BEB is associated with involuntary contractions or spasms of the orbicularis oculi muscles. This condition may cause excessive blinking or prolonged, involuntary eyelid closure. Patients suffering from such spasms are unable to open their eyes to continue their doing. Furthermore, BEB patients may suffer from involuntary contractions of other facial muscles, recognizable by uncontrolled movements of the paranasal muscles, mouth, and jaw [1]. Interestingly, most BEB patients use sensory tricks to alleviate their symptoms: They may touch themselves above their eyes, talk, sing, or hum to suppress spasms. More than 70% of those suffering from BEB apply such tricks to bring about muscle relaxation [2]. Additionally, anxiety and enhanced attention may improve symptoms. By contrast, exposure to strong light may worsen muscle spasms [3].

Besides muscle spasms, trigeminal hyperexcitability, manifesting in form of abnormal blink reflexes and photophobia, are characteristic of the disease. This may explain why many BEB patients have history of dry eyes or keratitis. It should be noted though that the vast majority of individuals presenting with dry eyes never develops BEB [4].

Pupil reflexes, eye movements, and visual acuity are not typically altered in BEB patients. Furthermore, blepharitis and decreased tear production as observed in case of keratoconjunctivitis sicca are not to be expected in those suffering from BEB.

• Movement Disorder

  […] the role of adaptive blink mechanisms in eyelid movement disorders. [ncbi.nlm.nih.gov]

  It is a form of dystonia, a movement disorder in which muscle contractions cause sustained eyelid closure, twitching or repetitive movements. BEB begins gradually with increased frequency of eye blinking often associated with eye irritation. [ninds.nih.gov]

  It is not life-threatening It is a form of dystonia, a movement disorder in which sustained muscle contractions cause twitching and repetitive movements. BEB begins gradually with occasional eye blinking and/or irritation. [brainfoundation.org.au]

  It is a form of dystonia, a movement disorder in which muscle contractions cause sustained eyelid closure, twitching or repetitive movements. [globalgenes.org]

• Disability

  Psychological distress in BEB, but not in HFS, correlated with physical disability and in particular with impairment of vision. [ncbi.nlm.nih.gov]

  The primary outcome was physician-rated videos, frequency and severity score on Jankovic rating scale, and patient-rated blepharospasm disability index. [n.neurology.org]

  Conclusions: BEB is a disabling condition whose etiology is unclear. Other disorders of neuromuscular function in the eyelid, such as myasthenia gravis, have shown response to cryotherapy as a diagnostic tool. [iovs.arvojournals.org]

  Box 12468 Beaumont, TX 77726 Get directions Related Disabilities Dystonia Go to Organizations List [askjan.org]

• Swelling

  The risks include incomplete eyelid closure, and postoperative bruising and swelling. If there is any drooping of the upper eyelids or excess upper eyelid skin, ptosis repair or upper eyelid blepharoplasty may help improve visual disability. [sfeyeplastics.com]

  After surgery, significant bruising, swelling, and soreness may develop. Patients can take pain medication, if necessary, and should sleep with their head elevated. Dr. [eyelidmd.com]

  Make an appointment if: The twitch lasts for more than 1 week Your eyelid closes completely Spasms involve other facial muscles You see redness, swelling, or discharge from an eye Your upper eyelid droops If your doctor suspects a brain or nerve problem [webmd.com]

• Ecchymosis

  Management (Botulinum toxin side effects/complications) • local bruise • ecchymosis • ptosis • keratopathy • diplopia • lagophtalmus • dry eyes • midfacial weakness • nasopharyngitis • respiratory tract infection • visual disturbance • dyspnea 14. [slideshare.net]

  […] improved after botulinum toxin injection. [50] 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%), ecchymosis [emedicine.medscape.com]

  Complications of botulinum toxin injections are ptosis, corneal exposure, dry eye symptoms, entropion, ectropion, photophobia, diplopia, ecchymosis and lower facial weakness. [eyeplastics.com]

  Complications include localized bruising, ecchymosis, ptosis, exposure keratopathy, diplopia, mid-facial weakness, lagophthalmos, and dry eye. [nature.com]

  […] poorly controlled with botulinum toxin injections alone.(25) Complications of botulinum toxin injections are well documented and include ptosis, corneal exposure, lagophthalmos, symptomatic dry eye, lid malposition, epiphora, photophobia, diplopia, ecchymosis [djo.harvard.edu]

• Epilepsy

  MeSH Descriptor Source: MeSH 2019 deskriptory Main Heading epilepsie benigní neonatální English Heading Epilepsy, Benign Neonatal See (Czech) novorozenecké křeče benigní [cze0024254] benigní familiární neonatální epilepsie [cze0084910] nefamiliární benigní [medvik.cz]

  The most common include drugs that treat psychosis and epilepsy. What Are the Types of Twitches? There are three common ones. [webmd.com]

• Hypertension

  전에 있던 본태성 고혈압: 前에 있던 本態性 高血壓: MMC KT0048201: pre-existing essential hypertension complicating pregnancy, childbirth or the puerperium: 임신, 출산 또는 산욕기에 합병된 전에 있던 본태성 고혈압: 妊娠, 出産 또는 産褥期에 合倂된 前에 있던 本態性 高血壓: C3R[complication]C5 [61.78.109.24]

  Hypertension was the most common medical disorder (42.6%), followed by diabetes mellitus (10.9%), heart disease (5.0%), and hypothyroidism (2.0%). [synapse.koreamed.org]

  People with systemic diseases such as hypertension and hyperlipidemia also tended to have a higher incidence of developing blepharospasm (p <0.001). [journals.plos.org]

  […] keratoplasti sonrası travmatik yara ayrışması B Kartal, B Kandemir, T Set, S Kuğu, S Keleş, E Ceylan, B Akmaz, A Apil, ... 2014Comparison of the efficacy of latanoprost, bimatoprost and travoprost in patients with primary open-angle glaucoma and ocular Hypertension [scholar.google.com.tr]

  Long term follow-up of patients with accelerated hypertensive optic neuropathy, retinopathy and choroidopathy. EVER 2002, November 2-5, Alicante, Spain. 10. Akova YA, Akman A, Cetinkaya A, Ertan A, Gedik S. [turkiyede-tedavi.com]

• Heart Disease

  Hypertension was the most common medical disorder (42.6%), followed by diabetes mellitus (10.9%), heart disease (5.0%), and hypothyroidism (2.0%). [synapse.koreamed.org]

• Photosensitivity

  At Axon Optics, all of our lenses are tinted with FL-41 for maximum protection against parts of the light spectrum which bother photosensitive people. [axonoptics.com]

  Sunglasses: Wearing tinted sunglasses with ultraviolet blocking may help in decreasing painful light sensitivity in those who show significant photosensitivity. Lid hygiene: Lid hygiene may decrease eye irritation. [checkorphan.org]

  Use of FL-41 tinted glasses (rose-colored) may also be helpful in those patients who have significant photosensitivity. [eyewiki.aao.org]

• Eye Irritation

  Initial symptoms include an increased frequency of blinking, dry eyes, and eye irritation. [checkorphan.org]

  BEB begins gradually with increased frequency of eye blinking often associated with eye irritation. Other symptoms may include increasing difficulty in keeping the eyes open, and light sensitivity. [ninds.nih.gov]

  Initial symptoms include eye irritation and frequent blinking, progressing to involuntary spasms of eyelid closure. Patients have normal eyes. The visual disturbance is due solely to the forced closure of the eyelids. [uniprot.org]

  There may be other symptoms more often associated with dry eye syndrome, such as eye irritation or excessive tearing. However, the significant symptom of BEB is uncontrollable blinking and forced eyelid closure. [blepharospasm.ca]

• Photophobia

  Most people with BEB have severe photophobia, which is sensitivity to light. It is often so painful that BEB sufferers avoid light. FL-41 is a therapeutic tint. [axonoptics.com]

  PURPOSE: The purpose of this study is to test the hypothesis that the photophobia of benign essential blepharospasm (BEB) is caused by sympathetically maintained pain. [ncbi.nlm.nih.gov]

  Glasses with FL-41 tint reduced functional limitations, blink frequency, and photophobia in a 2009 study. [theraspecs.com]

• Blepharoptosis

  […] lesions, management of periocular neoplasms, reconstruction of the lower eyelid, reconstruction of the upper eyelid, reconstruction of canthal defects, management of entropion and trichiasis, management of ectropion and floppy eyelids, management of blepharoptosis [books.google.com]

  Additional eyelid deformities, such as lid malposition, brow ptosis, blepharoptosis and dermatochalasis, were addressed at a later time, once the patient had fully recovered from myectomy surgery. [djo.harvard.edu]

  Complications Complications associated with botulinum toxin injection include: Bruising, blepharoptosis, ectropion, epiphora, diplopia, lagophthalmos, and corneal exposure. [eyewiki.aao.org]

• Visual Impairment

  A 57-year-old female had vague visual complaints of pressure behind her right eye during an ocular examination. One month later the patient was visually impaired due to uncontrollable spasms of both eyelids. [ncbi.nlm.nih.gov]

  Sources of support If eye dystonia is causing visual impairment, the following may be helpful sources of support: The Royal National Institute for Blind People (RNIB) Your local Sensory Support service. [dystonia.org.uk]

  Occasionally, it can be so intense it results in severe visual impairment. Aetiology [ 1, 2 ] Blepharospasm is a subtype of focal dystonia. Most cases are idiopathic and termed benign essential blepharospasm or primary blepharospasm. [patient.info]

  Causes of blindness and visual impairment in a population of older Americans : The Salisbury Eye Evaluation Study. Arch Ophthalmol 2000 ; 118 : 819-25. [5] Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. [em-consulte.com]

• Anger

  And I say that not in anger (I'm writing this a decade later). I'm saying this because it is true. Any one of those Neurologists should have sent me to get a CAT scan or an MRI. [frankgerry.com]

• Dystonia

  Oromandibular dystonia is the commonest association with blepharospasm leading to a diagnosis of Cranial Dystonia or Meige's Syndrome. Neuroimaging MRI studies are not done routinely in focal eyelid dystonia. [collections.lib.utah.edu]

  With regards to the former, family members may have suffered from BEB themselves, or may have been affected by other types of dystonia such as focal hand dystonia, foot dystonia, cervical dystonia, or spasmodic dysphonia. [symptoma.com]

  Blepharospasm is a rare disease with the incidence from 1 in 10,000 to 1 in 25,000, but it is related to other adult onset focal dystonias such as cervical dystonia (spasmodic torticollis), spasmodic dysphonia and focal hand dystonia (such as writer's [research.weill.cornell.edu]

  UniProtKB/Swiss-Prot : 73 Benign essential blepharospasm: A primary focal dystonia affecting the orbicularis oculi muscles. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. [malacards.org]

• Stroke

  He is a Fellow of the American Academy of Neurology, American Neurological Association, American College of Physicians, and the Stroke Council of the American Heart Association. [books.google.com]

  National Institute of Neurological Disorders and Stroke (NINDS). Benign Essential Blepharospasm Information Page. Last Updated:June 15, 2018. [rarediseases.org]

• Excitement

  Abnormal neuronal excitability and activity are currently presumed to be the cause of BEB. [symptoma.com]

  The BRR revealed an increased excitability in the BEB group compared to healthy controls. rTMS therapy did not induce any significant change in the BRR curve. [mdsabstracts.org]

  Blink-adaptive control systems can act on the blink reflex excitability and main-sequence relationships, changing these either together or independently. [ncbi.nlm.nih.gov]

  Previous research found modulation of anterior cingulate cortex (ACC) excitability with rTMS therapy could alleviate BEB symptoms. [n.neurology.org]

  Brain imaging and electrophysiologic studies suggest additional pathologic changes in excitability in the anterior cingulate, primary and secondary motor areas.2 BEB is typically a chronic disorder.3 Botulinum neurotoxin is the medical therapy of choice [omicsonline.org]

Both individual and familial anamnesis may provide valuable hints: BEB patients are likely to have a family history of dystonia, benign tremor, or Parkinson's disease. With regards to the former, family members may have suffered from BEB themselves, or may have been affected by other types of dystonia such as focal hand dystonia, foot dystonia, cervical dystonia, or spasmodic dysphonia [2]. Shortly before the onset of BEB-associated symptoms, patients may have had stressful experiences. Some report depression, anxiety, or psychological strains due to death or illness of a family member, problems at work or at home, while others mention previous head trauma as a possible trigger of muscle spasms [5] [2]. Because symptoms similar to those observed in BEB may be triggered by levo-dopa and neuroleptic antipsychotic agents, it is important to enquire whether such drugs have been used by the patient [1].

Because there is no diagnostic test for BEB, detailed clinical data have to be collected after conducting a thorough anamnesis. Possible differential diagnoses include hemifacial spasm and facial myokymia, whereas those diseases generally affect one eye only. It may be particularly difficult to distinguish BEB from psychogenic blepharospasm, though. Young age and acute onset, constant eye closure, unusual aggravating or relieving factors, or an unusual - sometimes immediate - response to botulinum toxin injections rather suggest psychogenic blepharospasm than BEB [3]. However, BEB patients may also suffer from psychiatric conditions and such comorbidity may result in complex disease patterns. Electrophysiological measurements of brainstem interneuron excitability have been proposed as an option to distinguish BEB from psychogenic blepharospasm. Schwingenschuh et al. reported that an abnormal enhancement of brainstem excitability is to be expected in BEB patients, but not in those suffering from psychogenic blepharospasm [3]. Nevertheless, further studies are required to confirm their findings.

Brain imaging does not usually yield any pathological results.

Injections of botulinum toxin type A into the periocular and facial musculature are the treatment of choice, but other therapeutic approaches have also been taken:

• Bbotulinum toxin injections have been proven effective and safe even after several years of therapy [6]. Botulinum toxin causes a local inhibition of acetylcholine release. Bbotulinum toxin injections aim at reducing the strength of the orbicularis oculi muscles and possibly other facial musculature, thereby decreasing the severity of involuntary contractions. Dosage and treatment frequency have to be adapted to the necessities of the individual patients. Generally, partial recovery of muscle function is observed about four weeks after the injections and acetylcholine release reaches previous levels during the third month after treatment. Consequently and according to long-term studies, the average time between treatments is three months [1]. Diplopia and ptosis are among the most common side effects of botulinum toxin injections and affect approximately 5-10% of all patients treated [1].
• The efficacy of botulinum toxin injections may be increased by combining them with oral benzodiazepine therapy.
• In a minor group of patients, tinted lenses have been used to block the passage of certain wavelengths. These lenses have improved the patients' reading abilities, fluorescent light sensitivity, overall light sensitivity, blepharospasm frequency, and blepharospasm severity [7].
• In those patients who don't respond to either of the aforementioned treatment options, myectomy may be considered [8].

Patients may be rendered functionally blind if suffering from severe spasms. Involuntary eyelid closure may severely affect the patients' ability to cope with everyday life, particularly with regards to activities like driving and machine controlling. Frequently, those suffering from BEB fear their appearance in social settings. Thus, BEB does significantly lower the patients' quality of life. Affected individuals are at increased risk of depression and anxiety [9].

The fact that about three in four patients are able to alleviate symptoms applying so-called sensory tricks is the reason why BEB has been considered a psychogenic disease for a long time. Although conclusive evidence regarding etiology and pathogenesis of the disease is still lacking, this hypothesis no longer holds true today. Indeed, it is known today that psychogenic blepharospasm constitutes a separate entity.

Abnormal neuronal excitability and activity are currently presumed to be the cause of BEB [3]. Brain regions most likely involved in the pathogenesis of BEB comprise brainstem and trigeminal blink circuits, the basal ganglia, and the cerebellum [3] [4]: The excitability of brainstem interneurons and blink circuits have been found to be abnormal in BEB patients. In fact, measurements of the blink reflex recovery cycle have been proposed as a specific method to differentiate BEB from other pathological conditions [3]. Furthermore, adaptive modifications of trigeminal reflex blink circuits may be enhanced or suppressed by basal ganglia and under pathological conditions, this may result in maladaption. The cerebellum seems to support and maintain blink circuit adaptions regardless of their appropriateness [4].

Because most BEB patients have a familial history of BEB or other types of dystonia, a genetic component most likely plays an important role in BEB etiology. However, it has not yet been possible to associate the disease with particular seqeunce anomalies. Thus, BEB patients may be predisposed genetically, but environmental factors seem to trigger the onset of symptoms.

The overall incidence of BEB has been estimated to 32 in 100,000 individuals [10]. The median age at symptom onset is 53 years, but the disease has been diagnosed in people of any age, including children and the elderly [5]. BEB is most frequently observed in Caucasian women. In general, females are affected about three times as often as men [2] [5]. Studies have been conducted to test whether there are clinical differences between men and women affected by BEB and indeed, the disease seems to follow a more severe course in female patients [11].

BEB is a central nervous system disorder. According to current knowledge, involuntary contractions of the orbicularis oculi muscles as seen in BEB result from functional disturbances in the brainstem and abnormal central neurotransmitter levels:

• In detail, it has been speculated that serotonin-mediated hyperexcitability of facial motoneurons may be the cause of the disease [12]. And indeed, some BEB patients have successfully been treated with injections of serotonin antagonists. More recently, supranuclear inhibition of the facial motor nucleus has been proposed as a possible pathogenetic mechanism [1]. The fact that additional facial muscles may be affected in cases of BEB indicates the involvement of higher structures and may support either hypothesis.
• Furthermore, dopamine may play a major role in BEB pathogenesis. Dopamine depletion and dopamine receptor dysfunction may both contribute to the development of abnormal blink reflexes. However, investigations regarding this issue have yielded contradictoray results. In one study, a polymorphism in the gene encoding for dopamine receptor D5 has been found to be associated with BEB [13]. In a later study though, this finding could not be reproduced [14].

Due to considerable knowledge gaps regarding etiology and pathogenesis of the disease, no recommendations can be given at this time to prevent BEB.

Lid closure occurs upon contraction of the orbicularis oculi muscle. Consequently, diseases affecting this muscle may induce insufficient, excessive, involuntary, or otherwise disturbed shutting of the ipsilateral eyelid. Several conditions affect the function of the orbicularis oculi muscle. For instance, patients suffering from facial nerve palsy may show lagophthalmus, usually unilaterally. BEB, however, is a primary dystonia associated with excessive blinking, squeezing, and involuntary contractions of both orbicularis oculi muscles [5]. Trigeminal hyperexcitability is another hallmark of this disease and is associated with abnormal blink reflexes and photophobia [5].

Unfortunately, the causal relation between BEB, abnormal neuronal excitability and anomalies of blink reflex circuits remains poorly understood. According to current knowledge, genetically predisposed individuals exposed to certain environmental factors are most likely to develop the disease. However, neither gene mutations nor causal environmental influences could be clearly identified so far. To date, BEB is still considered a disabling condition that may severely affect the patient's quality of life with regards to vision. Treatment options are limited and currently, most patients receive botulinum toxin injections to alleviate orbicularis oculi muscle contractions and spasms [1]. Pilot studies have been conducted to assess the efficacy of tinted lenses and myectomy in BEB therapy [7] [8], but comprehensive and reliable data have not yet been presented in this regard.

Of note, patients suffering from blepharospasm and oromandibular dystonia are to be diagnosed with Meige syndrome. It has been estimated that about one third of BEB patients also shows symptoms of oromandibular dystonia and thus of Meige syndrome. The interested reader is referred to the article dealing with that entity. Meige syndrome will not be discussed in this article.

Benign essential blepharospasm (BEB) is a central nervous system disorder and primary dystonia. Due to as of yet poorly understood anomalies of neuronal excitability, BEB patients suffer from involuntary contractions of the orbicularis oculi muscles. Under physiological conditions, these muscles contract to mediate eyelid closure, either as part of the blink reflex circuit or if initiated by the patient.

BEB most commonly affects people aged 50 years and older. Women are more prone to develop this disease than men, and most patients have a positive family history of BEB, other types of dystonia, or Parkinson's disease. In some cases, symptom onset occurs after periods of psychological stress, after head trauma or eye disease, while no definite trigger can be identified in others. Frequency and severity of involuntary eyelid muscle contractions vary from patient to patient, but may considerably disturb their vision or even render them functionally blind. Additionally, BEB patients may show involuntary movements of their mouth, jaws, and other facial regions. Affected individuals may also report increased sensitivity to light. Indeed, exposure to strong light may provoke or worsen muscle spasms. On the other hand, most patients are able to alleviate their symptoms by touching certain areas of their face, singing, humming, or applying other so-called sensory tricks. Nevertheless, in order to maintain their quality of life, medical treatment is usually necessary.

Most patients benefit from regular botulinum toxin injections. This toxin interferes with neurotransmitter release and thus reduces muscle contractibility. Patients may require several treatment per year, but the therapy is usually well tolerated. If the efficacy of botulinum toxin injections is not satisfactory, oral benzodiazepine therapy, use of tinted contact lenses and surgical interventions may be considered as additional or alternative treatment options.

1. Czyz CN, Burns JA, Petrie TP, Watkins JR, Cahill KV, Foster JA. Long-term botulinum toxin treatment of benign essential blepharospasm, hemifacial spasm, and Meige syndrome. Am J Ophthalmol. 2013; 156(1):173-177.e172.
2. 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):382-386.
3. Schwingenschuh P, Katschnig P, Edwards MJ, et al. The blink reflex recovery cycle differs between essential and presumed psychogenic blepharospasm. Neurology. 2011; 76(7):610-614.
4. Evinger C. Animal models for investigating benign essential blepharospasm. Curr Neuropharmacol. 2013; 11(1):53-58.
5. Digre KB. Benign Essential Blepharospasm--There Is More to It Than Just Blinking. J Neuroophthalmol. 2015; 35(4):379-381.
6. Streitová H, Bareš M. Long-term therapy of benign essential blepharospasm and facial hemispasm with botulinum toxin A: retrospective assessment of the clinical and quality of life impact in patients treated for more than 15 years. Acta Neurol Belg. 2014; 114(4):285-291.
7. Blackburn MK, Lamb RD, Digre KB, et al. FL-41 tint improves blink frequency, light sensitivity, and functional limitations in patients with benign essential blepharospasm. Ophthalmology. 2009; 116(5):997-1001.
8. Pariseau B, Worley MW, Anderson RL. Myectomy for blepharospasm 2013. Curr Opin Ophthalmol. 2013; 24(5):488-493.
9. Hall TA, McGwin G, Jr., Searcey K, et al. Health-related quality of life and psychosocial characteristics of patients with benign essential blepharospasm. Arch Ophthalmol. 2006; 124(1):116-119.
10. Cossu G, Mereu A, Deriu M, et al. Prevalence of primary blepharospasm in Sardinia, Italy: a service-based survey. Mov Disord. 2006; 21(11):2005-2008.
11. Lee MS, Johnson M, Harrison AR. Gender differences in benign essential blepharospasm. Ophthal Plast Reconstr Surg. 2012; 28(3):169-170.
12. Fasanella RM, Aghajanian GK. Treatment of benign essential blepharospasm with cyproheptadine. N Engl J Med. 1990; 322(11):778.
13. Misbahuddin A, Placzek MR, Chaudhuri KR, Wood NW, Bhatia KP, Warner TT. A polymorphism in the dopamine receptor DRD5 is associated with blepharospasm. Neurology. 2002; 58(1):124-126.
14. Clarimon J, Brancati F, Peckham E, et al. Assessing the role of DRD5 and DYT1 in two different case-control series with primary blepharospasm. Mov Disord. 2007; 22(2):162-166.