Ocular Flutter Triggered by Saccades Pursuit and Convergence

Abstract

Ocular flutter and opsoclonus represent saccadic oscillations that are distinguished from other saccadic disorders by the absence of an inter-saccadic interval. While ocular flutter is purely horizontal, opsoclonus is horizontal, vertical and torsional. Notably, the diagnostic and therapeutic implications of ocular flutter and opsoclonus are the same. Structures that play a significant role in the generation and termination of saccades have been implicated in the genesis of ocular flutter and include the paramedian pontine reticular formation (PPRF), the excitatory burst neurons (EBN, which are in the PPRF) and inhibitory burst neurons (IBN), the cerebellar fastigial nucleus (which has dense connections with the brainstem burst neurons, especially IBN), and the omnipause cells of the pontine nucleus raphe interpositus. It was initially postulated that damage to the omnipause neurons in the pontine nucleus raphe interpositus was responsible for ocular flutter, however; animal models and autopsy data from two patients with saccadic oscillations did not show evidence to support this hypothesis. The main theory underlying ocular flutter is related to the intrinsic properties of the burst neurons in the PPRF. Burst neurons are able to fire rapidly because of their membrane property of post-inhibitory rebound discharge. There is also an inherent instability built into the saccadic oscillation system because of positive feedback between the EBN and IBN. One example of this instability is that blinking and sustaining eye closure can trigger saccadic oscillations in normal subjects. A specific ion channel in the burst neuron, Ih, a hyperpolarization-activated inward mixed cation channel, is likely responsible for generating the post-inhibitory rebound discharge which results in the high speed of saccades. This ion channel is very sensitive to pH and osmolarity, increasing the excitability of the burst neurons in certain disease states, which can manifest as saccadic oscillations. The fastigial nucleus in the cerebellum projects to the IBN and EBN and altered activity of these projections could result in increased firing of burst neurons causing saccadic oscillations and could explain how cerebellar disease has also been linked to opsoclonus. Ocular flutter and opsoclonus can be triggered by saccades, smooth pursuit, convergence, and/or gentle closure of the eyelids, likely due to further disruption of already unstable EBN/IBN feedback loops and post-inhibitory rebound discharge.1. Wada T, Higashiyama Y, Kunii M, et al. Ocular flutter as the presenting manifestation of autoimmune glial fibrillary acidic protein astrocytopathy. Clinical Neurology and Neurosurgery. 2022;219:107307. doi:10.1016/j.clineuro.2022.107307. 2. Schon F, Hodgson TL, Mort D, Kennard C. Ocular flutter associated with a localized lesion in the paramedian pontine reticular formation. Annals of Neurology. 2001;50(3):413-416. doi:10.1002/ana.1140. 3. Zaro-Weber O, Galldiks N, Dohmen C, Fink GR, Nowak DA. Ocular Flutter, Generalized Myoclonus, and Trunk Ataxia Associated With Anti-GQ1b Antibodies. Arch Neurol. 2008;65(5):659-661. doi:10.1001/archneur.65.5.659. 4. Ramat S, Leigh RJ, Zee DS, Optican LM. Ocular oscillations generated by coupling of brainstem excitatory and inhibitory saccadic burst neurons. Exp Brain Res. 2005;160(1):89-106. doi:10.1007/s00221-004-1989-8. 5. Oh EH, Choi JH, Park SJ, Kim HS, Choi SY, Choi KD. Triggered saccadic oscillations: case series and review of the literature. J Neurol. 2024;271(8):5622-5628. doi:10.1007/s00415-024-12533-8. 6. Verhaeghe S, Diallo R, Nyffeler T, Rivaud‐Péchoux S, Gaymard B. Unidirectional ocular flutter. J Neurol Neurosurg Psychiatry. 2007;78(7):764-766. doi:10.1136/jnnp.2006.107797. 7. Leigh R, Zee D. The Neurology of Eye Movement