Here we summarize the evidence from our prior studies to support the hypothesis that the PGSF are relatively spared in ocular myasthenia, because of their structural characteristics, which in turn accounts for some typical eye movement findings.3
We studied interocular conjugacy (i.e., how well the eyes move together) of fast eye movements (saccades) from a group of patients affected by ocular myasthenia. As previously shown, interocular conjugacy of horizontal saccades in patients with myasthenia gravis affected by disturbance of horizontal gaze was consistently preserved in the initial portion of the eye movement, despite the later component being markedly and variably dysconjugate.24–25
This was in contrast to consistent normal conjugacy of saccades made by control subjects and abnormal conjugacy of saccades made by patients with lesions at a site other than the NMJ (i.e., abducense nerve palsy or internuclear ophthalmoparesis),25
who showed instead early and sustained interocular dysconjugacy. However, a minimal dysconjugacy of horizontal saccades exists even in normal subjects, due the physiological delay of signal transmission imposed by the presence of the medial longitudinal fasciculus (MLF) between one set of burst neurons and one group of motoneurons for the medial rectus muscle.26–27
Thus, in a later study we focused on vertical saccades in patients with myasthenia gravis who showed disturbances of vertical gaze,3
as in healthy people vertical saccades are tightly yoked (burst neurons in the midbrain rostral interstitial nucleus of the medial longitudinal fasciculus directly project to motoneurons innervating yoke muscle pairs).
In particular, we recorded horizontal and vertical saccades from six patients with MG (age range 40–73 years; median 63), three age-matched patients with cranial nerve palsies (1 oculomotor, 1 trochlear, 1 abducens) and 10 age-matched control subjects. All patients and control subjects gave informed written consent in accordance with the Declaration of Helsinki and the Institutional Review Board of the Cleveland Veterans Affairs Medical Center. On clinical examination of patients with MG, in three cases dysconjugate saccades were evident horizontally; in two cases dysconjugate saccades were evident both horizontally and vertically; and in one case saccades were dysconjugate vertically. During the experimental protocol, subjects viewed a laser spot projected onto a tangent screen at 1.2 m. Saccades were tested as the visual target jumped at 0.25 Hz with amplitude ranging 5–40 degrees horizontally and 5–20 degrees vertically; the direction of target jumps was non-predictable. Binocular eye movements were recorded using the magnetic search coil technique; coil signals were filtered (0–150 Hz) before digitization at 500 Hz; eye velocity and acceleration were computed as previously described.28
The interocular conjugacy of horizontal and vertical saccades was assessed using the binocular phase-plane technique.26
For each saccade, the displacement (change in position) and velocity of each eye were normalized by assigning a value of 1.0 to the maximum displacement, and to the peak velocity, of the eye making the larger movement. Thus, the phase plane plotted the normalized velocity of each eye against the normalized displacement in 1% (0.01) position increments; this way, we were able to compare the velocity of each eye for the same normalized eye displacement during the entire saccadic movement as a velocity dysconjugacy plot. We applied this technique to over a thousand saccades from the 10 age-matched normal subjects and used linear regression to define 5% to 95% prediction intervals (PIs). Finally, for each patient, the average velocity dysconjugacy was calculated from at least 10 saccades and was then compared with the PI of the control subjects.
Representative records of an upward saccade from a control subject, a patient with ocular myasthenia, and a patient with oculomotor nerve palsy are shown in . To the left in each row of the panels is a time plot; to the right are corresponding phase-plane plots of the upward saccades shown in the time plots. The vertical saccade made by the control subject () is tightly conjugate, as expected. The vertical saccade made by the patient with ocular myasthenia () is quite disjunctive, with greatly reduced movement of his left eye. However, as shown in the corresponding phase plane plot, the upward saccade was initially conjugate (indicated by black arrow). In contrast, the saccade from the patient with oculomotor nerve palsy () was disjunctive throughout its course, including the onset (indicated by gray arrow on the phase-plane plot).
Figure 2 Representative records of a vertical upward saccade made by one healthy control subject (row A), a patient with ocular myasthenia manifest as left pseudo-oculomotor nerve palsy (row B), and a patient with right oculomotor nerve palsy (row C). Each row (more ...)
The three distinct patterns of vertical saccades were consistent from saccade to saccade when we systematically compared normalized phase planes of patients and control subjects: saccades of patients with ocular myasthenia invariably fell within the normal 95% prediction intervals for at least the first 10% of the movement (although later components did not), but saccades of patients with cranial nerve palsies always fell outside the normal 95% prediction intervals from their start. Similarly to what previously shown with horizontal saccades,26
patients with ocular myasthenia exhibited a consistent initial interocular conjugacy of vertical saccades, from saccade to saccade, even though later components of saccades varied, reflecting fatigue.