Neurons in the nucleus prepositus hypoglossi and adjacent medial vestibular nucleus have an important role in generating the commands to hold eccentric positions of gaze, especially horizontal gaze.

The paramedian pontine reticular formation (PPRF) contains excitatory burst neurons, which are inhibited by omnipause neurons; when the PPRF is activated by the contralateral frontal eye field, in turn it activates the adjacent abducens nucleus via the excitatory burst neurones: horizontal gaze is then mediated by abducens motor neurones which innervate the ipsilateral lateral rectus muscle and, via excitatory abducens interneurones crossing and then ascending in the MLF, the medial rectus subnucleus of the contralateral oculomotor nucleus.

Lesions of the PPRF, abducens nucleus and the MLF

1. The PPRF contains neurons that project to the abducens nucleus on the same side and is important for horizontal saccade generation.

• Lesions of the PPRF cause a conjugate horizontal gaze palsy (in which neither eye can look towards the side of the lesion)¹, which may also involve all classes of conjugate eye movements (including pursuit and the VOR) if the most caudal portions of the PPRF are affected².  
• Isolated PPRF lesions are uncommon but can be a feature of the syndrome of selective saccadic palsy following cardiac surgery, as described below (Video 2).
• Acutely, a lesion of the PPRF manifests as contralesional gaze deviation³.
• There may be horizontal gaze-evoked nystagmus on looking contralesionally, with quick phases directed away from the side of the lesion³.
• Bilateral lesions result in total horizontal gaze palsy (involvement of fibers of passage for horizontal VOR, pursuit and gaze-holding) and slowing of vertical saccades (involvement of omnipause neurons), due to impaired programming of vertical saccades by the riMLF, which is dependant on PPRF input⁴.

2. Lesions of the abducens nucleus may cause a loss of horizontal gaze toward the same side, since the nucleus contains internuclear neurons with projections through the opposite MLF to the opposite medial rectus subnucleus of the oculomotor nucleus. Lesions restricted to the abducens nucleus are rare since adjacent structures, such as the PPRF, MLF, and the seventh cranial nerve, are commonly also affected.  Lesions of the abducens nucleus do not affect vertical and vergence eye movements¹. 

3. Damage to the MLF on one side (resulting in failure of adduction of the ipsilateral eye), as well as to the 6^th cranial nerve fasciculus on the contralateral side can mimic a horizontal gaze palsy⁵.
 

Causes of Horizontal Gaze Palsy

1. Structural lesions 
2. Spinocerebellar Ataxias
3. Gaucher disease. The chronic neuronopathic form (GD3) is associated with a severe slowing of the horizontal saccades, which leads progressively to horizontal supranuclear palsy with impairment of all horizontal eye movements including smooth pursuit and the VOR⁶.  To compensate for the deficits of the horizontal saccades, patients perform torsional saccades as an expression of compensation by the initially intact vertical saccade system. The other compensatory mechanism is the VOR: the head is quickly rotated to the contralateral side, bringing the eyes to the desired position. This manifests clinically as fast thrusting head movements (differential diagnosis: Cogan syndrome).

(vv)WrayLeft Gaze Palsy.mp4(tt)

From: Wray S. Unilateral Horizontal Gaze Palsy. Retrieved from  https://collections.lib.utah.edu/ark:/87278/s6w123g6

         -With the head fixed, volitional saccades are very slow, but eventually reach the target. Downward saccades are slightly faster.
         -Pursuit is normal, and its extent is normal, both horizontally and vertically, even at higher frequencies.  Visually enhanced vestibulo-ocular reflex is normal.
         -When the patient views a horizontally rotating optokinetic drum, her eyes became fixed laterally in the orbits without any corrective quick phases.
         -Torsional head rolling produced normal ocular counter-rolling but without any torsional quick phases.

(vv)Saccpalsy.mp4(tt)

From: Eggers SD, Horn AK, Roeber S, et al. Saccadic palsy following cardiac surgery: a review and new hypothesis. Ann N Y Acad Sci. 2015;1343(1):113-119. doi:10.1111/nyas.12666
 

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