Oculomotor and vestibular findings in Gaucher disease type 3 and their correlation with neurological findings

Tatiana Bremova-Ertl, Raphael Schiffmann, Marc C. Patterson, Nadia Belmatoug, Thierry Billette de Villemeur, Stanislavs Bardins, Claudia Frenzel, Vera Malinová, Silvia Naumann, Juliane Arndt, Eugen Mengel, Jörg Reinke, Ralf Strobl, Michael Strupp

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8 Scopus citations

Abstract

Objectives: To evaluate the function of the oculomotor and vestibular systems and to correlate these findings with the clinical status of patients with Gaucher disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was to find oculomotor biomarkers for future clinical trials. Methods: Twenty-six patients with GD3 were assessed for eligibility and 21 were able to perform at least one task. Horizontal and vertical reflexive saccades, smooth pursuit, gaze-holding, optokinetic nystagmus, and horizontal vestibulo-ocular reflex (VOR) were examined by video-oculography/video-head impulse test and compared concurrently with 33 healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA), the modified Severity Scoring Tool (mSST), and Grooved Pegboard Test (GPT) were administered to assess overall neurological function. Eleven patients were also re-assessed after 1 year. Results: Nine out of 17 patients exhibited gaze-holding deficits. One patient had upbeat nystagmus. Three patients presented with bilateral abducens palsy in combination with central oculomotor disorders, suggesting a bilateral involvement of the abducens nucleus. Horizontal angular VOR gain was reduced in all patients (0.66 ± 0.37) compared with controls (1.1 ± 0.11, p < 0.001). Most strongly correlated with clinical rating scales were peak velocity of downward saccades (SARA: ρ = -0.752, p < 0.0005; mSST: ρ = -0.611, p = 0.003; GPT: ρ = -0.649, p = 0.005) and duration of vertical saccades (SARA: ρ = 0.806, p < 0.001; mSST: ρ = 0.700, p < 0.0005; GPT: ρ = 0.558, p = 0.02) together with the VOR gain (SARA: ρ = -0.63, p = 0.016; mSST: ρ = -0.725, p = 0.003; GPT: ρ = -0.666, p = 0.004). Vertical smooth pursuit gain decreased significantly at follow-up. Interpretation: This study shows neuronal degeneration of the brainstem and cerebellum with combined involvement of both supranuclear and nuclear oculomotor structures and the vestibular system in GD3. We also identified oculomotor parameters that correlate with the neurological status and can be used as biomarkers in future clinical trials.

Original languageEnglish (US)
Article number711
JournalFrontiers in Neurology
Volume8
Issue numberJAN
DOIs
StatePublished - Jan 15 2018

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Keywords

  • Gaucher disease type 3
  • Horizontal supranuclear saccade palsy
  • Metabolic disease (inherited)
  • Neuro-ophthalmology
  • Neuronopathic Gaucher disease
  • Ocular motility
  • Saccades
  • Vertical supranuclear saccade palsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Bremova-Ertl, T., Schiffmann, R., Patterson, M. C., Belmatoug, N., de Villemeur, T. B., Bardins, S., Frenzel, C., Malinová, V., Naumann, S., Arndt, J., Mengel, E., Reinke, J., Strobl, R., & Strupp, M. (2018). Oculomotor and vestibular findings in Gaucher disease type 3 and their correlation with neurological findings. Frontiers in Neurology, 8(JAN), [711]. https://doi.org/10.3389/fneur.2017.00711