L Luis1,2,3, J Costa1,4, E Muñoz4, M de Carvalho1, S Carmona5, E Schneider6, C R Gordon7,8, J Valls-Solé4. 1. Clinical Translational Physiology Unit, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. 2. Department of Surgical Specialties and Anesthesia, Otolaryngology Unit, Hospital de Cascais, Portugal. 3. Institute of Health Sciences, Portuguese Catholic University, Lisbon, Portugal. 4. Department of Neurology, EMG and Motor Control Unit, Hospital Clínic, Universitat de Barcelona, IDIBAPS, Spain. 5. Department of Neuro-otology and Pain and Headache, Instituto de Neurociencias de Buenos Aires INEBA, Buenos Aires, Argentina. 6. Institute of Medical Technology, Brandenburg University of Technology Cottbus - Senftenberg, Germany. 7. Department of Neurology, Meir Medical Center, Kfar Saba, Tel Aviv University, Tel Aviv, Israel. 8. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
OBJECTIVE: Although the diagnosis of inherited ataxias is ultimately genetic, this usually means an extensive and expensive process. This justifies the search for distinct clinical signs that may potentially help orient molecular diagnosis. METHODS: We explored the vestibulo-ocular reflex (VOR) with the video Head Impulse Test in patients diagnosed with spinocerebellar ataxia (SCA) type 3 (n = 15), type 1 (n = 4) and type 2 (n = 4), Friedreich's ataxia (FA) (n = 9) and healthy controls (n = 40). We estimated the latency, regression (VORr) and instantaneous VOR gain at 40, 60 and 80 ms (VOR40, VOR60 and VOR80), and determined the latency, peak-velocity and occurrence rate of catch-up saccades triggered with head-impulses. RESULTS: VOR latency was higher in FA (p < 0.001) and SCA3 (p = 0.02) as compared to controls, discriminating FA from other ataxic patients with an overall diagnostic accuracy of 88%. VORr, VOR40 and VOR60 were significantly lower in FA and SCA3 (p < 0.01). VOR80 was only significantly lower than controls in SCA3 (p < 0.01), discriminating these from other ataxic patients with an overall diagnostic accuracy of 78%. Covert saccades were only triggered in SCA3 but with low occurrence rate and peak velocity (11.1 ± 28.5% and 77.50 ± 15.30°/s) whereas overt saccades were present in all groups. VORr gain showed a negative correlation with disease severity evaluated with SARA (Spearman r = -0.46, p = 0.01). CONCLUSIONS: vHIT provides phenotypic information that differentiates these autosomal ataxias and can serve as a strategy to orient genetic diagnosis. A correlation between VOR and SARA raises the possibility of using VOR gain as a neurophysiologic biomarker for disease severity.
OBJECTIVE: Although the diagnosis of inherited ataxias is ultimately genetic, this usually means an extensive and expensive process. This justifies the search for distinct clinical signs that may potentially help orient molecular diagnosis. METHODS: We explored the vestibulo-ocular reflex (VOR) with the video Head Impulse Test in patients diagnosed with spinocerebellar ataxia (SCA) type 3 (n = 15), type 1 (n = 4) and type 2 (n = 4), Friedreich's ataxia (FA) (n = 9) and healthy controls (n = 40). We estimated the latency, regression (VORr) and instantaneous VOR gain at 40, 60 and 80 ms (VOR40, VOR60 and VOR80), and determined the latency, peak-velocity and occurrence rate of catch-up saccades triggered with head-impulses. RESULTS: VOR latency was higher in FA (p < 0.001) and SCA3 (p = 0.02) as compared to controls, discriminating FA from other ataxicpatients with an overall diagnostic accuracy of 88%. VORr, VOR40 and VOR60 were significantly lower in FA and SCA3 (p < 0.01). VOR80 was only significantly lower than controls in SCA3 (p < 0.01), discriminating these from other ataxicpatients with an overall diagnostic accuracy of 78%. Covert saccades were only triggered in SCA3 but with low occurrence rate and peak velocity (11.1 ± 28.5% and 77.50 ± 15.30°/s) whereas overt saccades were present in all groups. VORr gain showed a negative correlation with disease severity evaluated with SARA (Spearman r = -0.46, p = 0.01). CONCLUSIONS: vHIT provides phenotypic information that differentiates these autosomal ataxias and can serve as a strategy to orient genetic diagnosis. A correlation between VOR and SARA raises the possibility of using VOR gain as a neurophysiologic biomarker for disease severity.
Authors: Gabriel Vasata Furtado; Camila Maria de Oliveira; Gabriela Bolzan; Jonas Alex Morales Saute; Maria Luiza Saraiva-Pereira; Laura Bannach Jardim Journal: Genet Mol Biol Date: 2019-06-10 Impact factor: 1.771