Dear Editor,
Episodic ataxia (EA) is a group of disorders characterized by recurrent attacks of truncal ataxia and incoordination.1,2 Among the eight subtypes, EA type 2 (EA2) is the most common and is inherited in an autosomal dominant pattern due to mutations in the voltage-gated Cav2.1 P/Q-type calcium channel (CACNA1A).2,3 Patients with EA2 typically present with recurrent ataxia that lasts minutes to hours with interictal ocular motor abnormalities mostly due to cerebellar dysfunction.1 Here we report vertical saccade slowing in a patient with EA2, which is a previously undescribed finding in this disorder.
A 17-year-old man with a family history of EA2 had been followed up in a dizziness clinic for 7 years. His elder sister had a confirmed EA2 diagnosis based on characteristic clinical features and a heterozygous mutation (c.4953+1G>A) at the intron 31 splice donor site in the CACNA1A gene (reference sequence=NG_011569).4 Findings of the initial evaluation at 10 years old were conspicuous for gaze-evoked and downbeat nystagmus during lateral gaze (side-pocket nystagmus), and rebound upbeat nystagmus when resuming the straight-ahead gaze.4 There was a curved trajectory in the upward saccades, but the velocity was within the normal range.4 Smooth pursuit and visual enhancement of the vestibulo-ocular reflex were impaired in both the horizontal and vertical directions.4 The other findings of the patient and his family members have been described previously.4 A follow-up evaluation 7 years later additionally indicated slowing of the vertical saccades in both directions (Fig. 1; Supplementary Video 1 in the online-only Data Supplement). Horizontal saccades were normal (Fig. 1). Other findings of the neurological examination remained unchanged. Genetic analysis confirmed the same mutation as the one found in his sister.
Fig. 1. Findings for saccades in the patient. A: Video-oculography (SLMED, Seoul, Korea) revealed vertical saccade slowing in both the upward and downward directions. B: Horizontal saccades were normal. C: Plotting of the saccadic velocities over the amplitude (main sequence) also confirmed vertical saccade slowing in both directions (blue dots). In contrast, the velocities of horizontal saccades were largely within the normal range (red dots). Upward deflection in panels (A) and (B) indicates rightward and upward motions, respectively. The positive amplitude values in panel (C) denote rightward and upward saccades. EH, horizontal position of the left eye; EV, vertical position of the left eye; TH, target motion for horizontal saccades; TV, target motion for vertical saccades.
Our patient with EA2 due to a mutation in the CACNA1A gene presented with vertical saccade slowing during the follow-up at 7 years after the initial presentation. Premotor commands for saccades are generated in the brainstem via interactions between the burst and omnipause neurons.5 Disruption of these brainstem neural networks results in saccade slowing. The excitatory burst neurons for horizontal saccades lie in the paramedian pontine reticular formation, while those for vertical saccades reside in the rostral interstitial nucleus of the medial longitudinal fasciculus.5 In EA2, interictal ocular motor abnormalities have mostly been ascribed to cerebellar dysfunction and include downbeat nystagmus, gaze-evoked nystagmus, positional nystagmus, impaired smooth pursuit, and hypermetric saccades.2,6 However, the selective vertical saccade slowing observed in our patient with EA2 indicated an additional involvement of the upper midbrain in this disorder.7 It is interesting that previous reports also described slow horizontal saccades8 and internuclear ophthalmoparesis9 as rare findings in EA2, which also indicates a brainstem involvement in this disorder. Indeed, recent studies have found various phenotypes related to mutations that involve CACNA1A.10 Our report expands the clinical spectrum of EA2 and support extracerebellar involvements in this disorder.
Footnotes
Ethics Statement: This study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-2209-779-701). The patient gave an informed and written consent to participate in this study.
- Conceptualization: Hyo-Jung Kim.
- Data curation: Seondeuk Kim, Seonkyung Lee.
- Formal analysis: Seoyeon Kim.
- Funding acquisition: Hyo-Jung Kim.
- Writing—original draft: Seoyeon Kim.
- Writing—review & editing: Hyo-Jung Kim.
Conflicts of Interest: The authors have no potential conflicts of interest to disclose.
Funding Statement: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (No. NRF-2021R1F1A1063826).
Availability of Data and Material
Data sharing not applicable to this article as no datasets were generated or analyzed during the study.
Supplementary Materials
The online-only Data Supplement is available with this article at https://doi.org/10.3988/jcn.2022.18.6.726.
Video-oculography revealed vertical saccade slowing in both the upward and downward directions.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Video-oculography revealed vertical saccade slowing in both the upward and downward directions.
Data Availability Statement
Data sharing not applicable to this article as no datasets were generated or analyzed during the study.