Continuing Education Activity

Meige syndrome is a focal dystonic movement disorder involving blepharospasm, or involuntary eyelid spasm, and oromandibular dystonia, or involuntary spasms of tongue, jaw, pharynx, and face. This activity describes the evaluation, diagnosis, and management of Meige syndrome and stresses the role of team-based interprofessional care for affected patients.

Objectives:

• Describe the pathophysiology of Meige syndrome.
• Describe the presentation of Meige syndrome.
• Summarize the treatment options for Meige syndrome.
• Explain the importance of enhancing care coordination amongst interprofessional team members to improve outcomes for patients with Meige syndrome.

Introduction

Meige syndrome is one of the focal dystonic movement disorders identified as blepharospasm (double eyelid spasm) and oromandibular dystonia. Dystonia is defined as abnormal involuntary posturing or body movements due to sustained muscle contractions, usually happens due to neurological and medical reasons. In the early 20th century, Henry Meige, a French neurologist, had found abnormal contractions of midline facial muscles in some patients, those he first named as “spasm facial median.” These patients also had a similar clinical picture in the muscles of jaw and oropharynx. Dr. George Paulson first proposed the term “Meige syndrome” in 1972 for patients having facial muscle spasm, particularly blepharospasm and dystonia of oromandibular muscles. After several years, the term “Brueghel syndrome” was introduced, used by Gilbert, for a case of jaw dystonia. It is differentiated from Meige syndrome by the absence of blepharospasm.[1][2][3]

Etiology

Primary Meige Syndrome

Several studies and clinical scenarios have provoked the significance of genetic components in the generation of disease. The patients with p.Gly213Ser, or p.Ala353thr mutations have been found to have clinical manifestations of Meige syndrome. Recently GNAL (gene for guanine nucleotide-binding protein G, subunit alpha) mutations are reported to be the cause of cranial and cervical dystonia, but more evidence is needed.[4][5][6]

Secondary Meige Syndrome

One-fourth of the patients who have been taking neuroleptic medications for more than a year develop alterations in receptor function, which causes facial or cervical dystonia due to denervation hypersensitivity that is thought to be due to the increased central dopaminergic activity, which is further supported by the fact that it improves with dopamine-depleting agents. Those medications which increase central dopamine activity include antiemetics (metoclopramide), antipsychotics, antidepressants, selective serotonin reuptake inhibitors, antihistamines, and dopaminergic agonists. Moreover, head trauma, stroke, demyelination of brain stem region, normal pressure hydrocephalus, cerebral hypoxia, postoperative (bilateral thalamotomy), kernicterus, space-occupying lesions, post-encephalitis. Meige syndrome can be associated with other movement disorders, like Parkinson disease, Wilson disease, olivopontocerebellar atrophy, or Lewy body disease.[7]

Epidemiology

There is a wide clinical presentation of Meige syndrome. The patients with Meige syndrome usually belong to the age group of 30 to 70 years old (mean age is 55.7 years), but there are reports of teenage patients. There is a variable data available regarding the prevalence of isolated blepharospasm and craniocervical dystonias, estimated to be around 2% to 20%. More cases were reported in females as it has been hypothesized that specific estrogen receptors make females prone to involuntary muscle spasms.

Pathophysiology

The most widely accepted hypothesis for the pathogenesis of Meige syndrome is dopaminergic and cholinergic hyperactivity, as explained earlier, but it may also be caused by decreased functioning of inhibitory neurons (for example, GABAergic neurons) in the cortex; moreover, various environmental and genetic factors make the patient prone to craniocervical dystonia. Some researchers postulate that there is abnormal sensorimotor processing in these patients, as a positron emission tomographic scans in the patients have shown decreased blood flow to the sensorimotor area in response to lower face vibrations. Silent functional magnetic resonance imaging (MRI) has shown decreased activation of the primary motor cortex (Brodmann Area 4) and premotor cortex (Brodmann Area 6) in the mouth representing areas in the patients of Meige syndrome having isolated blepharospasm. It might be caused by abnormal control of cranial nerve nuclei in the brain stem by basal ganglia.

Brain imaging identifies a grey matter volume reduction in the cerebellum, superior frontal gyrus, insular cortex, and calcarine fissure in patients with craniocervical dystonia.

Focal dystonias also share the genetic component in their etiopathogenesis. At a cellular level, mutation of the torsinA gene appears to cause disturbed exchange of vesicles into and out of the nucleus, which in turn causes transcriptional dysregulation. A related mechanism is found to be the cause of other primary focal dystonias, for example, mutations in central nervous system (CNS) transcriptional factors (TAF1, THAP1). The studies on animal and human models show evidence on the above mentioned genetic mutations that may lead to the disrupted development of the neuronal network.

In 33% of patients with Meige syndrome, emotional stress may be a factor as their primary symptoms are anxiety, depression, and sleep problems.

History and Physical

The pattern of presentation varies from patient to patient. It may appear first as unilateral blepharospasm that will later become bilateral. One of the most bothersome features of Meige syndrome is having different phenotypic forms, ranging from tonic spasm or prolonged closure of eye, clonus of orbicularis oculi to complete inability to open the eyes as eyelid weakness or blepharoptosis is also very common. It is a kind of progressive muscle dysfunction. It appears first as a focal neurological function, in other words, as either essential blepharospasm or oromandibular dystonia, and later spreads to other muscles such as muscles of the neck (antecollis, retrocollis, torticollis), respiratory muscles or muscles of upper limb (dystonic tremors). Commonly involved oromandibular muscles are temporalis, masseter, and platysma. Involuntary lower facial and masticatory movements such as lip pursing, chewing, grimacing, jaw thrusting, opening, or closing/clenching. It has been noticed that the risk of the spread of dystonic contractions to nearby muscle groups is most common in the first year of the appearance of initial symptoms, and the probability of spread lasts for the next 3 to 5 years. In patients with blepharospasm, older age-of-onset, female gender, and history of head trauma may increase the risk of spread.[8][9]

Sensory tricks are the sensory stimuli, learned by the patients to alleviate the dystonia. They are common among patients with Meige syndrome; examples include sleeping, relaxing, talking, pulling the upper eyelid, blowing cheeks, walking, exposure to cold water, yawning, or drinking beverage. More than half of the patients with blepharospasm have one or more sensory tick.

Evaluation

Workup should include:

• Facial electromyography
• MRI/CT brain to rule out the stroke or any other brain lesion
• Serum SSA/SSB level
• Serum Cu and ceruloplasmin level
• Beck's depression inventory
• Serum drug screen

Treatment / Management

Treatment includes various interventions under the medical and surgical domains. Knowing the mechanism of Meige syndrome, one can easily understand why anticholinergics (e.g., trihexyphenidyl), dopamine antagonists (e.g., tiapride, tetrabenazine), GABA receptor agonists (e.g., benzodiazepines, baclofen) are effective for such patients. Other medications include antiepileptics (e.g., valproic acid), and a number of psychoactive drugs. Eszopiclone and nitrazepam react at those specific subunits (omega-1 and omega-2) of the GABA receptor complex that alleviate the eyelid spasming. According to some case reports, zolpidem is effective in such patients as it is highly specific for a GABA omega-1 receptor. Long-term use of psychoactive drugs can cause eyelid spasming that is more often associated with the use of typical antipsychotics, though worsening of blepharospasm has been reported with the use of olanzapine.[10][11][12]

Botulinum A injection is showing promising results and is reserved for those patients who are poorly responsive to oral medication or are having side effects of these medications. What hinders the excessive use of botulinum A injection is a therapeutic resistance that occurs due to antibody production after recurrent and long-term use. Moreover, it would cause weakness of nearby muscles or cause worsening of existing dysphagia or dysarthria.

Deep brain stimulation of globus pallidus interna (GPi) has proved to be an effective treatment option in whom botulism toxin and other conservative treatment options are not providing the required results. Placement of electrodes should be planned schematically as ventral and posterior portions of globus pallidus interna are the topographical representation of face while the cervicofacial area is more toward anterior.[13]

Differential Diagnosis

• Xeromas
• Spinocerebellar ataxia
• Progressive supranuclear palsy
• Wilson disease
• Ischemic stroke
• Autoimmune/inflammatory disease (multiple sclerosis, lupus erythematosus, Behcet disease)
• Metabolic (hypoxia, pontine myelinolysis)
• Neoplasm (meningioma, metastatic tumor)
• Myoclonus-dystonia syndrome
• Psychogenic craniocervical dystonia
• Generalized anxiety disorder

Enhancing Healthcare Team Outcomes

Meige syndrome is best managed by an interprofessional team including primary care providers, neurologists, neurosurgeons, pharmacists, and nurses. The current treatments for Meige syndrome are not ideal and many therapies exist. Botulinum A does work for a short while but resistance build-up is common. Deep brain stimulation has been hyped as a panacea for many brain disorders but in Meige syndrome, the technique has not worked with any reliability, nor does it consistently provide relief of symptoms. Neuroscience nurses work with patients, provide education to them and their families, and communicate with the team about issues. Pharmacists review causative and treatment medications, check for drug drug interactions and provide education about proper administration. [Level 5]