Neuro-Ophthalmic Features and Pseudo-MG Lid Signs in Miller Fisher Syndrome (Figure 1)

This is a 51-year-old woman who presented with imbalance, acute onset dizziness and diplopia that developed over three days following two weeks of upper respiratory infection and bacterial conjunctivitis. When she was initially seen as an outpatient, nystagmus was noted to the right and left, and a skew deviation was diagnosed as well. Initially, this was thought to be related to a posterior fossa stroke and the patient was referred to the emergency room. After another 24 hours or so, examination was remarkable for limb and gait ataxia, absent deep tendon reflexes, ptosis OS, lid retraction OD (patient had a history of hyperthyroidism with baseline lid retraction presumably from thyroid eye disease [TED], although this was slightly more prominent - there was intermittent ptosis OD as well), a Cogan's lid twitch and enhanced ptosis, in addition to sluggish pupils OU. There were abduction>adduction and milder vertical motility deficits OU in addition to gaze-evoked nystagmus horizontally and vertically. Given the constellation of sluggish pupils, ataxia, areflexia and ptosis with ophthalmoparesis in the setting of the preceding URI, suspicion was high for Miller Fisher syndrome (MFS). LP was done within 4 days of the onset and was unrevealing as was MRI with and without contrast. IVIG was started, and Gq1b returned + at 1:800 several days later. From a neuro-ophthalmic/otologic standpoint, there were several interesting findings: • Although there was ophthalmoparesis with a Cogan's lid twitch, fatigable and enhanced ptosis (based on Herring's law of equal innervation of bilateral levator palpebrae muscles - these are features that are highly suspicious for myasthenia gravis), from an ocular standpoint, the sluggish pupils should make the clinician think of Miller Fisher syndrome or even botulism instead. This case also highlights the fact that the Cogan's lid twitch is not exclusively seen with MG. • In her case, there was also lid retraction OD, which was slightly more than her baseline which was due to presumed mild TED given the chronicity and her hyperthyroidism. Since she had mainly ptosis OS, more levator tone was required to elevate the left eyelid. However, given Herring's law of equal levator innervation, there was corresponding increased levator tone on the right which resulted in an increase in her baseline lid retraction. However, as she became more fatigued throughout the exam, ptosis was apparent OU. • There was no spontaneous nystagmus, although there were ocular motor signs that are typically seen with posterior fossa dysfunction including impaired (sometimes referred to as choppy or saccadic) smooth pursuit and vestibulo-ocular reflex suppression (VORS), in addition to gaze-evoked nystagmus (GEN). GQ1b antibodies have been reported to have an affinity for the molecular layer of the cerebellum, 1,2 and this may provide an explanation for cerebellar ataxia and central ocular motor abnormalities (the abnormal eye movements in her case mainly point towards the flocculus/paraflocculus). It has also been demonstrated that GQ1b ganglioside antibodies bind to nerve terminals inside muscle spindles3, or that dorsal root ganglia may be a target4, thus providing potential peripheral mechanisms for the genesis of limb and gait ataxia in the Miller Fisher syndrome. Given the ocular motor abnormalities in our patient, it's quite possible that both central and peripheral mechanisms were at play. • With bedside horizontal head impulse testing (HIT), which evaluates the function of the horizontal semicircular canals, there were no catch-up saccades to either side. This is referred to as a normal HIT, and suggests normal vestibulo-ocular reflex (VOR) function. However, video HIT (vHIT) demonstrated low gains (calculated as the eye velocity/head velocity) to the right and to the left of 0.4 where higher than 0.7 is considered normal (Figure). The combination of GEN, loss of the horizontal VOR, ophthalmoparesis (commonly 6th nerve palsies) and ataxia is highly suspicious for Wernicke's encephalopathy, although there was no history of alcoholism or malnutrition. However, in her case, MFS seemed much more likely and her nutritional labs were normal. Furthermore, it was thought that the low vHIT gains were related to slow abducting and adducting saccades (i.e., low eye velocities due to motility deficits) due to her ophthalmoparesis as opposed to vestibular loss. Also suggestive of normal vestibular reflexes in her case was the normal appearing bedside VOR, and the fact that VOR suppression was also impaired - in a patient with bilateral vestibular loss who also has impaired smooth pursuit (e.g., due to cerebellar disease), VOR suppression should look normal because there is no VOR to suppress. In her case, the impaired VOR suppression suggests that her VOR was intact. ; •; Finally, this patient presented with acute onset prolonged dizziness and imbalance, consistent with the acute vestibular syndrome (AVS, defined as prolonged vertigo >24 hours, imbalance, nausea, vomiting, nystagmus, head motion intolerance). According to HINTS (Head Impulse, Nystagmus, Test of Skew), which is a 3 step ocular motor exam designed to differentiate peripheral (e.g., vestibular neuritis) from central (e.g., stroke) vestibular etiologies of the AVS, the normal bedside HIT, gaze-evoked nystagmus and vertical refixation saccades noted with alternate cover testing (+ test of skew, even though her vertical deviation turned out not to be a skew deviation) are all indicative of a central cause. MFS is a very rare cause of the AVS. [[Number of Figures and legend for each: 1, Video HIT demonstrating low gains in the planes of the right and left semicircular canals.]] [[Number of Videos and legend for each: 1, Patient with eyelid signs typical of myasthenia gravis, but with sluggish pupils and areflexia that were more suspicious for Miller Fisher syndrome. .]] For case video, CLICK HERE: https://collections.lib.utah.edu/details?id=1282769