Essential Blepharospasm

Robert L. Tomsak, MD, PhD · Brian N. Maddux, MD, PhD

Introduction

Essential blepharospasm, also called benign essential blepharospasm, is a focal cranial dystonia consisting of involuntary contractions of the obicularis oculi muscles and other muscles of the upper face. These adventitious movements can be disabling for activities such as reading, driving, and walking.

Clinical Findings

Essential blepharospasm tends to be a progressive phenomenon beginning as increased frequency of blinking, often accompanied by dry eye sensation. Essential blepharospasm may initially begin unilaterally in up to 20% of patients affected, but it always involves both eyes as the disease progresses. In approximately two thirds of patients with essential blepharospasm, the condition develops after 50 years of age, and women are more often affected than men by 2:1. The prevalence of essential blepharospasm is estimated to be 5 per 100,000. Factors that may exacerbate essential blepharospasm include reading, talking, bright light, stress, and driving.

Diagnosis is often delayed due to lack of recognition; often the disorder is mistaken for psychogenic. Spontaneous remissions are reported in 3% to 11% of cases, but most often, the untreated disease progresses over the first 1 to 5 years and then stabilizes. Functional blindness is reported in 15% of untreated patients. Secondary eye complications include dermatochalasis and/or blepharoptosis from manual pulling of the lids, ectropion, entropion, and tear film abnormalities.^1,2

Pathophysiology

A family history of movement disorder is present in 20% to 30% of patients with essential blepharospasm. Recent positron emission tomography (PET) scan studies show that patients with essential blepharospasm have increases in metabolic activity in specific regions of the pons, cerebellum, basal ganglia, and thalamus during waking hours.^3,4 During sleep, when essential blepharospasm is inactive, PET scans show hypometabolism in areas of the parietal lobes concerned with control of eyelid movements, suggesting that essential blepharospasm is a disorder of the modulation of stimulatory and inhibitory pathways involved in blinking. Previous head and/or ocular trauma is reported in approximately 12% of patients with essential blepharospasm.

Differential Diagnosis

• Drug-induced blepharospasm. It is important to elicit history of use of neuroleptic agents and antiemetics such as metoclopramide or prochlorperazine.
• Blepharospasm secondary to central nervous system lesions. The clinician should examine the patient for associated clinical findings such as stroke, multiple sclerosis, thalamotomy, hydrocephalus, pontine tumor. Also, magnetic resonance imaging should be performed to detect central nervous system lesions.
• Blepharospasm in neurodegenerative disorders, such as Parkinson disease or progressive supranuclear palsy. Characteristic clinical features are present; initial clinical presentation as isolated blepharospasm would be unusual.
• Meige syndrome (craniocervical dystonia). Patients experience blepharospasm plus lower facial and/or cervical involvement. Symptoms are often tardive. The clinician should elicit history of neuroleptic use.
• Eyelid opening apraxia (eyelid freezing). Patients are unable to activate levator palpebrae muscles. This condition may be seen in isolation or in Parkinsonian syndromes.
• Facial myokymia. Waves of muscle activity are evident with specific electromyelography findings; however, symptoms are not limited to eyelids. Facial myokymia usually results from intrinsic pontine lesions near facial nucleus: demyelinating, neoplastic, and ischemic.
• Hemifacial spasm. Hemifacial spasm is usually secondary to VIIth nerve compression by ectatic branches of basilar artery. Not dystonia. Hemifacial spasm is unilateral (upper and lower face), with rapid or sustained twitches.
• Spastic paretic hemifacial contracture. Spastic paretic hemifacial contracture presents unilaterally as a paradoxical combination of hemifacial spasms and facial weakness due to intrinsic pontine lesion.
• Aberrant regeneration of the facial nerve; synkinesis. The clinician should elicit history of Bell's palsy.
• Benign eyelid fasciculations. Benign eyelid fasciculations are generally unilateral and are exacerbated by caffeine, fatigue, and stress. Patients are unable to close eyelid.
• Facial tics. Generally, the facial tic would not be the only motor tic. The clinician should elicit history of (or directly observe) other tic-like behaviors. Onset is rare past childhood. Usually, patients report urge and relief.
• Whipple disease. Oculomasticatory myorhythmia is noted.
• Wilson disease. Generally, Wilson disease affects young patients. Often, neurologic involvement includes limb or axial tremor. Slit lamp examination should be performed and ceruloplasmin should be evaluated in any young patient with movement disorder.
• External ocular diseases irritating the eyelids, cornea, and conjunctiva.

Treatment

Botulinum Toxin Injections
The most widely used and effective treatment for essential blepharospasm is injection of Botox (botulinum toxin type A, Allergan) into the orbicularis oculi and adjacent muscles, a technique that has been tried and proven for over 10 years. Botox inhibits release of acetylcholine from cholinergic nerve endings at the neuromuscular junction. Its intracellular target is SNAP-25, a synaptosome associated protein required for the release of vescicles containing acetylcholine. Botox permanently disables the SNAP-25 molecule by cleaving it.

Generally, 2.0 to 5.0 units of Botox are injected at separate sites in a volume of 0.1 mL of diluent. The details of injection methods can be found elsewhere.⁶

The clinical effect of Botox is maintained for approximately 3 months, and beneficial results occur in 72% to 92% of patients. Recurrence of blepharospasm results from reestablishment of neuromuscular transmission through growth of collateral axonal sprouts.

Adverse effects of Botox injection include ptosis, dry eye syndrome or sensation, keratitis, epiphora, corneal epithelial defects, corneal ulcers, and diplopia.^1,7 Cumulative doses of 800 U and higher of Botox given frequently for disorders such as cervical dystonia can stimulate neutralizing antibody formation and decreased effect of the toxin.⁸ Neutralizing antibody formation is not a practical problem in most patients treated for blepharospasm with Botox when lower cumulative doses are used.

NeuroBloc (botulinum toxin type B, Elan Corporation) is now available for treatment of cervical dystonia. NeuroBloc is antigenically different from Botox and works by a different mechanism. Therefore, NeuroBloc is a potential alternative treatment for essential blepharospasm, if patients should develop resistance to Botox.⁹

Medications
Many medications of different classes have been tried for the treatment of essential blepharospasm with limited effect, including benzodiazepines (e.g., clonazepam), anticholinergics (e.g., trihexyphenidyl HCl; benztropine), and GABAergics (e.g., baclofen).¹ Generally, with these medications, significant adverse effects occur before blepharospasm is reduced.

Chemomyectomy
Doxorubicin injections are being studied as treatment for essential blepharospasm.¹⁰ This chemotherapeutic medication causes permanent destruction of muscle tissue. Adverse effects include skin ulcers and other dermatologic problems.

Surgical Myectomy of Orbicularis Muscles
Extirpation of portions of the orbicularis oculi, procerus, and corrugator supercilii muscles has been used to treat essential blepharospasm. The success rates are approximately 70% for the first operation.^11,12

References

1. Miller NR, Newman NJ, eds. Walsh and Hoyt's Clinical Neuro-ophthalmology, 5th ed. Baltimore, Md: Williams and Wilkins; 1998;(1):1565-1580.
2. Tomsak RL, Costin JA, Levine MR. Eyelid and facial disorders. In: Parrish RK II, ed. The University of Miami Bascom Palmer Eye Institute Atlas of Ophthalmology. Woburn, Mass: Butterworth-Heinemann; 2000.
3. Hutchinson M, Nakamura MD, Moeller JR, et al. The metabolic topography of essential blepharospasm: A focal dystonia with general implications. Neurology. 2000;55:673-677.
4. Esmaeli-Gutstein B, Nahmias C, Thompson M. Positron emission tomography in patients with essential blepharospasm. Plast Reconstr Surg. 1999;15:23-27.
5. Aramideh M, Ongerboer de Visser BW, Holstege G, et al. Blepharospasm in association with a lower pontine lesion. Neurology. 1996;46:476-478.
6. Price J, Farish S, Taylor H, O'Day J. Blepharospasm and hemifacial spasm. Randomized trial to determine the most appropriate location for botulinum toxin injections. Ophthalmology. 1997;104:865-868.
7. Dutton JJ. Botulinum-A toxin in the treatment of craniocervical muscle spasms: short- and long-term, local and systemic effects. Surv Ophthalmol. 1996;41:51-65.
8. Sankhla C, Jankovic J, Duane D. Variability of the immunologic and clinical response in dystonic patients immunoresistant to botulinum toxin injections. Mov Disord. 1998;13:150-154.
9. Lew MF, Brashear A, Factor S. The safety and efficacy of botulinum toxin type B in the treatment of patients with cervical dystonia: Summary of three controlled clinical trials. Neurology. 2000;55(suppl 5):S29-S35.
10. Wirtschafter JD, McLoon LK. Long-term efficacy of local doxorubicin chemomyectomy in patients with blepharospasm and hemifacial spasm. Ophthalmology. 1998;105:342-346.
11. Jones TW, Waller RR, Samples JR. Myectomy for essential blepharospasm. Mayo Clin Proc. 1985;60:663-666.
12. Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders, 3rd ed. Baltimore, Md: Williams and Wilkins; 1998.