BENIGN ESSENTIAL BLEPHAROSPASM

Signs and Symptoms

Blepharospasm represents an eye-specific form of dystonia, a neurological condition marked by involuntary movements and extended muscular contractions.1 Benign essential blepharospasm (BEB) refers to the tonic spasm of the orbicularis oculi muscle and associated musculature of the upper face, including the corrugator and procerus muscles.1 In its earliest stages, patients with BEB experience intermittent bouts of uncontrolled blinking instigated by external stimuli, including such elements as wind, airborne pollutants, bright lights, loud noises or rapid head movement.1 As BEB progresses, patients may experience more forceful closure of the eyelids lasting for longer periods, resulting in temporary functional blindness. Long-standing blepharospasm may lead to the development of lid and brow ptosis, dermatochalasis or entropion. In advanced stages, involvement of adjacent facial musculature becomes likely.

When blepharospasm is associated with dystonia of the platysma, muscles of the lower face and muscles of mastication, it may be referred to as Meige syndrome or segmental craniocervical dystonia.1,2 Patients with Meige syndrome characteristically demonstrate pronounced bruxism (clenching of the jaw), as well as difficulty with speech, eating and swallowing.

The onset of BEB most often occurs in middle age, with 53 years being the median age at the time of diagnosis.3 Women are affected nearly three times more frequently than men.1,3,4 A majority of patients report some type of life-altering or emotionally stressful event immediately prior to the development of symptoms, according to one study.3 The subsequent development of clinical depression and feelings of social isolation is also common.1

Pathophysiology

Since the motor division of the seventh cranial nerve (CN VII) is responsible for delivering the voluntary motor innervations to the muscles of facial expression (and to the stapedius muscle of the inner ear, which dampens loud sounds), any irritation by adjacent or direct infection, infiltration, inflammation or compression of cranial nerve VII nuclei or its fascicles can produce involuntary contracture of the affected region.5-7

BEB is poorly understood and in most cases, despite extensive laboratory testing and neuroimaging, there is no clearly identifiable etiological factor.8 As such, BEB must be considered a diagnosis of exclusion. Abnormal levels of neurotransmitters or alterations of the structure, function or architecture of the basal ganglia or midbrain have been postulated.1 Additionally, recent research has uncovered a potential neurochemical connection.9 Altered kynurenine metabolism, a neuroactive metabolite that plays a role in the normal physiology of the brain, has been identified as a contributor in neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease and now the pathogenesis of focal dystonia.9

Management

The treatment of choice for benign essential blepharospasm is chemodenervation via direct subcutaneous injection.1,8,10 Botox (onabotulinumtoxin A, Allergan) is generally accepted as a first-line treatment for patients suffering from spasms secondary to facial dystonias of all kinds.11 This medication works by blocking neuromuscular transmissions via the inhibition of acetylcholine release into the synaptic cleft.10,12 These treatments are extremely effective and well tolerated.11 The onset of effect typically occurs within one to three days and can last up to four months for cases of BEB.11 Treatment failures due to antibody production are possible, so injections should be given no more frequently than every three months.1 Adjunctive or alternative therapy with dopamine-depleting agents, neuroleptics, sedatives, centrally acting cholinergic medications and gamma-aminobutyric acid agonists have all had variable documented success; the drugs with the highest percentages of favorable patient response include Ativan (lorazepam, Valeant), Klonopin (clonazepam, Roche) and Artane (trihexyphenidyl HCl, Lederle Laboratories).1

While most patients will achieve successful amelioration of symptoms related to BEB with periodic Botox injections, some may not achieve adequate control with pharmaceutical therapy alone. In some instances, the medication may become less effective after prolonged use.13 In such cases, surgical myectomy of the upper eyelid may be an effective additive treatment. Myectomy must also be considered for patients who demonstrate apraxia of eyelid opening, a complication associated with BEB and those who acquire blepharospasm-associated deformities. Myectomy is also an option for those who cannot afford or who refuse Botox injections.13,14

In all cases of blepharospasm, an easy-to-use disability scale has been developed to quantify the contractures along with the changes that occur when treatment is instituted.15 This allows both the patient and the treating physician to understand the overall inconvenience and functioning of the patient as well as the effectiveness of the mode of intervention.15

Clinical Pearls

BEB is often initially misdiagnosed as a psychiatric condition rather than a true neurological phenomenon. This can unfortunately delay appropriate management.1

Physical and emotional stress can aggravate the symptoms of BEB. Even something as simple as participation in a social gathering can cause an exaggeration of the symptoms.

Both Parkinson’s disease and Huntington’s chorea (ceaseless jerky movements with mental status changes) are worthy of being placed into the differential diagnosis of BEB.

BEB must also be differentiated from secondary blepharospasm, a normal phenomenon that can occur following exposure to direct or indirect, painful ocular stimuli. Secondary blepharospasm presents as reflexive wincing and squeezing of the lids, as the patient attempts to find relief from intense ocular discomfort. Unlike BEB, secondary blepharospasm is transient and resolves when the root cause is eliminated.

Patients with complete eyelid closure, having lost the ability to open their eyes voluntarily, are said to have apraxia of eyelid opening.8 This finding may be seen in advanced cases of BEB. More commonly, however, apraxia of eyelid opening is related to a supranuclear disorder, presenting without forceful orbicularis contraction.8

 

1. Ben Simon GJ, McCann JD. Benign essential blepharospasm. Int Ophthalmol Clin. 2005;45(3):49-75.

2. LeDoux MS. Meige syndrome: what’s in a name? Parkinsonism Relat Disord. 2009;15(7):483-9.

3. Peckham EL, Lopez G, Shamim EA, et al. Clinical features of patients with blepharospasm: a report of 240 patients. Eur J Neurol. 2011;18(3):382-6.

4. Cossu G, Mereu A, Deriu M, et al. Prevalence of primary blepharospasm in Sardinia, Italy: A service-based survey. Mov Disord. 2006;21(11):2005-8.

5. Tan EK, Chan LL. Young onset hemifacial spasm. Acta Neurol Scand. 2006;114(1):59-62.

6. Nakamura T, Osawa M, Uchiyama S. Arterial hypertension in patients with left primary hemifacial spasm is associated with neurovascular compression of the left rostral ventrolateral medulla. Eur Neurol. 2007;57(3):150-5.

7. Jowi JO, Matende J, Macharia MI, et al. Hemifacial spasm: case report. East Afr Med J. 2006;83(7):401-4.

8. Kerty E, Eidal K. Apraxia of eyelid opening: clinical features and therapy. Eur J Ophthalmol. 2006;16(2):204-8.

9. Hartai Z, Klivenyi P, Janaky T, et al. Peripheral kynurenine metabolism in focal dystonia. Med Chem. 2007;3(3):285-8.

10. Harrison AR. Chemodenervation for facial dystonias and wrinkles. Curr Opin Ophthalmol. 2003;14(5):241-5.

11. Czyz CN, Burns JA, Petrie TP, et al. Long-term botulinum toxin treatment of benign essential blepharospasm, hemifacial spasm, and Meige syndrome. Am J Ophthalmol. 2013;156(1):173-177.e2.

12. Alshadwi A, Nadershah M, Osborn T. Therapeutic applications of botulinum neurotoxins in head and neck disorders. Saudi Dent J. 2015;27(1):3-11.

13. Kent TL, Petris CK, Holds JB. Effect of upper eyelid myectomy on subsequent chemodenervation in the management of benign essential blepharospasm. Ophthal Plast Reconstr Surg. 2014 Sep 4. [Epub ahead of print].

14. Georgescu D, Vagefi MR, McMullan TF, et al. Upper eyelid myectomy in blepharospasm with associated apraxia of lid opening. Am J Ophthalmol. 2008;145(3):541-547.

15. Grivet D, Robert PY, Thuret G, et al. Assessment of blepharospasm surgery using an improved disability scale: study of 138 patients. Ophthal Plast Reconstr Surg. 2005;21(3):230-4.