Eyelid Movements in Health and Disease. the Supranuclear Impairment of the Palpebral Motility

ORIGINAL ARTICLE

Eyelid movements in health and disease.The supranuclear impairment of the palpebralmotility

Ángel Esteban *, Alfredo Traba, Julio PrietoService of Clinical Neurophysiology, Hospital General Universitario “Gregorio Marañón”,c/ Dr. Esquerdo, 46, 28007 Madrid, Spain

Received 12 September 2003; in revised form accepted 13 January 2004

KEYWORDSEyelid movements;Blinking;Blink reflex;Lid retraction;Blepharospasm;Blepharocolysis;Eyelid openingdisorders;Dystonia;Bell’s phenomenon;Cerebral ptosis

Abstract The eyelid movements are mediated mainly by the orbicularis oculi (OO) and thelevator palpebrae superioris (LPS) muscles. Dissociated upper lid functions exhibit differ-ent counterbalanced action of these muscles, and in blinking they show a strictlyreciprocal innervation. The disturbance of this close LPS–OO relationship likely leads tomany of the central lid movement disorders. Three groups of supranuclear motorimpairment of lid movements are considered: the disorders of the lid-eye movements’coordination, the disturbances of blinking and lid “postural” maintenance, and thealteration of voluntary lid movements. Nuclei of the posterior commissure control theinhibitory modulation of LPS motor-neuronal activity and they are involved in the lid-eyecoordination disorders such as lid retraction, which is observed in the Parinaud’s syn-drome and also in parkinsonism and progressive supranuclear palsy. Spontaneous (SB) andreflex blinking consist of two components: the inhibition of the basal tonic LPS activity,which keeps the eyes open, and the concurrent activation of the OO muscles. LPSinhibition precedes and outlasts the OO activation. This normal configuration is impairedin parkinsonism and blepharospasm (BSP). SB shows a highly interindividual rate variation(among 10–20 per minute in adults) and abnormal blink rates occur in neurologicaldiseases related to dopaminergic transmission impairments. Lid postural abnormalitiesinclude involuntary eyelid closure, which is usually associated with inability to open theeyes. Two major disorders share these two aspects: BSP and blepharocolysis (BCO). BSPconsists of an involuntary overactivity of the OO, with LPS co-contraction activity, and isexpressed as frequent and prolonged blinks, clonic bursts, prolonged tonic contraction ora blend of all of them. BCO (commonly named “so-called lid opening apraxia”) is anoverinhibition of the LPS with no evidence of ongoing OO activity. BSP and BCO occur inmany instances of idiopathic dystonias and basal ganglia diseases and, less frequently, inrostral brainstem lesions. Both may coincide in the same patient. Voluntary lid movementdisorders comprise the impairment of Bell’s phenomenon, the voluntary eyelid closurepalsy and the so-called cerebral ptosis, all related to lesions of frontal cortical areasand/or the corticospinal system.© 2004 Elsevier SAS. All rights reserved.

* Corresponding author. Tel.: +34-91-5868338; fax: +34-91-5868018.E-mail address: [email protected]

Neurophysiologie clinique 34 (2004) 3–15

www.elsevier.com/locate/neucli

© 2004 Elsevier SAS. All rights reserved.doi: 10.1016/S0987-7053(04)00003-6

MOTS CLÉSMouvements despaupières ;Clignements ;Rétractation despaupières ;Blepharospasme ;Blepharocolysis ;Troubles del’ouverture despaupières ;Dystonie ;Phénomène de Bell ;Ptose cérébrale

Résumé Les mouvements des paupières sont commandés essentiellement par les musclesorbicularis oculi (OO) et levator palpebrae superioris (LPS). Les fonctions dissociées despaupières supérieures nécessitent une action contre-balancée de ces muscles qui, dansleur fonction de clignement, montrent une innervation réciproque stricte. Le dysfonc-tionnement de cette relation LPS–OO entraine l’apparition des principaux troubles desmouvements des paupières. Il existe trois groupes de troubles supra-nucléaires dumouvement des paupières: les troubles de coordination des mouvements palpébraux, lestroubles du clignement et du maintien de la posture des paupières, et enfin l’altérationdes mouvements palpébraux volontaires. Les noyaux de la comissure postérieure con-trôlent la modulation inhibitrice de l’activité du motoneurone du LPS et sont impliquésdans les troubles de la coordination des mouvements des paupières tels que la rétracta-tion des paupières qui est observée dans le syndrome de Parinaud, la maladie deParkinson ou la paralysie supranucléaire progressive. Les clignements spontanés etréflexes sont dûs à deux phénomènes différents: l’inhibition de l’activité tonique de basedu LPS qui permet de maintenir les yeux ouverts et l’activation concomittante du muscleOO. L’inhibition du LPS précède et dépasse l’activation du OO. Cette configurationnormale est détériorée dans la maladie de Parkinson et le blepharospasme (BSP). Il existeune très grande variation interindividuelle dans la fréquence des clignements spontanés(de 10 à 20 par minute chez les adultes) et des fréquences anormales des clignementsapparaissent dans les cas de troubles neurologiques liés au dysfonctionnement de latransmission dopaminergique. Les anomalies de la posture des paupières comprennent lafermeture involontaire des paupières, généralement associée à l’incapacité d’ouvrir lesyeux. Deux troubles montrent ces deux aspects, le BSP et le blepharocolysis (BCO). Dansle BSP il existe une suractivité involontaire du muscle OO avec co-contraction du LPS; cetrouble se caractérise par des clignements fréquents et prolongés, des salves d’activitécloniques, une contraction tonique prolongée ou un mélange de tous ces symptomes. Dansle BCO, appelé également ’apraxie de l’ouverture des paupières’, il apparaît unesurinhibition de l’activité du muscle LPS sans évidence d’activité concomitante du muscleOO. Le BSP et le BCO apparaissent dans les dystonies idiopathiques et les troubles desganglions de la base et, moins fréquemment, dans les lésions du tronc cérébral rostral.Les deux peuvent coexister chez le même patient. Parmi les troubles des mouvementsvolontaires des paupières on trouve le phénomène de Bell, la paralysie de la fermeturevolontaire des paupières et anomalie dénommée « ptosis cérébral », tous ces troublesétant liés à des lésions des aires corticales frontales et/ou des lésions du systèmecorticospinal.

© 2004 Elsevier SAS. All rights reserved.

Introduction

Their eyelids participate in blinking and, in thecoordinated displacement with the conjugate ver-tical eyes movements, in maintaining the upperpalpebral margin near the upper edge of thecorneo-scleral junction at all positions of the eye-ball [1]. Eyelids also move in the voluntary action ofthe eyes’ opening and closing.The eyelid movements are mediated mainly by

the orbicularis oculi (OO) and the levator palpebraesuperioris (LPS) muscles; the sympathetic depen-dent tarsal muscle of Muller is also implicated inmaintaining an open lid position. The first twomuscles exhibit a strictly balanced reciprocal inner-vation, whose derangement probably leads to manyof the lid movement disorders. In the downward lidmotion, some passive forces perform an importantfunction, interacting with the relaxation of the LPS;these passive forces are mainly represented by the

tendon-aponeurotic apparatus of the upper eyelid,that is the levator aponeurosis, the palpebral can-thal tendons and the superior transverse ligament[2]. Other physical factors involving the upper eye-lid, such as stiffness and viscosity, may provide anelastic energy which should contribute to the pas-sive downward tension leading to eyelid closure asthe tonic activity of the LPS decreases [1,3].Dissociated upper lid functions exhibit different

counterbalanced actions of the LPS and OOmuscles: variable LPS tonic activation with the OOinactive occur in the maintaining of the ocularopening, the gentle closing and opening of theeyes, and the lid adjustment to the vertical globepositions, whereas LPS inhibition with the OO acti-vation are the case for all types of blinking and thefirm closure of the eyes [4–7].Apart from the OO and LPS muscles, and espe-

cially in subprimates species, the extraocularmuscles in the coordinated lid/eye movements, as

4 Esteban et al.

well as in blinking and voluntary lid movements,except the obliquus superior, play a concomitantnotable role [1,8,9].Neuromuscular and peripheral nerve lesions may

cause an impairment of the eyelid motility. Well-known conditions of this kind, among many others,are fluctuating palpebral ptosis in myasthenia, pto-sis in oculomotor nerve palsy or progressive ptosisin mitochondrial myopathy, congenital blepharop-tosis, Graves upper eyelid retraction or III nervesynkinesis by aberrant reinnervation. On this occa-sion, however, we will focus attention exclusivelyon the motor lid impairments of supranuclear ori-gin.In attempting a general grouping of the supra-

nuclear motor eyelid abnormalities, three maingroups will be considered: (1) the disorders of thelid-eye coordination movements, (2) the distur-bances of blinking and lid “postural” maintenance,and (3) the alteration of voluntary lid movements.

Disorders of lid-eye coordinationmovements. Lid retraction and lid lag

It is generally assumed that lid retraction of neuro-genic origin might be the consequence of the LPSmuscle overactivity; it is known as the Collier’s signand is typically found in rostral brainstem lesions.In the dorsal midbrain syndrome (Parinaud’s syn-drome), where the pretectal region is involved,conjugate gaze deficits in the vertical plane (pre-dominantly in the up gaze) are usually associated.In this syndrome, however, the inhibition of theLPS-emg activity within spontaneous blinking, vol-untary eye closure, and sleep is preserved [10]. Onrare occasions lid retraction may exhibit an associ-ated lid-lag phenomenon. A detailed clinico-

pathological correlation study of a few cases of lidretraction reported in the literature [10], showedthat the lesional areas were concentrated aroundthe nuclei of the posterior commissure. Thesestructures are involved in the inhibitory modulationof levator motor neuronal activity in the lid-eyecoordination movements. Conversely, in a fewother cases with vertical gaze paralysis without lidretraction, the nuclei and fibres of the posteriorcommissure were preserved and lesions were foundmore rostrally, involving the interstitial nucleus ofCajal, the rostral interstitial nucleus of the mediallongitudinal fasciculus (riMLF) and the periaque-ductal grey matter. The authors stress the crucialrole of the implication of the nuclei and fibres ofposterior commissure in provoking lid retraction. Inthe same way, experimental lesions in monkeysinvolving these structures have provoked variabledegrees of lid retraction [11], and in humans lidclosure has been obtained with the electricalstimulation of a region made up of the periaque-ductal grey matter close to the superior colliculusand the posterior commissure [12] (Table 1 andFig. 1). Lid lag without lid retraction has beendescribed in some rare cases of the pretectal syn-drome [13]. In human pathology, aside from theParinaud’s syndrome, lid retraction has also beendescribed as a relatively frequent sign in parkin-sonism, and a variable degree of lid retraction iscommonly observed in the progressive supranuclearpalsy (PSP), which contributes to patients’ charac-teristic staring face expression from the disease[14].Lid nystagmus consists of a jerky movement of

the eyelids associated or not to ocular nystagmus. Itis usually evoked by lateral gaze and ocular conver-gence and has been ascribed to different levels ofbrainstem lesions and of the cerebellar system.

Table 1 Anatomical data for eyelid movement (brainstem and diencephalic levels).

Authors Animal Experimental/clinicalsetting

Anatomical sites (movements characteristics)Eyelids opening Eyelids closing

Weinstein andBender [76]

Monkey Lesion – Tegmental pons (OO contralateral)

Van Buren [52] Human Stimulation Caudate n. (“rapid burst of blinking”)Nashold et al. [12] Human Stimulation Dorsolateral midbrain

tegmentum, belowsuperior colliculi

Periaqueductal grey matter, superiorcolliculus, posterior commissure

Nashold and Gills [77] Human Lesion – Prerubral fields of Forel and rednucleus (“loss of volitional eyelidopening”)

Pasik et al. [11] Monkey Lesion Pretectal-posteriorcommissure (upper lidretraction)

–

Nashold et al. [50],Nashold [51]

Human Stimulation – Midbrain, ventral to the superiorcolliculus and central grey matter(“...and rhythmic lid flutter”)

5Eyelid movements in health and disease. The supranuclear impairment of the palpebral motility

Disturbances of blinking and lid posturalmaintenance

Blinking and blink abnormalities

Spontaneous blinking (SB) is a continuous, almostperiodic and symmetrical brief movement of clos-ing and opening of the eyelids which occurs in theabsence of an obvious external stimulus or internaleffort. The SB is part of an intrinsic system whosecentral generator may be composed of differentpremotor structures in the brainstem [9], highlyinfluenced by dopaminergic activity. Reflex blinksare rapid responses to different external stimuli;their afferent pathways are mainly trigeminal, vi-sual and acoustic, and the premotor areas involvepontine and medullary tegmental levels of thebrainstem [15,16]. Voluntary blinks depend on theindividual will under internal or external com-mands. Cortical areas close to those of the frontaleye fields probably mediate these movements [17].Blinking has a fundamental function in corneal

wetting and eye protection (especially spontaneousand reflex blinks) but also is involved in the visualinformation processing. Other lid movements par-ticipate in motor synchronization with eye saccadesand with compensation of the eye position in theorbit, and in the motor expression of behaviouralstates [8]. All eyelid movements are precisely con-jugated between both eyes.Spontaneous and reflex blinking normally con-

sists of two different components. One is the inhi-bition of the sustained activity of the LPS musclesthat keep the eyes open and the other is the brief,

concurrent activation of the OO muscles. Once ablink stops, normal tonic activity of LPS is immedi-ately resumed, while the OO returns to a restingposition [4,5,7]. The kinematics of the superior lidduring blinks, explored by means of the electro-magnetic search coil technique, consist of a firstrapid down phase, followed by a slower up-phasewith a variable total duration; reflex blinks show aduration of around 200 ms [9] which is shorter thanthe voluntary or spontaneous ones [2]. The loweringof the eyelid occurs during the down-phase, and isdirectly related to a brief contraction of the OO;their respective durations show a linear relation-ship [2]. The closing tendon-aponeurotic forces,already mentioned, released by the immediatelyprior LPS inhibition, help promote ultimate closure.The following up-phase depends entirely on theresumption of LPS activity, which may exhibit aninitial reinforcement over the level previous to theblink, a facilitation postinhibition [5,18], or it maysimply resume the same basal level of its tonicactivity with the eyes open; the former patternresults in a shorter up-phase [2].In normal SB, as well in voluntary or reflex blink-

ing, the total duration of the OO activation is lessthan the inhibition period in LPS; that is, LPS inhi-bition precedes and outlasts the total span of theOO activation (Fig. 2). In spontaneous and voluntaryblinking, the OO-EMG activity is gradually built-upand has a longer duration and smaller peak ampli-tude than that of the reflex blink. The pretarsalportion of this muscle is the one principally oruniquely involved in the phasic OO contraction dur-ing the SB, whereas the activation of the parsorbitaria is predominant in the mechanically elic-

Figure 1 Schematic depiction of brainstem loci regarding movements of the eyelids based on data described in Table 1. PC, posteriorcommissure; MLF, medial longitudinal fascicle; SC, superior colliculus; PGM, periaqueductal grey matter; RN, red nucleus; SN,substantia nigra; PT, pyramidal tract.

6 Esteban et al.

ited reflex blink [19]. In humans, the duration ofthis EMG phenomenology has been estimated atabout 70–130 ms [4,5,7,18,19]. In the differenttypes of blinks and in all animal species studiedincluding humans, eye movements accompany theeyelid movements [1,7–9]. Eyeball shows a retrac-tion and rotation in different planes, which areprobably due mainly to the co-contraction of thesuperior and inferior rectus muscles [1]. A briefupward movement of the eyeballs in SB was firstobserved by Bell [20] and later corroborated byBender [21]. A phasic reinforcement of the rectussuperior EMG activity has been described during SBand the glabellar tapping [7,22]. More recently,however, a predominant eye movement of down-ward and nasalward direction has been reported[9].In blink reflex induced by the electrical stimula-

tion of the supraorbital nerve, two related pausesof inhibition appears within the tonic activity of theLPS muscles [7], besides the known R1 and R2components of the OO reflex response [23]. Unlikethe unilateral R1 and bilateral R2 components ofthe OO reflex response configuration, the two LPS

inhibitory components, I1 and I2, are bilaterallyobtained with unilateral stimulation from each side[16]. The duration of the I2 LPS inhibitory compo-nent is greater than the duration of the R2 OOactivation, preceding and outlasting respectivelythe onset and the end of the orbicular component.Furthermore, the inhibitory pauses of the LPS activ-ity appear that the active responses of the OOmuscles [7,16].The spontaneous blinking has an interindividual

variable rate and is highly influenced by multiplefactors, especially of the emotional and attentivetype. In adults, rates show a wide variation be-tween 10 and 20 blinks per minute [24–26], al-though it is remarkably constant in a given indi-vidual [27]. In a personal observation on non-neurologic adults patients in a hospitalenvironment, a mean blinking rate of 16 (range9–22) was found. Rates are low in infancy, increasein childhood years, and stabilize in adulthood [24].In elderly people, blink rate exhibits no substantialchanges, while blink kinematic shows a decrease inamplitude and velocity [28]. A close relationshipbetween blink rate and dopaminergic level trans-

Figure 2 EMG recording of the LPS and different portions of the OO muscle. (A) Normal spontaneous blinking. LPS inhibition periodprecedes and outlasts the total span of the OO activation. (B) Dystonic spontaneous blinking in blepharospasm. Co-contraction of theLPS and OOmuscles activities. A longer duration of the OO activity related to the inhibition of the LPS is shown. LPS, levator palpebraesuperioris muscle; OO, orbicularis oculi muscle; UE, upper eyelid; LE, lower eyelid; PP, pars palpebralis; PO, pars orbitaria.


mission is supported, based on the variations ob-served in a series of diseases with impairment ofthis neurotransmitter. SB rate has been proposed asa marker for the central dopaminergic activity [29]but a serotonergic implication has also been sug-gested [30].Variation of blinking rate has been observed in a

number of neurological diseases, many, but not all,related to alteration of the dopaminergic transmis-sion. In Parkinson’s disease, rate of blinking isdecreased [29,31] and prolonged blinks are ob-served due to the delay of levator in resuming theactivity after the end of the orbicularis twitch [6].In PSP, blink rate is extremely reduced, aroundthree per minute, and “slow blinks” have also beendescribed [32] Patients with either schizophrenia orHuntington’s disease show higher blink rates thannormal subjects [31,33]. Blink frequency in BSP isincreased, especially during the onset phase of thedisease [26,34,35]. Configuration of spontaneousblink is also abnormal in this focal dystonia; in aseries of 13 cases, the mean blinking rates wereincreased and many instances of blinking showed alonger duration of the OO activity related to theinhibitory period of the LPS, resulting in a partialco-contraction of these antagonistic muscles(Fig. 2). Mean duration of the OO activation (parspretarsalis) in BSP (123 ± 10 ms) was significantlylonger than in patients without central motor eye-lids disturbances (89 ± 14.7 ms) while the durationof the LPS inhibition remained almost identical inthe both groups (102 ± 8.5 ms and 104 ± 14.5 ms,respectively) [36]. This is what we have termed

dystonic blinks. Loss of SB, with preservation ofreflex and voluntary blinks, has been reported in apatient with Ballint’s syndrome, suggesting that theparietal cortex should act in the generation/modulation of this kind of blink [37].Blepharoclonus consists of an abnormal rhythmic

eyelid closure by the involuntary contraction of theorbicularis oculi muscles (Fig. 3). The eccentric orvertical gaze [38,39] and the gentle voluntary clo-sure of the eyes [40–42] are common contributingfactors of blepharoclonus, and these conditions arewhere it has its maximal clinical relevance. Ble-pharoclonus has been observed in multiple sclerosis(MS) [38,43], on recovery from severe head trauma[40,41], and in Parkinson’s disease and syndromes[6,42,44]. It has also been described as associatedwith a heterogeneous group of neurological signs ordiseases, such as headaches, Arnold-Chiari malfor-mation, tremor, cranial synkinesis or myoclonus[45–48]. Abnormal eyelids movements similar tothat of the blepharoclonus may occur as part of theBSP [14], but sometimes they has been differen-tially considered [49]. No common defined CNStopographical lesion can be associated with ble-pharoclonus; scattered periventricular and brain-stem lesions have been found in patients with MS[43] and a dysfunction of the cerebellar system hasbeen postulated in a post-traumatic case [40]. Onthe other hand, the stimulation of the midbrain,ventral to the superior colliculus and in the centralgrey matter [50,51], and in the head of the caudatenucleus [52] have provoked rhythmic lid flutteringand rapid bursts of blinking in humans (Table 1).

Figure 3 Blepharoclonus. Repetitive clonic bursts of the OO muscles during the near fixed look in a patient with right trigeminal lesionafter surgery treatment for trigeminal neuralgia. No other neurological signs were present. Fr, frontalis; OO, orbicularis oculi; OOr,orbicularis oris muscles; R, right; L, left.

8 Esteban et al.

The paroxysmal blinking episodes, frequently ob-served as an epileptic phenomenon, have no patho-physiological relationship with the blepharoclonus;their close clinical resemblance, however, couldmake convenient a differential diagnosis in somecases.

Involuntary eyelid closure with inability toopen the eyes

In the normal awake state, eyes are kept open.Brief closing–opening lid movements periodicallyappear corresponding to the normal SB and someintermingled reflex blinks may also occasionallyoccur. The more sustained closing and opening ofthe eyes depends of the subject’s will. The lids dropinvoluntarily when the level of alertness decreases,and they completely close during sleep.There are patients suffering from involuntary

eyelid closure in the waking state, which is usuallyassociated with difficulty in opening them. Thefailure to keep the eyelids open and the inability toinitiate lid elevation should be, therefore, parts ofthe same motor eyelid disturbance [53]. The sameopinion has been recently stressed by Defazio et al.[54]. Two major disorders sharing these character-istics are recognized: blepharospasm and blepharo-colysis. Blepharospasm is an excessive involuntaryclosure of the eyelids characterized by spasms ofcontraction of the orbicularis oculi muscles [34];blepharocolysis is an excessive involuntary closureof the eyelids characterized by a prolonged inhibi-tion of the LPS muscles in the absence of a demon-strated OO contraction [55–57]. In both, the diffi-culty or inability to open the eyes is systematicallyassociated.Blepharospasm is a chronic and progressive dis-

ease which may adopt different clinical aspects,ranging from frequent and strong blinking to clonicspasm to tonic spasm of the eyelids, or a blend of allthem [34,58]. They are usually related to the timeit takes for the disease to evolve and its intensity.

When it reaches a well-developed clinical state,orbicularis oculi muscles can be observed in a moreor less permanent fluctuating contraction with theeyebrows located beneath the superior rim of theorbit (Charcot’s sign). Not infrequently it causes afunctional blindness. Blepharospasm is considereda form of progressive focal dystonia. Idiopathic BSPfrequently occurs in isolation or along with contrac-tion spasms of other cranial muscles (Meige’s syn-drome); many cases with familial generalized orfocal dystonias show BSP; it also can be associatedwith other neurological diseases, such as Parkin-son’s disease, post-encephalitic parkinsonism andPSP, or may be induced by neuroleptics and L-dopatreatments (Table 2) [59]. Secondary BSP has beendescribed in patients with lesions at different lociof the CNS, predominantly the rostral brainstemregion [26,60–64].Simultaneous electromyographic recording of

LPS and OO muscles shows variable patterns, rang-ing from frequent and prolonged blinks that showan impairment in the timing and reciprocity of thetwo OO and LPS activities (“dystonic” blinks) [36],to clonic bursts of the OO to prolonged tonic activ-ity of these muscles. Commonly these patternscoincide, and a precise co-contraction betweenboth LPS and OO muscles is observed (Fig. 4). Acharacteristic finding in the neurophysiologicalevaluation of the BSP is the facilitation of the R2recovery curve of the blink reflex [65,66].A “minor” form of BSP is called pretarsal BSP [67]

which consists of a localized contraction of this OOmuscular portion, only demonstrated with com-plete accuracy by a EMG study which carefullyevaluates the different portions of the OO muscle[68]. This type of BSP does not show Charcot’s signand clinically may resemble BCO.Blepharocolysis (from the Greek blepharon, eye-

lid; and colysis, inhibition) was first described byGoldstein and Cogan [55] in four patients with “anonparalytic motor abnormality characterized bythe patient’s difficulty in initiating the act of lidelevation”. They coined the term “apraxia of lid

Table 2 Clinical settings where involuntary eyelid closure with inability to open the eyes have been described.

Type of disorder Idiopathic forms Secondary to In other extrapyramidal disordersBlepharospasm Isolated Focal CNS lesions (rostral

brainstem and diencephalicregions)

Pk’s diseasePostencephalitic PkPSP

With other cranial dystonias Neuroleptic and L-dopatreatments

Familial cases Lithium intoxicationBlepharocolysis Isolated Bilateral subthalamotomy Pk’s disease

Postencephalitic PkWith blepharospasm PSPIn familial cranial dystonias Lithium intoxication


opening” for the disorder, which has since been sowidely used and widely criticized as inappropriate[59]. In 1973 and later in 1988, a prolonged inter-mittent or sustained over-inhibition of the LPS ac-tivity with no evidence of consistent OO dischargeswas electrophysiologically demonstrated as thephysiopathological basis of this eyelid motor im-pairment [53,56] (Fig. 5). From a clinical point ofview Lepore and Duvoisin [57] suggested an invol-untary levator inhibition as the underlying mecha-nism, and defined some of its diagnostic criteria:(1) inability to initiate lid opening; (2) no evidenceof ongoing OO contraction; (3) marked frontalismuscle contraction during a period of inability toraise eyelids; and (4) no ocular motor or ocularsympathetic nerve dysfunction and no ocular my-opathy.These criteria were first critically discussed by

Fueyo et al. [69] who proposed that the secondstatement should read “no evidence of ongoing OOcontraction recorded by EMG” and more recentlyan amendment has also been proposed by Aramidehet al. [70] by introducing two important points: theinability to sustain lid elevation, that is the invol-untary closure of the eyelids, in the first criterion,and the necessity of an EMG recording to exclude atleast the presence of an abnormal OO activity, as

had already been proposed by Fueyo et al. [69], inthe second.The episodes of involuntary drooping of the eye-

lids may last for long period of time and like BSP, inits maximal intensity may render the patients func-tionally blind. Similar to BSP and other focal dysto-nias some patients exhibit a “geste antagonistique”[71] (Fig. 6). Reflex blinks are normal but some-times their occurrence in a repetitive manner (i.e.,by means of eyelash touching or glabellar tapping)precipitate prolonged episodes of BCO, which alsooccurs in many cases of BSP.Blepharocolysis is found in various clinical set-

tings (Table 2). It can occur in isolation [54,71–73]and more commonly associated with idiopathic ble-pharospasm (Fig. 5). It is a frequent disturbance inpost-encephalitic parkinsonism and PSP, and hasalso been described in Parkinson’s disease[56,57,71]. Some cases have a familial history ofcranial dystonias [54,71] and a few of these haveimproved with levodopa treatment [74] and lessfrequently with anticholinergic drugs [64]. A com-bined BSP–BCO picture has been described inlithium intoxication [75]. The anatomical basis ofBCO is unclear; the impairment of some pons androstral midbrain areas may be relevant [76,77](Table 1 and Fig. 1) and a bilateral subthalamotomy

Figure 4 Different EMG patterns in blepharospasm. (A) Increased frequency of spontaneous blinking, many of which showing aprolonged duration and dystonic configuration. (B) Burst of clonic discharges in the OO muscle, with variable duration and coincidingin this case with a tonic activity within its pars orbitaria. (C). Fluctuant tonic activity of OO, predominant in its pars palpebralis, witha complete disruption of the reciprocal innervation between this muscle and the LPS. Legends, as in Fig. 2.

10 Esteban et al.

for treatment of an idiopathic torsion dystonia hasbeen blamed [64] for provoking a combinedBCO–BSP disorder. The medial frontal and basalganglia hypometabolism found in PET studies insome “lid opening apraxia” cases [78] are uncertainbecause it is likely these cases actually correspondto pretarsal BSP disorders. Progressive supra-nuclear palsy is considered the most common aeti-ology for BCO [79] and some cases of palpebralptosis reported in this disease [80–82] would actu-

ally pertain to this disorder. Conversely, some caseswith ptosis secondary to cerebral hemispheric inf-arctions or motor neuron disease have been errone-ously referred to as suffering from BCO [83,84].Detailed electrophysiological studies by means

of simultaneous EMG recordings of the LPS and OOmuscles, have drawn precise descriptions of thedifferent components comprised in cases of invol-untary eyelid closure [53,73] which may be of greatimportance in establishing the proper treatment

Figure 5 EMG recording in two patients showing blepharocolysis. In (A) after a gradual decrease, an almost complete cessation of theLPS activity occurs. It is followed by an intermittent irregular inhibition until the total return of the basal tonic LPS activity with thefinal opening of the eyes. Only an unmodified scarce OO activity is seen. In (B) different degrees of inhibition of LPS coexist with clonicand tonic phases of blepharospasm. In both cases, the eyelids dropped despite the continuous effort of patients to keep the eyesopened.

Figure 6 Blepharocolysis. Involuntary closure of the eyes; the patient is attempting to open them and a marked folding of theforehead is evident. On the right, “geste antagonistique” (sensory trick) trying to facilitate the opening of the eyes.


with botulinum toxin. In some cases, the presenceof EMG activity in the pretarsal portion of the OO,positively precludes a BCO condition, with whichsometimes the pretarsal BSP is confused [78,85].Recovery of the R2 response of the blink reflex hasbeen found normal in three patients with BCO andbasal ganglia disease [86].Many others different terminologies have been

used to designate this motor eyelid disturbance:focal eyelid dystonia, pretarsal BSP, atypical BSP,eyelid freezing, akinesia of lid function, akinesia oflid opening, apractic type of essential BSP, involun-tary levator palpebrae inhibition, etc. Until now,however, none has achieved a general consensus.From the very beginning, the most common usedterm “apraxia of eyelid opening”—frequently re-ferred to as “so-called apraxia...”—has been re-peatedly criticized based on the essential argumentof the presence of severe motor system impairmentin the great majority of patients who suffer thecomplaint. Blepharocolysis is a concise descriptiveterm that defines the physiopathological mecha-nism of this motor disturbance—which is alwayscomprised of a double component of involuntaryclosing and difficulty in raising the eyelids—insteadof the partial description of the symptom (distur-bance of eyelid opening) or, even worst, the mis-leading interpretation of its nature. This term alsodefines a movement disorder which is frequentlyfound closely related with BSP, stressing on the onehand their clinical similarity as a dystonic motordisturbance and, on the other, their differences inthe underlying mechanism of production (See Este-ban and Giménez-Roldán, [53] for further discus-sion).BSP and BCO could be considered as different

expressions of a focal dystonic disturbance of eye-lid motility, likely related to the different compo-nent of the blinking mechanism affected: the in-crease of the OO activation should be the base inBSP and the increase of the levator inhibition in theBCO. The releasing of the inhibitory components ofa motor pattern could be hypothesized as a patho-physiological mechanism likely to induce a motordisorder. In the case of palpebral motility, theisolated predominance of the LPS inhibition shouldgive way to the postural abnormality found in BCO.The motor persistence of orbicularis oculi

muscle has been described as a third variant ofeyelid-opening disorders [70]. It should be clinicallydifferentiated from BSP and BCO because there isno involuntary drooping of the eyelids and thedifficulty in opening the eyes only occurs aftervoluntary closure of the eyelids. Simultaneous LPSand OO-EMG revealed persistent activity of thepretarsal portion of the OO despite the command to

open the eyes, although clinical examination didnot give evidence of ongoing OO contraction. Of thethree patients mentioned, one occurred in isola-tion, and in the other two it was an additional EMGabnormality to their respective BSP and BCO prob-lems.

Voluntary eyelid movementsand disorders

In other voluntary movements of the eyelids, apartfrom voluntary blinks, reciprocal innervation be-tween LPS and OO also plays a predominant role.Voluntary sustained closure of the eyes can beachieved either by inhibition of the steady tonicactivity of LPS without OO activation, leading tosoft eyelid closure, or by LPS inhibition plus sus-tained OO contraction, causing forced closing ofthe eyes. In both cases, LPS inhibition is a relevantfeature for being the unique factor in the gentleclosing and for preceding the appearance of the OOactivity in the forceful closing [5].During voluntary occlusion of the eyes, a conju-

gate upward movement of the eyeball normallyoccurs, which corresponds to the facio-ocular syn-kinesia clinically known as Bell’s phenomenon.Some 10% of the normal healthy population mayhave no Bell’s phenomenon [21], although in ourexperience it was constantly present [87]. Rectussuperior muscle, contrary to LPS, shows a suddenintensification of its tonic basal activity, whichbegins soon after the closure of the eyelids andcontinues until after their opening [7,22,87].Ocular saccade and pursuit movements in the

vertical plane exhibit a precise coordinated move-ment of the lids. In these coordinated lid/eyemovements, LPS muscles, which act with perfectsynchronization on both sides, is activated duringupward displacements of the eyes and inactivatedduring downward displacements, whereas the or-bicularis oculi is not involved [1,88]. The steady LPSbasal activity in the primary gaze position increasesin amplitude and density when a slow upper move-ment is carried out and progressively diminisheswith the downward movement until ceasing com-pletely in the extreme downgaze [5]. Activity inrectus superioris parallels that of the LPS [7].Gentle closing of the eyes and, to an even greaterextent, the full down gaze are the positions wherethe maximal relaxation of the LPS occurs andpresent the opportunity to establish an eventualpresence of abnormal spontaneous activities in theEMG studies of this muscle.For voluntary eyelid opening, the LPS alone is the

responsible.

12 Esteban et al.

Supranuclear palsy of voluntary eyelid closure isa motor dysfunction that reflects the inability toclose the eyes either wilfully or on command, withpreservation of reflex blinking. It has been de-scribed in different processes as cerebral infarc-tion, biopercular syndrome, Creutzfeldt–Jakob dis-ease and amyotrophic lateral sclerosis, whichinvolve pathology of cortical frontal areas or corti-cospinal system [87,89–93]. Although a bilateralprocess is the common pathological substrate ofthis dysfunction, a unilateral frontal lesion on thenon-dominant side [94] or “right brain damage”[95] has also been described as provoking a com-plete failure to voluntarily close the eyes. Moreinfrequently, similar motor eyelid impairment hasbeen observed in PSP [14]. In this case, a simulta-neous EMG recording of LPS and OO showed preser-vation of spontaneous and reflex blinks. A mild lidclosure was obtained only after a series of rapidrepetitive stimulation of the eyelashes. This gaveway to modest OO activity, coinciding with partialinhibition of LPS activity, which was rapidly fol-lowed by an impersistence of closure in which OOactivity subsided and LPS recovered the basal con-traction. A possible predominant deficit of LPS inhi-bition rather than insufficient OO activation wasproposed as the physiopathological mechanism. Inboth acute unilateral and bilateral hemisphere le-sions, motor impersistence keeping the eyes volun-tarily closed is not uncommonly found; it predomi-nantly occurs within lesions on the non-dominantside and progressively subsides in several weeks[95–97].Bell’s phenomenon impairment has been noted

in cases of amyotrophic lateral sclerosis [87] andCreutzfeldt–Jakob’s disease [92]. Several degreesmay exist and the bilateral decreasing of the supra-nuclear motor driving caused by loss of the facialcortical motor neurons or the corticogeniculatetract lesions should constitute the pathophysiologi-cal basis [87,92]. Some previous cases with bilat-eral supraspinal pyramidal pathway damage hadbeen described showing an absence of Bell’s phe-nomenon and vertical gaze palsy [87,92,98]. Cor-ticogeniculate lesions of a mild degree can producean isolated disturbance of Bell’s phenomenon, andits presence should draw attention to a probablecranial level of involvement in some otherwise dif-fuse pyramidal syndromes restricted to the limbs(personal observation).The so-called cerebral ptosis is a supranuclear

motor eyelid disorder associated with hemisphericlesions [99] consisting in a sustained drooping of theeyelids with a more or less pronounced inability toraise them. Although commonly bilateral, withsome degree of asymmetry, it may also be unilat-

eral. It usually follows a cerebral stroke with bilat-eral frontal lesions or extensive infarcts of theright, non-dominant, hemisphere [100,101]. Insome few cases, cerebral ptosis has been describedto be associated with BSP [102]; this associationshould probably not be so surprising if a minuteclinical observation is made, and likely depends onan eventual involvement of the basal ganglia. Nev-ertheless, cerebral ptosis is a transient situationthat progressively subsides, generally reaching nor-mality in some weeks. The clinical background eas-ily leads to its differentiation from other supra-nuclear eyelid opening impairments, namely BCO,with which, however, it has been occasionally con-fused [83,103,104].

References

[1] Evinger C, Shaw MD, Peck CK, Manning KA, Baker R. Blink-ing and associated eye movements in humans, guinea pigs,and rabbits. J Neurophysiol 1984;52:323–39.

[2] Evinger C, Manning KA, Sibony PA. Eyelid movements.Mechanisms and normal data. Invest Ophthalmol Vis Sci1991;32:387–400.

[3] Kennard DW, Smyth GL. The causes of downward eyelidmovements with changes of gaze, and a study of thephysical factors concerned. J Physiol 1963;166:178–90.

[4] Gordon G. Observations upon the movements of the eye-lids. Br J Ophthalmol 1951;35:339–51.

[5] Björk A, Kugelberg E. The electrical activity of the musclesof the eye and eyelids in various positions and duringmovements. EEG Clin Neurophysiol 1953;5:595–602.

[6] Loeffler J, Slatt B, Hoyt W. Motor abnormalities of theeyelids in Parkinson’s disease. Arch Ophthalmol 1966;76:178–85.

[7] Esteban A, Salinero E. Reciprocal reflex activity in ocularmuscles: implications in spontaneous blinking and Bell’sphenomenon. Eur Neurol 1979;18:157–65.

[8] Gruart A, Blazquez P, Delgado-Garcia JM. Kinematics ofspontaneous, reflex, and conditioned eyelid movements inthe alert cat. J Neurophysiol 1995;74:226–48.

[9] Bour LJ, Aramideh M, de Visser BW. Neurophysiologicalaspects of eye and eyelid movements during blinking inhumans. J Neurophysiol 2000;83:166–76.

[10] Schmidtke K, Buttner-Ennever JA. Nervous control of eye-lid function. A review of clinical, experimental and patho-logical data. Brain 1992;115:227–47.

[11] Pasik P, Pasik T, Bender MB. The pretectal syndrome inmonkeys. I. Disturbances of gaze and body posture. Brain1969;92:521–34.

[12] Nashold Jr BS, Gills JP, Wilson WP. Ocular signs of brainstimulation in the human. Confin Neurol 1967;29:169–74.

[13] Galetta SL, Raps EC, Liu GT, Saito NG, Kline LB. Eyelid lagwithout eyelid retraction in pretectal disease. J Neurooph-thalmol 1996;16:96–8.

[14] Grandas F, Esteban A. Eyelid motor abnormalities in pro-gressive supranuclear palsy. J Neural Transm Suppl 1994;42:33–41.

[15] Holstege G, Blok BFM, Horst GJ. Brain stem systemsinvolved in the blink reflex, feeding mechanisms, andmicturation. In: Paxinos G, editor. The rat nervous system.San Diego: Academic Press; 1995. p. 257–75.


[16] Esteban A. A neurophysiological approach to brainstemreflexes. Blink reflex. Neurophysiol Clin 1999;29:7–38.

[17] Bruce CJ, Goldberg ME, Bushnell MC, Stanton GB. Primatefrontal eye fields. II. Physiological and anatomical corre-lates of electrically evoked eye movements. J Neuro-physiol 1985;54:714–34.

[18] Holder DS, Scott A, Hannaford B, Stark L. High resolutionelectromyogram of the human eyeblink. Electromyogr ClinNeurophysiol 1987;27:481–8.

[19] Esteban A. Blinking and eyelids’ motor central disorders.EMG study. EEG Clin Neurophysiol 1997;103:62.

[20] Wilkins RH, Brody IA. Bell’s palsy and Bell’s phenomenon.Arch Neurol 1969;21:661–2.

[21] Bender MB. Comments on the physiology and pathology ofeye movements in the vertical plane. J Nerv Mental Dis1960;130:456–66.

[22] Björk A. Electromyographic studies on the coordination ofantagonistic muscles in cases of abducens and facial palsy.Br J Ophthalmol 1954;38:605–15.

[23] Kugelberg E. Facial reflexes. Brain 1952;75:385–96.[24] Zametkin AJ, Stevens JR, Pittman R. Ontogeny of sponta-

neous blinking and of habituation of the blink reflex. AnnNeurol 1979;5:453–7.

[25] Karson CN, Berman KF, Donnelly EF, Mendelson WB, Klein-man JE, Wyatt RJ. Speaking, thinking, and blinking. Psy-chiatry Res 1981;5:243–6.

[26] Jankovic J, Havins WE, Wilkins RB. Blinking and ble-pharospasm. Mechanism, diagnosis, and management.JAMA 1982;248:3160–4.

[27] Ponder E, Kennedy WP. On the act of blinking. Quart J ExpPhysiol 1928;18:89–110 [taken from Stevens, 1978].

[28] Sun WS, Baker RS, Chuke JC, et al. Age-related changes inhuman blinks. Passive and active changes in eyelid kine-matics. Invest Ophthalmol Vis Sci 1997;38:92–9.

[29] Karson CN, LeWitt PA, Calne DB, Wyatt RJ. Blink rates inparkinsonism. Ann Neurol 1982;12:580–3.

[30] LeDoux MS, Lorden JF, Smith JM, Mays LE. Serotonergicmodulation of eye blinks in cat and monkey. Neurosci Lett1998;253:61–4.

[31] Karson CN. Spontaneous eye-blink rates and dopaminergicsystems. Brain 1983;106:643–53.

[32] Golbe LI, Davis PH, Lepore FE. Eyelid movement abnor-malities in progressive supranuclear palsy. Mov Disord1989;4:297–302.

[33] Stevens JR. Disturbances of ocular movements and blinkingin schizophrenia. J Neurol Neurosurg Psychiatry 1978;41:1024–30.

[34] Grandas F, Elston J, Quinn N, Marsden CD. Blepharospasm:a review of 264 patients. J Neurol Neurosurg Psychiatry1988;51:767–72.

[35] Elston JS, Granje FC, Lees AJ. The relationship betweeneye-winking tics, frequent eye-blinking and ble-pharospasm. J Neurol Neurosurg Psychiatry 1989;52:477–80.

[36] Esteban A, Traba A, Grandas F. Blinking and ble-pharospasm. A neurophysiological study. EEG Clin Neuro-physiol 1997;103:90.

[37] Watson RT, Rapcsak SZ. Loss of spontaneous blinking in apatient with Balint’s syndrome. Arch Neurol 1989;46:567–70.

[38] Keane JR. Gaze-evoked blepharoclonus. Ann Neurol 1978;3:243–5.

[39] Sethi KD, Hess DC, Harbour RC, Holmes GL. Gaze-evokedinvoluntary movements. Mov Disord 1990;5:139–42.

[40] Safran AB, Moody JF, Gauthier G. Sustained blepharoclo-nus upon eye closure. J Clin Neuroophthalmol 1983;3:133–6.

[41] Behrman S, Scott DF. Blepharoclonus provoked by volun-tary eye closure. Mov Disord 1988;3:326–8.

[42] Gatto M, Micheli F, Pardal MF. Blepharoclonus and parkin-sonism associated with aqueductal stenosis. Mov Disord1990;5:310–3.

[43] Jacome DE. Blepharoclonus in multiple sclerosis. Acta Neu-rol Scand 2001;104:380–4.

[44] Hsieh BH, Deng JF, Ger J, Tsai WJ. Acetylcholinesteraseinhibition and the extrapyramidal syndrome: a review ofthe neurotoxicity of organophosphate. Neurotoxicology2001;22:423–7.

[45] Jacome DE. Headache in Ehlers-Danlos syndrome. Ceph-alalgia 1999;19:791–6.

[46] Jacome DE. Synkinetic blepharoclonus. J Neuroophthalmol2000;20:276–84.

[47] Jacome DE. Blepharoclonus and Arnold-Chiari malforma-tion. Acta Neurol Scand 2001;104:113–7.

[48] Jacome DE. Blepharoclonus, pseudoasterixis, and restlessfeet. Am J Med Sci 2001;322:137–40.

[49] Obeso JA, Artieda J, Marsden CD. Stretch reflex ble-pharospasm. Neurology 1985;35:1378–80.

[50] Nashold Jr BS, Wilson WP, Slaughter DG. Sensations evokedby stimulation in the midbrain of man. J Neurosurg 1969;30:14–24.

[51] Nashold BS. Ocular reactions from brain stimulation inconscious man. Neuroophthalmology 1970;5:92–103.

[52] Van Buren JM. Confusion and disturbance in speech fromstimulation in vicinity of the head of the caudate nucleus.J Neurosurg 1963;20:148–57.

[53] Esteban A, Gimenez-Roldan S. Involuntary closure of eye-lids in parkinsonism. Electrophysiological evidence for pro-longed inhibition of the levator palpebrae muscles. J Neu-rol Sci 1988;85:333–45.

[54] Defazio G, Livrea P, Lamberti P, et al. Isolated so-calledapraxia of eyelid opening: report of 10 cases and a reviewof the literature. Eur Neurol 1998;39:204–10.

[55] Goldstein JE, Cogan DG. Apraxia of lid opening. ArchOphthalmol 1965;73:155–9.

[56] Esteban A, Gimenez-Roldan S. Intermittentblepharocolysis; a study of its mechanism in striatal disor-ders. X International Congress of Neurology. ExcerptaMedica ICS, 296. 1973. p. 130.

[57] Lepore FE, Duvoisin RC. “Apraxia” of eyelid opening: aninvoluntary levator inhibition. Neurology 1985;35:423–7.

[58] Tolosa E, Marti MJ. Blepharospasm-oromandibular dystoniasyndrome (Meige’s syndrome): clinical aspects. Adv Neurol1988;49:73–84.

[59] Hallett M, Daroff RB. Blepharospasm: report of a work-shop. Neurology 1996;46:1213–8.

[60] Jankovic J, Patel SC. Blepharospasm associated with brain-stem lesions. Neurology 1983;33:1237–40.

[61] Lee MS, Marsden CD. Movement disorders following lesionsof the thalamus or subthalamic region. Mov Disord 1994;9:493–507.

[62] Kostic VS, Stojanovic-Svetel M, Kacar A. Symptomatic dys-tonias associated with structural brain lesions: report of16 cases. Can J Neurol Sci 1996;23:53–6.

[63] Aramideh M, Ongerboer de Visser B, Holstege G, Majoie CB,Speelman JD. Blepharospasm in association with a lowerpontine lesion. Neurology 1996;46:476–8.

[64] Klostermann W, Vieregge P, Kompf D. Apraxia of eyelidopening after bilateral stereotaxic subthalamotomy. JNeuroophthalmol 1997;17:122–3.

[65] Berardelli A, Rothwell JC, Day BL, Marsden CD. Pathophysi-ology of blepharospasm and oromandibular dystonia. Brain1985;108:593–608.

14 Esteban et al.

[66] Tolosa E, Montserrat L, Bayes A. Blink reflex studies infocal dystonias: enhanced excitability of brainstem inter-neurons in cranial dystonia and spasmodic torticollis. MovDisord 1988;3:61–9.

[67] Elston JS. A new variant of blepharospasm. J Neurol Neu-rosurg Psychiatry 1992;55:369–71.

[68] Aramideh M, Koelman JH, Speelman JD, Ongerboer deVisser B. Eyelid movement disorders and electromyogra-phy. Lancet 2001;357(9258):805–6.

[69] Fueyo J, Oliveras C, Pou A, Espadaler JM. Proposal for aclinical definition of blepharokolysis. Mov Disord 1991;6:185–6.

[70] Aramideh M, Ongerboer de Visser B, Koelman JH, Speel-man JD. Motor persistence of orbicularis oculi muscle ineyelid-opening disorders. Neurology 1995;45:897–902.

[71] Krack P, Marion MH. “Apraxia of lid opening,” a focaleyelid dystonia: clinical study of 32 patients. Mov Disord1994;9:610–5.

[72] Aramideh M, Ongerboer de Visser B, Devriese PP, Bour LJ,Speelman JD. Electromyographic features of levatorpalpebrae superioris and orbicularis oculi muscles in ble-pharospasm. Brain 1994;117:27–38.

[73] Aramideh M, Ongerboer de Visser B, Koelman JH, Bour LJ,Devriese PP, Speelman JD. Clinical and electromyographicfeatures of levator palpebrae superioris muscle dysfunc-tion in involuntary eyelid closure. Mov Disord 1994;9:395–402.

[74] Dewey Jr RB, Maraganore DM. Isolated eyelid-openingapraxia: report of a new levodopa-responsive syndrome.Neurology 1994;44:1752–4.

[75] Micheli F, Cersosimo G, Scorticati MC, Ledesma D, Moli-nos J. Blepharospasm and apraxia of eyelid opening inlithium intoxication. Clin Neuropharmacol 1999;22:176–9.

[76] Weinstein EA, Bender MB. Integrated facial patterns elic-ited by stimulation of the brainstem. Arch Neurol Psychiat1943;50:34–42.

[77] Nashold Jr BS, Gills Jr JP. Ocular signs from brain stimula-tion and lesions. Arch Ophthalmol 1967;77:609–18.

[78] Smith D, Ishikawa T, Dhawan V, Winterkorn JS, Eidel-berg D. Lid opening apraxia is associated with medialfrontal hypometabolism. Mov Disord 1995;10:341–4.

[79] Lepore FE. So-called apraxias of lid movement. Adv Neurol1988;49:85–90.

[80] Dix MR, Harrison MJ, Lewis PD. Progressive supranuclearpalsy (the Steele-Richardson-Olszewski syndrome). Areport of 9 cases with particular reference to the mecha-nism of the oculomotor disorder. J Neurol Sci 1971;13:237–56.

[81] Steele JC. Progressive supranuclear palsy. In: Vinken PJ,Bruyn GW, editors. System disorders and atrophies, Hand-book of clinical neurology, 22, part 2. Amsterdam: North-Holland Publishing Company; 1975. p. 217–29.

[82] Kristensen MO. Progressive supranuclear palsy—20 yearslater. Acta Neurol Scand 1985;71:177–89.

[83] Johnston JC, Rosenbaum DM, Picone CM, Grotta JC.Apraxia of eyelid opening secondary to right hemisphereinfarction. Ann Neurol 1989;25:622–4.

[84] Abe K, Fujimura H, Tatsumi C, Toyooka K, Yorifuji S,Yanagihara T. Eyelid “apraxia” in patients with motorneuron disease. J Neurol Neurosurg Psychiatry 1995;59:629–32.

[85] Piccione F, Mancini E, Tonin P, Bizzarini M. Botulinum toxintreatment of apraxia of eyelid opening in progressivesupranuclear palsy: report of two cases. Arch Phys MedRehabil 1997;78:525–9.

[86] Aramideh M, Eekhof JL, Bour LJ, Koelman JH, Speel-man JD, Ongerboer de Visser B. Electromyography andrecovery of the blink reflex in involuntary eyelid closure: acomparative study. J Neurol Neurosurg Psychiatry 1995;58:692–8.

[87] Esteban A, De Andres C, Giménez-Roldán S. Abnormalitiesof Bell’s phenomenon in amyotrophic lateral sclerosis: aclinical and electrophysiological evaluation. J Neurol Neu-rosurg Psychiatry 1978;41:690–8.

[88] Becker W, Fuchs AF. Lid-eye coordination during verticalgaze changes in man and monkey. J Neurophysiol 1988;60:1227–52.

[89] Alajouanine Th, Thurel R. La diplégie facial cérébrale.Forme corticale de la paralysie pseudobulbaire. Rev Neurol(Paris) 1933;2:441–58 (Contribution à l’étude de la disocia-tion des activités volontaires et réflexes).

[90] Lessel S. Supranuclear paralysis of voluntary lid closure.Arch Ophthalmol 1972;88:241–4.

[91] Lapresle J, Salisachs P. Loss of voluntary control andretention of automatic reflex in certain muscles inner-vated by cranial nerves in 2 cases of amyotrophic lateralsclerosis. Rev Neurol (Paris) 1976;132:157–61.

[92] Russell RW. Supranuclear palsy of eyelid closure. Brain1980;103:71–82.

[93] Nishimura M, Tojima M, Suga M, Hirose K, Tanabe H.Chronic progressive spinobulbar spasticity with distur-bance of voluntary eyelid closure. J Neurol Sci 1990;96:183–90 Report of a case with special reference to MRI andelectrophysiological findings.

[94] Berlin L. Compulsive eye opening and associated phenom-ena. Arch Neurol Psychiat 1955;73:597–601.

[95] De Renzi E, Gentilini M, Bazolli C. Eyelid movement disor-ders and motor impersistence in acute hemisphere dis-ease. Neurology 1986;36:414–8.

[96] Fisher CM. Left hemiplegia and motor impersistence. JNerv Mental Dis 1956;123:201–18.

[97] Joynt RJ, Benton AL, Fogel ML. Behavioral and pathologicalcorrelates of motor impersistence. Neurology 1962;12:876–81.

[98] Alajouanine Th, Thurel R. Révision des paralysies des mou-vements associés des globes oculaires. Rev Neurol (Paris)1931;1:125–69 (Contribution à l’étude de la dissociationdes activités voluntaire et réflexe).

[99] Márquez M. La hendidura palpebral normal y patológica.Medicina Ibera (Madrid) 1936;1:209–22 [taken from Caplan,1974].

[100] Caplan LR. Ptosis. J Neurol Neurosurg Psychiatry 1974;37:1–7.

[101] Averbuch-Heller L, Stahl JS, Remler BF, Leigh RJ. Bilateralptosis and upgaze palsy with right hemispheric lesions. AnnNeurol 1996;40:465–8.

[102] Hijosa M, Esteban A, Sánchez Migallón MJ, Grandas F.Palpebral ptosis and blepharospasm secondary to hemi-spheric cerebral infarction. Neurología 1998;13:49–53.

[103] Sakajiri K, Matsubara N, Nakajima T, Fukuhara N, Ban-doh M. A case of “apraxia of eyelid opening” secondary toright hemisphere infarction. Assessment of various symp-toms of the eye and eyelid. Rinsho Shinkeigaku 1995;35:164–8.

[104]Waragai M, Shinotoh H, Kaneko M, Hattori T. Difficulty ineye opening following left hemispheric infarction. Caus-ative lesion and pathophysiology of abnormalities of theeye and eyelids movements. Rinsho Shinkeigaku 1996;36:577–83.


Documents

Eyelid Movements in Health and Disease. the Supranuclear Impairment of the Palpebral Motility