Journal of Neuro-Ophthalmology, December 2000, Volume 20, Issue 4

Synkinetic Blepharoclonus

OBJECTIVES: To analyze the clinical data and test results collected in a group of patients exhibiting eyelid-closure blepharoclonus (BLC) on clinical neurologic examination. MATERIALS AND METHODS: Thirty-five patients were referred for neurologic evaluation for reasons other than BLC. Clinical electrophysiologic evaluations, including cranial nerve testing and electromyograms, were done according to standards. All patients had neuroimaging studies, including brain magnetic resonance imaging and head computerized tomography, or both, and many had electroencephalograms. Additional tests were done based on the patient's symptoms or reasons for referral. RESULTS: Eight patients had reflex BLC. Two cases were precipitated by vertical gaze; one of these patients had hereditary palmoplantar keratoderma and cataplexy, and the other patient had Ehlers-Danlos syndrome and familial BLC. Other precipitants included speech in four cases, postural changes in two cases, and light stimulation in one case. Two patients had generalized myoclonus independent of their BLC, two patients had a history of sleep myoclonus, and several patients had BLC-associated facial myoclonus. One patient had BLC-associated myoclonus of the right shoulder. Synkinetic cranial movements were detected in 11 patients (four oculofacial, three oculopterygoid, one oculolingual, two dual cases, and one case of imitation synkinesis.) Three patients had familial BLC, seven patients had congenital developmental disorders, six patients had synkinetic tremors, and six patients had restless feet. Some indication of peripheral neuropathy was evident in eight patients. CONCLUSIONS: Eyelid-closure BLC is an underrecognized, sporadic or familial, mostly benign, chronic eyelid-movement disorder that may be associated with tremors, myoclonus, cranial synkinesis, and restless feet. Reflex mechanisms may be identified in some patients. Gaze-induced BLC seems to have the greatest clinical relevance. In the current series, there were no examples of posttraumatic BLC, multiple sclerosis, hydrocephalus, or blepharospasm conditions previously reported to be associated with BLC. No electroencephalographic abnormalities were recorded during BLC, ruling out eyelid-closure epilepsy.

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 col­lected in a group of patients exhibiting eyelid- closure blepharo­clonus ( BLC) on clinical neurologic examination. Materials and Methods: Thirty- five patients were referred for neurologic evaluation for reasons other than BLC. Clinical electrophysiologic evaluations, including cranial nerve testing and electromyograms, were done according to standards. All patients had neuroimaging studies, including brain magnetic resonance imaging and head computerized tomography, or both, and many had electroencephalograms. Additional tests were done based on the patient's symptoms or reasons for referral. Results: Eight patients had reflex BLC. Two cases were pre­cipitated by vertical gaze; one of these patients had hereditary palmoplantar keratoderma and cataplexy, and the other patient had Ehlers- Danlos syndrome and familial BLC. Other precipi-tants included speech in four cases, postural changes in two cases, and light stimulation in one case. Two patients had gen­eralized myoclonus independent of their BLC, two patients had a history of sleep myoclonus, and several patients had BLC-associated facial myoclonus. One patient had BLC- associated myoclonus of the right shoulder. Synkinetic cranial movements were detected in 11 patients ( four oculofacial, three oculo-pterygoid, one oculolingual, two dual cases, and one case of imitation synkinesis.) Three patients had familial BLC, seven patients had congenital developmental disorders, six patients had synkinetic tremors, and six patients had restless feet. Some indication of peripheral neuropathy was evident in eight pa­tients. Conclusions: Eyelid- closure BLC is an underrecognized, spo­radic or familial, mostly benign, chronic eyelid- movement dis­order that may be associated with tremors, myoclonus, cranial synkinesis, and restless feet. Reflex mechanisms may be iden­tified in some patients. Gaze- induced BLC seems to have the greatest clinical relevance. In the current series, there were no examples of posttraumatic BLC, multiple sclerosis, hydroceph­alus, or blepharospasm conditions previously reported to be associated with BLC. No electroencephalographic abnormali­ties were recorded during BLC, ruling out eyelid- closure epi­lepsy. Key Words: Blepharoclonus- Blepharospasm- Cranial syn­kinesis- Eyelids- Movement disorder- Myoclonus- Synkinetic movements. Manuscript received February 8, 1999; accepted February 16, 2000. From the Franklin Medical Center, Greenfield, Massachusetts, and the Section of Neurology, Dartmouth- Hitchcock Medical Center, Leba­non, New Hampshire. Address correspondence and reprint requests to Daniel E. Jacome, MD, 1 Burnham Street, Suite 2, Turners Falls, MA 01376. Blepharoclonus is the repetitive, easily detectable, myoclonic contractions of the orbicularis oculi muscle ( 1). It is commonly apparent with light eyelid closure and may be suppressed by forceful eyelid contraction ( 2). In contradistinction, blepharospasm ( BLS) is a focal dysto­nia manifested by forceful and sustained involuntary clo­sure of the eyelids, often accompanied by great difficulty in opening the eyes on command or free will, which is a clinical phenomenon called " apraxia of lid opening" ( 3,4). However, attempts to open the eyelids during epi­sodes of BLS may be confused with BLC, or with paretic tremors of the eyelids in a patient with partial denerva­tion of the orbicularis oculi. Blepharoclonus may be pro­voked by stretching of the obicularis oculi or by gaze deviations ( 5,6). Synkinetic BLC is defined here as: 1. the involuntary movements, fasciculations, or facial electromyogram ( EMG) motor units firing, triggered by, or associated with BLC, normally affecting muscles other than the orbicularis oculi; 2. BLC- enhanced cephalic and extracephalic focal, mul­tifocal, or generalized tremors; 3. BLC in patients exhibiting other cranial synkinesis ( synkinetic movements); 4. reflex BLC. The last subgroup may be identified by the specific mechanism that causes BLC ( see below). Those mecha­nisms are stretching of the orbicularis oculi, stimulation by sudden illumination, speech, changes in body posture, and gaze deviations. Although both patients reported by Obeso et al. ( 5) had reflex BLS and BLC, either one of these conditions may occur independently. In reflex BLS, the eyes are involuntarily forcefully shut, while in pure- reflex BLC, only rapid myoclonus of the eyelids is observed in the absence of sustained contraction of the orbicularis oculi. MATERIALS AND METHODS After a few patients with BLC referred for other neu­rologic disorders were identified by the author, a system­atic search for this condition was performed for all new patients in the author's practice. A total of 35 patients with BLC, ranging in age from 11 to 75 years, was collected over a 5- year period. These patients were iden­tified on routine neurologic examination when asked to 276 SYNKINETIC BLEPHAROCLONUS 277 TABLE 1. Reflex synkinetic blepharoclonus Patient/ Sex/ Age ( y) l/ F/ 38 2/ F/ 43 J/ F/ 44 4/ M/ 44 « 5/ F/ 47 6/ F/ 50 7/ F/ 66 8/ F/ 73 Signs Diagnoses Symptoms Tests Other Action tremors of hands, frequent rotational feet movements at rest; BLC with light eyelid closure enhanced by sitting or standing, greatly diminished lying down Hypermobile joints, soft skin with very visible veins, tenderness of the spine, left leg weakness, abnormal gait; downward gaze BLC and myokymia of lower eyelid; speech-related BLC; allodynia of teeth BLC with upward gaze; palmoplantar hyperkeratosis, greater over feet ( Fig. 1) Chronic ptosis and miosis OD; action tremors of hands on flexion-extension at the wrists; frequent involuntary 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 Eyelid- closure BLC triggered by speech and light stimulation BLC with light eyelid closure, greatly enhanced in supine position BLC with eyelid closure and during speech; ipsilateral deviation of jaw with lateral gaze; generalized deep- tendon hyporeflexia Eyelid closure and speech- induced BLC; leans toward left when sitting; rigidity, akinesia of right arm Demyelinating retrobulbar optic neuropathy and axonal peripheral neuropathy of unknown etiology; synkinetic ( reflex) BLC Synkinetic BLC; common migraine; EDS- related LS plexopathy, subcortical nodular gliosis Palmoplantar keratoderma, focal leukoencephalopathy, cataplexy, sciatica, gaze- evoked BLC Cluster headaches with residual chronic ipsilateral Homer syndrome; synkinetic BLC Migraine with aura, synkinetic BLC Synkinetic BLC; drug reaction; limited continuous facial muscle- fiber activity Monoclonal gammopathy-associated peripheral neuropathy, synkinetic BLC, oculopterygoid synkinesis, speech-induced BLC Synkinetic BLC, corticobasal ganglionic degeneration, truncal dystonia Objects blurred, lacked color in vision OS; V/ A 20/ 20 Back pain, numbness, tingling of left leg; left side pulsatile headaches without warnings, sensitive teeth Sudden falls precipitated by emotions, without loss of consciousness; right leg postexertional pain Episodic severe pain behind right eye, numbness of right thigh and right side of face Pounding headaches preceded by compulsive yawning Diplopia and transient confusion after ingestion of lorazepam Intermittent numbness of limbs and left side of face Writing tremors, poor mobility, abnormal posture VERS showed conduction slowing through optic nerve OS; brain MRI: normal; EMG legs; complex polyphasic MUPs recorded over leg muscles; no spontaneous activity LS spine MRI: normal; brain MRI: T2- weighted nodular subcortical white- matter high- intensity signals of greater prominence over the left frontal region; EMG of legs: spontaneous normal MUPs at rest over both TA and left EDB muscles EEG, ECG, MRI of the LS spine, 2D echocardiogram: normal; no organomegaly by CT of the abdomen; 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 Brain MRI/ MRA, CNT, CT, MRI of LS spine, VERs BAERs: normal Brain MRI: normal Brain MRI: normal; CNT: normal MUPs present • at rest over right orbicularis oris and both mentalis muscles on facial EMG; Anti- Yo, anti- Ri antibodies: negative IgG lambda monoclonal gammopathy; C- spine MRI: spinal stenosis; left leg EMG: complex prolonged polyphasic MUPs over RF and EDB muscles with no F- wave responses Head CT: cortical atrophy; EEG, CNT, SPECT: normal Progressive improvement of vision in follow- up with no new symptoms Family history of EDS, somnambulism, eyelid closure BLC Family history of hemophilia, common migraine Negative Mother had migraines preceded by compulsive yawning Breast cancer by history; no previous history of Bell palsy Hypertension Negative 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 10/ F/ 17 ll/ M/ 32 12/ F/ 37 13/ F/ 46 14/ M/ 49 15/ F/ 63 16/ F/ i; BLC, action tremors of hands on flexion-extension movements at the wrists; repetitive movements of feet at rest while sitting; BLC-induced generalized multifocal tumors Eyelid- closure BLC; action tremors of the hands on flexion- extension at the wrists; restless feet; hypermobile joints, scoliosis, fusion of second and third toes of each foot; unilateral twitching of mentalis and orbicularis oris muscles with ipsilateral gaze Cephalic tremors associated with eyelid- closure BLC Eyelid- closure BLC associated with head tremors; action tremors of hands Head/ postural hand tremors simultaneous with eyelid- closure BLC; pain on palpation of muscles; rare fasciculations of legs Eyelid- closure BLC; action tremors of hands on flexion- extension of wrists; restless feet; hypermobile joints, scoliosis, fusion of second and third toes on each foot; unilateral twitching of mentalis and orbicularis oris muscles with ipsilateral gaze Midline linear sebaceous nevus; eyelid- closure BLC and orbicularis oculi myokymia Eyelid closu. e BLC associated with facial myoclonus Synkinetic BLC, essential benign tremors (?), episodic tension headaches Catamenial migraine with postdromal fatigue; synkinetic familial BLC; EDS, continuous muscle fiber activity; action tremors of the hands and restless feet Synkinetic BLC; posttraumatic right brachial plexopathy, right arm paroxysmal dystonia essential nonepileptic subcortical myoclonus Synkinetic BLC; antiphospholipid antibody syndrome; migraine with aura and persistent visual phenomena; transformed migraine Right sciatica (?), C6 and L4 disc herniations; postexertional fatigue and myalgias; autoimmune disorder ( celiac disease without gastrointestinal manifestations?); synkinetic BLC Synkinetic BLC, axonal peripheral neuropathy ( lithium?), action tremors of hands, chronic unilateral deafness Vasodepressor syncope, familiar midline linear sebaceous nevus, silent lacunar strokes, synkinetic BLC Synkinetic BLC Generalized morning tremors; headaches Monthly pulsatile headaches around menses followed by fatigue for 5 days, " internal shaking"; easy bruising Generalized intermittent shaking, right shoulder pain, right hand numbness and painless spasms of right arm induced by exercise, beginning after serious chest injury Recurrent pulsatile headaches preceded by phosphenes; daily background headaches Right leg pain, weakness; left facial numbness, " internal shaking," postexertional muscle pain, fatigue Numbness and tingling of hands and feet Fainting Headaches Normal EEG, EMG/ NCV of the legs, MRI of the brain Normal EEG, MRI of the brain, NCV; CNT: delayed left; R2 component of blink reflex; EMG: spontaneous normal MUPs at rest over right TA and EDB muscles Normal EEG during generalized tremors; normal head CT and EMG/ NCV of right arm Elevated IgG/ IgA cardiolipin antibodies; brain MRI, EEG, CNT, CSF studies: normal Brain MRI, EEG, EMG/ NCV of legs, CNT, CSF studies; normal; MRI of C- spine: mild central herniation C6 disc; MRI of LS- spine: right side L4 disc herniation; gliadin antibodies: positive; TPO titer: 59 u/ mL; euthyroid EMG/ NCV testing left arm: complex prolonged MUPs of FDI, APB, biceps, deltoid, pronator teres muscles; low amplitude left ulnar sensory potential Normal carotid ultrasound and EEG; head CT: multiple small subcortical white- matter lacunar strokes Head CT: normal Mother and sister had somnambulism Mother and maternal grandmother with BLC; family history of ruptured intracranial aneurysms, somnambulism, EDS Negative Family history of migraine Hashimoto thyroiditis, anemia, leukopenia Bipolar affective illness treated with lithium for 18 y Hypertension; son and grandson with midline nevus Somnambulisn; attention deficit disorder; mother has migraine and history of somnambulism as a child See Table 1 for definitions of additional abbreviations. CSF, cerebrospinal fluid; NCV, nerve conduction velocities; TPO, thyroid peroxidase antibody. lightly close their eyelids for a minimum of 10 seconds. The patients were also examined for clinical or electro­physiologic cranial nerve testing evidence of facial syn­kinesis and for evidence for any reflex precipitants, in­cluding stretching of the orbicularis oculi, sudden illu­mination of the eyes, speech, changes in body posture, and gaze deviations. The patients were classified at a 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 2), myoclonus ( Table 3), synkinetic movements ( Table 4), or presence of synkinesis evident by facial EMG only ( Table 5). The patients were examined by the author on more than one occasion and followed for a minimum of 2 years. There was no consanguinity among the patients examined. The patients were referred for neurologic con­sultation for reasons other than BLC. The majority of patients were women, in part due to local patterns of referral that include gynecologists in the role of primary care physicians. Patients either did not experience or were not inca­pacitated by their eye twitching, but most were aware of their involuntary eyelid movements, especially at night when they closed their eyes before falling asleep. None were aware of having cranial synkinesis. Myoclonus was distinguished from tremors based on the larger amplitude and slower frequencies of the movements in myoclonus. Restless feet consisted mostly of rotational movements of the feet while sitting or lying down and was differen­tiated from restless legs by the lack of sensory symptoms in the legs, the absence of premonitory urge to move the feet, and when attempts to control the movements did not generate anxiety in the patient. Cranial nerve testing con­sisted of blink reflexes, facial EMG, and mental and facial nerve latencies. Nerve conduction velocity testing included motor and sensory nerves. Cranial nerve testing and EMG/ nerve conduction velocity studies were per­formed at the author's office using a Nicolet Compass portable EMG unit ( Nicolet Biomedical Inc., Madison, WI), following standard procedure. Other laboratory and imaging studies were done at the local hospital. Addi­tional tests were completed according to the symptoms of each patient and according to the reasons for referral. RESULTS Of the eight patients with reflex BLC, none exhibited BLS or had BLC provoked by stretching of the orbicu­laris oculi muscle. Blepharospasm was not observed in the three patients with frequent blinking rates (> 30/ min). Gaze- evoked BLC was present in two patients; one pa­tient had Ehlers- Danlos syndrome and familial BLC, and the other patient had hereditary palmoplanar kerato-derma, focal hemispheric subcortical demyelination ( leu-koencephalopathy), and cataplexy without narcolepsy. TABLE 3. Blepharoclonus and myoclonus Patient/ Sex/ Age ( y) 17/ F/ 25 18/ F/ 39 19/ F/ 70 20/ F/ 73 21/ F/ 74 Signs Eyelid- closure BLC; ipsilateral facial myoclonus with monocular eyelid closure and BLC BLC with eyelid closure associated with right-shoulder myoclonus; action tremors of hands on flexion- extension at wrists with fingers hyperextended; restless feet BLC with light eyelid closure associated with rhythmic contraction of left frontalis muscle; old right Bell palsy and facial contracture; action tremors of left hand Generalized startle myoclonus without LOC; asymmetric eyelid- closure BLC (> OD) associated with bilateral facia! myoclonus; pectus excavatum Eyelid- closure BLC associated with facial myoclonus Diagnosis Notalgia paresthesica; chronic daily headaches; synkinetic BLC Synkinetic BLC, action tremors of hands; restless feet; axonal peripheral neuropathy Synkinetic BLC; temporal arteritis (?) Startle ( nonepileptic) myoclonus, synkinetic BLC, trigeminal neuralgia; remote history of left hemifacial spasms Synkinetic BLC, paroxysmal hyperhidrosis Symptoms Daily global headaches, burning sensation between scapulas Muscle pain, postexertional exhaustion, global daily headaches Severe, constant right temple pain Left facial paroxysmal " stabbing" pain; generalized severe body twitching triggered by startle Dizziness, poor balance, headaches with visual aura aborted by repetitive volitional eye movements; episodes of abrupt-onset generalized sweating Tests EMG/ NCV of left leg, CNT, brain MRI: normal; EEG: normal background with occasional brief, generalized, nonspecific theta discharges without clinical manifestations EEG, brain MRI: normal; EMG of legs: complex prolonged MUPs, no genetic duplication or deletion of PMP- 22 gene; TPO titer: 3.8 u/ mL; euthyroid Brain MRI, CSF studies: normal; temporal artery biopsy negative; sedimentation rate: 42 mL/ hr; TPO titer: 160 u/ mL; euthyroid Brain MRI, head CT, EEG: normal; delayed right R2 component of blink reflex Normal head CT Other Negative Hashimoto thyroiditis by history, IBS, chronic daily headaches, anxiety disorder, fibromyalgia Hashimoto thyroiditis, IBS Remote history of twitching/ spasms of left side of face relieved by posterior fossa vascular decompression; hypertension Ulcerative colitis, osteoarthritis, migraine with aura, family history of migraine 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; ipsilateral deviation of jaw with lateral gaze ( Figs. 3A, B, and C) 23/ F/ 14 Light eyelid- closure BLC with alternating periods of rapid/ slow myoclonic eyelid contractions; ipsilateral elevation of eyebrow and jaw deviation with lateral gaze 24/ M/ 20 Rhythmic elevation of eyebrows with eyelid- closure BLC; postural and action tremors of hands; tenderness of neck on palpation; hypoactive deep tendon reflexes 25/ F/ 22 Elevated optic discs with no exudation or peripapillary hemorrhages; normal venous pulsations; eyelid- closure BLC; ipsilateral jaw deviation with lateral gaze; obesity 26/ F/ 25 BLC, action tremors of hands, ipsilateral deviation of jaw with lateral gaze, occasional multifocal muscle fasciculations of limbs 27/ M/ 31 BLC with light eyelid closure; bilateral contraction of chin muscles on lateral gaze 28/ F/ 34 Alternating " see- saw" elevation of eyebrows during speech; light eyelid- closure BLC; forceful opening of mouth induced yawning ( Fig. 4); no echopraxia otherwise 29/ F/ 35 Monocular BLC, action tremors of hands, restless feet, tonic pupils, focal nodular atrophy of subcutaneous tissue; extreme startle response to unexpected stimuli; ipsilateral deviation of jaw and tongue with lateral gaze 30/ F/ 40 Right facial weakness and contracture; pulling of right comer of mouth with blinks; eyelid- closure BLC Mesial temporal sclerosis, secondary generalized seizures, eyelid- closure BLC, oculopterygoid synkinesis BLC with oculopterygoid and oculofrontalis synkinesis; familial BLC; episodic tension headaches Synkinetic BLC, posttraumatic headaches, cervical sprain; congenital Arnold Chiari malformation and cervical syrinx Idiopathy intracranial hypertension? ( declined lumbar puncture); " icepick- like pain"; synkinetic BLC, oculopterygoid synkinesis Posttraumatic basilar artery migraine, facial motor axonopathy and ( restricted) continuous muscle fiber activity; synkinetic BLC; oculopterygoid synkinesis Synkinetic BLC, postinfectious eustachian tube dysfunction, anxiety disorder, episodic tension headaches Focal epilepsy; complex partial seizures with secondary generalization; imitation synkinesis ( reflex yawning), BLC Synkinetic and monocular BLC; oculopterygoid and oculolingual synkinesis; hyperekplexia, continuous muscle fiber activity syndrome, restless feet; lipodystrophy, tension headaches, terminal axonal neuropathy Synkinetic BLC; catamenial left retroauricular pain, postparalytic facial synkinesis, facial contracture Recent onset of tonic- clonic seizures Pressure- like bilateral headaches Headaches and neck pain after lateral whiplash injury Headaches, sharp head pain; blurred vision 30 times/ d (" like looking through glass"); dizziness, occasional tinnitus Recurrent occipital headaches, neck pain, blurred vision after minor head trauma Global pressure headaches; occasional crackling sound of right ear after acute sinusitis Episodes of confusion and automatic behavior preceded by bad taste in mouth, exceptionally terminating in convulsions Headaches, back pain, nocturnal leg muscle twitching, postexertional exhaustion Pain behind left ear with menses; chronic pulling sensation of right side of face; muscle twitching after ipsilateral Bell palsy years earlier; facial twitching worse with menses Normal EEG; brain MRI, CT: right temporal ventricular enlargement and right mesial temporal atrophy with no enhancing lesions CNT, head CT: normal Normal EEG; Arnold Chiari malformation detected on brain MRI; small central syrinx on cervical MRI Normal EEG, brain MRI, head CT; CNT: MUPs at rest recorded from frontalis, orbicularis oris, and mentalis mucles bilaterally, greater on left side EEG, brain MRI, NCV right arm: normal; CNT: abnormal polyphasic MUPs recruited over right mentalis and orbicularis oris muscles; MUPs at rest of left mentalis and both frontalis muscles Brain MRI, CNT, EMG-NCV of left arm: normal Brain MRI, CT; normal; EEG: generalized slow wave discharges; CNT: absent right Rl blink reflex component; abnormal polyphasic MUPs of bilateral frontalis muscles CNT, MRI of LS- spine, EEG, left quadriceps muscle/ sural nerve biopsy and NCV of legs: normal; negative PMP- 22 genetic deletion or duplication; EMG of legs: spontaneous MUPs at rest of gastrocnemius, TA, and EDB muscles Brain MRI, EEG, CSF studies; normal; CNT: tonic motor unit discharges recorded over right zygomaticus major muscle with eye closure; BLC; complex prolonged MUPs over right facial muscles ( chronic reinnervation); no denervation Congenital ( surgically corrected) encephalocele and imperforated anus; family history of Polydactyly Asthma Negative Family history of epilepsy; congenita] strabismus corrected with surgery during childhood Negative Negative Negative Posttraumatic stress disorder; bipolar affective illness; asthma Negative J Neuro- Ophthalmol, Vol. 20, No. 4, 2000 SYNKINETIC BLEPHAROCLONUS 281 TABLE 4 { Continued) Patient/ Sex/ Age ( y) 31/ F/ 36 32/ F/ 56 Signs Eye- closure BLC; mild contraction at corners of mouth with eye blinks; sustained, eyelid- closure induced upward pulling of right corner of mouth; unable to wink OD Eyelid- closure BLC; ipsilateral deviation of the tongue with lateral gaze Diagnosis Recurrent vestibular neuronitis; synkinetic BLC Vestibular neuronitis, congenital venous angioma, eyelid- closure BLC, oculolingual synkinesis Sympt Paroxysmal nc vertigo Dizziness 3ms npositional Tests CNT: normal MUPs present at rest over both mentalis muscles; brain MRI, EEG, CSF studies, and EMG/ NCV of left arm: normal EEG: nonspecific brief generalized theta episodes while awake; brain MRI; right cerebellar venous angioma ( Fig. 5); normal CNT Other No history of Bell palsy, no evidence of subclinical peripheral neuropathy Nocturnal myoclonus and hypertension See Tables 1 and 2 for definitions of additional abbreviations. PMP, peripheral myelin protein, Blepharoclonus was induced by speech in only two pa­tients. In addition, one patient with light- induced BLC and one patient with gaze- induced BLC also exhibited speech- induced BLC. Speech- induced BLC was distin­guished from BLC- like tics during normal speech on the basis of a longer duration and a larger amplitude of eye­lid myoclonus in the former. In addition, these patients had eyelid- closure BLC. Unconscious sustained closure of the eyelids during speech may have precipitated the appearance of BLC in these four patients. Specific pos­ture was the precipitating mechanism of BLC in two of the patients. Several patients had BLC- associated facial myoclonus, but there were two patients with generalized myoclonus independent of BLC and two patients with nocturnal ( sleep) myoclonus. One patient had BLC-induced focal myoclonus of the right shoulder. Seven patients had BLC- associated tremors, three patients had abnormalities detected by facial EMG only, and 11 pa­tients had BLC- synkinetic movements ( three oculofacial and three oculopterygoid cases, and one oculolingual case; Figs. 3A- C). There were two cases of dual synki­netic movements; one with oculolingual and oculoptery­goid synkinesis, and the other with oculofacial and ocu­lopterygoid synkinesis. One patient had imitation synki­nesis ( reflex yawning with imitation of yawning by widely opening her mouth; Fig. 4), and another patient was unable to close her right eye voluntarily. One patient exhibited monocular BLC in isolation, and another pa­tient had asymmetric BLC. One patient had alternating rapid and slow BLC. Three patients with familial BLC and seven patients with congenital developmental disor­ders are described. Restless feet syndrome was present in six patients, three of whom had features of peripheral neuropathy. Eight patients had signs or symptoms of mild axonal peripheral neuropathy, including examples of continuous muscle fiber activity syndrome. Three pa­tients had Hashimoto thyroiditis, but they were euthyroid and had low thyroid peroxidase antibody titers. There were no examples of multiple sclerosis or brain tumors. 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); eyelid- closure BLC 34/ M/ 42 Pain on pressure applied behind right ear, radiating to ipsilateral frontal region and eye; mild right facial hemiatrophy ( no history of facial palsy) 35/ F/ 75 Frequent blinking (> 30 blinks/ min); eyelid-closure BLC, hypoacusis in left ear Familial synkinetic BLC Congenital facial hemiatrophy, synkinetic BLC, osteoarthritis of C- spine, great auricular neuralgia, sleep myoclonus Midbrain lacunar stroke? synkinetic BLC Pounding, recurrent bilateral headaches Intermittent right retroauricular pain, generalized nocturnal body twitching Transient diplopia with downward gaze Brain MRI and EEG: normal; CNT: MUP discharges both mental and right orbicularis oris muscles with right lateral gaze Brain MRI with contrast and EEG: normal; sleep myoclonus recorded during overnight sleep studies; C- spine x- rays: DJD. CNT: MUPs at rest recorded at right mentalis muscle during light eyelid closure Head CT: normal; CNT: spontaneous normal MUPs of orbicularis oris bilaterally at rest and during eyelid closure Asthma, seasonal depression, migraine without aura; mother and maternal grandmother had similar BLC Negative Osteoarthritis 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 epilep­tic 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 dif­ferent subgroups. DISCUSSION I believe BLC is underdetected because it is not spon­taneously reported by patients; its presence is frequently missed by the examiner during routine neurologic ex­amination 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, hydrocephalus, 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 Hash­imoto thyroiditis ( patients 13, 18, and 19), but they were euthyroid and had no cognitive disturbance or alteration of consciousness level. Their blood thyroid peroxidase titers were not significantly elevated to explain their BLC on the basis of Hashimoto encephalopathy that po­tentially may have caused myoclonus of the orbicularis oculi muscles ( 8). History of Bell palsy was elicitable only in two patients ( patients 19 and 30), and only two patients ( patients 32 and 34) had nocturnal ( sleep) my­oclonus. No patients showed evidence of epilepsy on EEG during BLC, including the two individuals with epilepsy, and no patients exhibited EEG epileptic activity associated with their tremors, synkinesis, or myoclonus. Although six patients ( patients 1, 4, 9, 10, 18, and 29) had restless feet, and three patients ( patients 4, 33, and 35) had frequent blinking, none developed additional in- FIG. 1. Plantar hyperkeratosis ( keratoderma) of the left foot ( pa­tient 3). / Neuro- Ophthalmol, Vol. 20, No. 4, 2000 FIG. 2. Brain MRI T2- weighted images show an area of white-matter increased signal over the left hemisphere corona radiata compatible with focal demyelination ( patient 3). voluntary movements, including dystonia, BLS, and ocu­logyric crisis. Patient 3 had palmoplantar keratoderma, which is an inherited condition recently reported in association with leukoencephalopathy ( 9) ( Fig. 1). She presented with painful gaze- evoked BLC and cataplexy similar to the cases of Niemann Pick disease type C ( 10). Her brain MRI showed a small globular area of hyperintensity on the T2- weighted images localized to the left centrum semiovale, which was consistent with focal demyelina­tion ( restricted leukoencephalopathy) ( Fig. 2). However, her cultured skin fibroblasts did not demonstrate the cy-tochemical abnormalities typical of Niemann Pick dis­ease type C ( 10). To my knowledge, neither of these clinical signs have been reported in patients with pal­moplantar keratoderma. Cranial synkinesis is often overlooked by the exam­iner 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 ac­quired, 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 nerves may be postulated. Patient 34, who had congenital facial hemiatrophy, is an example that supports the de- I 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 palsy), misdirected regeneration of cranial nerve axons is the usual explanation without excluding the potential participation of the mechanisms of peripheral ephapsis and central synaptic reorganization ( 11- 13). Because synkinetic movements do not always involve the facial FIG. 4. Forceful mouth opening triggers reflex yawning ( patient 28). muscles, it cannot be proposed in every case that the associated movements were precipitated by peripheral facial nerve fibers, or that BLC represents an abnormal­ity of the innervation of the obicularis oculi muscle. In examples of BLC- induced or enhanced tremors, a state 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 neu­rologic illness, at least on a short- term basis. Instead, the clinical data presented here indicate the following: 1. BLC is a focal tremor 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 discov­ered clinical sign; 4. BLC at times is associated with ( underdiagnosed) cra­nial synkinesis and has a benign course in most indi­viduals; 5. BLC may have different precipitants, but gaze-evoked BLC probably has the greater clinical rel­evance 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 FIG. 5. Venous angioma of the right cerebellar hemisphere ( brain MRI T1- weighted images) ( patient 32). 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. Neu­rology 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 blepharo­spasm. Neurology 1985; 35: 1378- 80. 6. Keane JR. Gaze- evoked blepharoclonus. 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