Objective:

To elucidate the characteristics and mechanisms of spontaneous nystagmus violating the Alexander’s law.

Background:

Alexander's law states that spontaneous nystagmus increases when looking in the direction of fast-phase and decreases during gaze in slow-phase direction. Disobedience to Alexander’s law is occasionally observed in central nystagmus, but the underlying neural circuit mechanisms are poorly understood. 

Design/Methods:

We measured the mean and slope of slow-phase velocities (SPVs) and time constant of nystagmus during the straight ahead and lateral gaze in 17 patients with Wallenberg syndrome and violation of the Alexander’s law. Twenty patients with vestibular neuritis served as a control. We also implemented a mathematical model to simulate the nystagmus violating Alexander’s law.

Results:

Patients showed a violation of Alexander’s law in one or both directions of lateral gaze. When Alexander’s law is violated, the Tc was larger than that in the controls (median [IQR]: 14.4 s [6.4-38.9] vs 9.0 s [5.5-12.6], p=0.036) while the Tc did not differ between the groups when Alexander’ law is obeyed (9.6 s [3.6-16.1] vs 9.0 s [5.5-12.6], p=0.924). Three patients showed nystagmus with an increasing SPV (n=3) or centripetal nystagmus (n=1) during lateral gazes, both of which indicate an unstable neural integrator. In a mathematical model with normal integrator function, the false rotational cue generates nystagmus following Alexander’s law. The first lesion, which changes the brainstem neural integrator, and the second lesion, which causes the Purkinje synapse to exert excitatory input, both lead to nystagmus that violates Alexander’s law.

Conclusions:

We propose that when the neural integrator is unstable with lesions in the brainstem neural integrator itself or the neural synapse between Purkinje cells and the brainstem vestibular nucleus, nystagmus violates Alexander’s law.