23,34-36,42,80 The first pattern (pretarsal blepharospasm, ptBSP) shows involuntary subclinical dystonic discharges in the pretarsal OO alone with minimal or no abnormalities in other portions of the orbicularis muscle (n = 26/94 [27.6%]).23,36,80 This is usually combined with normal reciprocal innervation and inhibition between the OO and LPS muscles and, therefore, normal tonic activity of the LPS. Rarely, there may be brief episodes of co-contraction of the LPS/pretarsal OO (incomplete reciprocal inhibition) or a few episodes of inappropriate LPS inhibition.35 This firing pattern, the clinical picture of which is nearly identical to scAEO, qualifies as a dystonia and is considered a variant or subtype of blepharospasm with a selective isolated contraction of the pretarsal OO.10,15,35,80–82

The second EMG pattern (disturbed reciprocal innervation, DRI) consists of involuntary dystonic discharges in the pretarsal OO muscle, with intermittent episodes of involuntary inhibition of the LPS intermingled with brief bursts of LPS contractions.10,17,34-37,45,79,80 This pattern is difficult to distinguish electromyographically from ptBSP since the motor persistence of the OO is also localized to the pretarsal fibers while the preseptal and orbital portions of the OO remain quiet. It is the more widespread abnormal activity in the LPS that differentiates these 2 types but both types may be regarded as a continuum. These irregular bursts in LPS activity in DRI are initially insufficient to overcome the persistent pretarsal OO contractions and appear clinically as episodes of involuntary impairment of eyelid opening that continue until the LPS regains its usual tonic activity.8,35 This pattern was the most common type among the 94 reported cases (n = 53/94 [56.38%]) and represents a disturbed reciprocal innervation/inhibition of these 2 antagonistic muscles, the activity of which needs to be precisely coordinated to modulate eyelid blinking.4,35 Of note is that similar agonist/antagonist muscle cocontraction abnormalities are a typical characteristic of dystonic disorders and are partly responsible for the abnormal twisting movements seen in dystonias.1,4,7,38 This predominant EMG pattern is also in agreement with a dystonic label.3–6

The third EMG pattern, (involuntary levator inhibition [ILPI]) is the rarest type (n = 15/94 [15.9%]) and is hallmarked by a normal reciprocal relation between the OO and the LPS, along with episodes of involuntary LPS inhibition during periods of complete OO inactivity that involves the entire muscle including the pretarsal OO.8,17,23,34,36,80 This electromyographic silence of the LPS along with a quiescent and normal OO is consistent with the classic description of AEO and has been referred to as “involuntary levator palpebrae inhibition” (ILPI), or the true type of eyelid apraxia.22,41 According to some authors, ILPI is not compatible with a dystonia, but may more properly conform to the definition of a true apraxia,22,27,37 a notion which has already been discredited in the previous section about clinical evidence.

Is scAEO Part of the BSP Spectrum?

From a clinical viewpoint, ptBSP, DRI, and ILPI are nonparalytic disorders with a nearly identical clinical picture,3–6 and it is tempting to conceive that they are also etiologically interrelated. However, the electromyographic findings outlined above show that only 84% of scAEO cases are focal dystonias, but the levator silence in ILPI does not fit the definition of a dystonia, and it is not clear whether ILPI is (1) a rare curiosity; a completely separate condition with an enigmatic pathophysiology,5,6,22 or (2) simply a variant of BSP which lies along the same BSP dystonic spectrum that also includes ptBSP, DRI, and frequent blinking. In contrast to these conditions, an underlying muscle responsible for LPS inhibition in ILPI is not yet known.4,6,17,34,36,37

The Case for Splitting ILPI From ptBSP and BSP

There is plenty of evidence in the literature to suggest that ILPI does not fit in as a dystonic disorder or as a subtype of BSP and may indeed be a distinct disorder with a different pathophysiological basis.33,62,80 In addition to the unique EMG features of either type outlined above, there are additional clinical, electromyographic, and radiologic features that suggest that both conditions are not identical.

It is possible, although quite difficult, to clinch the diagnosis of ILPI clinically and without EMG.8,23,34,41,42,80 The shared clinical feature in patients with ILPI and patients with ptBSP is the inability to open the eyelids,42 although there may be subtle differentiating clinical points. Patients with ptBSP may present with lower eyelid elevation41 or involutional entropion18 due to a sustained contraction of the pretarsal OO in the lower eyelids while patients with ILPI do not. On the other hand, patients with ptBSP, once they manage to open the eyelids after a bout of involuntary closure, do not experience the characteristic difficulty in keeping them open since the tonic activity of the LPS is relatively intact. This is in contrast to patients with true levator silence (ILPI) who typically show episodes of involuntary drooping and may not be able to keep their eyelids open.8,41,42

Blink reflex studies have been used to assess the pathway from the trigeminal nerve through the brainstem to the facial muscles. The afferent limb of the blink reflex is mediated by sensory fibers of the ophthalmic division of the trigeminal nerve (CN V) and the efferent limb by motor fibers of the facial nerve. The blink reflex has 2 components, an early R1, and a late R2 response. The R1 response is usually present ipsilaterally to the side being stimulated, whereas the R2 response is typically present bilaterally. The R1 response is thought to represent the disynaptic reflex pathway between the main sensory nucleus of CN V in the mid-pons and the ipsilateral facial nucleus in the lower pontine tegmentum. The R2 responses are mediated by a multisynaptic pathway between the nucleus of the spinal tract of CN V in the ipsilateral pons and medulla, and interneurons forming connections to the ipsilateral and contralateral facial nuclei.3–6,45,65,83,84 Studying brain stem reflexes such as the R2 blink reflex recovery cycle may shed indirect light on the excitability of brain stem interneurons and may give some clues about the pathophysiological mechanisms underlying BSP or its allied disorders.3,4,45,65,83,84 The R2 reflex is known to be abnormally enhanced in patients with generalized dystonia, focal dystonia, oromandibular dystonia, as well as in BSP and ptBSP and even hemifacial spasm.21,75,80,83-87 However, the only study in the literature that examined the R2 reflex in ILPI found it to be completely normal, which implies that ILPI may possibly be a distinct entity.80 Of note is that linking R2 findings to the underlying pathology in conditions where it is found to be abnormal remains challenging.22 All that is established so far is that the blink reflex recovery is not an endophytic marker for the diagnosis of BSP or its allied disorders since it is also abnormal in other conditions. On the contrary, it may be considered an index of disease severity,88,89 and as discussed later, it is quite possible that the R2 reflex may be normal in ILPI patients due to a focal involvement of a small but discrete portion of the OO muscle.

The widespread distribution of CNS lesions in patients with scAEO also suggests that it is not a single disease entity, because scAEO has been described in association with basal ganglia, frontal lobe, and brain stem diseases, as well as other cortical dysfunctions including nondominant or dominant hemisphere lesions.90 Although the technical accuracy of some of these case reports has been contested,6 a clinical phenomenon that cannot be ascribed to a specific location in the nervous system cannot automatically be considered a single disease entity without further scrutiny. However, as discussed later, the variable results obtained with neuroimaging may merely suggest that similar to BSP, scAEO is also a network disorder that is not circumscribed to a single anatomic location.

The Case for Lumping ILPI With ptBSP and BSP

As mentioned earlier, ptBSP/DRI and ILPI are closely interrelated clinically, and since ptBSP is a subtype of BSP, it is quite possible that all 3 conditions belong to the same atypical focal dystonic eyelid spectrum. However, the clinical picture of ILPI is of a hypotonic anomaly that defies the central etiopathogenic event in focal dystonias, which is increased muscle activity.

Several recent studies have clearly identified BSP as a phenomenologically heterogeneous disease.50,91–93 This heterogeneity may manifest with variability in the duration of muscle spasms (short, long, or combined short/long spasms), and the presence of additional associated symptoms including increased blinking (DB) or bouts of involuntary eyelid rim closure (scAEO).48–50,93 This clinical and electrophysiologic heterogeneity may be related to the involvement of different anatomic parts of the OO including the pretarsal, preseptal, or orbital OO,50 a notion that has been confirmed repeatedly by EMG testing in patients with ptBSP. Most anatomic descriptions of the OO refer to 3 contiguous portions, the orbital, preseptal, and pretarsal portions. A fourth region of the OO that is anatomically separate from the others is the muscle of Riolan along the eyelid margin.94 Although all 4 portions of the OO muscle complement each other in eyelid closure, the muscle of Riolan has long been neglected in BSP research, and there are few clinical/surgical reports that single out the involvement of this muscle.95–97 Furthermore, no electrophysiologic studies have ever been conducted on the muscle of Riolan either in the setting of BSP or in scAEO, probably due to obvious technical difficulties. The authors of the present study propose that a subclinical dystonic spasm of the muscle of Riolan might impair reactivation or resetting of the LPS, which might then explain the anomalous clinical and electrophysiologic manifestations of ILPI. While the idea of a focal dystonic involvement of that tiny portion of OO that occupies the eyelid margin might seem remotely possible, there is ample supporting evidence that a remarkable selectivity of these “weak and scrawny”98 muscle bundles are quite possibly the culprit.

The biologic maxim that “structure dictates function” is beautifully illustrated in the OO muscle.99 Microscopic examination of the different portions of the OO shows that there are several distinguishing ultrastructural features that differ between one part of the muscle and the other, such as muscle fiber length, the proportion of muscle/fat/fibrous tissue, the ratio of fast (type II) versus slow (type I) muscle fibers, and the extent of neuroinnervation (per surface area).99-103 These dissimilar microscopic findings could help explain the divergent biologic functions of each segment of the OO and could lend credence to the notion that BSP heterogeneity is based on selective involvement of certain subsets of the OO muscle.50 While the preseptal and to a greater extent the orbital OO control forceful volitional blinks and the pretarsal OO mediates involuntary blinking,99 the muscle of Riolan, despite its delicate structure, can play a significant role in crucial eyelid functions like eyelid apposition, eyelash position, and meibomian expression,50,94,99,104 and it is believed to be a major instigator in maintaining eyelid position both at rest and during blinking.95–97,105 This tiny muscle can also wreak havoc on meibomian gland function in paralytic conditions like facial nerve palsy,106 and may even cause visual disturbances following pretarsal injection of BTX due to the buildup of meibomian debris on the corneal surface.107 Of note is that previous generations of researchers were aware of the functional relevance of this muscle and considered it a no-go zone in OO myectomy procedures for refractory BSP because of the potential for lagophthalmos.97 Yet for reasons unknown, the muscle of Riolan has rarely been implicated in the pathogenesis of BSP/scAEO.95–97

Neuroanatomically, it is also established that the facial motor neuron pool shows somatotopic compartmentalization within specific regions of the nuclei, sending efferent motor neurons to specific facial muscles, and presumably to localized regions within individual muscles that subserve different functions.108,109 The concept of dividing individual muscles in distinct neuromuscular sub-compartments, each with its unique physiological attributes and heterogeneous functions is well established in the literature and is termed the “muscle partitioning hypothesis”.108,109 This potential compartmentalization of function has been demonstrated repeatedly in the OO muscle by tracer studies where the proportion and location of the motor neuron pool allocated to the representation of the OO muscle in different facial subnuclei appeared to differ and to have a specific distribution pattern according to the innervated portion of the OO. This probably reflects the different functions that each of these OO muscle portions subserves.110–112

Indirect EMG evidence also supports the Riolan hypothesis. The discrepancies in eyelid kinematics depicted by EMG in patients with scAEO and occasionally in BSP/DB patients4,6,8,34,79 suggest that the reciprocal contractile relation between the LPS and the OO is imprecise not just in scAEO but in BSP and DB as well. As mentioned earlier, some phasic contribution from the OO is required to regulate or refresh the activity of the LPS after a blink ends.4 Traditionally, this regulatory action was thought to reside in the pretarsal OO.6 However, there is histological and clinical evidence to suggest that this resetting action is mediated at least in part by the muscle of Riolan.95,96 Ultrastructurally, the muscle of Riolan is almost completely composed (91.7%) of fast type II muscle fibers, a ratio that is significantly higher than any other portion of the OO including the pretarsal OO.100 The predominance of fast muscle fibers is generally required for the execution of rapid or phasic muscle actions (e.g., spontaneous blinking), whereas the predominance of slow muscle fibers is responsible for tonic or slow contractions.113,114 Of the 3 studies in the literature that have evaluated the possible role of the muscle of Riolan in scAEO or BSP,95–97 2 studies injected BTX in the vicinity of the Riolan muscle “as close as possible” or “as near as practical” to the edge of the eyelid margin in patients with typical BSP, scAEO, and in patients with BSP refractory to regular BTX injections.95,96 Both studies noted a substantial beneficial effect with some patients showing an unexpected almost immediate symptomatic improvement following the Riolan injections, and the majority of patients preferred the new injection site over traditional ones. A third study evaluated the beneficial effect of disabling the muscle of Riolan in combination with standard OO myectomy in patients with BSP refractory to BTX and reported better outcomes than previous studies employing conventional protractor myectomy techniques.97 It would be interesting to speculate whether, in the future, with the refinement of neurophysiologic techniques, the results of an EMG study in ILPI patients would support or refute the authors’ concept that persistent involuntary discharges of the Riolan muscle may impede the ability to reactivate or reset the LPS causing eyelid opening impairment.

This apparent shift of interest towards the muscle of Riolan remains unproven and is merely a hypothesis that is put forward by the authors for future studies. However, there are other indicators from current dystonia research that may help provide an alternative explanation for the neurophysiological silence of the levator muscle in ILPI, which supports the concept that ILPI is a dystonia although the evidence is less clear. Traditionally, focal dystonias including BSP were erroneously believed to be classic textbook examples of basal ganglia disease,7,86 but contemporary understanding suggests that other brain regions are involved in the pathogenesis of dystonias and BSP.4,7,52,53,70,71,115-120 In this broader view, BSP is viewed as a network disorder where the basal ganglia would represent only one node in a wider dysfunctional sensorimotor network that is ultimately involved in abnormal motor performance.7,45–48,52,115–124 A similar dysfunctional sensorimotor network model centered around the cerebellum has been recently demonstrated in hemifacial spasm (HFS), a presumably independent hyperkinetic movement disorder that was traditionally considered to be an exclusively peripheral disorder and was not attributed to central mechanisms.125 scAEO is also ascribed to several different anatomic locations in the brain rather than a single dominant brain region,90 which suggests that such a network dysfunction model could be hypothetically adopted for scAEO. Nevertheless, this hypothetical dystonic network model still misses out on the hypokinetic nature of ILPI unless the controversial hypokinetic features of dystonia are taken in consideration52,60,120,126–128 Allegedly, patients with focal dystonia may paradoxically present with subtle paretic (strength deficits) or bradykinetic (movement slowness) symptoms, and they may occasionally exhibit deficits in the ability to produce maximum motor output.65,121-123,129-132 Although these hypokinetic features do not fit the standard model of dystonia as an exclusively hyperkinetic movement disorder,52,65,116,117 several researchers have attested that despite their overwhelming hyperkinetic features, some dystonia patients do have a phenomenologically heterogenous spectrum with a variable muscle tone.38,39,65,133,134 Of note is that all 3 EMG patterns that were outlined above in scAEO patients have also been observed before in other focal dystonias.65 These include as follows: (1) excessive isolated activity of a target muscle, or (2) co-contraction of agonist and antagonist muscles; and counterintuitively, (3) failure to activate one of the target muscles voluntarily.38,60,65,127 Although failure of muscle activation may appear contrary to the principal EMG deficit in dystonia, which is over-facilitation of muscle action,60,127 there are confirmed clinical scenarios where dystonic patients could not resume the normal range of movement after all the overactive muscles have been treated, probably due to failure of central activation of the agonist muscle.38,127,129,109-111 These atypical features of dystonia support the controversial “negative dystonia” concept, which argues that the overall muscle disturbance in dystonia etiologically occurs due to a defective central regulation of muscle activity, a notion which agrees with the network model for dystonia.38,72,134-145 Proponents of the negative dystonia hypothesis arguably contend that in addition to the core dystonia feature of spasmodic muscle contractions, hypotonia resulting from the failure to activate a muscle required for the performance of a specific type of movement is an overlooked aspect of dystonia and hence the term “negative dystonia” or “minus dystonia”.38,39,72,134,146,147 To the best of the authors’ knowledge, only recently has the concept of negative dystonia been supported in the literature, and so far only in the palate, where negative dystonia of the levator veli palatini, the muscle that normally elevates the velum during phonation, is hypothesized to be responsible for a hypernasal tone of voice in patients with dystonia.72 Although the evidence is underpowered, it resonates with levator silence in patients with ILPI.


This systematic review evaluated 3 mutually exclusive hypotheses on the most likely nature of scAEO; that it either represents an apraxia, a freezing phenomenon, or a dystonia. This evaluation was based on both clinical and electromyographic evidence. In contrast to BSP, which fulfills the definition of a focal hyperkinetic dystonia,54 scAEO suffers from a duality paradox both clinically and electrophysiologically. Although scAEO shares several cardinal features with dystonic phenomena (e.g., gestes antagonsites and modulation by action) and may coexist with BSP in the same patient, it clinically resembles a hypokinetic phenomenon as it is hallmarked by the complete absence of any visible spasmodic contractions in 100% of patients. As the authors discussed in detail earlier, the apraxia label is clearly a misnomer, and scAEO is a hypotonic condition that is clinically reminiscent of a freezing phenomenon, but it has some peculiar dystonic features which do not fully concur with labeling the condition as a freezing phenomenon.

On the other hand, data from electrophysiologic testing shows that the vast majority of scAEO patients (84%) predominantly express a typical dystonic pattern due to subclinical spasmodic contractions of the pretarsal OO or a disturbed reciprocal relation between the pretarsal OO and the LPS, and thus easily qualify as dystonic. However, 16% of patients suffer from a hypokinetic levator silence (ILPI) which does not fit the dystonic spectrum. The authors propose that similar to ptBSP and DRI, the remaining 16% are also dystonic due to a subclinical spasmodic contraction in the muscle of Riolan, which impedes the ability to reactivate or reset the levator in ILPI patients. Thus, although the neuromuscular apparatus of the LPS is intact and the reciprocal relation between both muscles is preserved, spasmodic contractions of the muscle of Riolan may be responsible for the levator silence in ILPI patients which has confused clinicians for decades. Although this unproven hypothesis is intuitively plausible and solves the contradictory dilemma about ILPI patients who do not completely fit into any of the 3 established categories (apraxia, dystonia or freezing), it remains a concept that is not yet confirmed and requires future verification with EMG testing or functional imaging if refinements in either technique overcome the current technical limitations for examining a remarkably minute muscle. Table 1 summarizes the contractile pattern of the different portions of the orbicularis oculi and the levator palpebrae superioris muscles in normal and abnormal blinking that have already been demonstrated in the literature, as well as those proposed by the authors.

TABLE 1. - The contractile pattern of the different portions of the orbicularis oculi and the levator palpebrae superioris muscles in normal and abnormal blinking
Involuntary blinking* Forceful (volitional) blinking BSP ptBSP DRI rmBSP
Orbital OO Quiescent Contracts Contracts Quiescent Quiescent Quiescent
Preseptal OO Contracts Contracts Contracts Quiescent Quiescent Quiescent
Pretarsal OO Contracts Contracts Contracts Subclinical contraction Subclinical contraction Quiescent
Muscle of Riolan Contracts Contracts Contracts Subclinical contraction Subclinical contraction Subclinical contraction
LPS Reciprocal inhibition Reciprocal inhibition Reciprocal inhibition Reciprocal inhibition Intermittent reciprocal inhibition Reciprocal inhibition
Data compile from3-6,99.
* This category encompasses both spontaneous and reflex blinking.
Presumptive contraction. No data is available to support or refute the authors’ designation.
BSP, blepharospasm; DRI, disturbed reciprocal innervation; OO, orbicularis oculi; ptBSP, pretarsal blepharospasm; rmBSP, Riolan muscle BSP.

An alternative less credible explanation is that as a network disorder, BSP as well as other focal dystonias may have a negative hypotonic aspect as part of their neural signature that has been overlooked so far, which if proven could explain the levator silence of ILPI. However, solid neurophysiologic and/or functional radiologic evidence is largely lacking. Dystonia is a remarkably heterogeneous entity, and it is quite possible that this may be verified in the future if the alleged negative or hypokinetic features of dystonia are linked to specific unexplored areas in the sensorimotor network that is etiologically responsible for dystonias. Until such time when either hypothesis is established, the authors suggest coining the term Riolan muscle BSP (rmBSP) instead of the term ILPI and substituting the term scAEO with the term atypical focal eyelid dystonia (AFED); as these updated terms (rmBSP & AFED) holistically encompasses both the clinical and EMG data illustrated above and concur with the authors’ theorem.


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