Benign Essential Blepharospasm

Etiology

• Idiopathic
• Possible thalamic, basal ganglion, mesencephalic, or brainstem lesions
• Can be associated with systemic movement disorders including Parkinson disease

Epidemiology

• Mean age is 56 years
• Women outnumber men 3:1

History

• Variable periods of bilateral blepharospasm lasting seconds to minutes
• Progression can be asymmetric.
• Progression to complete eyelid closure with functional blindness in 12% of patients
• Can progress to include mid and lower facial muscles
• Some patients cannot open eyelids (apraxia of eyelid opening).
• Spasms are not present during sleep.

Clinical features

• Social withdrawal with inability to work or drive can result from the visual and systemic limitations.
• Patients who are most severely incapacitated find that their lids clamp shut and must be pried open with fingers.
• Associated anatomic problems can result or accompany essential blepharospasm.
• Brow ptosis
• Blepharoptosis, associated levator disinsertion
• Dermatochalasis
• Entropion or ectropion
• Eyelid phimosis
• Punctate epithelial keratopathy is common
• Triggers of blepharospasm include sunlight, stress, wind, noise, eyelid, movement, reading, and fatigue.
• Some patients learn techniques to diminish the spasms, known as “geste antagonistique,” such as tongue thrusting, humming, mouth opening, extending the neck, closing one eye or rubbing the face. Sleep and rest can improve symptoms.
• Blepharospasm can remain stable, improve or progress, sometimes to almost complete incapacitation due to visual limitations.
• Association with Parkinson disease
• In a study of 28 blepharospasm patients, the most common systemic neurologic association among known Parkinson’s patients treated at a Toronto clinic between 2005 and 2011 was with atypical Parkinson’s disease (Rana, European Neurology 2012).
• There are 3 categories of Parkinsonism.
• Primary Parkinsonism is the most recognized form, marked by hypokinesia and resting tremor, rigidity or postural instability.
• Secondary Parkinsonism implies toxic exposure to a neurotoxin, although there is no definitive epidemiologic evidence for a specific solvent of class of solvents that causes Parkinsonism. A social and employment history can imply possible links (Lock, Toxicol Appl Pharm 2013).
• Atypical Parkinsonism is the form most relevant to Blepharospasm. It usually has no tremor or dementia, responds poorly to levodopa and has subcategories including progressive supranuclear palsy, which is a neurologic condition seen in patients with blepharospasm.
• Blepharospasm can also be associated with primary Parkinson’s, and in those cases disease progression is slower and response to levodopa might be better.
• Blepharospasm and apraxia of lid opening are specifically linked with atypical Parkinson’s and progressive supranuclear palsy.
• An important consideration when differentiating patients with Parkinson’s and blepharospasm is that patients with progressive supranuclear palsy have “motor recklessness” and can be prone to injury from falling (Aerts, Practical Neurology, 2012).
• Brow protractor spasm helps differentiate benign essential blepharospasm from apraxia of eyelid opening
• Patient with blepharospasm can develop lower facial dystonia (Meige syndrome) but the strength of the association has not been definitively determined.

The diagnosis of blepharospasm is a clinical diagnosis relying on patient history and examination.

• Although only a research tool, PET scans on patients with benign essential blepharospasm demonstrate abnormalities in cortical and subcortical areas that control blinking.
• Clusters of increased glucose uptake are detected in the inferior frontal gyri, right posterior cingulate gyrus, left middle occipital gyrus, fusiform gyrus of the right temporal lobe, and left anterior cingulate gyrus.
• Clusters of decreased glucose uptake are observed in the inferior frontal gyri.
• Subcortical abnormalities, include increased glucose uptake in the right caudate and decreased glucose uptake in the left inferior cerebellar hemisphere and thalamus (Kerrison, AJO, 2003).
• Neurologic evaluation is indicated if a systemic association is suspected.
• If concern for bilateral hemifacial spasm is present, neuroimaging might be warranted.

• Hemifacial spasm, which can be bilateral and have a neoplastic or vascular etiology.
• Aberrant regeneration following facial nerve palsy (Bell’s palsy, trauma, surgery, etc.), mostly unilateral and more commonly creates a picture similar to hemifacial spasm
• Apraxia of eyelid opening
• Apraxia of lid opening is a nonparalytic inability to open the eyes at will in the absence of visible contraction of the orbicularis oculi muscle.
• In apraxia of lid opening, abnormally persistent septal and pretarsal orbicularis activity can be detected by electromyogram (EMG).
• Also seen on EMG is latency to onset and to complete eye opening, suggesting a combination of levator inhibition and persistent orbicularis activity as the cause of apraxia of lid opening.
• Orbicularis myokymia
• Caffeine, stress, physical exertion, fatigue
• Reflex blepharospasm
• Corneal/ocular surface irritation
• Anterior uveitis
• Dry eye syndrome
• Medications causing facial dystonia

Natural history

• Blepharospasm tends to require treatment with botulinum injections at regular intervals over long periods of time.
• Among 238 patients with essential blepharospasm or Meige syndrome treated at Wilmer Eye Institute disease remission was observed in 11%, with intervals from presentation to remission ranging from 3 months to 22 years (Castelbuono, 1998).

Medical therapy

• Botulinum toxin
• Average duration of therapeutic effect is 3 months
• Injected subcutaneously in the upper and lower lids, over the brow and at the lateral canthus, taking care to avoid a central upper lid injection which can cause ptosis.
• Normal dosage 2.5–5 units per injection site.
• Onset of effect 2–7 days post injection.
• It may be necessary to use “supramaximal doses” totaling more than 100 units for refractory blepharospasm.
• Patients are advised to use ocular lubricants if exposure symptoms develop from incomplete eyelid closure.
• Muscle relaxants
• Muscle relaxants such as orphenadrine (Norflex) have been used effectively in mild cases of essential blepharospasm
• Methylphenidate, or Ritalin, has been described in a small case series to produce subjective improvement in 13 of 14 patients with blepharospasm (Price, OPRS, 2010).
• Ritalin is a central nervous system stimulant which blocks presynaptic dopamine reuptake by reversibly inhibiting the dopamine transporter, predominantly in the striatum.
• Ritalin also inhibits the presynaptic norepinephrine transporter to a lesser extent and norepinephrine neurons participate in regulating the release and storage of dopamine.
• Ritalin has been studied in patients with Parkinson disease and has been found to potentiate the response to L-dopa, but has no effect when administered alone.

Surgery

• Protractor Myectomy
• Originally described by Gillum and Anderson (Arch Ophthalmol 1981) to include orbicularis oculi, corrugators, and procerus. Often now performed with removal of orbicularis only.
• Reserved for patients with inadequate response to botulinum toxin
• Most still require botulinum neurotoxin even after successful myectomy, though ideally at decreased dose and frequency.
• Among 17 patients treated with myectomy or partial seventh nerve avulsion no statistically significant difference in botox response before vs. after surgery (Engstrom, 1987).
• Others have found that myectomy decreases botox injection frequency and dose (Kent, 2015).
• Surgical technique is similar to blepharoplasty, removing segments of the orbicularis, pretarsal muscle is preserved so the involuntary blink remains.
• In a series of 27 patients who underwent myectomy for chemodenervation-refractory benign essential blepharospasm, Kent and co-authors identified a decreased frequency and dose requirement after myectomy. (Kent, OPRS 2015)
• Selective facial neurectomy
• Historically the first line of treatment, now rarely performed.
• Success rate had been considered 50% initially but nerve regeneration with aberrancy created an even more uncomfortable clinical picture than blepharospasm, prompting the move toward botulinum injections.
• Selective facial neurectomy targeting the zygomatic branches can reduce the adverse effects of aberrant regeneration but still can cause abnormal eyelid function and perioral muscle weakness.

Other management considerations

FL-41 tinted glasses can be helpful in reducing light stimulation.

Some patients might benefit from biofeedback or hypnosis.

Patients with apraxia of eyelid opening might benefit from ptosis surgery including levator advancement, frontalis sling (adjustable materials) or eyelid crutches.

• The objective is to facilitate eyelid opening, once the neurologic input can be generated.

Doxorubicin chemomyectomy has been reported as treatment for blepharospasm (Wirtschafter, Ophthalmology, 1998).

• Complications among 9 patients treated in the case series included skin ulcer, cicatricial ectropion, conjunctival edema, pigment mottling of skin, fat atrophy, diplopia due to Brown’s syndrome.
• The minimum effective dose per treated eyelid for ranged from 1.0 to 4.2 mg.
• This treatment option should be considered only in very rare circumstances of severely resistant disease.

Botulinum toxin

• From inadvertent injection or tracking around muscles
• Ptosis
• Diplopia
• To prevent movement of the botulinum toxin, instruct patients not to compress the just-injected areas.
• The secondary effects will diminish and resolve as the medication effects subside.
• The maximal dose of botulinum toxin for blepharospasm has been suggested to be 50 units per side injected every 2 months.
• Some patients resist treatment at this maximal dose and a supramaximal dose of 62–75 units per side might be needed to decrease the interval between injections and to improve the quality of life (Levy, Ophthalmology, 2006).
• Lagophthalmos and superficial keratitis due to reduced orbicularis tone and blinking might require aggressive lubrication.
• Ectropion might require surgical intervention to allow continued botulinum injections.

Myectomy

• More aggressive removal of orbicularis enhances the effectiveness of the surgery, but increases the secondary adverse sequelae including exposure keratopathy, lymphedema, and eyelid malposition from scarring.
• Necrosis of overlying skin can occur from loss of vascularity.
• Lagophthalmos, retraction, ectropion, ptosis

Selective nerve destruction

In a review of 228 blepharospasm patients, 85% were successfully treated with botulinum toxin over a 10-year period.

• 34 (15%) underwent protractor myectomy for failure of botulinum toxin, and 27 (80%) had alleviation of spasms.
• Of those 27, 6 required continued botulinum toxin injections.
• Selective nerve destruction was performed in the 7 patients who were not helped by myectomy and symptoms improved in 3 (42%).
• Lower eyelid ectropion occurred in 2 patients treated with nerve destruction (27%), and all patients had perioperative lagophthalmos, epiphora, and punctate keratopathy that spontaneously improved over 6 months.
• 2 of the patients who did not respond to surgery responded to a second nerve destruction.
• 1 required a 3rd attempt at nerve destruction (Fante, OPRS, 2001).

• Although intraocular pressure can increase as much as 100 mm Hg with forced eyelid closure, the likelihood of developing glaucoma was not found to be increased in patients with benign essential blepharospasm.
• Among 1,350 patients with benign essential blepharospasm compared with a matched cohort of nonblepharospasm patients, the hazard ration for developing primary open angle glaucoma was 1.159 (95% confidence interval, 0.876–1.534) (Lee, OPRS, 2010).
• Visual dysfunction with lifestyle limitation
• Cosmetic deformity from spasms and excessive blinking

Meige described bilateral facial spasms in 1910 (Meige, Rev Neurol 1910).

Urist brought specific attention to the ocular problem of bilateral blepharospasm in 1957 (Urist, Arch Ophthalmol 1957) and described how, as an alternative to neurectomy, absolute alcohol could be injected over the facial nerve.

• The alcohol was injected anterior to the ear, the O’Brien technique used by cataract surgeons for facial akinesia.
• Absolute alcohol injections produced an effect similar to neurectomy but the nerve recovered, often with aberrancy after about six months.
• Absolute alcohol injections are not currently used in clinical practice.

The association between blepharospasm and Parkinson Disease was recognized as early as 1933 by Parker (Parker, Am J Ophthalmol 1933).

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