January 06, 2007

Benign Essential Blepharospasm

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The first record of blepharospasm and lower facial spasm was found in the 16th century in a painting titled De Gaper. At that time, and for several ensuing centuries, patients with such spasms were regarded as being mentally unstable and often were institutionalized in insane asylums. Little progress was made in the diagnosis or treatment of blepharospasm until the early 20th century, when Henry Meige (pronounced "mehzh"), a French neurologist, described a patient with eyelid and midface spasms, spasm facial median, a disorder now known as Meige syndrome. At about the same time, the first medical treatments became available, including alcohol injections into the facial nerve, facial nerve avulsion, neurotomy, and neurectomy. The adverse effects of these treatments, including loss of facial expression and movements, functional and cosmetic deformities of ptosis, and eyelid malposition, were often as bad as the disease.

Pathophysiology:

Modern physicians realize that blepharospasm is a neuropathologic disorder, rather than psychopathologic, as was once believed. The cause of blepharospasm is multifactorial. Although it is likely that a central control center for coordination and regulation of blink activity exists, somewhere in the basal ganglia, midbrain, and/or brain stem, it is unlikely that a single defect in this elusive control center is the primary cause of this disease.

Today, most view blepharospasm as a defect in circuit activity, rather than a defect at a specific locus. If the central control center fails to regulate blinking in blepharospasm, it is believed to be only one component of an overloaded, defective circuit. This circuit forms a blepharospasm vicious cycle, which has a sensory limb, a central control center located in the midbrain, and a motor limb. The sensory limb responds to multifactorial stimuli, including light, corneal or eyelid irritation, pain, emotion, stress, or various other trigeminal stimulants. These stimuli are transmitted to the central control center, which may be genetically predisposed or weakened by injury or age. This abnormal central control center fails to regulate the positive feedback circuit. The motor pathway is composed of the facial nucleus, facial nerve, and orbicularis oculi, corrugator, and procerus muscles. Other facial muscles also may be involved.

Frequency:
In the US: It is estimated that there are at least 50,000 cases of blepharospasm in the United States, with up to 2000 new cases diagnosed annually. The prevalence of blepharospasm in the general population is approximately 5 in 100,000.


Mortality/Morbidity: At one end of the clinical spectrum, essential blepharospasm is manifested by simple increased blink rate and intermittent eyelid spasms, while at the other end of the spectrum, blepharospasm is a disabling condition with ocular pain and functional blindness. Patients may report that they are disabled to the point where they have stopped watching television, reading, driving, and/or walking. Patients may develop anxiety, avoid social contact, become depressed, become occupationally disabled, and become suicidal.

History:
At onset, there is increased frequency of blinking, particularly in response to a variety of common stimuli, including wind, air pollution, sunlight, noise, movements of the head or eyes, and in response to stress or the environment. Patients may complain of photophobia and ocular surface discomfort, and especially of dry eye symptoms. These symptoms progress over a variable period to include involuntary unilateral spasms, which later become bilateral. Patients may report that they are disabled to the point where they have stopped watching television, reading, driving, and/or walking. A family history positive for dystonia or blepharospasm further aids in the diagnosis. Blepharospasm commonly is associated with dystonic movements of other facial muscles. Anatomic changes associated with long-standing blepharospasm include eyelid and brow ptosis, dermatochalasis, entropion, and canthal tendon abnormalities.

The early symptoms of blepharospasm include increased blink rate (77%), eyelid spasms (66%), eye irritation (55%), midfacial or lower facial spasm (59%), brow spasm (24%), and eyelid tic (22%).


Symptoms commonly preceding diagnosis include tearing, eye irritation, photophobia, and vague ocular pain. While these complaints are common in the average ophthalmology practice, awareness of this disorder and proper suspicion may aid in early diagnosis.
Conditions relieving blepharospasm included sleep (75%), relaxation (55%), inferior gaze (27%), artificial tears (24%), traction on eyelids (22%), talking (22%), singing (20%), and humming (19%).
Comorbid diagnoses include dry eyes (49%) and other neurologic disease (8%).


Physical:
In normal blinking, eyelid closure is the result of activity and co-inhibition of 2 groups of muscles, the protractors of the eyelids (ie, orbicularis oculi, corrugator superciliaris, procerus muscles) and the voluntary retractors of the eyelids (ie, levator palpebrae superioris, frontalis muscles). During the normal blink, the protractors and retractors have co-inhibition and function only at separate times. In patients with blepharospasm, this inhibition between the protractors and retractors is lost.

Causes:
A specific etiology for blepharospasm has yet to be identified. Some patients with blepharospasm report a familial occurrence of the affliction. In families with autosomal dominant familial dystonia, affected members may have a generalized or segmental dystonia, while other members have various focal dystonias, such as isolated blepharospasm.

Treatment
Medical Care:
Blepharospasm is a chronic condition, which too often progressively worsens. Although no cure currently exists, patients have excellent treatment options. Since the disease frequently progresses despite treatment, patients may become frustrated and resort to unconventional remedies, sometimes becoming the victims of charlatans.

The most effective of today's conventional treatments include education and support provided by the Benign Essential Blepharospasm Research Foundation (BEBRF), pharmacotherapy, botulinum toxin injections, and surgical intervention. Unconventional treatments have included faith healing, herbal remedies, hypnosis, and acupuncture.

The first line of treatment for all patients should address the sensory limb of the blepharospasm vicious cycle circuit. Such measures include wearing tinted sunglasses with ultraviolet blocking to decrease the poorly understood cause of painful light sensitivity (photo-oculodynia). Lid hygiene to decrease irritation and blepharitis should be encouraged. Frequent applications of artificial tears and punctal occlusion to alleviate dry eyes often improve symptoms.

Pharmacotherapy
Since the central control center for blepharospasm is unknown, drug therapy directed against this as of yet unidentified center tends to follow a “shotgun approach.” Historically, an extensive list of drugs has been used to treat blepharospasm, in part because blepharospasm initially was considered a manifestation of psychiatric illness, and because no one drug was demonstrably more efficacious than another. Recently, these psychoactive medicines have been used not for their psychotropic action but for their motor system action.

Most patients respond incompletely or not at all to pharmacotherapy. At best, pharmacotherapy provides only partial, transient relief. Patients react differently to the various pharmacologic agents, and there is no way to predict which patient may respond to any particular agent. Tricyclic antidepressants do not directly help blepharospasm but are useful if there is depression exacerbating the symptoms. Drugs with the highest percentages of favorable patient responses include lorazepam (67% of patients), clonazepam (42%), and Artane (41%). The relief provided by these agents is variable.

Although drugs from a variety of different classes have demonstrated some effectiveness in blepharospasm, drug therapy for blepharospasm and facial dystonias usually are based upon the following 3 unproven pharmacologic hypotheses: (1) cholinergic excess, (2) GABA hypofunction, and (3) dopamine excess. Pharmacotherapy is generally less effective than BOTOX® injections and, thus, is reserved as second-line treatment for spasms that poorly respond to BOTOX®, such as in mid-face and lower-face spasm.

Botulinum toxin
Botulinum A toxin, or BOTOX®, is regarded as the most effective treatment of choice for the rapid but temporary treatment of orbicularis spasm. More than 95% of patients with blepharospasm report significant improvement with use of the toxin. The toxin interferes with acetylcholine (ACh) release from nerve terminals, causing temporary paralysis of the associated muscles. Botulinum A toxin is the product of the bacteria, Clostridium botulinum (a large anaerobic, gram-positive, rod-shaped organism).


Once injected, the toxin rapidly and firmly binds at receptor sites on cholinergic nerve terminals in a saturable fashion. The toxin is internalized through the synaptic recycling process. Paralysis of muscle is a result of the inhibition of the release of vesicular ACh from the nerve terminal. It is assumed that the toxin attaches to the ACh-containing vesicles in the nerve terminal and prevents calcium-dependent exocytosis.

The paralytic effect is dose related, with a peak of effect at 5-7 days after injection. Patients typically note the onset of relief 2.5 days after injection, with a mean duration of relief from symptoms of 3 months. More than 5% of treated patients have sustained relief for more than 6 months, although some patients require injections as often as monthly. It takes as much as 6-9 months for the injected muscles to recover from the effects of the toxin, and, occasionally, muscles do not fully return to their preinjection level of function. Some have suggested that the development of antitoxin antibodies or the progressive atrophy of muscle may account for variations in the dose response curve, but no studies have supported these findings.

Complications of botulinum toxin injections include ptosis (7-11%), corneal exposure/lagophthalmos (5-12%), symptomatic dry eye (7.5%), entropion, ectropion, epiphora, photophobia (2.5%), diplopia (<1%),>

Meticulous technique in the administration of BOTOX® helps ensure reliable and consistent results. BOTOX® should be hydrated with 0.9% nonpreserved saline, which should be introduced slowly into the vacuum-sealed vial to prevent frothing. Once reconstituted, the solution should be used within a few hours or refrigerated.

At the first treatment, use of a total dose of no more than 25 units per eye, divided among 4-6 periocular injection sites is recommended to avoid adverse effects. Subsequent treatments should be adjusted depending on patient response to the initial doses. At each site, inject 2.5-10 units of BOTOX®. Use of lower volumes (higher concentrations) is suggested to avoid the risk of spread to adjacent areas. The solution should be injected subcutaneously over the orbicularis oculi and intramuscularly over the thicker corrugator and procerus muscles. Patients may return home without restrictions of activity. Most patients require repeated treatment every 3 months, but this ranges from 1-5 months.

Surgical Care:
In patients who do not develop sufficient improvement with an adequate trial of BOTOX® injections, surgical intervention may be considered. The mainstay of surgical treatment of spasm of the orbicularis oculi is myectomy. An older procedure, neurectomy, has almost completely been abandoned because of a higher complication rate than seen with myectomy. Many patients with BEB have a component of apraxia of eyelid opening. It is estimated that almost 50% of patients who are considered failures of BOTOX® treatment have apraxia of eyelid opening. Frontalis suspension and limited myectomy with complete removal of the pretarsal orbicularis should be considered for patients who are visually disabled by apraxia of eyelid opening.

Patients may fail BOTOX® therapy because they have eyelid malposition, aesthetic concerns, apraxia of eyelid opening, or photo-oculodynia. These conditions require surgeries in addition to or in place of myectomy.

Limited myectomy involves surgical extirpation of protractors of the eyelids, including the pretarsal, preseptal, and orbital portions of the upper and lower eyelid orbicularis oculi muscle. Extended myectomy includes removal of the procerus and corrugator muscles. Myectomy is a staged procedure with upper eyelid surgery typically performed first, followed by lower eyelid surgery if symptoms persist. Simultaneous upper and lower eyelid myectomy is avoided because it typically leads to chronic lymphedema.

Adequate access to the orbicularis oculi, corrugator, and lateral procerus muscle can be gained through an upper eyelid crease incision. Muscle is removed in 3 en block sections.
Dissection begins in a plane between the skin and the pretarsal muscle.
A 1- to 2-mm band of pretarsal muscle is preserved at the eyelid margin, and the rest of the pretarsal muscle is removed.


Dissection proceeds superior in a plane between the skin and the muscle to above the eyebrow. The orbital septum is left intact, and the preaponeurotic fat pad is not sculpted. The remaining preseptal and orbital orbicularis is removed. A thin band of muscle is left beneath the eyebrow to prevent alopecia.

Finally, the lateral orbicularis is removed over the lateral raphe and extending into the lateral portion of the inferior orbicular. The lateral dissection is aided by retroilluminating the skin muscle flap. When lower lid myectomy is required, adequate access can be obtained via a lower eyelid crease incision.

Many patients with BEB have aesthetic concerns about eyebrow ptosis or forehead rhytids, which can be addressed safely at the time of myectomy by sculpting or repositioning of the retro-orbicularis oculi fat pad or by endoscopic forehead lift surgery.
Superior cervical ganglion block


Treatment of BEB focuses heavily on reducing the motor component of the disease. Remember that there is also a sensory loop of the disease, which is harder to quantify because it involves the patient's subjective complaints of ocular surface irritation and photosensitivity. In some patients in which BOTOX® treatment fails, a careful history and examination reveals that BOTOX® does reduce spasm and weaken the orbicularis muscle but does not relieve the sensory symptoms of the disease. For patients who complain of debilitating light sensitivity (photo-oculodynia) intervention by a pain clinic may benefit the patient.
Two reports have demonstrated reduction of photo-oculodynia after superior cervical ganglion blocks to chemodenervate the orbital sympathetics. These preliminary studies suggest that the sympathetic nervous system may play a role in maintaining the afferent loop of the disease.

Miscellaneous
Individuals with untreated blepharospasm may be more likely to have work-related or driving accidents.

Selected References

Anderson RL, Patel BC, Holds JB, Jordan DR: Blepharospasm: past, present, and future. Ophthal Plast Reconstr Surg 1998 Sep; 14(5): 305-17 .
Asanuma K, Carbon-Correll M, Eidelberg D: Neuroimaging in human dystonia. J Med Invest 2005 Nov; 52 Suppl: 272-9
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Barnes MP, Best D, Kidd L: The use of botulinum toxin type-B in the treatment of patients who have become unresponsive to botulinum toxin type-A -- initial experiences. Eur J Neurol 2005 Dec; 12(12): 947-55
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Ben Simon GJ, McCann JD: Benign essential blepharospasm. Int Ophthalmol Clin 2005; 45(3): 49-75
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Bentivoglio AR, Daniele A, Albanese A: Analysis of blink rate in patients with blepharospasm. Mov Disord 2006 Apr 18;
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Bhidayasiri R, Cardoso F, Truong DD: Botulinum toxin in blepharospasm and oromandibular dystonia: comparing different botulinum toxin preparations. Eur J Neurol 2006 Feb; 13 Suppl 1: 21-9
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Bradley EA, Bradley D, Bartley GB: Evaluating health-related quality of life in ophthalmic disease: practical considerations. Arch Ophthalmol 2006 Jan; 124(1): 121-2 .

Adapted from: EMedicine