Meige Syndrome

Abdur Rehman (1), Adeel Memon (2)
1 - Shaikh Khalifa Bin Zayed Al-Nahyan Medical and Dental College, Lahore
2 -


Introduction

  • A type of cranial dystonia that consists of blepharospasm and oromandibular dystonia.
  • It has also been described as segmental cranial dystonia and segmental cranio-cervical dystonia.
  • Can be confused with Meig's Syndrome which is a triad of a benign ovarian tumor, ascites, and pleural effusion.

Epidemiology

  • Usually presents in the 30 to 70 year old age group.
  • Isolated blepharospasm and cranio-cervical dystonias are prevalent in around 2% to 20% of the patients.
  • A greater number of cases were reported in females and it was hypothesized that specific estrogen receptors influencing involuntary motor function increased the risk in women.

Etiology

Primary Meige Syndrome

  • p.Gly213Ser or p.Ala353thr mutations have been found in patients with clinical manifestations of Meige syndrome.
  • GNAL (gene for guanine nucleotide-binding protein G, subunit alpha) mutations are reported to cause cranial and cervical dystonia.

Secondary Meige Syndrome

  • 1/4 of the patients taking neuroleptic medications for more than a year develop alterations in receptor function which causes facial or cervical dystonia as a result of denervation hypersensitivity caused by the increased central dopaminergic activity.
  • Medications which increase dopamine sensitivity include antiemetics (metoclopramide), antipsychotics, selective serotonin reuptake inhibitors and antidepressants.
  • Associated with Parkinson disease, Wilson disease, Olivopontocerebellar atrophy, or Lewy body disease.
  • Associated with head trauma, stroke, demyelination of brain stem region, cerebral hypoxia, kernicterus and space-occupying lesions.

Pathophysiology

  • The exact pathophysiology of Meige's syndrome is not known.
  • Dopaminergic and cholinergic hyperactivity or decreased functioning of inhibitory neurons in the cortex are accepted hypotheses.
  • Eye diseases and coffee are identified as risk factors.
  • PET scans indicate decreased blood flow to the sensorimotor area in response to lower face vibrations.
  • MRI shows decreased activation of primary motor cortex and premotor cortex in the mouth representing areas in isolated blepharospasm patients.
  • Grey matter volume reduction in the cerebellum, superior frontal gyrus, insular cortex, and calcarine fissure is present.
  • Mild abnormalities in the substantia nigra, locus coeruleus and midbrain tectum, and moderate neuronal loss and gliosis in the dentate nuclei occurs.
  • Recovery cycles of the R2 component of the blink reflex and SP2 component of the masseter inhibitory reflex are increased.
  • Isolated cervical dystonia patients also show enhanced R2 recovery.
  • Mutation of the torsin-A gene causes disturbed exchange of vesicles into and out of the nucleus.
  • This causes transcriptional dysregulation leading to poor development of the neuronal network.
  • Emotional stress can be a factor in 33% patients.
  • Some studies show that it is a low penetrance autosomal dominant disorder.
  • Brain metabolism is decreased in the internal globus pallidus and parietal lobe in the left hemisphere and in the frontal lobe and postcentral gyrus in the right hemisphere.
  • Glucose hypometabolism is present in thalamus and cerebellum in both hemispheres.

Clinical Presentation

  • May appear first as unilateral blepharospasm which can later become bilateral.
  • Appears first as an essential blepharospasm or oromandibular dystonia.
  • May later spread to muscles of the neck, respiratory muscles or muscles of upper limb.
  • Blepharospasm presents as tonic spasms with prolonged spasms of eye closure, and clonic spasms with recurrent contractions of orbicularis oculi.
  • Temporalis, masseter, and platysma are involved.
  • Rarely may spread to more distant muscles in the arms and legs.
  • Lower facial and masticatory muscle involvement is common including involuntary movements such as lip pursing, chewing, grimacing and jaw thrusting.
  • Lower facial and jaw movements can be rhythmic or tremor-like.
  • Spread of dystonic contractions to nearby muscle groups is common in the first year after symptoms appear and in older patients , female gender and in patients with a history of head trauma.
  • Patients learn sensory tricks like sleeping , biting a toothpick, humming, singing, looking downwards, talking ,exposure to cold water and yawning to alleviate dystonia.

Investigations

  • Facial electromyography(blink reflex)
  • MRI/CT brain to rule out ischemic stroke
  • Serum SS-A/SS-B level to rule out autoimmune or inflammatory diseases
  • Serum copper and ceruloplasmin level to rule out Wilson disease
  • Serum drug screen

Differential Diagnosis

  • Xeromas
  • Parkinson disease
  • Spinocerebellar ataxia
  • Lesch-Nyhan syndrome
  • Multiple system atrophy
  • Wilson disease
  • Dopa-responsive dystonia (DYT5)
  • Ischemic stroke
  • Cerebral palsy
  • Multiple sclerosis
  • Lupus erythematosus
  • Toxins manganese, carbon disulfide
  • Neuroleptics, antiemetics, anticonvulsants
  • Glioblastoma or a metastatic tumor
  • Generalized anxiety disorder

Management

Botulinum toxin Injection

  • Starting doses for each toxin are 1.25–2.5 Units per site.
  • Electromyography is used for guidance when injecting masticatory, laryngeal and cervical muscles.
  • Accurate targeting of affected muscles and using an appropriate amount of toxin affect results.
  • Botulinum toxin type A is approved by the United States FDA for treatment of blepharospasm and cervical dystonia and botulinum toxin type B is approved for cervical dystonia.
  • It is more effective in the treatment of blepharospasm than oromandibular dystonia.

Deep brain stimulation

  • Internal segment of the Globus Pallidus is targeted.
  • Benefits develop gradually over several months.
  • Long-term DBS may correct neural networks abnormalities responsible for dystonia.
  • It is associated with a risk of stroke, infection and the development of hemiparesis, visual field deficits and dysarthria.

Anticholinergic

  • Trihexyphenidyl; 5-15 mg/day PO divided every 6-8 hours.
  • Benztropine; 1-2 mg/day, not to exceed 6 mg/day.
  • Block acetylcholine receptors

Benzodiazepine

  • Clonazepam 0.5 mg PO at bedtime, not to exceed 6 mg/day.
  • Lorazepam 1 to 2 mg/day.
  • Increase the effects of GABA on GABA-A receptors.
  • More effective treatment of blepharospasm than the oromandibular dystonia.

GABA-B receptor agonists

  • Baclofen 5 mg PO TID initially, may increase by 5 mg/dose every 3 days up to 20 mg.
  • Stimulates GABA-B receptors.

Dopamine receptor agonist

  • Bromocriptine 1.25-2.5 mg PO, not to exceed 100 mg/day.
  • Stimulates D2 dopamine receptors and is a 5-HT2 antagonist.

Dopamine precursor

  • Levodopa 84 mg inhaled orally via supplied inhaler, not to exceed 5 doses/day.
  • Converts to dopamine.

Neuroleptics

  • Haloperidol 0.5-2 mg every 8-12 hours, not to exceed 30 mg/day.
  • Pimozide 1-2 mg PO, not to exceed 10 mg/day.
  • Blocks dopamine receptors.

Anticonvulsants

  • Levetiracetam, not to exceed 3000mg/day.
  • Binds to synaptic vesicle protein SV2A.
  • More effective in treatment of blepharospasm than oromandibular dystonia.
  • Lithium is also found to be a good alternative.

Further Reading

  • Pandey, S., & Sharma, S. (2017). Meige’s syndrome: History, epidemiology, clinical features, pathogenesis and treatment. Journal of the Neurological Sciences, 372, 162–170. doi:10.1016/j.jns.2016.11.053

Bibliography

  1. Mark S. LeDoux,Meige syndrome: What's in a name?,Parkinsonism & Related Disorders,Volume 15, Issue 7,2009,Pages 483-489,ISSN 1353-8020 https://doi.org/10.1016/j.parkreldis.2009.04.006
  1. Jahngir MU, Ameer MA, Patel BC. Meige Syndrome. [Updated 2021 Sep 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; https://www.ncbi.nlm.nih.gov/books/NBK513358/
  1. Pedrero-Escalas MF, García-López I, Santiago-Pérez S, Vivancos F, Gavilán J. Clinical experience with patients with spasmodic dysphonia and primary Meige syndrome. Acta Otorrinolaringol Esp (Engl Ed). 2019 Jan - Feb;70(1):1-5.
  1. Jochim A, Li Y, Gora-Stahlberg G, Mantel T, Berndt M, Castrop F, Dresel C, Haslinger B. Altered functional connectivity in blepharospasm/orofacial dystonia. Brain Behav. 2018 Jan;8(1):e00894
  1. Horisawa S, Ochiai T, Goto S, Nakajima T, Takeda N, Kawamata T, Taira T. Long-term outcome of pallidal stimulation for Meige syndrome. J Neurosurg. 2018 Jan 19;130(1):84-89.
  1. Gautam P, Bhatia MS, Kaur J, Rathi A. Meige's syndrome. Ind Psychiatry J. 2016 Jul-Dec;25(2):232-233
  1. Berardelli A, Rothwell JC, Day BL, Marsden CD. Pathophysiology of blepharospasm and oromandibular dystonia. Brain. 1985 Sep;108 ( Pt 3):593-608. doi: 10.1093/brain/108.3.593. PMID: 4041776
  1. Pauletti G, Berardelli A, Cruccu G, Agostino R, Manfredi M. Blink reflex and the masseter inhibitory reflex in patients with dystonia. Mov Disord. 1993 Oct;8(4):495-500. doi: 10.1002/mds.870080414. PMID: 8232360
  1. J. Kulisevsky; M. J. Marti; I. Ferrer; Dr. E. Tolosa (1988). Meige syndrome: Neuropathology of a case. , 3(2), 170–175. doi:10.1002/mds.870030209
  1. Defazio G, Brancati F, Valente EM, Caputo V, Pizzuti A, Martino D, Abbruzzese G, Livrea P, Berardelli A, Dallapiccola B. Familial blepharospasm is inherited as an autosomal dominant trait and relates to a novel unassigned gene. Mov Disord. 2003 Feb;18(2):207-12. doi: 10.1002/mds.10314. PMID: 12539217.
  1. Pandey, S., & Sharma, S. (2017). Meige’s syndrome: History, epidemiology, clinical features, pathogenesis and treatment. Journal of the Neurological Sciences, 372, 162–170. doi:10.1016/j.jns.2016.11.053
  1. Liu J, Li L, Chen L, Liu R, Jiang Y, Fang J, Wang D, Liu Z, Ouyang J. Grey matter changes in Meige syndrome: a voxel-based morphology analysis. Sci Rep. 2020 Sep 3;10(1):14533. doi: 10.1038/s41598-020-71479-9. PMID: 32884000; PMCID: PMC7471903.
  1. Meige disease Acute and chronic cholinergic effects Caroline M. Tanner, Russell H. Glantz, Harold L. Klawans Neurology Jul 1982, 32 (7) 783; DOI: 10.1212/WNL.32.7.783
  1. Hinrich Cramer & Klaus Otto (1986) Meige's syndrome: Clinical findings and therapeutic results in 50 patients, Neuro-Ophthalmology, 6:1, 3-15, DOI: 10.3109/01658108608997319
  1. Hipola D, Mateo D, Giménez-Roldán S: Meige’s Syndrome: Acute and Chronic Responses to Clonazepan and Anticholinergics. Eur Neurol 1984;23:474-478. doi: 10.1159/00011573
  1. An JY, Kim JS, Kim YI, Lee KS. Successful treatment of the Meige syndrome with oral zolpidem monotherapy. Mov Disord. 2008 Aug 15;23(11):1619-21. doi: 10.1002/mds.22179. PMID: 18581473
  1. Zesiewicz TA, Louis ED, Sullivan KL, Menkin M, Dunne PB, Hauser RA. Substantial improvement in a Meige's syndrome patient with levetiracetam treatment. Mov Disord. 2004 Dec;19(12):1518-21. doi: 10.1002/mds.20233. PMID: 15390069
  1. Blepharospasm Recent advances Mark Hallett Neurology Nov 2002, 59 (9) 1306-1312; DOI: 10.1212/01.WNL.0000027361.73814.0E
  1. Craig N. Czyz, John A. Burns, Thomas P. Petrie, John R. Watkins, Kenneth V.Cahill, Jill A. Foster,Long-term Botulinum Toxin Treatment of Benign Essential Blepharospasm,Hemifacial Spasm, and Meige Syndrome,American Journal of Ophthalmology,Volume 156, Issue 1,2013,Pages 173-177.e2,ISSN 0002-9394,https://doi.org/10.1016/j.ajo.2013.02.001
  1. Wataru Sako, Ryoma Morigaki, Yoshifumi Mizobuchi, Takashi Tsuzuki, Hiroyuki Ima, Yukitaka Ushio, Shinji Nagahiro, Ryuji Kaji, Satoshi Goto,Bilateral pallidal deep brain stimulation in primary Meige syndrome,Parkinsonism & Related Disorders,Volume 17, Issue 2,2011,Pages 123-125,ISSN 1353-8020,https://doi.org/10.1016/j.parkreldis.2010.11.013
  1. Mauriello JA, Dhillon S, Leone T, et alTreatment selections of 239 patients with blepharospasm and Meige syndrome over 11 years.British Journal of Ophthalmology 1996;80:1073-1076.
  1. Ma Hongying, Qu Jian, Ye Liangjun, Shu Yi, Qu Qiang Blepharospasm, Oromandibular Dystonia, and Meige Syndrome:Clinical and Genetic Update Frontiers in Neurology 12 2021 422 https://www.frontiersin.org/article/10.3389/fneur.2021.630221 DOI 10.3389/fneur.2021.630221ISSN=1664-2295
 
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