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.

• Short Arm

  The DRD5 gene, located on the short arm of chromosome 4 (4p16.1), encodes a known dopamine D5 receptor, located in the brain protein. This protein interacts with dopamine. [ivami.com]

• Long Arm

  The TOR1A gene, also known as DYT1, located on the long arm of chromosome 9 (9q34), encodes a protein called torsion A. This protein is found in the space between the nuclear envelope and endoplasmic reticulum. [ivami.com]

• Eye Irritation

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

  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]

• Chronic Pelvic Pain Syndrome

  pelvic pain syndromes, arthritis joint pain, and wound healing. [books.google.com]

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.

• Gram-Positive Rods

  Botulinum A toxin is the product of the bacteria, Clostridium botulinum (a large anaerobic, gram-positive, rod-shaped organism). [emedicine.medscape.com]

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.

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