Vertical Gaze Palsy

A localising neurological sign reflecting impairment of voluntary vertical eye movement. It most classically results from a lesion affecting the dorsal midbrain (rostral interstitial nucleus of the medial longitudinal fasciculus and the posterior commissure, the key structures coordinating vertical gaze).

The specific combination of upgaze palsy together with additional associated features (convergence retraction nystagmus, pupillary light near dissociation, and eyelid retraction) constitutes the classically recognised Parinaud syndrome (dorsal midbrain syndrome).

This provides important localising value in the neurological assessment of a patient with this specific pattern of ocular motor dysfunction.

Pathophysiology and causes

• The dorsal midbrain integrates the neural pathways controlling vertical conjugate gaze, convergence, and pupillary light response, with compression, infiltration or direct structural disruption of this region producing the characteristic constellation of findings comprising Parinaud syndrome.
• Pineal region tumours are a classic and important cause requiring active exclusion in any patient, particularly a child, presenting with this pattern of findings.
• Pineal region tumours are particularly relevant in children and young adults, given the anatomical proximity of the pineal gland to the dorsal midbrain and the propensity for mass effect or direct invasion from this specific tumour location to affect these structures.
• Other causes include:
  • hydrocephalus (with dorsal midbrain compression from third ventricular dilation, sometimes producing a reversible gaze palsy that improves with appropriate cerebrospinal fluid diversion)
  • midbrain stroke
  • multiple sclerosis with a relevant demyelinating lesion
  • in older adults, progressive supranuclear palsy
• Progressive supranuclear palsy typically produces a more gradual, progressive vertical gaze impairment as part of a broader neurodegenerative syndrome. This contrasts with the more acute presentation typical of a discrete structural dorsal midbrain lesion.

• Impaired upward voluntary gaze, typically more pronounced than any accompanying downward gaze impairment, represents the core defining feature, with the specific pattern and completeness of impairment varying according to the underlying cause and its severity.
• Convergence retraction nystagmus, a characteristic finding elicited on attempted upgaze (particularly when tested using a downward moving optokinetic stimulus), comprises simultaneous convergence and retraction of both globes, reflecting co-contraction of the extraocular muscles in the setting of impaired normal vertical gaze coordination.
• Pupillary light near dissociation is the finding in which the pupillary response to accommodation (near reflex) is preserved while the response to direct light is impaired. Together with eyelid retraction (Collier sign), it completes the classical tetrad of findings constituting full Parinaud syndrome.
• Not all components of the tetrad are necessarily present in every case, particularly with milder or evolving lesions.
• Associated features reflecting the underlying specific cause should be actively sought, given their relevance to both diagnosis and urgency of further investigation. These include signs of raised intracranial pressure (headache, papilloedema, particularly relevant with an obstructing pineal region mass causing secondary hydrocephalus), or other focal neurological signs reflecting the specific underlying pathology.

• Magnetic resonance imaging of the brain, with specific attention to the pineal region and dorsal midbrain, is the essential investigation, given the range of potentially serious, treatable underlying causes (particularly pineal region tumour and hydrocephalus) requiring prompt identification.
• Formal ophthalmological and orthoptic assessment characterises the specific pattern and completeness of vertical gaze impairment, together with confirming or excluding the other associated findings comprising the full Parinaud syndrome tetrad.
• Where a pineal region mass is identified, further evaluation including tumour markers (relevant to specific germ cell tumour subtypes that can arise at this location, particularly in children and young adults) and, where appropriate, biopsy for histological diagnosis guides subsequent oncological management.
• Cerebrospinal fluid examination is performed where hydrocephalus or an inflammatory or infiltrative process is suspected as the underlying cause.
• In the appropriate clinical context, assessment for multiple sclerosis (given its own specific diagnostic approach) completes the diagnostic evaluation according to the specific differential diagnosis suggested by the overall clinical picture.

• Management is directed entirely at the underlying identified cause, given that vertical gaze palsy itself represents a clinical sign rather than a specific disease requiring direct treatment in isolation.
• Pineal region tumours are managed according to the specific histological diagnosis:
  • germ cell tumours (particularly germinoma, which carries a generally favourable prognosis) are frequently highly responsive to radiotherapy and chemotherapy
  • other pineal region tumour types (pineoblastoma, pineal parenchymal tumours, glial tumours arising at this location) require management tailored to their specific histological characteristics, following the general oncological principles applicable to central nervous system tumours
  • neurosurgical biopsy or resection, where feasible and appropriate, forms an important component of both diagnosis and treatment planning
• Hydrocephalus causing dorsal midbrain compression is managed with appropriate cerebrospinal fluid diversion (ventriculoperitoneal shunting or endoscopic third ventriculostomy). The associated gaze palsy frequently shows significant, sometimes complete, improvement following successful relief of the compressive hydrocephalus, given the reversible nature of this specific mechanism of dorsal midbrain dysfunction.
• Where the underlying cause is a demyelinating lesion (multiple sclerosis) or ischaemic stroke, management follows the standard principles for the underlying condition. The gaze palsy itself is managed supportively (including, where relevant, prism correction or other optical measures for any associated functional visual disturbance) alongside treatment of the underlying disease process.
• Ongoing neurological and, where relevant, oncological follow up is directed according to the specific underlying diagnosis established. The presence and evolution of the vertical gaze palsy itself serves as a useful clinical marker for monitoring disease activity or treatment response in several of the underlying conditions responsible for this finding.