Ocular Motor & Vestibular Features of the MLF Syndrome

𝗢𝗿𝗶𝗴𝗶𝗻𝗮𝗹 𝗗𝗲𝘀𝗰𝗿𝗶𝗽𝘁𝗶𝗼𝗻: This 61-year-old woman with HTN and DM presented for evaluation of acute onset diagonal diplopia. Adduction OS was about 60% of normal while medialization OS improved with convergence. In right gaze, dissociated abducting nystagmus was present OD, and there was a clear adduction lag when asking her to look from left to right. These findings are characteristic of a left internuclear ophthalmoplegia (INO), caused by a lesion in the left medial longitudinal fasciculus (MLF). While INO is the most commonly and most easily recognized feature of an MLF lesion, it is often accompanied by other less commonly recognized features. She was seen 1 week following the onset, and while the MRI report did not mention acute MLF injury (images were not available for review), given her vascular risk factors, a small stroke involving the basilar artery perforators was assumed (MRA head normal). • Ocular tilt reaction (OTR - skew deviation, ocular counterroll, head tilt) - With alternate cover and cover-uncover testing, there was an expected exodeviation that was maximal in right gaze due to an adduction deficit OS. However, there was also a left hypertropia that was comitant in all directions of gaze, consistent with a skew deviation. Dilated fundoscopic examination demonstrated another feature of the OTR, ocular counterroll, or extorsion of the (lower) right eye and intorsion of the (higher) left eye. In contrast, the hypertropic eye in a 4th nerve palsy should be excyclodeviated. There was also a mild rightward head tilt; therefore, a complete OTR was seen. The perceptual consequence of the OTR is a shift involving the subjective visual vertical (SVV). The SVV, as measured at the bedside with the bucket test, is tilted in the same direction as the OTR. When the lesion is 1) caudal to the decussation (pontomedullary region) of the utricle-ocular motor pathways as in a right lateral medullary (Wallenberg) syndrome, the OTR and SVV will be ipsiversive - e.g., right head tilt, counterroll of both eyes towards right ear, right hypotropia and SVV tilted to the right. When the lesion is 2) rostral to the decussation ofthe utricle-ocular motor pathways as in a left MLF or interstitial nucleus of Cajal (INC) lesion the OTR and SVV will be contraversive as in this patient - e.g., right head tilt, counterroll of both eyes towards right ear, left hypertropia and SVV tilted to the right. • Nystagmus - In addition to dissociated abducting nystagmus, MLF lesions usual cause other patterns of vertical and torsional nystagmus. o Gaze-evoked nystagmus - Upbeat nystagmus (UBN) in upgaze and downbeat nystagmus (DBN) in downgaze is more often seen with bilateral MLF injury, although may be seen with unilateral pathology as well. It is not clear whether this results from descending fibers going from interstitial nucleus of Cajal (INC) to the medullary nucleus of Roller and/or the nearby paramedian tract (PMT) cell groups; involvement of PMT cell groups alone; or involvement of pathways from vestibular nuclei to the INC that have a role in neural integration. The PMT cell groups are thought to receive inputs from the INC that are transmitted to the flocculus. o Spontaneous torsional or vertical-torsional nystagmus - This patient had spontaneous (primarily) torsional nystagmus, with quick phases of the superior poles directed towards the ipsilesional (left) side. When spontaneous nystagmus with a torsional nystagmus component is seen in the setting of acute MLF injury, it is almost always ipsilesional. In the case of a left MLF lesion, this has to do with injury to the central anterior and posterior semicircular canal pathways that originated in the right labyrinth but decussated and ascended via the contralateral (left) MLF. This creates an unopposed torsional slow phase towards the right ear (generated by the unaffected left anterior and posterior canals which decussate and ascend the right MLF), with a subsequent ipsiversive torsional quick phase (towards the left ear with left MLF injury). This vertical semicircular canal asymmetry also explains the dissociated vertical nystagmus that can be seen with an acute MLF lesion (utricle imbalance may also play a role here - e.g., jerky or hemi-seesaw). • Vertical VOR - It has also been demonstrated that central pathways from the contralateral vertical SCC traverse the MLF. The posterior SCC pathway is much more affected by a unilateral MLF injury as compared to the anterior SCC pathway. This is because the fibers originating in the anterior SCC also travel through the brachium conjunctivum and ventral tegmental tract; therefore, anterior SCC function is relatively preserved. For this reason, patients with bilateral MLF injuries commonly complain of oscillopsia with head movements due to bilateral vertical VOR weakness. Objectively, this can be demonstrated by a significant decrement in dynamic visual acuity vertically but not horizontally, or with vertical head impulse testing (HIT) in the planes of anterior and posterior SCCs. Vertical HIT can be technically challenging, which is why video head impulse testing can be helpful in this setting. In our patient there were reduced right posterior SCC VOR gains on vHIT, with overt catch-up saccades in the plane of the right posterior SCC on bedside exam. Additionally, there were abnormal head impulses in the plane of the left anterior SCC, and it's possible that this resulted from additional involvement of the left brachium conjunctivuum if the left MLF was affected more laterally. • Horizontal VOR - During horizontal VOR testing using the HIT, the velocity of the adducting eye (ipsilateral to an MLF lesion) movement can be relatively preserved - i.e., much better than what would be expected based on bedside testing with a significant adduction lag due to an INO. This is proposed to be caused by an extra-MLF pathway, the ascending tract of Dieters, which goes directly from the vestibular nuclei to the oculomotor nucleus. However, when a refixation saccade is necessary - e.g., adducting saccade OS with leftward HIT in the setting of a left INO may look normal due to an extra-MLF pathway - a much slower adducting saccade OS will be generated (abnormal as this is using the MLF pathway). References 1. Zwergal, et al. Unilateral INO is associated with ocular tilt reaction in pontomesencephalic lesions: INO plus. Neurology. 2008 Aug 19;71(8):590-3 2. Jeong, et al. Patterns of dissociate torsional-vertical nystagmus in internuclear ophthalmoplegia. Ann N Y Acad Sci. 2011 Sep;1233:271-8. 3. Lee, et al. Preferential impairment of the contralesional posterior semicircular canal in internuclear ophthalmoplegia. Front Neurol. 2017 Sep 22;8:502. 4. Aw, et al. J Neurol. 2017 Sep 6. Epub ahead of print. [[[SEE ASSOCIATED FIGURES _ CLICK HERE: https://collections.lib.utah.edu/details?id=1278695 ]]] 𝗡𝗲𝘂𝗿𝗼-𝗼𝗽𝗵𝘁𝗵𝗮𝗹𝗺𝗼𝗹𝗼𝗴𝘆 𝗮𝗻𝗱 𝗡𝗲𝘂𝗿𝗼-𝗼𝘁𝗼𝗹𝗼𝗴𝘆 𝗧𝗲𝘅𝘁𝗯𝗼𝗼𝗸 𝗟𝗲𝗴𝗲𝗻𝗱: This patient suffered a left MLF stroke causing 1) left internuclear ophthalmoplegia (INO) due to involvement of the interneurons traveling from right 6th nucleus to left medial rectus subnucleus via the MLF (responsible for conjugate rightward gaze) 2) contraversive (rightward) ocular tilt reaction (OTR - skew deviation causing a left hypertropia; ocular counterroll with the top poles rotated toward the right ear; right head tilt) due to involvement of the utriculo-ocular motor pathways (originating in the right labyrinth), 3) spontaneous (primarily) torsional nystagmus, with quick phases of the superior poles directed towards the ipsilesional (left) side (due to involvement of the central anterior and posterior semicircular canal pathways that originated in the right labyrinth - acute nystagmus is usually mixed upbeat-torsional or downbeat- torsional), 4) vestibulo-ocular reflex (VOR) loss in the planes of the vertical semicircular canals (posterior canal [PC] > anterior canal [AC] pathway involvement because there's only 1 brainstem pathway for PC compared to 3 pathways for AC), 5) horizontal VOR - with the horizontal head impulse test, the velocity of the adducting eye (ipsilateral to an MLF lesion) movement can be relatively preserved - i.e., much better than what would be expected based on bedside testing with a significant adduction lag due to an INO. This is presumably due to an extra-MLF pathway, the ascending tract of Dieters, which goes directly from the vestibular nucleus to the ipsilateral medial rectus subnucleus, thus bypassing the MLF pathways, 6) vertical gaze-evoked nystagmus - there was upbeat nystagmus (UBN) in upgaze and downbeat nystagmus (DBN) in downgaze, although it's not clear whether this results from descending fibers going from interstitial nucleus of Cajal (INC) to the medullary nucleus of Roller and/or involvement of the nearby paramedian tract (PMT) cell groups (thought to receive inputs from the INC that are transmitted to the cerebellar flocculus). (Video and legend created with the assistance of Dr. Tony Brune) https://collections. lib.utah.edu/ark:/87278/s68m15w9