Eye movements in chorea-acanthocytosis
Libe Gradstein1, Adrian Danek, Jordan Grafman
1Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA. libe@nei.nih.gov
Insights
Chorea-acanthocytosis (ChAc) patients show significant eye movement abnormalities, including saccadic intrusions and impaired saccades. These findings suggest brainstem involvement and aid in ChAc diagnosis and monitoring.
Area of Science:
- Neuro-ophthalmology
- Neurodegenerative diseases
- Genetics
Background:
- Chorea-acanthocytosis (ChAc) is a rare, autosomal recessive neurodegenerative disorder characterized by movement abnormalities and acanthocytosis.
- Mutations in the VPS13A gene cause ChAc, leading to basal ganglia degeneration.
- Ocular involvement in ChAc has been historically understudied compared to other neurodegenerative conditions like Huntington's disease.
Purpose of the Study:
- To systematically describe and quantify eye movement abnormalities in patients diagnosed with chorea-acanthocytosis (ChAc).
- To investigate potential neurodegeneration in brainstem regions beyond the basal ganglia in ChAc patients.
- To evaluate the utility of eye movement recordings for diagnosing ChAc and monitoring disease progression.
Main Methods:
- Included three ChAc patients (ages 26, 30, 44) and six healthy controls (ages 31-48).
- Patients exhibited clinical signs of ChAc, including dystonia, chorea, parkinsonism, and cognitive deficits, alongside acanthocytosis and VPS13A mutations.
- Neuro-ophthalmic examinations and magnetic search coil technique recorded eye movements (fixation, saccades, pursuit, antisaccades) for comparison between patients and controls.
Main Results:
- ChAc patients displayed significantly increased square-wave jerks (>30/min) compared to controls (0-8/min).
- Abnormalities included fractionated, hypometric saccades, and reduced saccadic peak velocity, particularly for vertical movements.
- Low gain in pursuit and abnormal antisaccade testing were observed in patients, suggesting widespread ocular motor dysfunction.
Conclusions:
- Eye movement abnormalities in ChAc indicate neurodegeneration extending to the brainstem, beyond the basal ganglia.
- Pronounced ocular motor deficits are characteristic of this progressive neurodegenerative disease.
- Eye movement analysis offers a valuable tool for ChAc diagnosis, progression monitoring, and potential therapeutic assessments.
Purpose:
To describe the eye movement abnormalities in patients with chorea-acanthocytosis (ChAc), a form of neuroacanthocytosis. This autosomal recessive, neurodegenerative disorder with aberrant erythrocyte morphology (acanthocytosis) is caused by mutations in the VPS13A gene. In contrast to Huntington's disease (for which ChAc has occasionally been mistaken), ocular involvement in ChAc has not been systematically studied.
Methods:
Three patients aged 26, 30, and 44 years with ChAc and six normal volunteers aged 31 to 48 years were included. Patients had dystonia, chorea, parkinsonism, dysarthria, dysphagia, seizures, cognitive abnormalities, and acanthocytosis. All had heterozygous VPS13A mutations and degeneration of the basal ganglia on magnetic resonance imaging (MRI) typical of ChAc. Patients had an extensive clinical and laboratory work-up. Neuro-ophthalmic examinations and eye movement recordings made with the magnetic search coil technique assessed patients' fixation characteristics, horizontal and vertical saccades, pursuit, and antisaccades. These were compared to the data of control subjects.
Results:
Patients exhibited more than 30 square-wave jerks (small saccadic intrusions) per minute, versus 0 to 8 in the control subjects, as well as fractionated (multistep) and hypometric horizontal and vertical saccades. Decreased saccadic peak-velocity and reduced saccadic range were more pronounced for vertical saccades. Pursuit testing performed in two patients showed low gain. Results of antisaccade testing done in one patient were abnormal.
Conclusions:
The findings suggest brain stem involvement as an additional site of neurodegeneration outside the basal ganglia in ChAc. Patients with this progressive, intractable disease have pronounced ocular motor abnormalities. Eye movement recordings could assist in diagnosing ChAc, monitoring its progression and possible treatment evaluation.
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