Research reportOculomotor deficits affect neuropsychological performance in oculomotor apraxia type 2
Introduction
Ataxia with oculomotor apraxia type 2 (AOA2) is a rare and early-disabling neurodegenerative disease that, with ataxia with oculomotor apraxia type 1 (AOA1), belongs to a subgroup of oculomotor apraxia-associated autosomal recessive cerebellar ataxia (ARCA) (Moreira et al., 2001, Moreira et al., 2004).
The onset of AOA2 occurs between age 10 and 22 years (Criscuolo et al., 2006, Le Ber et al., 2004, Tazir et al., 2009). Elevated serum α-fetoprotein and creatine kinase (CK) concentrations and cerebellar atrophy have been reported (Criscuolo et al., 2006, Le Ber et al., 2004). AOA2 is characterized by optional oculomotor apraxia (saccade of elevated latency due to a failure to initiate the saccade present in about 50% of subjects), peripheral neuropathy, and extrapyramidal signs, including choreiform movements, dystonia, and tremor. Recently, in line with the importance of cerebellum in cognition (Leggio et al., 2011), cognitive impairments have been also reported (Le Ber et al., 2004). However, most neuropsychological tests require unimpaired visual scanning abilities that might be affected by AOA2-induced oculomotor deficits.
In this study, we analyzed the neuropsychological profiles of 2 Italian siblings who were affected by AOA2 and their oculomotor patterns during nonverbal and verbal tasks to determine the influence of impairments in visual scanning on cognitive performance.
Section snippets
Subjects
We studied 2 patients from a family in central Italy, patient 1 and patient 2, who were affected by AOA2, harboring a large homozygous deletion that encompassed 8 exons in senataxin (SETX) gene.
Patient 1 was a 38-year-old woman, and patient 2 was a 40-year-old man. Both patients were right-handed and had 13 years of education. The pedigree of the family and its molecular data have been reported by Criscuolo et al. (2006) (Patients 3 and 4 in Family 3). The procedures were approved by the Santa
Apparatus and general procedure
Eye movements were recorded at a sample rate of 500 Hz from the dominant eye (Porac and Coren, 1981) in binocular vision using an infrared eye tracker (for details, see De Luca et al., 1999). The participant sat in front of a 15″ computer screen (60-cm eye-screen distance), with the head fixed. A calibration was run before each experimental trial, acquiring gaze position only during steady fixation and excluding intrusive movements.
A simple fixation task was used to evaluate the ability to
Eye movements
Eye movement traces showed oculomotor disturbances—both patients had highly frequent SI, the amplitude of which was particularly large in patient 1. Nystagmus was observed only in patient 2. Excerpts of the traces that were recorded during the tasks are presented in Fig. 2. As shown in the figure, both patients presented clear pathological features. To provide a direct comparison, patients’ results were compared to those of the healthy sibling that was representative of the healthy population’s
Discussion
In this study, eye movement recordings and cognitive tasks were used to examine oculomotor and cognitive deficits in 2 siblings with AOA2. The patients presented with similar general clinical conditions, corresponding to the hallmarks of AOA2 (Anheim et al., 2009, Le Ber et al., 2004), with few differences between them with regard to oculomotor and cognitive symptoms.
Notably, the accurate oculomotor screen allowed us to detect new features of the oculomotor pattern in AOA2. Based on eye
Acknowledgments
We thank patient 1 and patient 2 for the hours of testing that they patiently endured. The editing support of Blue Pencil Science is also acknowledged. This work was supported in part by grants to Marco Molinari and Maria G. Leggio from the Italian Ministry of Instruction, University and Research and the Italian Ministry of Health.
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S.C. and M.D. contributed equally to this work and should be considered co-first authors.