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Clinical Features of Blepharospasm and Hemifacial Spasm

Joseph Jankovic, M.D.
Professor of Neurology, Distinguished Chair in Movement Disorders
Director, Parkinson's Disease Center and Movement Disorders Clinic
Department of Neurology
Baylor College of Medicine
Houston, Texas
2010
Blepharospasm

Involuntary facial movements have been recognized for a long time and were depicted by artists who were fascinated by how these movements distorted the facial expression. For example, the 16th century Flemish artist Brueghel painted a woman with apparent blepharospasm and involuntary jaw opening. Although the eponym "Meige syndrome" sometimes has been used to designate idiopathic cranial-cervical dystonia, this term is not appropriate because Talkow in Germany and Wood in the United States described blepharospasm and orofacial dystonia several decades before the 1910 publication by the French neurologist's report. It was not until the 1970s that blepharospasm was recognized as a form of focal dystonia.

Before the development of sustained closure of the eyelids, about a third of the patients report increased frequency of blinking, suggesting that blepharospasm may be due to impairment of mechanisms associated with normal blinking. Although healthy individuals blink more frequently during conversation than at rest, in patients with blepharospasm the pattern is reversed, suggesting that conversation may act as a "sensory trick" or "geste antagonistique". The increased blinking that precedes blepharospasm is commonly associated with a feeling of irritation in the eyes and photophobia (better termed "photosensitivity" or "photodynia"). It usually progresses to clonic and later tonic (sustained) contractions of the orbicularis oculi, leading to forceful closure of eyelids, often associated with involvement of the corrugator and procerus muscles and compensatory contractions of the frontalis muscles. Up to 20% of patients have unilateral involvement at the onset, but the opposite eye becomes involved later in all patients. Blepharospasm is seldom an isolated condition. This form of dystonia is often associated with dystonia in other facial cervical perioral and mandibular muscles (oromandibular dystonia). In addition, patients with blepharospasm may have dystonia in the limbs, trunk, and vocal cords (spasmodic dysphonia). Unlike idiopathic blepharospasm, which is most prominent when the patient is active, secondary blepharospasm often persists during rest. This distinction, however, is not reliable enough to differentiate primary from secondary blepharospasm.

Blepharospasm may vary from only a slightly annoying condition to a disabling disorder that interferes with daily activities such as reading, watching television, and driving. In our original study of botulinum toxin in patients with cranial dystonia, we used a rating scale, currently referred to as the Jankovic Rating Scale (Jankovic et al 2009a), to assess the severity and frequency of involuntary eyelid contractions. The self-rating response scale Blepharospasm Disability Index has been found to correlate well with the Jankovic Rating Scale. With the recent emphasis on quality-of-life outcome measures, there is a need to develop instruments that measure this domain. In this regard the cranio-cervical dystonia questionnaire (CDQ-24) will be helpful in evaluating the effects of botulinum toxin treatment on blepharospasm and cervical dystonia (Kenney and Jankovic, 2009).

Up to two thirds of patients are rendered functionally blind by their blepharospasm. Blepharospasm is usually exacerbated by bright light; as a result, many patients wear sunglasses both outside and inside. The spasms may be transiently alleviated by pulling on an upper eyelid or an eyebrow, pinching the neck, talking, humming, yawning, singing, sleeping, relaxing, reading, concentrating, looking down, and performing other maneuvers or sensory tricks (geste antagonistique). Although adult onset focal dystonias tend to remain focal, among the focal dystonias, the risk of spread was highest in patients with blepharospasm (31% past the head) compared to those starting in the upper extremities (16%), larynx (12%), or the neck (9%) (Weiss et al 2006). In most cases of blepharospasm, the spread occurs in the first 5 years after onset, as shown in several studies (Abbruzzese et al 2008). Another study, involving 124 patients presenting with blepharospasm (73 with cervical dystonia and 24 with focal hand dystonia; all with 10 years or more of symptom duration), showed that age at dystonia onset, age at initial spread, and the risk of initial spread were higher, and the time from onset to initial spread was shorter for the blepharospasm patients compared to other focal dystonias (Abbruzzese et al 2008). Similar findings were seen in a group of 132 patients followed for a mean of 7.5 years (Svetel et al 2007). Risk factors for spread of blepharospasm include previous head or face trauma with loss of consciousness, young age at onset of blepharospasm, and female gender.

Psychiatric symptoms, such as anxiety, depression, and psychosis, may be present even before or at onset of blepharospasm and were identified in 18% of 264 patients. The prevalence of obsessive-compulsive symptoms, often attributed to basal ganglia dysfunction, in patients with blepharospasm was significantly higher than in those with hemifacial spasm, despite the clinical similarities. This coexistence with mild psychiatric symptoms may explain the tendency to label blepharospasm as a psychogenic problem. However, psychogenic forms of blepharospasm are extraordinarily rare, and there is usually little or no evidence of any psychopathology in patients with blepharospasm.

That blepharospasm represents a forme fruste of idiopathic (primary) torsion dystonia is now well accepted (Hallett et al 2008). In addition to the frequent coexistence of blepharospasm and dystonia in other body segments, the relatively frequent occurrence of family history of dystonia, essential-type tremor, or both supports the hypothesis that blepharospasm and other forms of dystonia may be genetically related. In our experience, one third of all patients with cranial-cervical dystonia have an action hand tremor similar to essential tremor or dystonia, and one third of patients have a first-degree relative with tremor or dystonia. Family history of blepharospasm has been reported to range between 9.5% and 27% among first-degree relatives of patients with blepharospasm. In a study of 56 families that included 436 first-degree relatives of probands, 233 of whom were examined, 27% of the index cases had at least 1 first-degree relative with blepharospasm, with estimated 20% penetrance if autosomal dominant transmission is assumed (Defazio et al 2006).

The study of blepharospasm due to some specific, identifiable cause (secondary blepharospasm) can provide insights into the pathogenesis of the primary, idiopathic disorder, sometimes referred to as "benign, essential blepharospasm." Although the most common cause of blepharospasm is adult-onset idiopathic torsion dystonia, there are many other less common causes (Table 1). Even though most patients initially consult ophthalmologists, ocular disorders probably only rarely cause blepharospasm (Martino et al 2005).

Table 1. Etiology of Blepharospasm
Primary dystonia
Sporadic
Inherited (all autosomal dominant)
  • classic (Oppenheim) dystonia (DYT1-TorsinA)
  • childhood and adult-onset cranial-cervical-limb dystonia (DYT6-THAP1)
  • adult-onset cervical and other focal dystonia (DYT7-18p)
  • adult-onset cranial-cervical dystonia (DYT13-1p36.13-36.32)
Associated with neurodegenerative disorders
Primarily sporadic
  • Parkinson disease
  • progressive supranuclear palsy
  • multiple system atrophy
  • multiple sclerosis
  • central pontine myelinolysis
  • juvenile parkinsonism-dystonia
  • progressive pallidal degeneration
  • intraneuronal inclusion disease
  • infantile bilateral striatal necrosis
  • familial basal ganglia calcifications
Primarily inherited
  • dystonia-plus syndromes
  • atypical autosomal dominant dystonia (not DYT1 gene)
  • myoclonic dystonia
  • dopa-responsive dystonia (DRD) (DYT5-GTP cyclohydrolase I 14q22.1)
  • rapid-onset dystonia-parkinsonism
  • early-onset parkinsonism with dystonia
  • X-linked dystonia parkinsonism or Lubag
  • paroxysmal dystonia-choreoathetosis
  • Wilson disease
  • Tourette syndrome
  • Huntington disease
  • Neurodegeneration with Brain Iron Accumulation (Hallervorden-Spatz disease)
  • SCA3, SCA6, SCA16, SCA17, Friedreich's ataxia
  • Machado-Joseph disease
  • ataxia telangiectasia
  • neuroacanthocytosis
  • dentato-rubral-pallidoluysian atrophy
  • hereditary spastic paraplegia with dystonia
  • Fragile-X syndrome
  • Mohr-Tranebjaerg syndrome
Associated with metabolic disorders
Amino acid disorders
  • glutaric academia
  • methylmalonic academia
  • homocystinuria
  • Hartnup disease
  • tyrosinosis
Lipid disorders
  • metachromatic leukodystrophy
  • ceroid lipofuscinosis
  • dystonic lipidosis ("sea blue" histiocytosis) gangliosidoses
  • hexosaminidase A and B deficiency
Miscellaneous metabolic disorders
  • mitochondrial encephalopathies
  • Leigh disease, Leber disease
  • Lesch-Nyhan syndrome
  • triosephosphate isomerase deficiency
  • vitamin E deficiency
  • biopterin deficiency
  • pseudohypoparathyroidism
Due to a specific cause
Perinatal cerebral injury and kernicterus
  • athetoid cerebral palsy
  • delayed onset dystonia
Infection
  • viral encephalitis
  • encephalitis lethargica
  • Reye syndrome
  • subacute sclerosing panencephalitis
  • Jakob-Creutzfeldt disease
  • AIDS
  • other: tuberculosis, syphilis, tetanus
Other disorders
  • collagen vascular disorder
  • paraneoplastic brainstem encephalitis
  • cerebral vascular or ischemic injury (stroke)
  • brain tumor
  • arteriovenous malformation
  • head trauma and brain surgery
  • peripheral trauma
  • toxins: MN, CO, CS2, methanol, disulfiram, wasp sting
  • drugs: levodopa, bromocriptine, antipsychotics, metoclopramide, fenfluramine
  • flecainide, ergot, anticonvulsants, certain calcium channel blockers
Due to an ophthalmologic cause
Reflex blepharospasm
  • blepharitis, conjunctivitis, "dry eye syndrome," keratitis, iritis, uveitis
  • albinism, achromatopsia, maculopathies
  • lesions in the nondominant temporoparietal lobe (Fisher sign)
Peripherally induced
  • hemifacial spasm
  • tic convulsif
  • Bell palsy
  • aberrant facial regeneration with facial synkinesis
  • hemimasticatory spasm
  • facial myokymia
  • Schwartz-Jampel syndrome
  • amyloidosis
  • oculomasticatory myorhythmia (Whipple disease)

Tardive dystonia is probably the most common cause of secondary dystonia, including blepharospasm. Tardive dystonia consists of a persistent dystonic movement involving chiefly the face, jaws, neck, trunk, and arms. Blepharospasm may be the initial presentation of tardive dystonia. In addition to dopamine-receptor blocking drugs (neuroleptics), other drugs that can cause blepharospasm are lithium, lamotrigine, and others.

A variety of CNS lesions involving the rostral brainstem, thalamus, and the basal ganglia (eg, stroke, multiple sclerosis, thalamotomy, hydrocephalus) have been reported in association with blepharospasm and other forms of cranial dystonia. These reports of lesions producing blepharospasm, oromandibular dystonia, or both support the notion that in addition to the basal ganglia, other subcortical and brainstem structures play an important role in the pathophysiology of cranial dystonia.

Peripheral trauma is increasingly recognized as a cause of dystonia, and peripheral trauma may trigger dystonia in carriers of the idiopathic torsion dystonia gene (Jankovic 2009b). Up to 12% of patients with blepharospasm report the occurrence of ocular trauma prior to the onset of their movement disorder. About 11% of otherwise healthy individuals have dry eyes, but most patients do not have dry-eye syndrome as seen in Sjögren disease, although they may have dry-eye symptoms. Many patients experience symptoms of "dry eyes" and other ocular symptoms shortly before the onset of blepharospasm, suggesting that disorders of the anterior segment of the eye may actually trigger blepharospasm. Whether dry eye syndrome is the cause or result of blepharospasm is not known. People with dry eyes blink more frequently than those without dry eyes, presumably to reduce the chance of holes developing in the tear film and blink oscillations help thicken the lipid layer of the tear film. The production of proteins, particularly lacritin, normally secreted by the lacrimal glands is markedly reduced in some patients with blepharitis, which reduces the lipid layer. Although blepharitis often precedes blepharospasm, it is not clear that it is a risk factor for blepharospasm as blepharitis is a frequent symptom in otherwise normal individuals. It is possible that some form of injury to the anterior segment of the eye causes trigeminal sensitization leading to photophobia, increased blinking, and blepharospasm. The mechanisms of photophobia and dry eyes are complex and may be due to an ocular problem as well as a central effect. Furthermore, dryness may be more related to the make-up of the tear film and its dynamics than the actual amount of tears produced.

In addition to dystonia, other conditions can lead to closure of the eyelids. Ptosis may result from weakness or paralysis of the levator palpebrae muscle or the smooth muscle of Müller. Some patients are unable to open their eyes because they cannot "activate" the levator palpebrae muscles. This is analogous to the motor blocks or the freezing phenomenon experienced by some, and the terms "apraxia of eyelid opening". Progressive supranuclear palsy is the most common cause of eyelid freezing seen in the Parkinson clinic, but other parkinsonian syndromes, Huntington disease, hemispheric cerebral vascular disease, and neuroacanthocytosis are occasionally associated with this phenomenon. Apraxia of eyelid opening, however, can occur in isolation without any other motor deficits, and it may improve with levodopa and recur when levodopa is reduced as may be the case after deep brain stimulation (Umemura et al 2008).

Hemifacial Spasm

Hemifacial spasm, a form of segmental myoclonus, is characterized by unilateral, involuntary, paroxysmal tonic or clonic contractions of the muscles innervated by the 7th cranial nerve (Wang and Jankovic 1998). The presumed pathophysiologic mechanism of hemifacial spasm involves the generation of ortho- and antidromic impulses by a damaged area of the facial nerve. The constant antidromic stimulation may result in "kindling," causing neuronal discharge in the facial motor nucleus, leading to hemifacial spasm. Typically, at onset the patients experience occasional twitches in the eyelids, but with progression the spasms and twitches become more constant and involve the lower facial musculature. The clonic and tonic contractions are triggered by action (smiling, talking, eating, blinking). Hemifacial spasm is easily distinguished from blepharospasm caused by dystonia because it is virtually always unilateral, although there are rare exceptions (Tan and Jankovic 1999). Furthermore, in contrast to blepharospasm, patients with hemifacial spasm often exhibit paradoxical raising of the eyebrow as the eye closes (the "other" Babinski sign) (Stamey and Jankovic, 2007). The term "tic convulsif" describes the rare coexistence of painful trigeminal neuralgia and hemifacial spasm. The phenomenology of aberrant facial regeneration or facial synkinesis is similar to hemifacial spasm, but the onset usually follows facial palsy. Studies in macaque monkeys show that following facial nerve injury, the orbicularis oculi motoneurons innervate the perioral muscles causing co-contraction (synkinesia) of eyelid and perioral muscles. In one series of 164 patients with hemifacial spasm, 9 (5.5%) were thought to have coexistent blepharospasm (Tan et al 2004). Blepharospasm also has been reported after Bell palsy, but prospective studies could not demonstrate an association between Bell palsy and subsequent blepharospasm. Hemimasticatory spasm is a rare disorder whose underlying mechanism is similar to hemifacial spasm, but the trigeminal rather than the facial nerve is involved. The spasms of the masticatory muscles may or may not be associated with hemifacial atrophy. Facial myokymia, a rapid undulation and flickering of the facial muscles from the frontalis to the platysma, is thought to be due to an intramedullary lesion close to the facial motor nucleus. Multiple sclerosis is probably the most common cause, but intra-axial tumors and Guillain-Barré syndrome have also been described as associated with this movement disorder. Tetanus is caused by tetanus toxin, a product of Clostridium tetani, and it is characterized by hyperactivity of motor neurons, which causes forceful closure of the eyelids. Although rare in the United States, it still remains a major public health problem in underdeveloped areas. Amyloidosis V and Schwartz-Jampel syndrome (autosomal recessive disorder manifested by combination of blepharospasm, blepharophimosis, dwarfism, muscular hypertrophy, generalized muscular stiffness and myotonia) represent additional causes of blepharospasm.

Blepharoclonus refers to rhythmic contractions of the orbicularis oculi closely resembling tremor, present during gentle closure of the eyelids. Although no apparent cause can be identified in many cases, blepharoclonus is occasionally associated with multiple sclerosis, obstructive hydrocephalus, and Arnold-Chiari malformation. Blinking, the most common motor tic present in 70% of patients with Tourette syndrome, is characterized by bursts of rapid, nonsustained contractions of the orbicularis oculi. On the other hand, dystonic tics of the eyelids, found in 15% of patients, can cause diagnostic difficulties because they are transiently sustained and may resemble blepharospasm.

An important cause of facial movements is Whipple disease. In addition to gastrointestinal symptoms, patients with Whipple disease typically exhibit supranuclear ophthalmoparesis and rhythmic contractions of the eyelids, face, and mouth in synchrony with convergent eye oscillations. This oculomasticatory myorhythmia is usually associated with contractions of neck as well as the pharyngeal and proximal and distal musculature.

The phenomenology of blepharospasm is usually the same regardless of its cause. The presence of associated findings, however, may suggest a specific etiology. The recognition of stereotypies (repetitive, patterned, seemingly purposeful but purposeless movements), for example, suggests the diagnosis of tardive dystonia, whereas corneal Kayser-Fleischer ring and evidence of hepatic failure indicate Wilson disease (Svetel et al 2007).

References

Abbruzzese G, Berardelli A, Girlanda P, et al. Long term assessment of the risk of spread in primary late-onset focal dystonia. J Neurol Neurosurg Psychiatry 2008;79(4):392-6.

Defazio G, Martino D, Aniello MS, et al. A family study on primary blepharospasm. J Neurol Neurosurg Psychiatry 2006;77:252-4.

Hallett M, Evinger C, Jankovic J, Stacy M; BEBRF International Workshop. Update on blepharospasm: report from the BEBRF International Workshop. Neurology 2008;71(16):1275-82.

Jankovic J. Blepharospasm. In: Gilman S, ed. Medlink.com, Arbor Publishing, La Jolla, CA, http://medlink.com, annual updates 1995-2009.

Jankovic J, Kenney C, Grafe S, Goertelmeyer R, Comes G. Relationship between various clinical outcome assessments in patients with blepharospasm. Mov Disord 2009;24(3):407-13a.

Jankovic J. Peripherally-induced movement disorders. Neurologic Clinics 2009 (in press)b.

Kenney C, Jankovic J. Botulinum neurotoxin treatment of cranial-cervical dystonia. In: Jankovic J, Albanese A, Atassi MZ, Dolly JO, Hallett M, Mayer N. Botulinum Toxin. Therapeutic Clinical Practice and Science. Saunders (Elsevier), Philadelphia, PA, 2009:92-101.

Martino D, Defazio G, Alessio G, et al. Relationship between eye symptoms and blepharospasm: A multicenter case-control study. Mov Disord 2005;20:1564-70.

Stamey W, Jankovic J. The other Babinski sign in hemifacial spasm. Neurology 2007;69:402-4.

Svetel M, Pekmezovic T, Jovic J, et al. Spread of primary dystonia in relation to initially affected region. J Neurol 2007;254:879-83.

Tan EK, Chan LL, Koh KK. Coexistent blepharospasm and hemifacial spasm: overlapping pathophysiologic mechanism? J Neurol Neurosurg Psychiatry 2004;75(3):494-6.

Tan EK, Jankovic J. Bilateral hemifacial spasm: A report of 5 cases and a literature review. Mov Disord 1999;14:345-9.

Umemura A, Toyoda T, Yamamoto K, Oka Y, Ishii F, Yamada K. Apraxia of eyelid opening after subthalamic deep brain stimulation may be caused by reduction of levodopa. Parkinsonism Relat Disord 2008;14(8):655-7.

Wang A, Jankovic J. Hemifacial Spasm: clinical correlates and treatments. Muscle Nerve 1998;21:1740-7.

Weiss EM, Hershey T, Karimi M, et al. Relative risk of spread of symptoms among the focal onset primary dystonias. Mov Disord 2006;21:1175-81.





























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