Comparing ataxias with oculomotor apraxia: a multimodal study of AOA1, AOA2 and AT focusing on video-oculography and alpha-fetoprotein

Abstract

Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7–15 µg/L), AOA2 (15–65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.

Novel MAG Variant Causes Cerebellar Ataxia with Oculomotor Apraxia: Molecular Basis and Expanded Clinical Phenotype

“…In adulthood, the main clinical picture was of AOA with severe peripheral neuropathy and no pyramidal signs. As opposed to other AOA types [21,30], patients had no movement disorders, no suggestive biochemical anomalies, and all had optic neuropathy. When comparing with previously identified patients with MAG variants [8][9][10][11], the absence of pyramidal signs was a clear-cut difference.…”

Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature

“…2,5 A thorough study using video-oculography (VO) could not distinguish AOA2 from A-T or AOA1. 9 On the other hand, strabismus can precede ataxia and its presence is highly suggestive of AOA2. 2,3 In addition, early AO in AOA2 is associated with a higher frequency of strabismus.…”

Movement Disorders in Genetic Pediatric Ataxias

“…Upper limb dystonia was reported in approximately 36% to 50% of AOA1 patients, sometimes being the presenting feature and resulting in delayed diagnosis. 35,[40][41][42] Other movement disorders reported in a series of 11 AOA1 patients include tremor (36%), myoclonus (18%), and parkinsonism (9%). 40 AOA Type 2…”

“…35,[40][41][42] Other movement disorders reported in a series of 11 AOA1 patients include tremor (36%), myoclonus (18%), and parkinsonism (9%). 40 AOA Type 2…”