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Home , Blepharospasm, Synkinesis, Tremor

Journal of Neuro-Ophthalmology 20(4): 276-284, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia

Synkinetic Blepharoclonus

Daniel E. Jacome, MD

Objectives: To analyze the clinical data and test results col­ Blepharoclonus is the repetitive, easily detectable, lected in a group of patients exhibiting eyelid-closure blepharo­ myoclonic contractions of the (BLC) on clinical neurologic examination. (1). It is commonly apparent with light eyelid closure and Materials and Methods: Thirty-five patients were referred for may be suppressed by forceful eyelid contraction (2). In neurologic evaluation for reasons other than BLC. Clinical electrophysiologic evaluations, including cranial testing contradistinction, (BLS) is a focal dysto­ and electromyograms, were done according to standards. All nia manifested by forceful and sustained involuntary clo­ patients had neuroimaging studies, including brain magnetic sure of the eyelids, often accompanied by great difficulty resonance imaging and head computerized tomography, or in opening the eyes on command or free will, which is a both, and many had electroencephalograms. Additional tests clinical phenomenon called "apraxia of lid opening" were done based on the patient's symptoms or reasons for (3,4). However, attempts to open the eyelids during epi­ referral. sodes of BLS may be confused with BLC, or with paretic Results: Eight patients had reflex BLC. Two cases were pre­ of the eyelids in a patient with partial denerva­ cipitated by vertical gaze; one of these patients had hereditary tion of the orbicularis oculi. Blepharoclonus may be pro­ palmoplantar keratoderma and cataplexy, and the other patient voked by stretching of the obicularis oculi or by gaze had Ehlers-Danlos syndrome and familial BLC. Other precipi- deviations (5,6). Synkinetic BLC is defined here as: tants included speech in four cases, postural changes in two cases, and light stimulation in one case. Two patients had gen­ 1. the involuntary movements, , or facial eralized independent of their BLC, two patients had electromyogram (EMG) motor units firing, triggered a history of myoclonus, and several patients had BLC- associated facial myoclonus. One patient had BLC-associated by, or associated with BLC, normally affecting myoclonus of the right shoulder. Synkinetic cranial movements muscles other than the orbicularis oculi; were detected in 11 patients (four oculofacial, three oculo- 2. BLC-enhanced cephalic and extracephalic focal, mul­ pterygoid, one oculolingual, two dual cases, and one case of tifocal, or generalized tremors; imitation .) Three patients had familial BLC, seven 3. BLC in patients exhibiting other cranial synkinesis patients had congenital developmental disorders, six patients (synkinetic movements); had synkinetic tremors, and six patients had restless feet. Some 4. reflex BLC. indication of was evident in eight pa­ tients. The last subgroup may be identified by the specific Conclusions: Eyelid-closure BLC is an underrecognized, spo­ mechanism that causes BLC (see below). Those mecha­ radic or familial, mostly benign, chronic eyelid-movement dis­ nisms are stretching of the orbicularis oculi, stimulation order that may be associated with tremors, myoclonus, cranial by sudden illumination, speech, changes in body posture, synkinesis, and restless feet. Reflex mechanisms may be iden­ and gaze deviations. Although both patients reported by tified in some patients. Gaze-induced BLC seems to have the Obeso et al. (5) had reflex BLS and BLC, either one of greatest clinical relevance. In the current series, there were no examples of posttraumatic BLC, , hydroceph­ these conditions may occur independently. In reflex alus, or blepharospasm conditions previously reported to be BLS, the eyes are involuntarily forcefully shut, while in associated with BLC. No electroencephalographic abnormali­ pure-reflex BLC, only rapid myoclonus of the eyelids is ties were recorded during BLC, ruling out eyelid-closure epi­ observed in the absence of sustained contraction of the lepsy. orbicularis oculi. Key Words: Blepharoclonus—Blepharospasm—Cranial syn­ kinesis—Eyelids——Myoclonus— MATERIALS AND METHODS Synkinetic movements. After a few patients with BLC referred for other neu­ rologic disorders were identified by the author, a system­ Manuscript received February 8, 1999; accepted February 16, 2000. atic search for this condition was performed for all new From the Franklin Medical Center, Greenfield, Massachusetts, and patients in the author's practice. A total of 35 patients the Section of , Dartmouth-Hitchcock Medical Center, Leba­ non, New Hampshire. with BLC, ranging in age from 11 to 75 years, was Address correspondence and reprint requests to Daniel E. Jacome, collected over a 5-year period. These patients were iden­ MD, 1 Burnham Street, Suite 2, Turners Falls, MA 01376. tified on routine neurologic examination when asked to

276 SYNKINETIC BLEPHAROCLONUS 277

TABLE 1. Reflex synkinetic blepharoclonus

Patient/Sex/ Age (y) Signs Diagnoses Symptoms Tests Other l/F/38 Action tremors of hands, Demyelinating retrobulbar Objects blurred, lacked VERS showed conduction Progressive improvement frequent rotational feet optic neuropathy and color in vision OS; slowing through optic of vision in follow-up movements at rest; BLC axonal peripheral V/A 20/20 nerve OS; brain MRI: with no new with light eyelid closure neuropathy of unknown normal; EMG legs; symptoms enhanced by sitting or etiology; synkinetic complex polyphasic standing, greatly (reflex) BLC MUPs recorded over leg diminished lying down muscles; no spontaneous activity 2/F/43 Hypermobile joints, soft Synkinetic BLC; common Back pain, numbness, LS spine MRI: normal; Family history of EDS, skin with very visible ; EDS-related LS tingling of left leg; brain MRI: T2-weighted somnambulism, eyelid veins, tenderness of the plexopathy, subcortical left side pulsatile nodular subcortical closure BLC spine, left leg weakness, nodular gliosis without white-matter abnormal gait; downward warnings, sensitive high-intensity signals of gaze BLC and teeth greater prominence over of lower eyelid; speech- the left frontal region; related BLC; allodynia of EMG of legs: teeth spontaneous normal MUPs at rest over both TA and left EDB muscles J/F/44 BLC with upward gaze; Palmoplantar keratoderma, Sudden falls precipitated EEG, ECG, MRI of the LS Family history of palmoplantar focal leukoencephalopathy, by emotions, without spine, 2D echocardiogram: hemophilia, common hyperkeratosis, greater cataplexy, sciatica, loss of consciousness; normal; no organomegaly migraine over feet (Fig. 1) gaze-evoked BLC right leg postexertional by CT of the abdomen; pain EMG of the right leg: right sciatica; MRI of the brain: focal demyelination (Fig. 2), Hexososaminidase A, aryl sulphatase A, plasma aminoacid levels, cellular cholesterol esterification normal 4/M/44 Chronic and miosis Cluster headaches with Episodic severe pain Brain MRI/MRA, CNT, Negative OD; action tremors of residual chronic ipsilateral behind right eye, CT, MRI of LS spine, hands on flexion- Homer syndrome; numbness of right VERs BAERs: normal extension at the wrists; synkinetic BLC thigh and right side of frequent involuntary face movements of feet a( rest; eyelid-closure BLC; bilateral involuntary myoclonic contractions of the orbicularis oris with lateral gaze; frequent blinking (40-50 « blinks/min); BLC triggered by intense light stimulation without LOC 5/F/47 Eyelid-closure BLC Migraine with aura, Pounding headaches Brain MRI: normal Mother had triggered by speech and synkinetic BLC preceded by preceded by light stimulation compulsive yawning compulsive yawning 6/F/50 BLC with light eyelid Synkinetic BLC; drug Diplopia and transient Brain MRI: normal; CNT: Breast cancer by history; closure, greatly enhanced reaction; limited confusion after normal MUPs present • no previous history of in supine position continuous facial ingestion of lorazepam at rest over right Bell palsy muscle-fiber activity orbicularis oris and both mentalis muscles on facial EMG; Anti-Yo, anti-Ri antibodies: negative 7/F/66 BLC with eyelid closure Monoclonal gammopathy- Intermittent numbness of IgG lambda monoclonal Hypertension and during speech; associated peripheral limbs and left side of gammopathy; C-spine ipsilateral deviation of neuropathy, synkinetic face MRI: spinal stenosis; jaw with lateral gaze; BLC, oculopterygoid left leg EMG: complex generalized deep-tendon synkinesis, speech- prolonged polyphasic hyporeflexia induced BLC MUPs over RF and EDB muscles with no F-wave responses 8/F/73 Eyelid closure and Synkinetic BLC, corticobasal Writing tremors, poor Head CT: cortical atrophy; Negative speech-induced BLC; ganglionic degeneration, mobility, abnormal EEG, CNT, SPECT: leans toward left when truncal posture normal sitting; rigidity, akinesia of right arm

BAER, brain stem auditory-evoked responses; BLC, blepharoclonus; CNT, cranial nerve testing; CT, computed tomography; EDB, extensor digitorum brevis; ECG, electrocardiogram; EDS, Ehlers-Danlos; EEG, electroencephalogram; Ig, immunoglobulin; LOC, loss of consciousness; LS, lumbosacral; MRA, magnetic resonance angiogram; MRI, magnetic resonance imaging; MUP, motor unit potentials; RF, rectus femoris; SPECT, single proton emission CT; TA, tibilias anterior; V/A, visual acuity; VER, visual-evoked response.

J Neuro-Ophthalmol, Vol. 20, No. 4, 2000 278 D. E. JACOME

TABLE 2. Blepharoclonus and tremors

Patient/Sex/ Age (y) Signs Diagnoses Symptoms Tests Other 9/F/12 BLC, action tremors of Synkinetic BLC, essential Generalized morning Normal EEG, EMG/NCV Mother and sister had hands on flexion- benign tremors (?), tremors; headaches of the legs, MRI of the somnambulism extension movements at episodic tension brain the wrists; repetitive headaches movements of feet at rest while sitting; BLC- induced generalized multifocal tumors 10/F/17 Eyelid-closure BLC; action Catamenial migraine with Monthly pulsatile Normal EEG, MRI of the Mother and maternal tremors of the hands on postdromal fatigue; headaches around brain, NCV; CNT: grandmother with flexion-extension at the synkinetic familial BLC; menses followed by delayed left; R2 BLC; family wrists; restless feet; EDS, continuous muscle fatigue for 5 days, component of blink history of ruptured hypermobile joints, fiber activity; action "internal shaking"; reflex; EMG: intracranial aneurysms, scoliosis, fusion of tremors of the hands and easy bruising spontaneous normal somnambulism, EDS second and third toes of restless feet MUPs at rest over right each foot; unilateral TA and EDB muscles twitching of mentalis and orbicularis oris muscles with ipsilateral gaze ll/M/32 Cephalic tremors associated Synkinetic BLC; Generalized intermittent Normal EEG during Negative with eyelid-closure BLC posttraumatic right shaking, right shoulder generalized tremors; brachial plexopathy, right pain, right hand normal head CT and arm paroxysmal dystonia numbness and painless EMG/NCV of right essential nonepileptic of right arm arm subcortical myoclonus induced by exercise, beginning after serious chest 12/F/37 Eyelid-closure BLC Synkinetic BLC; Recurrent pulsatile Elevated IgG/IgA Family history of associated with head antiphospholipid antibody headaches preceded by cardiolipin antibodies; migraine tremors; action tremors syndrome; migraine with phosphenes; daily brain MRI, EEG, CNT, of hands aura and persistent visual background headaches CSF studies: normal phenomena; transformed migraine 13/F/46 Head/postural hand tremors Right sciatica (?), C6 and Right leg pain, weakness; Brain MRI, EEG, Hashimoto thyroiditis, simultaneous with L4 disc herniations; left facial numbness, EMG/NCV of legs, anemia, leukopenia eyelid-closure BLC; pain postexertional fatigue and "internal shaking," CNT, CSF studies; on palpation of muscles; myalgias; autoimmune postexertional muscle normal; MRI of rare fasciculations of legs disorder (celiac disease pain, fatigue C-spine: mild central without gastrointestinal herniation C6 disc; manifestations?); MRI of LS-spine: right synkinetic BLC side L4 disc herniation; gliadin antibodies: positive; TPO titer: 59 u/mL; euthyroid 14/M/49 Eyelid-closure BLC; action Synkinetic BLC, axonal Numbness and tingling EMG/NCV testing left Bipolar affective illness tremors of hands on peripheral neuropathy of hands and feet arm: complex treated with flexion-extension of (lithium?), action tremors prolonged MUPs of for 18 y wrists; restless feet; of hands, chronic FDI, APB, biceps, hypermobile joints, unilateral deafness deltoid, pronator teres scoliosis, fusion of muscles; low amplitude second and third toes on left ulnar sensory each foot; unilateral potential twitching of mentalis and orbicularis oris muscles with ipsilateral gaze 15/F/63 Midline linear sebaceous Vasodepressor syncope, Fainting Normal carotid ultrasound Hypertension; son and nevus; eyelid-closure familiar midline linear and EEG; head CT: grandson with midline BLC and orbicularis sebaceous nevus, silent multiple small nevus oculi myokymia lacunar , subcortical white-matter synkinetic BLC lacunar strokes 16/F/i; Eyelid closu.e BLC Synkinetic BLC Headaches Head CT: normal Somnambulisn; attention associated with facial deficit disorder; myoclonus mother has migraine and history of somnambulism as a child

See Table 1 for definitions of additional abbreviations. CSF, ; NCV, nerve conduction velocities; TPO, thyroid peroxidase antibody.

lightly close their eyelids for a minimum of 10 seconds. cluding stretching of the orbicularis oculi, sudden illu­ The patients were also examined for clinical or electro­ mination of the eyes, speech, changes in body posture, physiologic cranial nerve testing evidence of facial syn­ and gaze deviations. The patients were classified at a kinesis and for evidence for any reflex precipitants, in­ later time into five subgroups, based upon the kind of

J Neuro-Ophthalmol, Vol. 20, No. 4, 2000 SYNKINETIC BLEPHAROCLONVS 279 reflex mechanism (Table 1), associated tremors (Table generate in the patient. Cranial nerve testing con­ 2), myoclonus (Table 3), synkinetic movements (Table sisted of blink reflexes, facial EMG, and mental and 4), or presence of synkinesis evident by facial EMG only facial nerve latencies. Nerve conduction velocity testing (Table 5). The patients were examined by the author on included motor and sensory . Cranial nerve testing more than one occasion and followed for a minimum of and EMG/nerve conduction velocity studies were per­ 2 years. There was no consanguinity among the patients formed at the author's office using a Nicolet Compass examined. The patients were referred for neurologic con­ portable EMG unit (Nicolet Biomedical Inc., Madison, sultation for reasons other than BLC. The majority of WI), following standard procedure. Other laboratory and patients were women, in part due to local patterns of imaging studies were done at the local hospital. Addi­ referral that include gynecologists in the role of primary tional tests were completed according to the symptoms care physicians. of each patient and according to the reasons for referral. Patients either did not experience or were not inca­ pacitated by their eye twitching, but most were aware of RESULTS their involuntary eyelid movements, especially at night when they closed their eyes before falling asleep. None Of the eight patients with reflex BLC, none exhibited were aware of having cranial synkinesis. Myoclonus was BLS or had BLC provoked by stretching of the orbicu­ distinguished from tremors based on the larger amplitude laris oculi muscle. Blepharospasm was not observed in and slower frequencies of the movements in myoclonus. the three patients with frequent blinking rates (>30/min). Restless feet consisted mostly of rotational movements Gaze-evoked BLC was present in two patients; one pa­ of the feet while sitting or lying down and was differen­ tient had Ehlers-Danlos syndrome and familial BLC, and tiated from restless legs by the lack of sensory symptoms the other patient had hereditary palmoplanar kerato- in the legs, the absence of premonitory urge to move the derma, focal hemispheric subcortical demyelination (leu- feet, and when attempts to control the movements did not koencephalopathy), and cataplexy without narcolepsy.

TABLE 3. Blepharoclonus and myoclonus

Patient/Sex/ Age (y) Signs Diagnosis Symptoms Tests Other

17/F/25 Eyelid-closure BLC; Notalgia paresthesica; Daily global headaches, EMG/NCV of left leg, Negative ipsilateral facial chronic daily headaches; burning sensation CNT, brain MRI: myoclonus with synkinetic BLC between scapulas normal; EEG: normal monocular eyelid background with closure and BLC occasional brief, generalized, nonspecific theta discharges without clinical manifestations 18/F/39 BLC with eyelid closure Synkinetic BLC, action Muscle pain, postexertional EEG, brain MRI: normal; Hashimoto thyroiditis by associated with right- tremors of hands; restless exhaustion, global EMG of legs: complex history, IBS, chronic shoulder myoclonus; feet; axonal peripheral daily headaches prolonged MUPs, no daily headaches, action tremors of hands neuropathy genetic duplication or anxiety disorder, on flexion-extension at deletion of PMP-22 fibromyalgia wrists with fingers gene; TPO titer: 3.8 hyperextended; restless u/mL; euthyroid feet 19/F/70 BLC with light eyelid Synkinetic BLC; temporal Severe, constant right Brain MRI, CSF studies: Hashimoto thyroiditis, closure associated with arteritis (?) temple pain normal; temporal artery IBS rhythmic contraction of biopsy negative; left frontalis muscle; sedimentation rate: 42 old right Bell palsy and mL/hr; TPO titer: 160 facial contracture; u/mL; euthyroid action tremors of left hand 20/F/73 Generalized startle Startle (nonepileptic) Left facial paroxysmal Brain MRI, head CT, Remote history of myoclonus without myoclonus, synkinetic "stabbing" pain; EEG: normal; delayed twitching/spasms of LOC; asymmetric BLC, trigeminal generalized severe right R2 component of left side of face eyelid-closure BLC neuralgia; remote history body twitching blink reflex relieved by posterior (>OD) associated with of left hemifacial spasms triggered by startle fossa vascular bilateral facia! decompression; myoclonus; pectus hypertension excavatum 21/F/74 Eyelid-closure BLC Synkinetic BLC, paroxysmal Dizziness, poor balance, Normal head CT Ulcerative colitis, associated with facial hyperhidrosis headaches with visual osteoarthritis, myoclonus aura aborted by migraine with aura, repetitive volitional family history of eye movements; migraine episodes of abrupt- onset generalized sweating

See tables 1 and 2 for definitions of additional abbreviations. IBS, irritable bowel syndrome.

J Neuro-Ophihalmol, Vol, 20, No. 4, 2000 280 D. E. JACOME

TABLE 4. Blepharoclonus and synkinetic movements

Patient/Sexy Age (y) Signs Diagnosis Symptoms Tests Other 22/M;12 Eyelid-closure BLC; Mesial temporal sclerosis, Recent onset of Normal EEG; brain MRI, Congenital (surgically ipsilateral deviation of secondary generalized tonic-clonic CT: right temporal corrected) encephalocele jaw with lateral gaze seizures, eyelid-closure ventricular enlargement and imperforated anus; (Figs. 3A, B, and C) BLC, oculopterygoid and right mesial family history of synkinesis temporal atrophy with Polydactyly no enhancing lesions 23/F/14 Light eyelid-closure BLC BLC with oculopterygoid Pressure-like bilateral CNT, head CT: normal Asthma with alternating periods and oculofrontalis headaches of rapid/slow myoclonic synkinesis; familial BLC; eyelid contractions; episodic tension ipsilateral elevation of headaches eyebrow and jaw deviation with lateral gaze 24/M/20 Rhythmic elevation of Synkinetic BLC, Headaches and neck pain Normal EEG; Arnold Negative eyebrows with posttraumatic after lateral whiplash Chiari malformation eyelid-closure BLC; headaches, cervical injury detected on brain MRI; postural and action sprain; congenital Arnold small central syrinx on tremors of hands; Chiari malformation and cervical MRI tenderness of neck on cervical syrinx palpation; hypoactive deep tendon reflexes 25/F/22 Elevated optic discs with Idiopathy intracranial Headaches, sharp head Normal EEG, brain MRI, Family history of ; no exudation or hypertension? (declined pain; blurred vision 30 head CT; CNT: MUPs congenita] strabismus peripapillary lumbar puncture); times/d ("like looking at rest recorded from corrected with hemorrhages; normal "icepick-like pain"; through glass"); frontalis, orbicularis oris, during childhood venous pulsations; synkinetic BLC, dizziness, occasional and mentalis mucles eyelid-closure BLC; oculopterygoid synkinesis tinnitus bilaterally, greater on ipsilateral jaw deviation left side with lateral gaze; obesity 26/F/25 BLC, action tremors of Posttraumatic basilar artery Recurrent occipital EEG, brain MRI, NCV Negative hands, ipsilateral migraine, facial motor headaches, neck pain, right arm: normal; CNT: deviation of jaw with axonopathy and blurred vision after abnormal polyphasic lateral gaze, occasional (restricted) continuous minor head trauma MUPs recruited over multifocal muscle muscle fiber activity; right mentalis and fasciculations of limbs synkinetic BLC; orbicularis oris muscles; oculopterygoid synkinesis MUPs at rest of left mentalis and both frontalis muscles 27/M/31 BLC with light eyelid Synkinetic BLC, postinfectious Global pressure Brain MRI, CNT, EMG- Negative closure; bilateral eustachian tube dysfunction, headaches; occasional NCV of left arm: normal contraction of chin anxiety disorder, episodic crackling sound of muscles on lateral gaze tension headaches right ear after acute sinusitis 28/F/34 Alternating "see-saw" Focal epilepsy; complex Episodes of confusion Brain MRI, CT; normal; Negative elevation of eyebrows partial seizures with and automatic behavior EEG: generalized slow during speech; light secondary generalization; preceded by bad taste wave discharges; CNT: eyelid-closure BLC; imitation synkinesis in mouth, absent right Rl blink forceful opening of (reflex yawning), BLC exceptionally reflex component; mouth induced yawning terminating in abnormal polyphasic (Fig. 4); no echopraxia convulsions MUPs of bilateral otherwise frontalis muscles 29/F/35 Monocular BLC, action Synkinetic and monocular Headaches, back pain, CNT, MRI of LS-spine, Posttraumatic tremors of hands, BLC; oculopterygoid and nocturnal leg muscle EEG, left quadriceps disorder; bipolar restless feet, tonic oculolingual synkinesis; twitching, muscle/sural nerve affective illness; asthma pupils, focal nodular hyperekplexia, continuous postexertional biopsy and NCV of legs: atrophy of subcutaneous muscle fiber activity exhaustion normal; negative tissue; extreme startle syndrome, restless feet; PMP-22 genetic deletion response to unexpected lipodystrophy, tension or duplication; EMG of stimuli; ipsilateral headaches, terminal legs: spontaneous MUPs deviation of jaw and axonal neuropathy at rest of gastrocnemius, tongue with lateral gaze TA, and EDB muscles 30/F/40 Right facial weakness and Synkinetic BLC; catamenial Pain behind left ear with Brain MRI, EEG, CSF Negative contracture; pulling of left retroauricular pain, menses; chronic studies; normal; CNT: right comer of mouth postparalytic facial pulling sensation of tonic motor unit with blinks; synkinesis, facial right side of face; discharges recorded over eyelid-closure BLC contracture muscle twitching after right zygomaticus major ipsilateral Bell palsy muscle with eye closure; years earlier; facial BLC; complex twitching worse with prolonged MUPs over menses right (chronic reinnervation); no denervation

J Neuro-Ophthalmol, Vol. 20, No. 4, 2000 SYNKINETIC BLEPHAROCLONUS 281

TABLE 4 {Continued)

Patient/Sex/ Age (y) Signs Diagnosis Sympt 3ms Tests Other 31/F/36 Eye-closure BLC; mild Recurrent vestibular Paroxysmal nc npositional CNT: normal MUPs No history of Bell palsy, contraction at corners of neuronitis; synkinetic vertigo present at rest over both no evidence of mouth with eye blinks; BLC mentalis muscles; brain subclinical peripheral sustained, eyelid-closure MRI, EEG, CSF studies, neuropathy induced upward pulling and EMG/NCV of left of right corner of mouth; arm: normal unable to wink OD 32/F/56 Eyelid-closure BLC; Vestibular neuronitis, Dizziness EEG: nonspecific brief Nocturnal myoclonus and ipsilateral deviation of congenital venous generalized theta hypertension the tongue with lateral angioma, eyelid-closure episodes while awake; gaze BLC, oculolingual brain MRI; right synkinesis cerebellar venous angioma (Fig. 5); normal CNT

See Tables 1 and 2 for definitions of additional abbreviations. PMP, peripheral protein,

Blepharoclonus was induced by speech in only two pa­ case; Figs. 3A-C). There were two cases of dual synki­ tients. In addition, one patient with light-induced BLC netic movements; one with oculolingual and oculoptery­ and one patient with gaze-induced BLC also exhibited goid synkinesis, and the other with oculofacial and ocu­ speech-induced BLC. Speech-induced BLC was distin­ lopterygoid synkinesis. One patient had imitation synki­ guished from BLC-like tics during normal speech on the nesis (reflex yawning with imitation of yawning by basis of a longer duration and a larger amplitude of eye­ widely opening her mouth; Fig. 4), and another patient lid myoclonus in the former. In addition, these patients was unable to close her right eye voluntarily. One patient had eyelid-closure BLC. Unconscious sustained closure exhibited monocular BLC in isolation, and another pa­ of the eyelids during speech may have precipitated the tient had asymmetric BLC. One patient had alternating appearance of BLC in these four patients. Specific pos­ rapid and slow BLC. Three patients with familial BLC ture was the precipitating mechanism of BLC in two of and seven patients with congenital developmental disor­ the patients. Several patients had BLC-associated facial ders are described. Restless feet syndrome was present in myoclonus, but there were two patients with generalized six patients, three of whom had features of peripheral myoclonus independent of BLC and two patients with neuropathy. Eight patients had signs or symptoms of nocturnal (sleep) myoclonus. One patient had BLC- mild axonal peripheral neuropathy, including examples induced focal myoclonus of the right shoulder. Seven of continuous muscle fiber activity syndrome. Three pa­ patients had BLC-associated tremors, three patients had tients had Hashimoto thyroiditis, but they were euthyroid abnormalities detected by facial EMG only, and 11 pa­ and had low thyroid peroxidase antibody titers. There tients had BLC-synkinetic movements (three oculofacial were no examples of multiple sclerosis or brain tumors. and three oculopterygoid cases, and one oculolingual One patient had a cerebellar venous angioma (Fig. 5).

TABLE 5. Blepharoclonus and EMG synkinesis

Patient/Sex/ Age (y) Signs Diagnosis Symptoms Tests Other 33/F/15 Rapid blinking (>30/min); Familial synkinetic BLC Pounding, recurrent Brain MRI and EEG: Asthma, seasonal eyelid-closure BLC bilateral headaches normal; CNT: MUP depression, migraine discharges both mental without aura; mother and right orbicularis and maternal oris muscles with right grandmother had lateral gaze similar BLC 34/M/42 Pain on pressure applied Congenital facial Intermittent right Brain MRI with contrast Negative behind right ear, hemiatrophy, synkinetic retroauricular pain, and EEG: normal; sleep radiating to ipsilateral BLC, osteoarthritis of generalized nocturnal myoclonus recorded frontal region and eye; C-spine, great auricular body twitching during overnight sleep mild right facial neuralgia, sleep studies; C-spine x-rays: hemiatrophy (no history myoclonus DJD. CNT: MUPs at of facial palsy) rest recorded at right mentalis muscle during light eyelid closure 35/F/75 Frequent blinking (>30 Midbrain lacunar ? Transient diplopia with Head CT: normal; CNT: Osteoarthritis blinks/min); eyelid- synkinetic BLC downward gaze spontaneous normal closure BLC, MUPs of orbicularis hypoacusis in left ear oris bilaterally at rest and during eyelid closure

See tables 1 and 2 for definitions of additional abbreviations. DJD, degenerative joint disease.

/ Neuro-Ophthalmol, Vol. 20, No. 4, 2000 282 D. E. JACOME

Two patients had epilepsy but exhibited no focal epilep­ tic activity related to eye movements or eyelid closure during their electroencephalograms (EEGs). Details of the clinical data and results of testing for each patient are listed in the accompanying tables, which divide the dif­ ferent subgroups.

DISCUSSION I believe BLC is underdetected because it is not spon­ taneously reported by patients; its presence is frequently missed by the examiner during routine neurologic ex­ amination because the patient is asked to close his or her eyes only briefly, not waiting long enough for BLC to appear after a variable latency period, or because he or she is asked to close the eyes forcefully (to determine the presence of facial weakness), while at the same time suppressing BLC. Previously recognized causes of BLC are head trauma, , and multiple sclerosis (1,2,6,7). Multiple sclerosis was the underlying condition in the two patients of Keane (6) with gaze-evoked BLC. Obeso et al. (5) reported the case of a patient with essential BLS. None of the patients herein reported experienced major head trauma, had evidence of hydrocephalus, had signs of multiple sclerosis, or had BLS. Three patients had Hash­ imoto thyroiditis (patients 13, 18, and 19), but they were FIG. 2. Brain MRI T2-weighted images show an area of white- matter increased signal over the left hemisphere corona radiata euthyroid and had no cognitive disturbance or alteration compatible with focal demyelination (patient 3). of consciousness level. Their blood thyroid peroxidase titers were not significantly elevated to explain their BLC on the basis of Hashimoto that po­ voluntary movements, including dystonia, BLS, and ocu­ tentially may have caused myoclonus of the orbicularis logyric crisis. oculi muscles (8). History of Bell palsy was elicitable Patient 3 had palmoplantar keratoderma, which is an only in two patients (patients 19 and 30), and only two inherited condition recently reported in association with patients (patients 32 and 34) had nocturnal (sleep) my­ leukoencephalopathy (9) (Fig. 1). She presented with oclonus. No patients showed evidence of epilepsy on painful gaze-evoked BLC and cataplexy similar to the EEG during BLC, including the two individuals with cases of Niemann Pick disease type C (10). Her brain epilepsy, and no patients exhibited EEG epileptic activity MRI showed a small globular area of hyperintensity on associated with their tremors, synkinesis, or myoclonus. the T2-weighted images localized to the left centrum Although six patients (patients 1, 4, 9, 10, 18, and 29) semiovale, which was consistent with focal demyelina­ had restless feet, and three patients (patients 4, 33, and tion (restricted leukoencephalopathy) (Fig. 2). However, 35) had frequent blinking, none developed additional in- her cultured skin fibroblasts did not demonstrate the cy- tochemical abnormalities typical of Niemann Pick dis­ ease type C (10). To my knowledge, neither of these clinical signs have been reported in patients with pal­ moplantar keratoderma. Cranial synkinesis is often overlooked by the exam­ iner because it is rarely symptomatic. Some signs are very subtle and require close examination because syn- kinetic facial movements may be isolated, unsustained, or of small amplitude; they may be congenital or ac­ quired, as in the example of synkinesis after Bell palsy, in which case they are more apparent. Many types have been described before and after the landmark paper on the subject by Schwarz (11) in 1962. The pathogenesis of synkinetic BLC cannot be ascertained. In cases with no apparent immediate cause, aberrant crossed innervation established during fetal development of the cranial FIG. 1. Plantar hyperkeratosis (keratoderma) of the left foot (pa­ nerves may be postulated. Patient 34, who had congenital tient 3). facial hemiatrophy, is an example that supports the de-

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SYNKINETIC BLEPHAROCLONUS 283

FIG. 3. A-C: Lateral jaw deviation with lateral gaze (oculopterygoid synkinesis) (patient 22). velopmental theory. In acquired cases (i.e., after Bell muscles, it cannot be proposed in every case that the palsy), misdirected regeneration of cranial nerve axons is associated movements were precipitated by peripheral the usual explanation without excluding the potential facial nerve fibers, or that BLC represents an abnormal­ participation of the mechanisms of peripheral ephapsis ity of the innervation of the obicularis oculi muscle. In and central synaptic reorganization (11-13). Because examples of BLC-induced or enhanced tremors, a state synkinetic movements do not always involve the facial of central hyperexcitability could be adduced, although future additional electrophysiologic testing with somato- sensory-evoked potentials and transcranial magnetic stimulation are needed on similar patients in order to support this hypothesis. The original reports on BLC suggest that its presence constitutes a sign of major neurologic illness (1,2). None of these patients suffered from a serious progressive neu­ rologic illness, at least on a short-term basis. Instead, the clinical data presented here indicate the following: 1. BLC is a focal of the obicularis oculi, at times forming part of more widespread benign tremors or myoclonus; 2. BLC can be the expression of a familial trait (as in patients 10, 23, and 33); 3. BLC often constitutes an isolated fortuitously discov­ ered clinical sign; 4. BLC at times is associated with (underdiagnosed) cra­ FIG. 4. Forceful mouth opening triggers reflex yawning (patient nial synkinesis and has a benign course in most indi­ 28). viduals; 5. BLC may have different precipitants, but gaze- evoked BLC probably has the greater clinical rel­ evance or is more likely to be found in individuals with active or progressive neurologic disease (i.e., multiple sclerosis, Niemann Pick disease, palmoplan- tar keratoderma).

REFERENCES 1. Behrman S, Scott DF. Blepharoclonus provoked by voluntary eye closure. Mov Disord 1988;3:326-8. 2. Safran AV, Moody JF, Gauthier G. Sustained blepharoclonus upon eye closure. J Clin Neuroophthalmol 1983;3:133-6. 3. Hallett M, Daroff RB. Blepharospasm: report of a workshop. Neu­ rology 1996;46:1213-8. 4. Grandas F, Elston J, Quinn N, Marsden CD. Blepharospasm: a review of 264 patients. J Neurol Neurosurg Psychiatry 1988;51: 767-2. 5. Obeso JA, Artieda MD, Marsden CD. Stretch reflex blepharo­ . Neurology 1985;35:1378-80. FIG. 5. Venous angioma of the right cerebellar hemisphere (brain 6. Keane JR. Gaze-evoked blepharoclonus. Ann Neurol 1978;3: MRI T1-weighted images) (patient 32). 243-5.

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7. Gatto M, Micheli F, Fernandez-Pardal M. Blepharoclonus and par­ 10. Kandt RS, Emerson RG, Singer HS, Valle DL, Moser HW. Cata­ kinsonism associated with aqueductal stenosis. Mov Disord 1990; plexy in variant forms of Niemann-Pick disease. Ann Neurol 1982; 5:310-3. 12:284-8. 8. Shaw PJ, Walls TJ, Newman PK, Cleland PG, Carlidge NEF. 11. Schwarz GA. A note on an unusual facio-ocular synkinesis. Arch Hashimoto's encephalopathy: a steroid-responsive disorder asso­ Neurol 1962;6:36^13. ciated with high anti-thyroid antibody titers- report of five cases. 12 Sadjadpour K. Postfacial palsy phenomena: faulty nerve regenera­ Neurology 1991;41:228-33. tion or ephaptic transmission? Brain Res 1975;95:403-6. 9. Lossos A, Cooperman H, Soffer D, et al. Hereditary leukoencepha- 13 Montserrat L, Benito M. Facial synkinesis and aberrant regeneration lopathy and palmoplanar keratoderma: a new disorder with in­ of facial nerve. In: Facial . Jankovic J, Tolosa E, eds; creased skin collagen content. Neurology 1995;45:331-7. Advances in neurology. Vol. 49. New York: Raven Press, 1988.

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