Elsevier

Cortex

Volume 49, Issue 3, March 2013, Pages 691-701
Cortex

Research report
Oculomotor deficits affect neuropsychological performance in oculomotor apraxia type 2

https://doi.org/10.1016/j.cortex.2012.02.007Get rights and content

Abstract

Introduction

Ataxia with oculomotor apraxia type 2 is a rare and early-disabling neurodegenerative disease, part of a subgroup of autosomal recessive cerebellar ataxia, in which oculomotor symptoms (e.g., increased saccade latency and hypometria) and executive function deficits have been described.

The aim of this study was to evaluate the impact of oculomotor symptoms on cognitive performance and, in particular, over reading in 2 Italian siblings affected by ataxia with oculomotor apraxia type 2.

Methods

The neuropsychological profiles and the oculomotor patterns during nonverbal and verbal tasks were recorded and analyzed.

Results

Saccadic intrusions and/or nystagmus were observed in all eye movement tasks. The neuropsychological profiles were substantially preserved, with only subtle deficits that affected visuomotor integration and attention. Reading ability decreased and became impaired. The reading scan was disturbed by saccadic intrusions and/or nystagmus. However, an ad hoc reading task demonstrated that deficits appeared only when the items that were displayed enhanced oculomotor requests. The preservation of lexical-semantic processes confirmed that the reading disability was caused by oculomotor deficits, not cognitive problems.

Conclusion

Present findings indicate that in patients who are affected by ataxia with oculomotor apraxia type 2, performance on neuropsychological tests, especially those that require rapid performance and eye or hand–eye control, must be analyzed with respect to oculomotor components.

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.

References (43)

  • C.J. Stoodley et al.

    Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies

    NeuroImage

    (2009)
  • M. Tazir et al.

    Ataxia with oculomotor apraxia type 2: A clinical and genetic study of 19 patients

    Journal of the Neurological Sciences

    (2009)
  • P. Trouillas et al.

    International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome

    Journal of the Neurological Sciences

    (1997)
  • G. Villa et al.

    Double dissociation between temporal and spatial pattern processing in patients with frontal and parietal damage

    Cortex

    (1990)
  • P. Zoccolotti et al.

    Delayed naming cancels the word length effect in developmental dyslexia

    Brain & Language

    (2006)
  • M. Anheim et al.

    Ataxia with oculomotor apraxia type 2: Clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients

    Brain

    (2009)
  • K. Beery

    The Beery–Buktenica Developmental Test of Visual-motor Integration: VMI with Supplemental Developmental Tests of Visual Perception and Motor Coordination: Administration, Scoring and Teaching Manual

    (1997)
  • J.G. Borkowsky et al.

    Word fluency and brain damage

    Neuropsychologia

    (1967)
  • G. Carlesimo et al.

    The mental deterioration battery: Normative data, diagnostic reliability and quantitative analyses of cognitive impairment

    European Neurology

    (1996)
  • Corsi PM. Human memory and medial temporal region of the brain. [Dissertation Abstracts International] McGill...
  • J.R. Crawford et al.

    Comparison of a single case to a control or normative sample in neuropsychology: Development of a Bayesian approach

    Cognitive Neuropsychology

    (2007)
  • Cited by (15)

    • Neuro-ophthalmologic assessment and investigations in children and adults with cerebellar diseases

      2018, Handbook of Clinical Neurology
      Citation Excerpt :

      Macrosaccadic oscillations (runs of horizontal saccades with a crescendo–decrescendo amplitude pattern and a 200-ms intersaccadic interval), ocular flutter, and opsoclonus (see Table 19.1 for definitions) have all been associated with dysfunctional output of the caudal fastigial nuclei, resulting in premotor burst neuron oscillations (Otero-Millan et al., 2011; Lemos and Eggenberger, 2013). Square-wave jerks are observed in FRDA (Ell et al., 1984; Moschner et al., 1994; Spieker et al., 1995; Ribai et al., 2007; Fahey et al., 2008), MSA-C (Anderson et al., 2008), progressive supranuclear palsy (Otero-Millan et al., 2011), Huntington disease (Leigh et al., 1983; Blekher et al., 2006), SCA3 (Buttner et al., 1998; Kim et al., 2013) and SCA6 (Christova et al., 2008), AT (Shaikh et al., 2009), and ataxia with ocular motor apraxia type 2 (Anheim et al., 2009; Clausi et al., 2013). Macrosaccadic oscillations have been observed in various hereditary cerebellar ataxias (Ramat et al., 2007), while opsoclonus/ocular flutter may be a paraneoplastic manifestation linked to small-cell lung cancer and breast cancer, parainfectious encephalitis, autoimmune disorders, and thalamic or pontine hemorrhagic stroke (Beh et al., 2017).

    • Neuro-ophthalmic manifestations of cerebellar disease

      2014, Neurologic Clinics
      Citation Excerpt :

      The most common of saccadic intrusions, SWJs are small, conjugate couplets of horizontal saccades (about 0.5° in size) that take the eyes away from a fixation point, before a refixation saccade moves them back, after a normal intersaccadic interval of 200 to 400 milliseconds.1,58 They can be seen in healthy adults (especially in the elderly), but are a prominent finding in PSP and Huntington chorea, as well as certain ataxic disorders, including SCAs (particularly SCA3), Friedreich ataxia (FRDA), multiple system atrophy (MSA), and ataxia with ocular motor apraxia type 2 (AOA2).1,58–67 SWJs may also be increased following opioid use68 and cigarette smoking.69

    View all citing articles on Scopus
    1

    S.C. and M.D. contributed equally to this work and should be considered co-first authors.

    View full text