Peripheral (Vestibular) and Central (Gaze-Evoked) Patterns of Nystagmus in a Single Patient

A 55-year-old man experienced episodic vertigo and was diagnosed with Meniere's disease affecting the left ear (based on audiograms and his clinical course) about 1 year prior to presentation. About 6 months prior to presentation, intratympanic (IT) gentamicin was injected into the left ear, at which time dizziness and imbalance became more constant. Examination revealed spontaneous right-beating nystagmus (RBN) in the primary position that worsened in right gaze, with more robust RBN during removal of fixation and post-head-shaking. Head impulse test was abnormal to the left, although he had compensated fairly well for this by using covert corrective saccades (seen best in the video head impulse test [vHIT] traces that are displayed in the video - covert saccades occur with the head movement as opposed to overt saccades which occur after the head movement - both of these are apparent in the traces. Overt corrective saccades are the visible refixations that are seen at the bedside, while covert saccades are not seen at the bedside, and are thought to be compensatory). Overt corrective saccades can also be seen in the vHIT traces to the right, and contralesional overts are commonly seen with significant unilateral vestibular loss - this relates to altered dynamics between the ipsi- and contralesional vestibular nuclei, each of which has inhibitory influence over the other. In this case, during rightward (healthy side) head impulses, there will be less disinhibition of the contralesional right vestibular nucleus by the ipsilesional left vestibular nucleus, so that the vestibular response to the healthy side is slightly less than it would be normally. Taken together, these findings were consistent with left unilateral vestibular loss (UVL) related to his IT gentamicin injection. An uncompensated left UVL had been diagnosed previously. However, there were atypical features for this being purely a peripheral vestibular disorder: • After 6+ months, such robust spontaneous (particularly with fixation) RBN would not be expected - i.e., central compensatory mechanisms should have abolished or at least minimized spontaneous nystagmus this many months later. o Possible explanations included: 1) there was also "central" vestibular imbalance that was contributing to spontaneous RBN and/or 2) normal central compensation had been disrupted • Smooth pursuit was impaired (appeared saccadic or choppy) both horizontally and vertically, which is a central ocular motor sign. • If his spontaneous RBN were only due to semicircular imbalance from left unilateral vestibular loss from the gentamicin, seeing such prominent, sustained LBN in left gaze could not be easily explained on a peripheral basis. In his case, with video-oculography recordings, the peak slow phase velocity (SPV) of the LBN in left was 4 degrees/second (d/s) compared to -3 d/s SPV in primary and -8 d/s SPV in right gaze. Also, after coming back from left to primary gaze, the baseline RBN increased in intensity, suggesting the presence of rebound nystagmus. For these reasons, it was felt that the LBN in left gaze was due to pathologic gaze-evoked nystagmus (GEN) rather than physiologic end point nystagmus. RBN increased in right gaze in part due to his left unilateral vestibular loss (Alexander's law states that the nystagmus will increase in the direction of the fast phase), but probably also due to some degree of GEN. Given the clear "central" ocular motor signs that were appreciated on his exam in addition to the left UVL and a normal brain MRI with and without contrast, blood work looking for causes of posterior fossa dysfunction was sent. Serum anti-glutamic acid decarboxylase 65 (GAD65) antibody titer returned elevated at >250 (normal <5 IU/ml). There was no clinical concern for stiff person syndrome, but an anti-GAD associated posterior fossa syndrome was strongly suspected, and evaluation for malignancy and planning for immunosuppressant therapy is ongoing. Anti-GAD antibodies prevent formation of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), and dysfunction of cerebellar Purkinje cells can be one consequence. This could be the explanation for GEN and impaired pursuit in our patient. Also of note in this case is that he technically had Bruns nystagmus, where there is "vestibular nystagmus" contralesional to UVL and "gaze-evoked nystagmus" ipsilesional to cerebellar or brainstem dysfunction. The most common example is a large cerebello-pontine angle (CPA) tumor like an acoustic neuroma - e.g., a left sided CPA mass could cause left UVL with spontaneous RBN that increases in right gaze with GEN in left gaze. In our patient's case, the LBN in left gaze was GEN, but the RBN in right gaze was likely a combination of the left UVL (Alexander's law states that spontaneous vestibular nystagmus will increase in the direction of the fast phase) and GEN. In his case, it is likely that he had Meniere's initially and his posterior fossa syndrome subsequently developed over time.