Chapter 91 – Essential Blepharospasm
DONALD C. FAUCETT
• Essential blepharospasm is a variable, progressive bilateral focal dystonia characterized by contraction of the orbicularis oculi muscles, which causes spasmodic involuntary eyelid closure in the absence of any other ocular or adnexal cause.
• Bilateral involuntary spasmodic closure of the eyelids.
• Symptoms exacerbated by stress, fatigue, bright lights, interpersonal interactions.
• Fluctuation of symptoms marked by transient remissions and exacerbations.
• Spasms absent when asleep.
• Spasms improve with relaxation.
• Decrease in tear production.
• Dystonic activity of facial muscles (Meige’s syndrome).
• Dystonic activity of the neck muscles (cranial–cervical dystonia).
• Dystonic activity of the vocal cords (spastic dysphonia).
• Dysphagia, blepharoptosis, eyebrow ptosis, entropion, canthal tendon abnormalities.
Blepharospasm refers to a tonic spasm of the orbicularis oculi muscle that produces intermittent and often complete closure of the eyelids. Benign essential blepharospasm (BEB) is bilateral focal dystonia of idiopathic origin; in its most severe form, it results in functional blindness, depression, and social isolation.  Additionally, it is often misdiagnosed as a psychiatric disorder, which typically delays definitive treatment. Secondary blepharospasm is the result of adnexal or ocular disease. It is not uncommon to see both benign essential and secondary blepharospasm concurrently in a patient. Other disease entities, such as hemifacial spasm and tardive dyskinesia, may manifest similar clinical characteristics.
In the earliest stages of essential blepharospasm, patients frequently complain of photophobia and ocular surface disorders, especially dry eye symptoms. Associated with these symptoms is an increase in the frequency of blinking.  The blinking progresses over a variable period of 2–7 years to become more frequent, forceful, and sustained, and often results in intermittent functional blindness due to the inability to control these spasms ( Fig. 91-1 ).  The factors which seem to exacerbate the disease include stressful situations such as are found at the work place or in social gatherings. As with other dystonias, patients are often able to employ sensory “tricks” to arrest the spasms temporarily. These include whistling, singing, and application of pressure to points on the face. 
Figure 91-1 Involuntary spasms of the orbicularis and procerus muscles in essential blepharospasm. These spasms are associated with oromandibular dystonia involving the middle and lower face.
On clinical examination the spasms may be variable, ranging from absent to intense. For this reason, it is most important to question patients as to the subjective severity of their symptoms outside of the clinical environment. Spasms may spread to involve the midface over a variable period. This extension of essential blepharospasm to include adjacent focal oromandibular dystonia usually is referred to as Meige’s syndrome. As the disease progresses to involve the face, patients frequently complain of difficulty in talking, eating, or swallowing. In severe cases, pronounced bruxism occurs, often resulting in problems with dentition and, subsequently, nutritional deficiency.
Other associated features may include decreased tear production,  adjacent dystonias (such as spastic dysphonia and torticollis), and anatomical changes (such as eyelid and brow ptosis, dermatochalasis, entropion, and canthal tendon abnormalities). 
The diagnosis of essential blepharospasm is one of exclusion. For this reason, a careful examination must be conducted to rule out the various causes of secondary blepharospasm. The more common causes of secondary blepharospasm include blepharitis, trichiasis, dry eye syndrome, corneal and external disease, glaucoma, and uveitis. The diagnosis of this disease is rather straightforward from historical and clinical evidence alone. In atypical cases, however, in which dystonic activity may be associated with muscular weakness, associated signs and symptoms may alert the clinician to an alternative primary diagnosis. In such instances, a complete neurological evaluation and neuroimaging are mandatory to rule out other neurological diseases.
Numerous rating scales are useful in the development of new treatment modalities. The most widely used scale was developed by Jankovic with a severity rating as follows:
• 0 = No spasms
• 1 = Minimal spasms with increased blinking only with external stimuli (e.g., bright light, wind, reading, driving)
• 2 = Mild, noticeable eyelid fluttering without functional disability
• 3 = Moderate, very noticeable spasms involving the eyelids only and causing some visual disability
• 4 = Severe, incapacitating spasms, often involving other facial muscles and causing functional blindness
A number of disorders are associated with dystonic movements of the orbicularis muscles and, therefore, can simulate blepharospasm ( Table 91-1 ). A careful evaluation usually helps to differentiate these disorders.
The anatomical origin and the biochemical basis of essential blepharospasm are unknown. Most authorities feel that abnormalities
TABLE 91-1 — DIFFERENTIAL DIAGNOSIS OF BLEPHAROSPASM
Present in Sleep
Isolated spasms of the orbicularis oculi
None in typical cases
Blepharospasm plus midfacial spasm
Same as for BEB
Same as for BEB
Unilateral, L > R
Tonic–clonic spasms in the distribution of the 7th cranial nerve
Usually a vascular compression of the 7th cranial nerve root
CT or MRI; must rule out a poste rior fossa tumor
Apraxia of eyelid opening; involuntary levator inhibition
Passive involuntary closure of eyelids;raised eyebrows; relaxed eyelids
Occasionally seen with essential blepharospasm
Unknown;seen in extrapyramidal disease such as Parkinson’s, Huntington’s, Wilson’s disease, or with supranuclear palsy, and Shy–Drager syndrome
Orbicularis oculi muscle EMG inactive; total inhibition of Levator muscle
F = M
Rapid undulating flicking muscles
Multiple sclerosis, intramedullary tumor
F = M
Unilateral or bilateral
Stereotypic movements, brief repetitive, suppressible
F = M
Movements occurring with head; questionable eye deviation
Focal cortical lesion
Unilateral contracture with weakness
Prior history of facial paralysis
EMG evidence of synkinesis, fibrillation potential, reduced motor units
in the basal ganglia or midbrain are responsible. Abnormal auditory brainstem response potentials have been noted in patients who have BEB and Meige’s syndrome, which implicates involvement of the brainstem. Additionally, abnormal levels of neurotransmitters have been demonstrated in the midbrain and brainstem nuclei of patients with Meige’s syndrome.  Animal studies have demonstrated similar activity with stimuli near the facial, parabrachial, red, and interstitial nuclei. Postmortem studies and neuroimaging findings have been normal.
The goal in the treatment of essential blepharospasm is to minimize or eliminate the disabling spasms. Pharmacological measures have variable success. Selective peripheral facial nerve avulsion, along with other surgical measures, has been tried, but complications such as facial paralysis, ectropion, and high recurrence rates have decreased its popularity. 
Myectomy is the major surgical treatment for BEB, in which the orbicularis, procerus, and corrugator muscles are extirpated. A modified or limited myectomy has been introduced more recently,
in which only the orbicularis muscle in the upper lid is removed. The limited myectomy offers a quicker recovery and most of the benefits of the radical myectomy with less morbidity.
Chemomyectomy is another type of myectomy under investigation. Local injections of doxorubicin produce permanent orbicularis oculi weakness. In one study, over 50% of patients required no further treatment. However, high concentrations of drug can result in skin ulceration, but a modified technique may be less deleterious. Although doxorubicin is known to be carried in a retrograde fashion to the brain and is a known neurotoxin, animal studies have failed to demonstrate a measurable loss of facial neurons. 
Oral pharmacological agents have been used with variable results. Benzodiazepines, such as lorazepam 0.5–2.0?mg 2 to 3 times a day, clonazepam 0.5–5?mg 3 times a day, or oxazepam 10–30?mg 3 to 4 times daily, have been somewhat effective.
The treatment of choice for the initial treatment of BEB is botulinum toxin type A.  This is one of seven antigenic-specific neurotoxins (A, B, C1, D, E, F, and G) produced by the bacterium Clostridium botulinum. Botulinum neurotoxin blocks neuromuscular transmission by acting on peripheral cholinergic nerve endings to prevent acetylcholine release from presynaptic terminals.
The onset of effect is within 24–72 hours, with a plateau usually at 3–5 days but, occasionally, onset may be delayed as long as 2–4 weeks.   The duration of denervation averages 3 months for BEB and slightly longer for hemifacial spasm.  For BEB, the usual injection sites are as shown in Figure 91-2 . Frequently, the procerus and corrugator muscles also are involved and so require injection. Other periorbital or facial sites may require treatment, as determined on an individual basis. In the upper eyelid, the injections should be subcutaneous only in order to prevent migration of the toxin below the orbital septum, which otherwise results in paralysis of the levator muscle. Frequently, injections in the lower lid alone have a pronounced effect on spasms in the lower face, thus eliminating or decreasing the dosage required in the lower face for Meige’s syndrome and hemifacial spasm. The recommended starting dosage for botulinum toxin type A is 1.25–5 units per injection site. If a suboptimal response occurs, the dosage should be doubled. Less toxin usually is required with dystonic activity with paresis.
Recovery of function following toxin injection results from axonal sprouting and formation of new neuromuscular junctions. 
Figure 91-2 Sites of injection for botulinum toxin in the treatment of benign essential blepharospasm (BEB).
The reported response rate to botulinum toxin is 95–98%.  Antibody formation to previous or current toxin exposure may be responsible for the 2–5% failure rate with this modality and has been reported most often when high doses of toxin are used at frequent intervals. It, therefore, is recommended that toxin should not be given more frequently than every 3 months, and the dosage should not exceed 200 units in a 30-day period. In cases in which antibodies are demonstrated and no response occurs to botulinum toxin type A, other antigenically distinct serotypes, such as type F, may be of help.
The major adverse reactions to botulinum toxin include ptosis, epiphora, keratitis, dry eyes, and diplopia. These effects are usually transient and resolve long before the beneficial effects of the drug are exhausted. A flu-like syndrome has been reported following botulinum toxin injections for blepharospasm, most common with higher doses. Studies also suggest the possibility of a transient increase in intraocular pressure and an abnormal emptying of the gallbladder, with secondary biliary colic as additional side effects.
COURSE AND OUTCOMES
As noted above, botulinum toxin currently is the initial treatment of choice for BEB. Oral pharmacological agents often are helpful for milder cases of BEB or as adjunctive therapy, especially for dampening dystonic activity in the lower face in Meige’s syndrome and hemifacial spasm. Myectomy usually is reserved for those individuals who respond poorly to more conservative therapy or for those patients who have anatomical problems, such as ptosis, which need correction. Application of these various treatment modalities based on an individual assessment and the response characteristics of each patient usually results in a favorable prognosis for the vast majority of patients.
In hemifacial spasm, in which the pathology is an abnormal compression of the seventh cranial nerve root by a blood vessel, botulinum toxin is the initial treatment of choice. However, in the proper hands, neurosurgical decompression of the seventh nerve has a high success rate.
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