Vertical Gaze Palsy

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Article initiated by:

Roshan George, MD, Stacy V. Smith, MD

All contributors:

Kimberly Nguyen, Andrew Go Lee, MD, Nagham Al-Zubidi, MD, Stacy V. Smith, MD, Roshan George, MD, Ashwini Kini, MD

Assigned editor:

Nagham Al-Zubidi, MD

Review:

Assigned status Up to Date

 by Nagham Al-Zubidi, MD on August 21, 2024.

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Vertical Gaze Palsy

ICD-10

H51.0

Disease Entity

ICD10 H51.0

Disease

A vertical gaze palsy (VGP) is a conjugate, bilateral, limitation of the eye movements in upgaze and/or downgaze.

VGP can affect functional eye movements by selectively involving the saccadic pathway and may spare or involve smooth pursuit or optokinetic movements or non-selectively involve VGP for all types of eye movements. Eye movements can also be anatomically classified into supranuclear, nuclear, and infranuclear. In regards to this chapter on VGP, the focus is on supranuclear pathways involving three major anatomical structures. Combined bilateral lesions of the nuclear or infranuclear pathways including the neuromuscular junction (e.g., myasthenia gravis, MG) or muscles (e.g., restrictive thyroid ophthalmopathy) can also mimic VGP, but are usually asymmetric and in contrast to supranuclear VGP cannot be overcome with vestibulo-ocular reflex (VOR) or the doll’s head maneuver.

Etiology

A lesion of the vertical gaze pathways can occur from a number of causes:

• Tumor- pineal germinoma or teratoma (classically seen in adolescent male), pineocytoma, pineoblastoma, tecal glioma, or metastasis. VGP can also occur secondary to paraneoplastic effect (ex. anti-MA2 encephalitis).
• Hydrocephalus- aqueductal stenosis leading to dilation of third ventricle and enlargement of the suprapineal recess with pressure on the posterior commissure.
• Vascular- midbrain and/or thalamic hemorrhage or infarction, subdural hematoma, aneurysm. The posterior thalamo-subthalamic paramedian artery is a single perforating artery that supplies both riMLF.
• Metabolic- Niemann-Pick Type C, Gaucher disease, Tay-Sachs disease, maple syrup urine disease, Wilson disease, kernicterus.
• Drug-induced- barbiturates, carbamazepine, neuroleptic agents.
• Degenerative- Progressive supranuclear palsy (usually downward gaze palsy), Huntington disease, cortical basal degeneration, diffuse Lewy body disease, parkinsonism, hereditary spastic ataxia
• Infectious – Whipple disease, encephalitis, syphilis, tuberculosis
• Miscellaneous- multiple sclerosis, hypoxia, trauma, mesencephalic clefts, benign transient form of childhood.

Risk Factors

Depends on etiology

Pathophysiology

The three key structures that control the vertical gaze center include the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the interstitial nucleus of Cajal (INC), and the posterior commissure (PC).

The riMLF is located in the midbrain and helps with vertical and torsional saccades. The bilateral riMLF structures are connected dorsally via the PC. It normally has bilateral effects through the oculomotor subnuclei to the elevator muscles (i.e., the superior rectus and inferior oblique muscles) and unilateral effects on depressor muscles (i.e., the inferior rectus and superior oblique muscles), thus lesions to riMLF will have more effect on downward than up saccades. Vertical gaze holding, VOR, pursuit and horizontal saccades are usually preserved.

The INC is located in the midbrain and helps coordinate all other vertical eye movements except saccades. Unilateral lesions may result in an ocular tilt reaction and/or defects in vertical pursuit and gaze holding. The ocular tilt reaction is characterized by ipsilateral hypertropia and intorsion with contralateral extorsion and head tilt. Bilateral lesions cause reduced range in all vertical eye movements except saccades.

The PC is located on the dorsal aspect of the superior end of cerebral aqueduct and is involved with all vertical eye movements, especially upward eye movement. The upgaze fibers cross at the level of the PC and thus single lesions in this location can produce the upgaze VGP. Lesions here eventually result in impairment of all classes of vertical eye movements, especially upward with loss of vertical gaze-holding function.

The innervation for vertical gaze travels through nerve fiber pathways that start in the vestibular system ascending up both sides of MLF to the 3rd and 4th cranial nerve nuclei, INC and riMLF. A second descending pathway starts from the cerebral hemispheres through the midbrain pretectum to the 3rd and 4th cranial nerve nuclei. The riMLF synthesizes the two pathway inputs into a final gaze command.

Diagnosis

History

A careful history is important to the diagnosis and patient should be specifically questioned on features of the etiologies described above.

Physical examination

For any type of ocular motor dysfunction, it is very important to have a systematic approach due to the complexity of the system involved including the ocular motor, vestibular, and cerebellar pathways. Key tests to consider are noted below:

1. It is important to inspect the patient for any anomalous head position (e.g. chin up or chin down position) and to check for any gaze preferences or primary position deviations.
2. Orthoptic evaluation of the function of the extraocular muscles in all nine cardinal positions of gaze should be examined for any vertical misalignment, deficits of duction or versions, and the presence or absence of nystagmus.
3. The cover/uncover test and alternating cover tests may also be performed to assess for ocular alignment in the diagnostic positions of gaze and primary position.
4. Saccade testing is performed by asking the patient to look back and forth quickly between two targets to check for latency, velocity, and conjugacy of the fast eye movements.
5. Smooth pursuit is checked by having the patient visually track an object moving slowly in vertical direction while keeping the head stationary. If ocular movement fails to match the velocity of the moving object, a corrective saccade will occur. Because smooth pursuit involves many neural structures and may be affected by various factors, impaired smooth pursuit is typically non-localizing.
6. Optokinetic nystagmus is checked by using an optokinetic drum, where both the smooth pursuit and saccades are tested at the same time. This test is useful in patients who cannot voluntarily initiate saccades
7. If passive rotation of the head by the examiner while the patient fixates on an object results in improved or full vertical ocular movements, this indicates a supranuclear cause (i.e., the doll’s eye maneuver).

Signs

Along with VGP, patients can have several other signs that help identify specific syndromes.

Parinaud/Dorsal Midbrain syndrome The full or partial Parinaud syndrome results from lesions (e.g., pineal gland tumors) of the dorsal midbrain. As noted previously, posterior commissure lesions typically lead to limitations of upward gaze and may be associated with a downward gaze preference (i.e., the ‘setting sun’ sign). Other signs of the dorsal midbrain syndrome include bilateral lid retraction (Collier sign), skew deviation, convergence retraction nystagmus, and pupillary abnormalities (light-near dissociation).

Niemann- Pick Disease Type C This is a neurodegenerative disease caused by a genetic mutation in NPC1 (≥95% of cases) or NPC2 which leads to a defect in the intracellular lipid trafficking and an accumulation of cholesterol in peripheral organs and glycosphingolipids in the CNS causing cell dysfunction and death. The age at presentation for Niemann Pick disease is highly variable; however age at neurologic symptom onset and type of symptoms are prognostic factors for disease severity and life expectancy. Early on in this disease due to cell damage or dysfunction in the riMLF, patients develop slow vertical saccades in a downward direction along with frequent blinking. Facial dystonia with facial grimacing in the presence of supranuclear gaze palsy is characteristic for Niemann-Pick Disease Type C. Vertical saccade paresis may be present prior to the systemic, neurological, or psychiatric signs and may be the only sign in adults suffering from this disease, thus warranting further workup.

Progressive Supranuclear Palsy PSP is a neurodegenerative disease of unknown etiology in which neurons in the basal ganglia and brainstem degenerate. Clinical signs include downgaze palsy, loss of balance with backward falls, muscle rigidity, dysphagia, dysarthria, emotional lability (pseudobulbar palsy), mild dementia and resting tremor.A characteristic sign for PSP is the “round the houses” sign where vertical saccades follow a curved course due to inability to produce pure midline movement. Although Parkinson’s disease (PD) and PSP share several clinical features, downgaze palsy is not seen in PD and should lead clinicians to consider the diagnosis of PSP. The lesion is located above the cranial nerve nuclei that control vertical gaze, thus the name “supranuclear.” More information on PSP can be found elsewhere on EyeWiki.

Cortico-Basal Syndrome (CBS) CBS is a progressive neurodegenerative disease and is considered a parkinsonism-plus syndrome, an atypical form of parkinsonism. It shares clinical features with both PD and PSP; however, vertical gaze palsy in CBS is typically delayed more than 3 years after symptom onset. Other clinical features include inability to initiate saccades to verbal commands despite retained spontaneous saccades, blepharospasm, and eyelid opening apraxia.

Symptoms

Symptoms include blurred vision, decrease in visual acuity with worsening while reading, oscillopsia (bouncing images) if nystagmus is present, along with dizziness, vertigo, postural imbalance, gait disturbances/ataxia, and increased risk of falls.

Clinical diagnosis

VGP usually selectively affects saccades. Upgaze palsy is most common, then combined upgaze and downgaze followed by downgaze palsy. If the riMLF is affected, other signs include pupillary or ocular motor signs of third nerve palsies including wall-eyed bilateral internuclear ophthalmoplegia, impaired convergence, and skew deviation. If there is thalamic damage, behavioral disturbances can be noted such as hemineglect, akinetic mutism, or subcortical demented states with apathy and slowness of thought. If the posterior commissure is affected, pathologic lid retraction while looking straight ahead (Collier sign) can be present along with mid-dilated pupils that show a smaller reaction to light than to near stimulus stimulus (light-near dissociation). Attempted upward saccades producing a convergence-retraction nystagmus may also be present.

Diagnostic procedures

Neuroimaging (preferably magnetic resonance imaging of the brain with and without contrast) can help with both localization of the lesion and determination of etiology, especially if vascular or neoplastic in nature. If an infectious cause is suspected, consider serum and CSF testing for common chronic infections such as tuberculosis and syphilis. Whipple disease diagnosis requires special periodic acid-Schiff (PAS) stains of pathologic samples or PCR, typically obtained from the gastrointestinal tract or other affected tissues. In regards to metabolic conditions, such as Niemann-Pick type C, work-up may include serum transasminase evaluation, skin fibroblast assays for sphingomyelinase activity, and possibly genetic testing.

Differential diagnosis

Infranuclear disorders such as myasthenia gravis (MG) and thyroid eye disease (TED) should be considered in the differential when ruling out VGP. In thyroid eye disease, bilateral inferior recti involvement can mimic up gaze palsy. In MG, any ocular muscle can be affected, coincidentally leading to a VGP bilaterally. Both types of diseases, however, do not tend to be perfectly symmetric and MG should be variable over time. They can be diagnosed with lab testing (e.g. antithyroid and antiacetylcholine receptor antibodies), orbital ultrasound (for eye muscle enlargement in TED), and EMG (decremental response is seen in MG).

Management

General treatment

Management of supranuclear VGP is directed at treatment of the underlying disease and symptomatic management ophthalmic complaints. For example, vascular etiologies such as stroke may be managed with antiplatelet or anticoagulant therapy. Niemann-Pick Disease Type C may have improved prognosis with miglustat. Studies demonstrate that miglustat may delay neurological deterioration and prolong survival in adults. Levodopa treatment for Parkinson’s Disease may improve ophthalmic manifestations such as saccadic accuracy and smooth pursuit. Surgical management may be indicated for neoplasms or refractory symptoms. For diplopia and other ophthalmic complaints, treatments are typically conservative and may include refractive correction, a temporary Fresnel prism or ground-in prism glasses. Vision rehabilitation therapies in conjunction with physical and occupational therapy may also be of benefit. Single vision glasses and readers should be used in patients with downgaze palsy who cannot use a bifocal or progressive add lenses effectively.

Prognosis

The prognosis for VGP depends on the underlying etiology. If a medication is provoking the symptoms, improvement may be seen after medication discontinuation. Similarly, treatment of a compressive lesion or lowering of elevated intracranial pressure may result in improvement. The condition can be permanent due to the irreversible nature of the lesion in many cases. Neurodegenerative disease (e.g., PSP) typically exhibits slow progression. However, treatments should then focus on symptom management.