Clinical presentation
In December 2008, a 22-year-old woman presented with acute imbalance, nausea and vomiting. On examination, she had right axial lateropulsion, right upper extremity dysmetria and left hemi-hypoesthesia. She also exhibited right ocular lateropulsion right saccade lateropulsion, and horizontal left-beat nystagmus in primary straight-ahead position and in left gaze. The head impulse test was normal. An MRI revealed DWI and T2 signal in the right dorsolateral medulla and faint T2 signal in the right inferior olive (Fig. 1, left panel). CT angiography revealed dissection of the right vertebral artery. Recovery was incomplete, as she had persistent right face and left body sensory loss and mild incoordination of gait. Four months later, she developed acute weakness of the right side, increased imbalance, and new onset diplopia and oscillopsia. Subsequent examination revealed new right hemiparesis in addition to previous sensory and coordination deficits. She also had a horizontal/torsional right beating nystagmus that increased in right gaze; left gaze was associated with left beating nystagmus. Right horizontal saccades were hypermetric, and horizontal pursuit was bilaterally saccadic. She had decreased optokinetic nystagmus gain bilaterally (0.52 and 0.54). Bithermal caloric testing and head impulse tests were normal bilaterally. Ocular cross cover test detected a new large skew deviation with a 12-prism diopter right hypertropia. In a follow-up visit 6 weeks later, her neurological examination was unchanged except for the additional finding of pendular vertical eye oscillations and bilateral palatal tremor.
An MRI 1 month after her second stroke revealed an infarct extending from the left medullary pyramid posteriorly to the posterior surface of the medulla (Fig. 1, left panel). This infarct appeared to involve the medial left inferior olive, but there was no olivary hypertrophy. We found dissection of the left vertebral artery with CT angiography. Subsequent MRI scans at intervals of 2, 3, 8, and 10 years did not reveal additional infarcts or inferior olive hypertrophy.
Ten years after the very first event (May 2018), at the time of objective ocular motor assessment reported in this study, she had diplopia that was corrected with a right six-diopter base-down prism but still had mild right head tilt.
The general neurologic examination revealed a right hemiparesis with circumduction of the right leg, and she exhibited moderate right-sided extremity ataxia, although this was difficult to assess due to hemiparesis. She also exhibited right side hyperalgesias and impaired sensation to the sharp objects in the left hemi body. She had palatal tremor with a frequency of 1.8 Hz (Video), as measured by counting the movements in the video frames. She had a proximal tremor in her right upper limb during posture, movement but not at rest. The tremor was greatest in the wing-beating posture.
Additional file 1: Video 1. The first section shows a dissociated vertical pendular oscillation with a subtle torsional component noted during fixation at a target straight ahead. The second section shows the effect of fixation block. Note the conjugate horizontal, jerk right-beat nystagmus. The third section shows a rhythmic movement of the soft palate and uvula.
Quantitative ocular motor and tremor assessment
We performed quantitative ocular motor assessment in May 2018, and quantitative tremor analysis occurred in September 2018. Eye movement recording during straight-ahead fixation revealed a 2 Hz pendular vertical oscillation. The pendular oscillation was binocularly dissociated; the amplitude was greater in the right eye (Fig. 2, Video). She had impaired bi-directional horizontal and vertical pursuit, and rightward saccades were hypermetric with normal velocity and latency. With fixation block, she exhibited a straight-ahead horizontal right-beating nystagmus with a slow phase velocity of 7 deg/sec (Fig. 3B, Video 1 second section). She had modestly decreased horizontal left (0.7) compared to normal right horizontal (0.9) vestibulo-ocular reflex gain (normal range: 0.8–1.0). Occasional square wave jerks were present. Vestibulo-ocular reflex cancellation was normal. Her tremor was recorded with a triaxial accelerometer and gyroscope mounted on the dorsum of the right hand. Spectral analysis revealed a tremor frequency of 2.4 Hz during posture and movement.