Meige's syndrome

Overview

Not to be confused with Meigs syndrome

Meige syndrome is classified among the focal dystonic disorders, characterized by blepharospasm (double eyelid spasm) and oromandibular dystonia. Dystonia is described as unusual involuntary postures or movements resulting from continuous muscle contractions, typically arising from neurological and medical conditions. In the early 20th century, Henry Meige, a French neurologist, observed abnormal contractions in the midline facial muscles of certain patients, initially termed “spasm facial median.” These individuals also exhibited similar symptoms in the jaw and oropharyngeal muscles. The designation “Meige syndrome” was first suggested by Dr. George Paulson in 1972 for patients exhibiting facial muscle spasms, especially blepharospasm and oromandibular muscle dystonia. Subsequently, Gilbert introduced the term “Brueghel syndrome” for a case of jaw dystonia, which is distinguished from Meige syndrome by the lack of blepharospasm.

Pathophysiology

The predominant theory for the development of Meige syndrome centers on hyperactivity in dopaminergic and cholinergic systems, as previously mentioned. However, it may also stem from the reduced activity of inhibitory neurons, such as GABAergic neurons, within the cortex. Additionally, a mix of environmental and genetic factors may predispose individuals to craniocervical dystonia. Some studies suggest abnormal sensorimotor processing in these patients, evidenced by positron emission tomography scans showing diminished blood flow to the sensorimotor region when the lower face is vibrated. Silent functional MRI scans have revealed reduced activity in the primary motor cortex (Brodmann Area 4) and premotor cortex (Brodmann Area 6), particularly in the areas representing the mouth in patients with Meige syndrome who exhibit isolated blepharospasm. This could be due to irregular regulation of the cranial nerve nuclei in the brain stem by the basal ganglia. Brain imaging has detected a decrease in grey matter volume in the cerebellum, superior frontal gyrus, insular cortex, and calcarine fissure in individuals with craniocervical dystonia. Focal dystonias also share a genetic component in their pathogenesis. At the cellular level, mutations in the torsinA gene seem to disrupt the trafficking of vesicles into and out of the nucleus, leading to transcriptional dysregulation. Similar mechanisms have been implicated in other primary focal dystonias, such as mutations in CNS transcription factors (TAF1, THAP1). Animal and human model studies provide evidence of these genetic mutations disrupting the development of neuronal networks. Emotional stress may play a role in 33% of Meige syndrome cases, with primary symptoms including anxiety, depression, and sleep disturbances.

Etiology

Primary Meige Syndrome Research and clinical observations have underscored the role of genetic factors in the disease’s development. Clinical signs of Meige syndrome have been linked to patients with mutations such as p.Gly213Ser or p.Ala353thr. More recently, mutations in the GNAL gene (encoding the guanine nucleotide-binding protein G, alpha subunit) have been implicated in cranial and cervical dystonia, though further evidence is required.Secondary Meige Syndrome A quarter of patients on neuroleptic drugs for over a year experience receptor function changes, leading to facial or cervical dystonia due to denervation hypersensitivity. This condition is believed to result from increased central dopaminergic activity, a theory supported by the improvement observed with dopamine-depleting agents. Medications that elevate central dopamine levels include antiemetics (such as metoclopramide), antipsychotics, antidepressants, selective serotonin re-uptake inhibitors, antihistamines, and dopaminergic agonists. Additionally, head injuries, strokes, brain stem demyelination, normal pressure hydrocephalus, cerebral hypoxia, postoperative conditions (like bilateral thalamotomy), kernicterus, space-occupying lesions, and post-encephalitis can be associated. Meige syndrome may also co-occur with other movement disorders, including Parkinson’s disease, Wilson’s disease, olivopontocerebellar atrophy, or Lewy body disease.

Epidemiology

The clinical manifestations of Meige syndrome are diverse. Typically, affected individuals are between 30 to 70 years old, with an average age of 55.7 years, although cases in teenagers have been reported. The prevalence of isolated blepharospasm and craniocervical dystonia varies, with estimates ranging from 2% to 20%. A higher incidence has been noted in females, possibly due to specific estrogen receptors that may predispose them to involuntary muscle contractions.

Clinical Presentation

The clinical presentation of Meige syndrome can vary widely. It may initially manifest as unilateral blepharospasm before progressing to bilateral involvement. The syndrome is known for its diverse phenotypic expressions, which can range from tonic spasms or prolonged eye closure, clonus of the orbicularis oculi muscle, to complete inability to open the eyes due to eyelid weakness or blepharoptosis. This progressive muscle dysfunction typically starts as a focal neurological issue, manifesting as either essential blepharospasm or oromandibular dystonia, and may eventually spread to other muscle groups, including those in the neck (antecollis, retrocollis, torticollis), respiratory system, or upper limbs (dystonic tremors). The oromandibular muscles most frequently involved are the temporalis, masseter, and platysma. Patients may experience involuntary movements of the lower face and masticatory muscles, such as lip pursing, chewing, grimacing, jaw thrusting, and opening or closing/clenching. It has been observed that the risk of dystonic contractions spreading to adjacent muscle groups is highest in the first year following the onset of initial symptoms, with the possibility of spread continuing for the next 3 to 5 years. Factors that may increase the risk of spread in patients with blepharospasm include older age at onset, female gender, and a history of head trauma. Sensory tricks, which are sensory stimuli that patients learn to use to alleviate dystonia, are common in Meige syndrome. Examples include sleeping, relaxing, speaking, pulling the upper eyelid, blowing cheeks, walking, exposure to cold water, yawning, or drinking beverages. Over half of the patients with blepharospasm report having one or more sensory tricks.

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 for Meige syndrome encompasses a range of medical and surgical strategies. Given the underlying mechanisms of Meige syndrome, it’s understandable that anticholinergics (such as trihexyphenidyl), dopamine antagonists (like tiapride, tetrabenazine), and GABA receptor agonists (including benzodiazepines, baclofen) prove beneficial for patients. Additional therapeutic options include antiepileptics (for instance, valproic acid) and various psychoactive drugs. Eszopiclone and nitrazepam target specific subunits (omega-1 and omega-2) within the GABA receptor complex, helping to relieve eyelid spasms. Case studies indicate that zolpidem is particularly effective for these patients due to its specificity for the GABA omega-1 receptor. However, prolonged use of psychoactive drugs may induce eyelid spasms, commonly linked to typical antipsychotics, although an exacerbation of blepharospasm has also been observed with olanzapine use.Botulinum A injections have shown promise and are typically reserved for patients who do not respond well to oral medications or experience adverse effects from them. The main limitation to the widespread use of Botulinum A injections is the potential for therapeutic resistance, which can develop from antibody production after repeated and long-term treatment. Additionally, these injections may lead to muscle weakness in adjacent areas or exacerbate existing conditions like dysphagia or dysarthria. Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been recognized as an effective therapy for patients who do not achieve satisfactory results with botulinum toxin or other conservative treatments. The placement of DBS electrodes is carefully planned, as the ventral and posterior parts of the GPi correspond topographically to the facial region, while the cervicofacial area is more anteriorly located.

See also

• Blepharospasm
• Mogigraphia