Millard Gubler Syndrome

Article Author:
Raghachaitanya Sakuru
Article Editor:
Pradeep Bollu
Updated:
10/27/2018 12:31:43 PM
PubMed Link:
Millard Gubler Syndrome

Introduction

Millard-Gubler syndrome (MGS), also known as facial abducens hemiplegia syndrome or the ventral pontine syndrome, is an eponym after two French physicians Auguste Louis Jules Millard and Adolphe-Marie Gubler in 1858 who first described the features of this syndrome. MGS is one of the classical crossed brainstem syndromes characterized by a unilateral lesion of basal portion of the caudal pons involving fascicles of abducens (VI) and the facial (VII) cranial nerve, and the pyramidal tract fibers.[1]

Components of MGS

  • Ipsilateral weakness of the eye on abduction (VI nerve)
  • Ipsilateral facial muscle weakness (VII nerve)
  • Contralateral hemiparesis or hemiplegia of upper and lower extremities (pyramidal tract involvement)

MGS often presents with other neurological deficits such as contralateral hemiparesthesia and contralateral cerebellar ataxia as many other nuclei fibers exist near the root fibers of the facial nerve nucleus.

Etiology

Causes of Millard-Gubler syndrome (MGS) vary with age. In younger people, the leading causes are tumors, infectious diseases (neurocysticercosis and tuberculosis),[2] demyelinating diseases (multiple sclerosis), and viral infection (Rhomb encephalitis). In older patients, it is most frequently caused by vascular events such as hemorrhage and ischemia (secondary to stenosis of the basilar artery) or due to compression of the arteries by prepontine subarachnoid hematoma.[3] There have been some reported cases of MGS due to aneurysm of the basilar artery.

Epidemiology

Epidemiology varies according to the cause of the disease.

Pathophysiology

This syndrome is caused due to a lesion at ventral part of the pons that involves the fibers of cranial nerves VI, VII, and corticospinal tract fibers. Corticospinal and corticobulbar tracts are in the central region of the ventral pons. The medial lemniscus lies posteriorly on each side of the median raphe. Nuclei of abducens (VI) and facial (VII) nerves are found in a dorsal portion of the pons, and their fibers pass through the pontine tegmentum and emerge anteriorly at the cerebellopontine angle. The spinothalamic tract is located in the anteromedial tegmentum, medial to the descending tract and nucleus of trigeminal (V) nerve.[3] MGS lesion involves the ventromedial part of the pons which contains the corticospinal tract and fascicular intrapontine portion of the VII nerve, causing ipsilateral paralysis of the facial nerve and contralateral hemiplegia. Classical cases of MGS sometimes involve fibers of the VI nerve. The medial lemniscus and spinothalamic tract are typically spared in this syndrome, thus explaining the absence of the sensory symptoms.[4]

History and Physical

Symptoms and Signs

  1. Contralateral hemiplegia of the extremities (sparing the face) due to pyramidal tract involvement.
  2. Ipsilateral lateral rectus palsy leading to diplopia that is accentuated when the patient looks towards the side of the lesion, internal strabismus (i.e., Esotropia) and loss of power to rotate the affected eye outward due to the involvement of CN VI.
  3. Ipsilateral peripheral facial nerve paresis leads to flaccid paralysis of the muscles of the facial expression and loss of the corneal reflex due to cranial nerve VII involvement.[5]

Evaluation

Clinical Examination

The diagnosis of Millard-Gubler syndrome (MGS) is confirmed by a clinical examination of VI and VIII CN along with hemiplegia of upper and lower extremities. Because various etiologies might cause MGS, take a detailed history to exclude other causes like infection (fever) or vascular insult (presence of other neurologic deficits).

Imaging

Neurological Imaging, i.e., computed tomography (CT) and magnetic resonance imaging (MRI) are helpful in identifying the lesion. However, MRI of the brain is more sensitive and specific than CT scan to identify the infarcts at an early stage of onset, especially in the setting of small pontine lesions. Ischemic stroke of pons on CT brain shows a hypodense lesion in the anteromedial side of the pons. MRI brain shows a lesion in one side of the anteromedial pons, which is hypointense on T1 sequences and hyperintense on T2 /FLAIR sequences.[5] The Magnetic resonance imaging also shows diffusion restriction in the pontine ischemic lesion. However, there have been some reported cases presenting as MGS with no imaging findings.[6] Other associated lesions (tuberculoma, tumors, and cysticercus granulomas)[2] can also be identified using imaging.

Angiography

Vertebral angiography is helpful in cases if the lesion is caused due to the occlusion of the basilar artery.

Pontine-crossed syndromes are Foville, Raymond, Raymond–Cestan syndrome, Gasperini syndrome, and Brissaud-Sicard syndrome. These syndromes are unique as the lesion involves the brainstem above the decussation of the pyramidal tracts. Therefore, the clinical signs of the cranial nerve are ipsilateral to the lesion, and the long tract signs contralateral, resulting in crossed syndrome.

  • Foville syndrome: This syndrome is caused due to a unilateral lesion involving the dorsal pontine tegmentum in the caudal third of the pons and manifests as ipsilateral facial palsy and horizontal gaze palsy, and contralateral hemiparesis, Hemi sensory loss, Internuclear ophthalmoplegia.
  • Raymond syndrome: This syndrome is caused due to a lesion involving the ventral medial pons. It usually presents as two subtypes - Classical and common. Classical Raymond syndrome manifests as ipsilateral abducens palsy, contralateral central facial paresis, and contralateral hemiparesis. The common subtype of Raymond syndrome presents as ipsilateral lateral gaze paresis and contralateral hemiparesis sparing the face.[7]
  • Raymond–Cestan syndrome: This syndrome is caused due to the lesion involving the upper dorsal pons. It manifests as ipsilateral ataxia and coarse intention tremor, ipsilateral paralysis of muscles of mastication and sensory loss in the face, contralateral sensory loss in the body and contralateral hemiparesis of the face and the body.
  • Gasperini’s syndrome: This is a rare syndrome caused due to a lesion of the caudal pons tegmentum and mostly presents as ipsilateral impairment of the cranial nerves V, VI, VII, VIII and contralateral sensory loss.
  • Brissaud-Sicard syndrome: This is a very rare pontine syndrome caused due to damage of the anterolateral and inferior pons involving the corticospinal tract and CN VII nucleus and the nerve root. Classically this syndrome presents as ipsilateral facial cramps and contralateral hemiparesis.

Treatment / Management

Treatment mainly depends on the etiology of the disease. In some cases, patients presenting with multiple deficits require early conservative measures together with multidisciplinary rehabilitation.

Prognosis

  • Prognosis mainly depends on the extent and etiology of the disease.
  • A vertebrobasilar stroke usually leaves a significant neurologic deficit.
  • Patients with small lesions usually have a better prognosis.
  • Patients with acute basilar artery occlusion have a high mortality. 

Pearls and Other Issues

  • Millard-Gubler syndrome (MGS) is one of the classical brainstem-crossed syndromes caused due to a unilateral lesion in ventral pons, manifesting as ipsilateral palsy of CN VI and VII with contralateral hemiplegia.
  • Etiology varies with age. In younger people, the leading causes are tumors, infectious diseases (neurocysticercosis and tuberculosis), demyelinating disease (multiple sclerosis), and viral infection (Rhomb encephalitis). In older patients, it is more often due to hemorrhage and ischemic stroke.
  • MGS clinical features are an ipsilateral weakness of eye abduction and ipsilateral facial muscle weakness along with contralateral upper and lower extremity weakness.
  • Diagnosis of MGS depends on a detailed history and physical examination. Imaging studies such as CT and MRI are confirmatory.
  • Other pontine-crossed brainstem syndromes include Foville syndrome, Raymond syndrome, Gasperini syndrome, Brissaud-Sicard syndrome, and Raymond–Cestan syndrome.
  • Classical Raymond syndrome also has the same components as Millard-Gubler syndrome, but there is ipsilateral sixth nerve palsy along with contralateral facial paresis and hemiplegia.
  • Management mainly depends on the etiology of the disease.
  • Patients with small lesions usually have a better prognosis. However, MGS caused due to acute basilar artery occlusion has a high mortality rate.

References

[1] Ahdab R,Saade HS,Kikano R,Ferzli J,Tarcha W,Riachi N, Pure ipsilateral central facial palsy and contralateral hemiparesis secondary to ventro-medial medullary stroke. Journal of the neurological sciences. 2013 Sep 15     [PubMed PMID: 23849262]
[2] Prasad R,Kapoor K,Srivastava A,Mishra O, Neurocysticercosis presenting as Millard Gubler syndrome. Journal of neurosciences in rural practice. 2012 Sep     [PubMed PMID: 23189006]
[3] Kesikburun S,Safaz I,Alaca R, Pontine cavernoma hemorrhage leading to Millard-Gubler syndrome. American journal of physical medicine     [PubMed PMID: 20531153]
[4] CASERO, The Millard-Gubler syndrome. American journal of ophthalmology. 1948 Mar     [PubMed PMID: 18907091]
[5] Takahashi A, [Millard-Gubler syndrome]. Nihon rinsho. Japanese journal of clinical medicine. 1977 Spring     [PubMed PMID: 612889]
[6] Onbas O,Kantarci M,Alper F,Karaca L,Okur A, Millard-Gubler syndrome: MR findings. Neuroradiology. 2005 Jan     [PubMed PMID: 15647948]
[7] Zaorsky NG,Luo JJ, A case of classic raymond syndrome. Case reports in neurological medicine. 2012     [PubMed PMID: 22934209]